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Running Title:Olfactory Position PaperTYPE OF ARTICLE:OTHER (Position paper)Position Paper on Olfactory DysfunctionHummel T1, Whitcroft KL1-3, Andrews P2 4, Altundag A5, Cinghi C6, Costanzo RM7, Damm M8, Frasnelli J9,10, Gudziol H11, Gupta N12, Haehner A1, Holbrook E13, Hong SC14, Hornung D15, Hüttenbrink KB16, Kamel R17, Kobayashi M18, Konstantinidis I19, Landis BN20,21, Leopold DA22, Macchi A23, Miwa T24, Moesges R25, Mullol J26, Mueller CA27, Ottaviano G28, Passali GC29, Philpott C30,31, Pinto JM32, Ramakrishnan VJ33, Rombaux P34, Roth Y35, Schlosser RA36, Shu B37, Soler G38, Stj?rne P39, Stuck BA40, Vodicka J41, Welge-Luessen A42Author Affiliations:Smell and Taste Clinic, Department of Otorhinolaryngology, TU Dresden, Dresden, Germany UCL Ear Institute, Faculty of Brain Sciences, University College London, London, UKCentre for the Study of the Senses, Institute of Philosophy, School of Advanced Studies, University of London, London, UKRoyal National Throat Nose & Ear Hospital, London, UKDepartment of Otorhinolaryngoglogy, Istanbul Surgery Hospital, Istanbul, TurkeyDepartment of Otolaryngology; Eskisehir Osmangazi University, Istanbul, TurkeySmell and Taste Disorders Center, Department of Otolaryngology Head and Neck Surgery, VCU School of Medicine, Richmond, VA, USADepartment of Otorhinolaryngology, Head and Neck Surgery, University of Cologne Medical Center, Cologne, GermanyResearch Chair in Chemosensory Neuroanatomy, Department of Anatomy, Université du Québec à Trois-Rivières, Trois-Rivières, QC, CanadaCentre for Advanced Research in Sleep Medicine, H?pital du Sacré-Coeur de Montréal, Montréal, QC, CanadaDepartment of Otorhinolaryngology, University of Jena, Jena, GermanyDepartment of Otorhinolaryngology, University College of Medical Sciences and GTB Hospital, Delhi, IndiaDepartment of Otolaryngology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USADepartment of Otorhinolaryngology, Konkuk University Medical Center, Hwayang-dong, Gwangjin-gu, Seoul, South KoreaDept. of Biology, St. Lawrence University, Canton, NY, USADepartment of Otorhinolaryngology, University of Cologne, Cologne, GermanyDepartment of Otorhinolaryngology, Cairo University, Cairo, EgyptDepartment of Otorhinolaryngology-Head and Neck Surgery, Mie University Graduate School of Medicine, Mie, JapanSmell and Taste Clinic, Second Academic Otorhinolaryngology Department, Papageorgiou Hospital, Aristotle University of Thessaloniki, Thessaloniki, GreeceDepartment for ENT, Head and Neck Surgery, Bern University Hospital, Bern, SwitzerlandRhinology-Olfactology Unit, Department of Otorhinolaryngology-Head and Neck Surgery, University Hospital of Geneva Medical School, Geneva, SwitzerlandDivision of Otorhinolaryngology-Head and Neck Surgery, Department of Surgery, University of Vermont Medical Center, Burlington, Vermont, USAENT Clinic, University of Insubria, ASST, sette laghi, Varese, ItalyDepartment of Otorhinolaryngology, Kanazawa Medical University, Uchinada, Kahoku, Ishikawa, Japan Institute of Medical Statistics, Informatics and Epidemiology, University Hospital of Cologne, Cologne, GermanyRhinology Unit & Smell Clínic, IDIBAPS, University of Barcelona, Barcelona, Catalonia, SpainDepartment of Otorhinolaryngology, Medical University of Vienna, Vienna, AustriaDepartment of Neurosciences DNS, Otolaryngology Section, University, Padua, ItalyHead and Neck section, Department of Aging, Neurosciences, Head and Neck and Orthopedic; Catholic University of Sacred heart, “A. Gemelli” Hospital Foundation, Rome, ItalyNorwich Medical School, University of East Anglia, Norwich, UKThe Smell & Taste Clinic, James Paget University Hospital, Gorleston, UKSection of Otolaryngology-Head and Neck Surgery, The University of Chicago Medicine and Biological Sciences, Chicago, Ill, USADepartments of Otolaryngology and Neurosurgery, University of Colorado, Aurora, CO, USAUniversité Catholique de Louvain, Institute of Neurosciences, Unit of Otorhinolaryngology, Brussels, BelgiumThe Institute for Nose and Sinus Therapy and Clinical Investigations, Department of Otolaryngology - Head & Neck Surgery, Edith Wolfson Medical Center, Tel Aviv University Sackler Faculty of Medicine, Holon, Israel?Department of Otolaryngology – Head and Neck Surgery, Medical Univeristy of South Carolina, Charleston, SC, USADepartment of Otolaryngology, Taipei Veterans General Hospital, National Yang-Ming University School of Medicine Faculty of Medicine, Taipei, TaiwanDivision of Otorhinolaryngology, Area of Smell and Taste, Hospital de Clínicas, University of Buenos Aires, Buenos Aires City, ArgentinaSection of Rhinology, Department of Otorhinolaryngology, Karolinska University Hospital and Karolinska Institutet, Stockhollm, SwedenDepartment of Otorhinolaryngology, Head and Neck Surgery, University Hospital Essen, University Duisburg-Essen, GermanyDepartment of Otorhinolaryngology and Head and Neck Surgery, Hospital Pardubice, Faculty of Health Studies, University of Pardubice, Pardubice, Czech RepublicUniversity Hospital Basel - Otorhinolaryngology, Basel, SwitzerlandAuthor Email Addresses: thummel@mail.zih.tu-dresden.dek.whitcroft@aaltundagkbb@antje.haehner@uniklinikum-dresden.de jordan_orl@Basile.Landis@hcuge.chJMULLOL@clinic.catC.Philpott@uea.ac.ukphilippe.rombaux@uclouvain.beAntje.Welge-Luessen@usb.chjohannes.a.frasnelli@uqtr.castudiodottormacchi@virgilio.itschlossr@musc.educcingi@orl@wolfson..il?dhornung@stlawu.edumiwataka@kanazawa-med.ac.jpkarl-bernd.huettenbrink@uk-koeln.depar.stjarne@karolinska.seDonald.Leopold@write2drneelima@giancarlo.ottaviano@unipd.itboris.stuck@uk-essen.degiulio.passali@rm.unicatt.itmichael.damm@uni-koeln.dedragracielasoler@.arjan_vodicka@peterandrews@entpeterandrews.co.ukVijay.Ramakrishnan@ucdenver.educhihhung003@jpinto@surgery.bsd.uchicago.edurhinologyrhk@christian.a.mueller@meduniwien.ac.atralph@moesges.dem-koba@doc.medic.mie-u.ac.jpHilmar.Gudziol@med.uni-jena.derichard.costanzo@Eric_Holbrook@meei.harvard.edu20050692@kuh.ac.krCorresponding Author: Thomas Hummel, M.D.; Smell and Taste Clinic, Department of Otorhinolaryngology, TU Dresden, Fetscherstrasse 74, 01307 Dresden, Germany; phone +49-351-458-4189; thummel@mail.zih.tu-dresden.de Statement: All authors agree on the sections entitled “recommendations”. Key Words (MeSH headings): Smell, Olfaction Disorders, Therapeutics, Investigative Techniques SUMMARY:Background:Olfactory dysfunction is an increasingly recognised condition, associated with reduced quality of life and major health outcomes such as neurodegeneration and death. However, translational research in this field is limited by heterogeneity in methodological approach, including definitions of impairment, improvement and appropriate assessment techniques. Accordingly, effective treatments are limited. In an effort to encourage high quality and comparable work in this field, among others, we propose the following ideas and recommendations. Whilst full recommendations are outlined in the main document, key points include:Patients with suspected olfactory loss should undergo a full examination of the head and neck, including rigid nasal endoscopy. Subjective olfactory assessment should not be undertaken in isolation, given its poor reliability.Psychophysical assessment tools used in clinical and research settings should include reliable and validated tests of odour threshold, and/or one of odour identification or discrimination. Comprehensive chemosensory assessment should include gustatory screening.Smell training can be helpful in patients with olfactory loss of several aetiologies.Conclusions:We hope the current manuscript will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency and generalisability of work in this field. Word Count: 198Table of Contents6Introduction7Definitions9Epidemiology of Olfactory Dysfunction9Subjective Reporting10Psychophysical Testing13Anatomy and Physiology of Olfaction15Causes and Classification of Olfactory Loss16Olfactory Dysfunction Secondary to Sinonasal Disease17Post-Infectious Olfactory Dysfunction18Posttraumatic Olfactory Dysfunction19Olfactory Dysfunction Associated with Neurological Disease19Olfactory Dysfunction Associated with Exposure to Toxins/Medications20Congenital Olfactory Dysfunction20Olfactory Dysfunction Associated with Normal Aging21Other Causes of Olfactory Dysfunction22Idiopathic Olfactory Dysfunction23Clinical Assessment23History25Examination26Olfactory Testing27Subjective Assessment28Psychophysical Testing35Electrophysiology and Functional Imaging35Other Investigations37Treatment of Olfactory Dysfunction37Medications37Corticosteroids38Phosphodiesterase Inhibitors39Intranasal Calcium Buffers39Olfactory Training41Surgery43Conclusions44Acknowledgements44Authorship Contribution45Conflict of Interest46References73Corresponding Author74Tables90Legends for Tables IntroductionOlfactory dysfunction is an increasingly recognised condition. However, the sense of smell remains relatively poorly researched and is often neglected by the medical community: in 2007 a UK-based survey found that whilst 97% of consultant otorhinolaryngologists managed olfactory dysfunction, 55% did not formally test for chemosensory impairment, and of those who did, only 12% did so routinely (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1017/S0022215107006615", "ISBN" : "0022215107", "ISSN" : "1748-5460 (Electronic)", "PMID" : "17359559", "abstract" : "Background: The diagnosis and management of olfactory disorders is an often neglected topic in otolaryngology. This article evaluates current clinical practice within the United Kingdom, and provides a literature-based review of the diagnosis, management and prognosis of olfactory pathology. Design: A questionnaire was sent to consultant and associate specialist members of the British Association of Otolaryngologists and Head and Neck Surgeons. The responses were documented to gain an impression of how olfactory disorders are managed in the United Kingdom. The literature relating to olfactory dysfunction was then evaluated and the findings summarised. Conclusions: Management of olfactory pathology varies across the United Kingdom. The literature suggests that chemosensory testing is optimal and that both forced-choice and threshold testing should be applied if objective evaluation is required. Imaging can be of value but the appropriate technique should be used. Olfactory function can recover following head injury, viral infection and chronic sinonasal disease, although varying degrees of dysfunction are likely to persist. There is a role for the use of corticosteroids, particularly when administered systemically. More research is needed to establish the appropriate dose and length of treatment. \u00a9 2007 JLO (1984) Limited.", "author" : [ { "dropping-particle" : "", "family" : "McNeill", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramakrishnan", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carrie", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Laryngology and Otology", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "713-720", "title" : "Diagnosis and management of olfactory disorders: Survey of UK-based consultants and literature review", "type" : "article-journal", "volume" : "121" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "1", "plainTextFormattedCitation" : "1", "previouslyFormattedCitation" : "1" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }1).This putative neglect may be due to the perceived subtle effects of olfactory dysfunction and frustration at the apparent lack of treatment options. However, there is increasing evidence that olfactory impairment can affect quality of life, through environmental and social anxiety, food and weight disturbances and depression (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00415-016-8227-8", "ISSN" : "0340-5354", "author" : [ { "dropping-particle" : "", "family" : "Croy", "given" : "Ilona", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Neurology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2016", "7", "8" ] ] }, "title" : "Olfaction as a marker for depression", "type" : "article-journal", "volume" : "Epub ahead" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1093/chemse/bjt072", "ISBN" : "0379-864X", "ISSN" : "0379864X", "PMID" : "24429163", "abstract" : "Olfactory disorders are common and affect about one-fifth of the general population. The main causes of olfactory loss are post viral upper respiratory infection, nasal/sinus disease, and head trauma and are therefore very frequent among patients in ear, nose, and throat clinics. We have systematically reviewed the impact of quantitative, qualitative, and congenital olfactory disorders on daily life domains as well as on general quality of life and depression. From the extensive body of literature, it can be concluded that loss of the sense of smell leads to disturbances in important areas, mainly in food enjoyment, detecting harmful food and smoke, and to some extent in social situations and working life. Most patients seem to deal well and manage those restrictions. However, a smaller proportion has considerable problems and expresses a noticeable reduction in general quality of life and enhanced depression. The impact of coping strategies is discussed.", "author" : [ { "dropping-particle" : "", "family" : "Croy", "given" : "Ilona", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nordin", "given" : "Steven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemical Senses", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "185-194", "title" : "Olfactory disorders and quality of life-an updated review", "type" : "article-journal", "volume" : "39" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1093/chemse/bjw061", "ISBN" : "1464-3553 (Electronic) 0379-864X (Linking)", "ISSN" : "0379-864x", "PMID" : "27170667", "abstract" : "Previous studies on the relationship between olfaction and depression have revealed mixed results. In addition, few have focused on the reciprocity of this association. The aim of this study is to combine depression and olfactory data in two separate patient populations to further understand their association. A systematic literature review was conducted using 3 online databases to identify studies correlating olfaction and depression in patients presenting with either primary depression or primary olfactory dysfunction. For the depressed population, weighted means and standard deviations for the Sniffin' Sticks Test and the 40-item Smell Identification Test were combined using 10 studies. For the olfactory dysfunction population, weighted means of Beck's Depression Inventory were combined using 3 studies. Independent t-tests were used to compare differences between groups. Comparing primary depressed patients with controls, depressed patients showed decreased scores in olfactory threshold (6.31+/-1.38 vs. 6.78+/-0.88, P = 0.0005), discrimination (12.05+/-1.44 vs. 12.66+/-1.36, P = 0.0073), identification (12.57+/-0.74 vs. 12.98+/-0.90, P < 0.0001), and 40-Item Smell Identification Test (35.31+/-1.91 vs. 37.41+/-1.45, P < 0.0001). In patients with primary olfactory dysfunction, Beck's Depression Inventory scores were significantly different between patients classified as normosmics, hyposmics and anosmics (5.21+/-4.73 vs. 10.93+/-9.25 vs. 14.15+/-5.39, P </= 0.0274 for all 3 comparisons). In conclusion, patients with depression have reduced olfactory performance when compared with the healthy controls and conversely, patients with olfactory dysfunction, have symptoms of depression that worsen with severity of smell loss.", "author" : [ { "dropping-particle" : "", "family" : "Kohli", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soler", "given" : "Z M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nguyen", "given" : "S A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muus", "given" : "J S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schlosser", "given" : "R J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chem Senses", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "479-486", "title" : "The Association Between Olfaction and Depression: A Systematic Review", "type" : "article-journal", "volume" : "41" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1001/archotol.127.5.497", "ISBN" : "0886-4470 (Print)", "ISSN" : "0886-4470", "PMID" : "11346423", "abstract" : "To determine whether olfactory loss affects patients' quality of life or level of disability.", "author" : [ { "dropping-particle" : "", "family" : "Miwa", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Furukawa", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsukatani", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Costanzo", "given" : "R M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "DiNardo", "given" : "L J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reiter", "given" : "E R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of Otolaryngology Head Neck Surgery", "id" : "ITEM-4", "issue" : "5", "issued" : { "date-parts" : [ [ "2001" ] ] }, "page" : "497-503", "title" : "Impact of olfactory impairment on quality of life and disability.", "type" : "article-journal", "volume" : "127" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1093/chemse/bju043", "ISBN" : "1464-3553; 0379-864X", "ISSN" : "14643553", "PMID" : "25201900", "abstract" : "Olfactory disorders are believed to affect 5% of the general population and have been shown to bear significant psychosocial consequences to sufferers. Although more common than blindness and profound deafness in the United Kingdom, the impact of these disorders has not been assessed to date and the plight of British patients has yet to be quantified. In 2012, a patient support organization, Fifth Sense, was founded to provide information and support to sufferers of chemosensory disorders. Following a recent members conference, a survey of the membership was conducted anonymously using a series of questions based on an existing olfactory disorders questionnaire. From 496 respondents, this has demonstrated high rates of depression (43%) and anxiety (45%), impairment of eating experience (92%), isolation (57%), and relationship difficulties (54%). Women appear to have significantly more issues than men in terms of social and domestic dysfunction relating to olfactory loss (P = 0.01). Qualitative disorders also affected more than 1 in 5 members with parosmia reported in 19% and phantosmia in 24%. This paper discusses the details of the British story of anosmia and other related disorders as depicted by those most affected.", "author" : [ { "dropping-particle" : "", "family" : "Philpott", "given" : "Carl M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boak", "given" : "Duncan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemical senses", "id" : "ITEM-5", "issue" : "8", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "711-718", "title" : "The impact of olfactory disorders in the United kingdom", "type" : "article-journal", "volume" : "39" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.4193/Rhin15.209", "ISSN" : "03000729", "abstract" : "BACKGROUND: Olfactory loss is highly prevalent, and comorbid mood disorders are common. Considering olfactory input is highly interconnected with the limbic system, and that the limbic system manages mood, it is predictable that impairments in the sense of smell may result in mood changes. METHODOLOGY: Chronic olfactory deficits were induced by repeated intranasal irrigation of ZnSO4 for 12 weeks in BALB/c mice. H&E staining, OMP staining, and potato chip finding test were performed to confirm olfactory loss. Tail suspension, forced swim, and splash tests were performed to evaluate depression, as well as open field, elevated plus maze tests were applied to assess anxiety. The mRNA levels of glucocorticoid receptor (GR) and corticotropin releasing hormone (CRH) were measured by real-time PCR to confirm relevant molecular changes. RESULTS: Disruption of the olfactory epithelium and olfactory loss was confirmed in histological studies and potato chip finding test. Behavioral tests show that the chronic anosmic state caused increased depression and reduced anxiety. PCR data showed that mRNA levels of GR in the hypothalamus and CRH in the amygdala were significantly decreased. CONCLUSIONS: These results propose that ZnSO4-induced chronic anosmia can cause a depressive and anxiolytic state via decreased hypothalamic GR and amygdalar CRH.", "author" : [ { "dropping-particle" : "", "family" : "Ahn", "given" : "Sangzin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shin", "given" : "Hyun Woo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahmood", "given" : "Usman", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khalmuratova", "given" : "Roza", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jeon", "given" : "Sea Yuong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jin", "given" : "Hong R yul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Choi", "given" : "Jung Seok", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Hye Sun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Dae W oo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-6", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "80-87", "title" : "Chronic anosmia induces depressive behavior and reduced anxiety via dysregulation of glucocorticoid receptor and corticotropin-releasing hormone in a mouse model", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "2\u20137", "plainTextFormattedCitation" : "2\u20137", "previouslyFormattedCitation" : "2\u20137" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }2–7). Moreover, a growing body of evidence connects olfaction to major health outcomes, including neurodegenerative disease and death (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/gerona/glw036", "ISSN" : "1758-535X", "PMID" : "26946102", "abstract" : "BACKGROUND Sensory impairments increase with age and the majority of older people will experience a sensory impairment if they live long enough. However, the relationships of hearing, visual, and olfactory impairments with mortality are not well understood. METHODS Epidemiology of Hearing Loss Study participants (n = 2,418) aged 53-97 years (mean = 69 years) were examined in 1998-2000 and hearing, visual acuity, and olfaction were measured. Participants were followed for mortality for up to 17 years (mean = 12.8 years). Cox proportional hazards models were used to assess the association between prevalent sensory impairments and the 15-year cumulative incidence of death. RESULTS A total of 1,099 (45.4%) of participants died during the follow-up period. In age- and sex-adjusted Cox models, the risk of mortality was higher among participants with one (hazard ratio [HR] = 1.40, 95% confidence interval [CI] = 1.19, 1.64) or two or more (HR = 2.12, 95% CI = 1.74, 2.58) sensory impairments than among participants with no sensory impairments. Olfactory impairment at baseline was significantly associated with mortality (HR = 1.28, 95% CI = 1.07, 1.52) after adjusting for age, sex, sensory comorbidities, cardiovascular risk factors and disease, cognitive impairment, frailty, subclinical atherosclerosis, and inflammatory marker levels (n = 1,745). Hearing and visual impairment were not associated with mortality after adjusting for subclinical atherosclerosis and inflammation. CONCLUSION Olfactory impairment, but not hearing or visual impairment, was associated with an increased risk of mortality. These results suggest that olfactory impairment may be a marker of underlying physiologic processes or pathology that is associated with aging and reduced survival in older adults.", "author" : [ { "dropping-particle" : "", "family" : "Schubert", "given" : "Carla R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fischer", "given" : "Mary E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinto", "given" : "A. Alex", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klein", "given" : "Barbara E K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klein", "given" : "Ronald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tweed", "given" : "Ted S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cruickshanks", "given" : "Karen J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The journals of gerontology. Series A, Biological sciences and medical sciences", "id" : "ITEM-1", "issue" : "00", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "1-6", "title" : "Sensory Impairments and Risk of Mortality in Older Adults.", "type" : "article-journal", "volume" : "00" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1093/gerona/glu158", "ISBN" : "1079-5006", "ISSN" : "1758535X", "PMID" : "25182599", "abstract" : "BACKGROUND: The purpose of this study was to determine if subclinical markers of atherosclerosis are associated with a decline in olfactory function. METHODS: The San Diego Odor Identification Test was administered to 2,302 participants (age 21-84 years) at the baseline (2005-2008) and 5-year follow-up (2010-2013) examinations of the Beaver Dam Offspring Study. A decline in odor identification was defined as a decrease in San Diego Odor Identification Test score of 2 or more (range 0-8) from Beaver Dam Offspring Study 1 to Beaver Dam Offspring Study 2. Carotid intima media thickness and plaque, blood pressure, pulse wave velocity, and body mass index were measured and other risk factor data were obtained by interview. RESULTS: Overall 3.2% of participants had a decline in San Diego Odor Identification Test score at 5 years. In age- and sex-adjusted models, mean intima media thickness (odds ratio = 1.17, 95% CI = 1.01, 1.34, per 0.1 mm) and number of sites (range 0-6) with carotid artery plaque (odds ratio = 1.35, 95% CI = 1.11, 1.65, per site) at baseline were associated with an increased risk for decline. Plaque score (odds ratio = 1.24, 95% CI = 1.01, 1.53) remained a significant independent predictor of olfactory decline in a model that included age, sex, hypertension, body mass index, alcohol, and smoking. CONCLUSIONS: Subclinical atherosclerosis was associated with an increased risk for olfactory decline indicating that atherosclerosis may be one of the risk factors for the decline in olfactory function seen with aging. Strategies to improve vascular health may also benefit olfactory health.", "author" : [ { "dropping-particle" : "", "family" : "Schubert", "given" : "Carla R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cruickshanks", "given" : "Karen J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fischer", "given" : "Mary E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huang", "given" : "Guan Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klein", "given" : "Ronald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsai", "given" : "Michael Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinto", "given" : "A. Alex", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journals of Gerontology - Series A Biological Sciences and Medical Sciences", "id" : "ITEM-2", "issue" : "7", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "879-884", "title" : "Carotid intima media thickness, atherosclerosis, and 5-year decline in odor identification: The beaver dam offspring study", "type" : "article-journal", "volume" : "70" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "8,9", "plainTextFormattedCitation" : "8,9", "previouslyFormattedCitation" : "8,9" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }8,9). It is therefore important that olfactory dysfunction is both investigated and treated where possible, particularly amongst ENT specialists. This is reflected in the recent inclusion of olfactory impairment as part of the ENT-UK ‘GENERATE’ national agenda for research (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "URL" : "", "author" : [ { "dropping-particle" : "", "family" : "Bohm", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marshall", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fulop", "given" : "NJ", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lund", "given" : "VJ", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schilder", "given" : "AGM", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "ENT-UK", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "title" : "The Research Agenda for ENT , Hearing and Balance Care A UK Partnership of Patients , Professionals and the Public", "type" : "webpage" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "10", "plainTextFormattedCitation" : "10", "previouslyFormattedCitation" : "10" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }10), as well as continued emphasis within the United States National Institutes of Health/National Institute on Deafness and Other Communication Disorders strategic plan (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "URL" : "", "author" : [ { "dropping-particle" : "", "family" : "Health", "given" : "National Institutes of", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "US Department of Health and Human Services", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "title" : "National Institute on Deafness and Other Communication Disorders (NIDCD)", "type" : "webpage" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "11", "plainTextFormattedCitation" : "11", "previouslyFormattedCitation" : "11" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }11). At present, the literature on olfaction is limited by heterogeneity in methodological approach. This heterogeneity is reflected in varying definitions of impairment and improvement, lack of consensus regarding appropriate testing methods and wide variations in epidemiological estimates. Therefore, we propose the following definitions and ideas in an effort to improve this evidence base, and in so doing improve patient care. At the same time, we are aware that this cannot be a complete approach unifying all people working in this field of research, but rather a starting point for future development. DefinitionsOlfactory dysfunction can be classified as either quantitative, involving alteration in the strength but not quality of odours, or qualitative, in which the quality of odours is changed. Qualitative disorders, such as parosmia, often involve negatively perceived changes in quality of smell. Very often, qualitative changes are found in combination with quantitative changes, whereas it is much less frequent to find qualitative changes alone. With regards to qualitative changes, parosmia and phantosmia often occur together. Definitions of terms used to describe olfactory function and dysfunction are listed in Table 1.[Table 1]*There is some disagreement in the literature regarding terminology. Whilst ‘parosmia’ is generally used to indicate a qualitative olfactory distortion in the presence of a stimulus, it has on occasion been used to describe more general olfactory dysfunction (including quantitative loss) (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/chemse/27.7.611", "ISSN" : "14643553", "PMID" : "12200340", "abstract" : "Clinically, olfaction can fail in any of three ways: (i) decreased sensitivity (hyposmia, anosmia) and two types of distortion (dysosmia); (ii) distorted quality of an odorant stimulation (troposmia); (iii) perceived odor when no odorant is present (phantosmia, hallucination). The distortions are usually much more upsetting to a person's quality of life than a simple loss. An ipsilatersal loss of olfactory sensitivity is often identified in the nostril with any type of olfactory distortion. The pathophysiology of a stimulated distortion (troposmia) is likely a decreased number of functioning olfactory primary neurons so that an incomplete characterization of the odorant is made. In phantosmia, two possible causations include an abnormal signal or inhibition from the primary olfactory neurons or peripheral olfactory or trigeminal signals that \"trigger\" a central process. The clinician's goal is to carefully define the problem (e.g. taste versus smell, real versus perceived, one versus two nostrils), to perform the appropriate examination and testing and to provide therapy if possible. Treatment includes assurance with no active therapy (because many of these will naturally resolve), topical medications, systemic medications, anesthesia to parts of the nose and, rarely, referral for surgical excision of olfactory neurons. Endoscopic transnasal operations have the advantage of treating phantosmia and sometimes allowing a return of olfactory ability after the operation.", "author" : [ { "dropping-particle" : "", "family" : "Leopold", "given" : "Donald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemical Senses", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2002" ] ] }, "page" : "611-615", "title" : "Distortion of Olfactory Perception: Diagnosis and Treatment", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "14", "plainTextFormattedCitation" : "14", "previouslyFormattedCitation" : "14" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }14). ‘Dysosmia’ has been used by some to describe any distortion in olfaction, which would therefore include both quantitative and qualitative changes (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/chemse/27.7.611", "ISSN" : "14643553", "PMID" : "12200340", "abstract" : "Clinically, olfaction can fail in any of three ways: (i) decreased sensitivity (hyposmia, anosmia) and two types of distortion (dysosmia); (ii) distorted quality of an odorant stimulation (troposmia); (iii) perceived odor when no odorant is present (phantosmia, hallucination). The distortions are usually much more upsetting to a person's quality of life than a simple loss. An ipsilatersal loss of olfactory sensitivity is often identified in the nostril with any type of olfactory distortion. The pathophysiology of a stimulated distortion (troposmia) is likely a decreased number of functioning olfactory primary neurons so that an incomplete characterization of the odorant is made. In phantosmia, two possible causations include an abnormal signal or inhibition from the primary olfactory neurons or peripheral olfactory or trigeminal signals that \"trigger\" a central process. The clinician's goal is to carefully define the problem (e.g. taste versus smell, real versus perceived, one versus two nostrils), to perform the appropriate examination and testing and to provide therapy if possible. Treatment includes assurance with no active therapy (because many of these will naturally resolve), topical medications, systemic medications, anesthesia to parts of the nose and, rarely, referral for surgical excision of olfactory neurons. Endoscopic transnasal operations have the advantage of treating phantosmia and sometimes allowing a return of olfactory ability after the operation.", "author" : [ { "dropping-particle" : "", "family" : "Leopold", "given" : "Donald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemical Senses", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2002" ] ] }, "page" : "611-615", "title" : "Distortion of Olfactory Perception: Diagnosis and Treatment", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "14", "plainTextFormattedCitation" : "14", "previouslyFormattedCitation" : "14" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }14,ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3109/00016489.2012.659759", "ISBN" : "0001-6489", "ISSN" : "0001-6489", "PMID" : "22582778", "abstract" : "The sense of smell provides people with valuable input from the chemical environment around them. The human sense of smell generally fails in three ways; one is an intensity reduction and the other two are the quality of changes. Smell disorders can be classified into central or peripheral depending on their origin. Central causes can be related to an area of hyper-functioning brain cells generating this odor perception, thus olfactory distortions have also been observed with epilepsy and migraine. In this paper, we present a review of the current clinical understanding of olfactory distortions and discuss how they can be evaluated and therapies to treat this debilitating condition.", "author" : [ { "dropping-particle" : "", "family" : "Hong", "given" : "Seok-Chan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holbrook", "given" : "Eric H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leopold", "given" : "Donald A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Acta Oto-laryngologica", "id" : "ITEM-1", "issue" : "S1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "S27-S31", "title" : "Distorted olfactory perception: A systematic review", "type" : "article-journal", "volume" : "132" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "15", "plainTextFormattedCitation" : "15", "previouslyFormattedCitation" : "15" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }15). However, others have used this term with reference to qualitative dysfunction in the presence of an odourant stimulus only, thus making it synonymous with parosmia (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0-8247-0719-2", "author" : [ { "dropping-particle" : "", "family" : "Murphy", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doty", "given" : "Richard L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duncan", "given" : "H J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "chapter-number" : "22", "container-title" : "Handbook of Olfaction and Gustation", "edition" : "3rd", "editor" : [ { "dropping-particle" : "", "family" : "Doty", "given" : "Richard L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "461-478", "publisher" : "Marcel Dekker", "publisher-place" : "New York", "title" : "Clinical disorders of olfaction", "type" : "chapter" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "16", "plainTextFormattedCitation" : "16", "previouslyFormattedCitation" : "16" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }16). Whilst the term ‘cacosmia’ is generally accepted as a ‘negatively perceived olfactory distortion’, some consider this either a form of parosmia (stimulus present) (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0-8247-0719-2", "author" : [ { "dropping-particle" : "", "family" : "Murphy", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doty", "given" : "Richard L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duncan", "given" : "H J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "chapter-number" : "22", "container-title" : "Handbook of Olfaction and Gustation", "edition" : "3rd", "editor" : [ { "dropping-particle" : "", "family" : "Doty", "given" : "Richard L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "461-478", "publisher" : "Marcel Dekker", "publisher-place" : "New York", "title" : "Clinical disorders of olfaction", "type" : "chapter" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "16", "plainTextFormattedCitation" : "16", "previouslyFormattedCitation" : "16" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }16), phantosmia (stimulus absent) (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/chemse/27.7.611", "ISSN" : "14643553", "PMID" : "12200340", "abstract" : "Clinically, olfaction can fail in any of three ways: (i) decreased sensitivity (hyposmia, anosmia) and two types of distortion (dysosmia); (ii) distorted quality of an odorant stimulation (troposmia); (iii) perceived odor when no odorant is present (phantosmia, hallucination). The distortions are usually much more upsetting to a person's quality of life than a simple loss. An ipsilatersal loss of olfactory sensitivity is often identified in the nostril with any type of olfactory distortion. The pathophysiology of a stimulated distortion (troposmia) is likely a decreased number of functioning olfactory primary neurons so that an incomplete characterization of the odorant is made. In phantosmia, two possible causations include an abnormal signal or inhibition from the primary olfactory neurons or peripheral olfactory or trigeminal signals that \"trigger\" a central process. The clinician's goal is to carefully define the problem (e.g. taste versus smell, real versus perceived, one versus two nostrils), to perform the appropriate examination and testing and to provide therapy if possible. Treatment includes assurance with no active therapy (because many of these will naturally resolve), topical medications, systemic medications, anesthesia to parts of the nose and, rarely, referral for surgical excision of olfactory neurons. Endoscopic transnasal operations have the advantage of treating phantosmia and sometimes allowing a return of olfactory ability after the operation.", "author" : [ { "dropping-particle" : "", "family" : "Leopold", "given" : "Donald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemical Senses", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2002" ] ] }, "page" : "611-615", "title" : "Distortion of Olfactory Perception: Diagnosis and Treatment", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "14", "plainTextFormattedCitation" : "14", "previouslyFormattedCitation" : "14" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }14), or both (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3109/00016489.2012.659759", "ISBN" : "0001-6489", "ISSN" : "0001-6489", "PMID" : "22582778", "abstract" : "The sense of smell provides people with valuable input from the chemical environment around them. The human sense of smell generally fails in three ways; one is an intensity reduction and the other two are the quality of changes. Smell disorders can be classified into central or peripheral depending on their origin. Central causes can be related to an area of hyper-functioning brain cells generating this odor perception, thus olfactory distortions have also been observed with epilepsy and migraine. In this paper, we present a review of the current clinical understanding of olfactory distortions and discuss how they can be evaluated and therapies to treat this debilitating condition.", "author" : [ { "dropping-particle" : "", "family" : "Hong", "given" : "Seok-Chan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holbrook", "given" : "Eric H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leopold", "given" : "Donald A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Acta Oto-laryngologica", "id" : "ITEM-1", "issue" : "S1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "S27-S31", "title" : "Distorted olfactory perception: A systematic review", "type" : "article-journal", "volume" : "132" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "15", "plainTextFormattedCitation" : "15", "previouslyFormattedCitation" : "15" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }15). Euosmia is used to describe pleasant qualitative olfactory distortion in the presence of a stimulus and can therefore be considered a subtype of parosmia (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/00016480510043954", "ISBN" : "0001-6489 (Print)\\r0001-6489 (Linking)", "ISSN" : "0001-6489", "PMID" : "16308262", "abstract" : "The nature of qualitative olfactory disorders such as phantosmia and parosmia is a matter of debate. Parosmia and phantosmia mainly occur in combination with post-traumatic or post-infectious olfactory loss. Rare causes of these disorders such as brain tumors, side-effects of drugs, paraneoplastic syndromes, psychiatric disorders or intracerebral haemorrhage have been reported. Parosmias are distorted sensations of smell elicited by an odor, whereas phantosmias persist permanently or occur without the presence of an odor source. Phantosmias differ widely in terms of their nature. In contrast, parosmias always seem to be unpleasant. We report the case of a female with post-infectious hyposmia who reported a pleasant parosmia to selected odorants. We have called this rare clinical presentation euosmia.", "author" : [ { "dropping-particle" : "", "family" : "Landis", "given" : "B N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frasnelli", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Acta oto-laryngologica", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "101-103", "title" : "Euosmia: a rare form of parosmia.", "type" : "article-journal", "volume" : "126" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "17", "plainTextFormattedCitation" : "17", "previouslyFormattedCitation" : "17" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }17). Troposmia is generally considered to be synonymous with parosmia (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/chemse/27.7.611", "ISSN" : "14643553", "PMID" : "12200340", "abstract" : "Clinically, olfaction can fail in any of three ways: (i) decreased sensitivity (hyposmia, anosmia) and two types of distortion (dysosmia); (ii) distorted quality of an odorant stimulation (troposmia); (iii) perceived odor when no odorant is present (phantosmia, hallucination). The distortions are usually much more upsetting to a person's quality of life than a simple loss. An ipsilatersal loss of olfactory sensitivity is often identified in the nostril with any type of olfactory distortion. The pathophysiology of a stimulated distortion (troposmia) is likely a decreased number of functioning olfactory primary neurons so that an incomplete characterization of the odorant is made. In phantosmia, two possible causations include an abnormal signal or inhibition from the primary olfactory neurons or peripheral olfactory or trigeminal signals that \"trigger\" a central process. The clinician's goal is to carefully define the problem (e.g. taste versus smell, real versus perceived, one versus two nostrils), to perform the appropriate examination and testing and to provide therapy if possible. Treatment includes assurance with no active therapy (because many of these will naturally resolve), topical medications, systemic medications, anesthesia to parts of the nose and, rarely, referral for surgical excision of olfactory neurons. Endoscopic transnasal operations have the advantage of treating phantosmia and sometimes allowing a return of olfactory ability after the operation.", "author" : [ { "dropping-particle" : "", "family" : "Leopold", "given" : "Donald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemical Senses", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2002" ] ] }, "page" : "611-615", "title" : "Distortion of Olfactory Perception: Diagnosis and Treatment", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "14", "plainTextFormattedCitation" : "14", "previouslyFormattedCitation" : "14" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }14).Multiple chemical sensitivity (MCS; also known as ‘Idiopathic Environmental Intolerance’) is a condition in which patients describe a range of subjective symptoms following low-level exposure to various chemicals. Due to the range of organ systems affected, and disparity of offending substances, it has been suggested that MCS is not an organic clinical entity, but rather a predominantly psychological condition. This view has been supported by studies demonstrating no significant difference in patient response to ‘active’ substances versus placebo (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/15563650701742438", "ISSN" : "1556-9519", "PMID" : "18568800", "abstract" : "Multiple Chemical Sensitivity (MCS) is an acquired disorder with recurrent symptoms referable to multiple organ systems. No widely accepted test of physiologic function correlates with symptoms and it has not been recognized as a distinct entity by the scientific community. Few double-blind placebo-controlled studies have been done. The objectives of this study were to test two hypotheses: that patients with MCS can distinguish reliably between solvents and placebo, and that there are significant differences in objective biological and neuropsychological parameters between solvent and placebo exposures.", "author" : [ { "dropping-particle" : "", "family" : "Bornschein", "given" : "Susanne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hausteiner", "given" : "Constanze", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "R\u00f6mmelt", "given" : "Horst", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nowak", "given" : "Dennis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "F\u00f6rstl", "given" : "Hans", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zilker", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical toxicology (Philadelphia, Pa.)", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "443-9", "title" : "Double-blind placebo-controlled provocation study in patients with subjective Multiple Chemical Sensitivity (MCS) and matched control subjects.", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.jaci.2006.07.046", "ISBN" : "0091-6749 (Print)\\r0091-6749 (Linking)", "ISSN" : "00916749", "PMID" : "17137865", "abstract" : "A systematic review of provocation studies of persons reporting multiple chemical sensitivities (MCS) was conducted from databases searched from inception to May 2006. Thirty-seven studies were identified, testing 784 persons reporting MCS, 547 control subjects, and 180 individuals of whom a subset were chemically sensitive. Blinding was inadequate in most studies. In 21 studies odors of chemicals were probably apparent; 19 of these reported positive responses to provocations among chemically sensitive individuals, and 1 study demonstrated that negative expectations were significantly associated with increased symptom reporting after provocations. Seven studies used chemicals at or below odor thresholds, and 6 failed to show consistent responses among sensitive individuals after active provocation. Six studies used forced-choice discrimination and demonstrated that chemically sensitive individuals were not better at detecting odor thresholds than nonsensitive participants. Three studies tested individuals by using nose clips/face masks and confirmed response, possibly mediated through eye exposure. Three studies used olfactory masking agents to conceal stimuli, and none of these found associations between provocations and response. We conclude that persons with MCS do react to chemical challenges; however, these responses occur when they can discern differences between active and sham substances, suggesting that the mechanism of action is not specific to the chemical itself and might be related to expectations and prior beliefs. ?? 2006 American Academy of Allergy, Asthma and Immunology.", "author" : [ { "dropping-particle" : "", "family" : "Das-Munshi", "given" : "Jayati", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rubin", "given" : "G. James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wessely", "given" : "Simon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Allergy and Clinical Immunology", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "1257-1264", "title" : "Multiple chemical sensitivities: A systematic review of provocation studies", "type" : "article-journal", "volume" : "118" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "18,19", "plainTextFormattedCitation" : "18,19", "previouslyFormattedCitation" : "18,19" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }18,19). For this reason, MCS has not been considered further in this position paper. Recommendations:We recommend use of the terms highlighted in bold in the above table, with their associated definitions.Epidemiology of Olfactory DysfunctionThough olfactory dysfunction is increasingly recognised, the true prevalence and incidence is unclear. Estimates vary significantly according to sample demographics, definitions of impairment and assessment technique. The latter is particularly important, and the existing literature will therefore be classified according to assessment technique in the following sections [for a comprehensive review, please see ref (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s40136-016-0120-6", "ISBN" : "4013601601206", "ISSN" : "2167-583X", "author" : [ { "dropping-particle" : "", "family" : "Yang", "given" : "Jingpu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinto", "given" : "Jayant M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Otorhinolaryngology Reports", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "130-141", "publisher" : "Springer US", "title" : "The Epidemiology of Olfactory Disorders", "type" : "article-journal", "volume" : "4" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "20", "plainTextFormattedCitation" : "20", "previouslyFormattedCitation" : "20" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }20)]. Subjective reportingUsing subjective ‘self-reporting’, early household survey-based studies demonstrated conservative prevalence estimates. The 1994 Disability Supplement to the National Health Interview Survey (NHIS) addressed chemosensory impairment in a randomly selected cohort of 42,000 households (and thereby approximately 80,000 adults over 18) in the United States (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1749-6632.1998.tb10650.x", "ISBN" : "0077-8923 (Print)", "ISSN" : "0077-8923", "PMID" : "9929676", "abstract" : "Information about the prevalence of disorders of the chemical senses has been limited. In the late 1970s, the consensus among experts convened by the National Institutes of Health (NIH) was that more than 2 million adults in the United States had a disorder of smell or taste. A large, nonrandom survey conducted by the National Geographic Society in 1987 found that 1% of their 1.2 million respondents could not smell 3 or more of 6 odorants using a 'scratch and sniff' test. Age was an important factor, with a decline beginning in the second decade of life. No comparable data have been available for taste, although it has been suggested that the sense of taste remains more robust with age. The National Institute on Deafness and Other Communication Disorders (NIDCD), NIH, began collaborating with the National Center for Health Statistics (NCHS) in 1993 to acquire information on the prevalence of smell/taste problems using the Disability Supplement to the National Health Interview Survey (NHIS). This survey was administered to approximately 42,000 randomly-selected households (representing about 80,000 adults over 18 years of age) in 1994. Adjusted national estimates derived from this survey showed a prevalence of 2.7 million (1.4%) U.S. adults with an olfactory problem. Also, 1.1 million (0.6%) adults reported a gustatory problem. When smell or taste problems were combined, 3.2 million (1.65%) adults indicated a chronic chemosensory problem. The prevalence rates increased exponentially with age. Almost 40% with a chemosensory problem (1.5 million) were 65 years of age or greater. In a multivariate analysis, the individual's overall health status, other sensory impairments, functional limitations (including difficulty standing or bending), depression, phobia, and several other health-related characteristics were associated with an increase in the rate of chemosensory disorders.", "author" : [ { "dropping-particle" : "", "family" : "Hoffman", "given" : "H J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ishii", "given" : "E K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "MacTurk", "given" : "R H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the New York Academy of Sciences", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "1998" ] ] }, "page" : "716-722", "title" : "Age-related changes in the prevalence of smell/taste problems among the United States adult population. Results of the 1994 disability supplement to the National Health Interview Survey (NHIS).", "type" : "article-journal", "volume" : "855" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "21", "plainTextFormattedCitation" : "21", "previouslyFormattedCitation" : "21" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }21). Using adjusted national estimates, the authors concluded that 2.7 million persons (1.4% of the US adult population) had experienced a problem with their sense of smell that had lasted longer than three months. This prevalence increased markedly with age, with approximately 40% of persons over the age of 65 reporting smell problems (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1749-6632.1998.tb10650.x", "ISBN" : "0077-8923 (Print)", "ISSN" : "0077-8923", "PMID" : "9929676", "abstract" : "Information about the prevalence of disorders of the chemical senses has been limited. In the late 1970s, the consensus among experts convened by the National Institutes of Health (NIH) was that more than 2 million adults in the United States had a disorder of smell or taste. A large, nonrandom survey conducted by the National Geographic Society in 1987 found that 1% of their 1.2 million respondents could not smell 3 or more of 6 odorants using a 'scratch and sniff' test. Age was an important factor, with a decline beginning in the second decade of life. No comparable data have been available for taste, although it has been suggested that the sense of taste remains more robust with age. The National Institute on Deafness and Other Communication Disorders (NIDCD), NIH, began collaborating with the National Center for Health Statistics (NCHS) in 1993 to acquire information on the prevalence of smell/taste problems using the Disability Supplement to the National Health Interview Survey (NHIS). This survey was administered to approximately 42,000 randomly-selected households (representing about 80,000 adults over 18 years of age) in 1994. Adjusted national estimates derived from this survey showed a prevalence of 2.7 million (1.4%) U.S. adults with an olfactory problem. Also, 1.1 million (0.6%) adults reported a gustatory problem. When smell or taste problems were combined, 3.2 million (1.65%) adults indicated a chronic chemosensory problem. The prevalence rates increased exponentially with age. Almost 40% with a chemosensory problem (1.5 million) were 65 years of age or greater. In a multivariate analysis, the individual's overall health status, other sensory impairments, functional limitations (including difficulty standing or bending), depression, phobia, and several other health-related characteristics were associated with an increase in the rate of chemosensory disorders.", "author" : [ { "dropping-particle" : "", "family" : "Hoffman", "given" : "H J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ishii", "given" : "E K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "MacTurk", "given" : "R H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the New York Academy of Sciences", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "1998" ] ] }, "page" : "716-722", "title" : "Age-related changes in the prevalence of smell/taste problems among the United States adult population. Results of the 1994 disability supplement to the National Health Interview Survey (NHIS).", "type" : "article-journal", "volume" : "855" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "21", "plainTextFormattedCitation" : "21", "previouslyFormattedCitation" : "21" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }21). Newer survey-based studies have reported higher, though still fairly conservative estimates. In 2013, results were published from the 2009 Korea National Health and Nutrition Examination Survey (KNHANES). In this study, olfactory dysfunction was estimated at 4.5%, with prevalence increasing with age (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0062725", "ISSN" : "1932-6203 (Electronic)", "PMID" : "23671628", "abstract" : "BACKGROUND: Population-based studies for olfactory dysfunction are lacking. The aim of this study is to evaluate the prevalence of subjective olfactory dysfunction and its risk factors in the Korean general population. METHODS: The data were obtained from the 2009 Korea National Health and Nutrition Examination Survey (KNHANES), which was a cross-sectional survey of non-institutionalized population all around the country (n = 10,533). All interviewees underwent medical interviews, physical examinations, endoscopic examination and blood/urine tests. Whether sense of smell has been normal or abnormal during the last 3 months was asked. Complete olfaction data were obtained from 7,306 participants and the participants were divided into normosmic and hyposmic group. Multivariate logistic regression analyses were performed to identify its risk factors. RESULTS: The weighted prevalence of subjective olfactory dysfunction was 4.5%. Its increased prevalence was significantly associated with the increasing age for both men and women. In the multivariate analyses, low income (adjusted odds ratio [OR] = 1.43, 95% Confidence Interval [CI] = 1.01-2.03), habitual exposure to air pollutants (adjusted OR = 2.18, CI = 1.33-3.55), a history of hepatitis B (adjusted OR = 3.10, CI = 1.25-7.68), rhinitis (adjusted OR = 1.78, CI = 1.26-2.51) and chronic sinusitis (adjusted OR = 14.55, CI = 10.06-21.05) were risk factors of olfactory dysfunction. CONCLUSION: Our population-based study showed that olfactory dysfunction was quite prevalent and several risk factors were associated with impaired sense of smell. Given its prevalence, further researches for its prevention and management are required.", "author" : [ { "dropping-particle" : "", "family" : "Lee", "given" : "Woo Hyun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wee", "given" : "Jee Hye", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Dong-Kyu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rhee", "given" : "Chae-Seo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Chul Hee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ahn", "given" : "Soyeon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Ju Hyun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cho", "given" : "Yang-Sun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Kun Hee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Kyung Soo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Si Whan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Ari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Jeong-Whun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "e62725", "title" : "Prevalence of subjective olfactory dysfunction and its risk factors: korean national health and nutrition examination survey.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "22", "plainTextFormattedCitation" : "22", "previouslyFormattedCitation" : "22" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }22). The US based National Health and Nutrition Examination Survey (NHANES) also included a chemosensory component. Two studies analysing the prevalence of self-reported olfactory impairment have been published from this data. The first of these was by Bhattacharyya and Kepnes in 2015 (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/lary.24999", "ISSN" : "15314995", "author" : [ { "dropping-particle" : "", "family" : "Bhattacharyya", "given" : "Neil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kepnes", "given" : "Lynn J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Laryngoscope", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1102-1106", "title" : "Contemporary assessment of the prevalence of smell and taste problems in adults", "type" : "article-journal", "volume" : "125" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "23", "plainTextFormattedCitation" : "23", "previouslyFormattedCitation" : "23" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }23). Using results gathered from 3,549 adults between 2011 and 2012, they estimated that 10.6% ± 1.0% of the US population had experienced a smell disturbance in the last 12 months. Of these, 50.2% ± 1.8% reported their problem to be ‘always there’; 45.2% ± 2.2% reported that their problem ‘comes and goes’; and 4.5% ± 0.9% reported that their problem was ‘only present with a cold’. Again, prevalence increased with age (odds ratio 1.15, 95% confidence interval 1.00–1.31). Sex did not affect prevalence. In 2016, Rawal and colleagues also published results from the 2011-2012 NHANES project, though from a slightly larger cohort of 3,603 adults (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/chemse/bjv057", "ISSN" : "0379-864X", "PMID" : "26487703", "author" : [ { "dropping-particle" : "", "family" : "Rawal", "given" : "Shristi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoffman", "given" : "Howard J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bainbridge", "given" : "Kathleen E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huedo-medina", "given" : "Tania B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duffy", "given" : "Valerie B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemical Senses", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "69-72", "title" : "Prevalence and Risk Factors of Self-Reported Smell and Taste Alterations: Results from the 2011-2012 U.S. National Health and Nutritions Survey (NHANES)", "type" : "article-journal", "volume" : "41" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "24", "plainTextFormattedCitation" : "24", "previouslyFormattedCitation" : "24" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }24). They reported a higher prevalence of subjective olfactory dysfunction at 23%. However in this case, impairment was defined ‘since age 25’, rather than in the preceding 12 months, as was used by Bhattacharyya and Kepnes.Within the context of epidemiological research primarily investigating the prevalence of chronic rhinosinusitis, work from the Global Allergy and Asthma European Network (GA2LEN) has demonstrated self-reported smell loss in 7.6% of 57,128 respondents from across Europe (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1398-9995.2011.02646.x", "ISBN" : "1398-9995 (Electronic)\\n0105-4538 (Linking)", "ISSN" : "01054538", "PMID" : "21605125", "abstract" : "Background: Chronic rhinosinusitis (CRS) is a common health problem, with significant medical costs and impact on general health. Even so, prevalence figures for Europe are unavailable. In this study, conducted by the GA 2LEN network of excellence, the European Position Paper on Rhinosinusitis and nasal Polyps (EP 3OS) diagnostic criteria are applied to estimate variation in the prevalence of Chronic rhinosinusitis (CRS) for Europe. Method: A postal questionnaire was sent to a random sample of adults aged 15-75 years in 19 centres in Europe. Participants reported symptoms of CRS, and doctor diagnosed CRS, allergic rhinitis, age, gender and smoking history. Definition of CRS was based on the EP 3OS diagnostic criteria: the presence of more than two of the symptoms: (i) nasal blockage, (ii) nasal discharge, (iii) facial pain/pressure or (iv) reduction in sense of smell, for >12 weeks in the past year - with at least one symptom being nasal blockage or discharge. Results: Information was obtained from 57 128 responders living in 19 centres in 12 countries. The overall prevalence of CRS by EP 3OS criteria was 10.9% (range 6.9-27.1). CRS was more common in smokers than in nonsmokers (OR 1.7: 95% CI 1.6-1.9). The prevalence of self-reported physician-diagnosed CRS within centres was highly correlated with the prevalence of EP 3OS-diagnosed CRS. Conclusion: This is the first European international multicentre prevalence study of CRS. In this multicentre survey of adults in Europe, about one in ten participants had CRS with marked geographical variation. Smoking was associated with having CRS in all parts of Europe. \u00a9 2011 John Wiley & Sons A/S.", "author" : [ { "dropping-particle" : "", "family" : "Hastan", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fokkens", "given" : "W. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bachert", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Newson", "given" : "R. B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bislimovska", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bockelbrink", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bousquet", "given" : "P. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brozek", "given" : "G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruno", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dahl??n", "given" : "S. 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L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lange", "given" : "B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lundb??ck", "given" : "B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salagean", "given" : "E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Todo-Bom", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tomassen", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Toskala", "given" : "E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drunen", "given" : "C. M.", "non-dropping-particle" : "Van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bousquet", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zuberbier", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jarvis", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burney", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Allergy: European Journal of Allergy and Clinical Immunology", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "1216-1223", "title" : "Chronic rhinosinusitis in Europe - An underestimated disease. A GA 2LEN study", "type" : "article-journal", "volume" : "66" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "25", "plainTextFormattedCitation" : "25", "previouslyFormattedCitation" : "25" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }25). Within the United States, Hirsch and colleagues demonstrated a prevalence of 9.4% subjective smell loss in their source population (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/all.13042", "ISBN" : "5702144880", "ISSN" : "1398-9995", "abstract" : "BACKGROUND: The objective of this study was to describe the first US-based study to use the European Position Paper on Rhinosinusitis (EPOS) criteria to study the prevalence of chronic rhinosinusitis (CRS) in a general-population sample.\nMETHODS: A CRS symptom questionnaire was mailed to 23 700 primary care patients from Geisinger Clinic, a health system serving 45 counties in Pennsylvania. CRS cases were categorized into four unique subgroups based on EPOS symptoms: obstruction and discharge with no smell loss or pain/pressure; smell loss without pain/pressure; facial pain and/or pressure without smell loss; and both smell loss and pain/pressure. All cases were required to have nasal obstruction or discharge. Logistic regression was used to evaluate potential factors associated with CRS subgroups.\nRESULTS: We found that 11.9% of patients met criteria for CRS. Prevalence peaked at 15.9% between ages 50 and 59 years and then dropped to 6.8% after age 69. The odds of CRS was higher among patients who were white, younger, smokers, had a history of Medical Assistance, and had other diseases. When CRS subgroups were modeled separately, these associations were no longer significant for some CRS subgroups. Comorbid diseases were most strongly associated with CRS cases who reported smell loss and facial pain and/or pressure and had the weakest associations with CRS cases who did not report these symptoms.\nCONCLUSIONS: CRS is a highly prevalent and heterogeneous condition. Differences in risk factors and health outcomes across symptom subgroups may be indicative of differences in etiology that have implications for disease management.", "author" : [ { "dropping-particle" : "", "family" : "Hirsch", "given" : "A. G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stewart", "given" : "W. F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sundaresan", "given" : "A. S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Young", "given" : "A. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kennedy", "given" : "T. L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott Greene", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Feng", "given" : "W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tan", "given" : "B. K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schleimer", "given" : "R. P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kern", "given" : "R. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lidder", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwartz", "given" : "B. S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Allergy", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2016" ] ] }, "title" : "Nasal and sinus symptoms and chronic rhinosinusitis in a population-based sample", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "26", "plainTextFormattedCitation" : "26", "previouslyFormattedCitation" : "26" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }26). This was based on results from their postal survey of 7,847 people (the aim of which was to determine prevalence of patient reported chronic rhinosinusitis). Psychophysical testingPrevious studies have suggested that olfactory self-rating may be unreliable (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/chemse/bjg061", "ISBN" : "0379-864X (Print)", "ISSN" : "0379864X", "PMID" : "14627537", "abstract" : "The aim of this study was to investigate the accuracy of self-reported ratings of olfactory function in 83 healthy subjects. Such ratings were compared with quantitative measures of olfactory function, as well as with ratings of nasal patency. In experiment 1 subjects rated olfactory function and nasal patency before olfactory testing, whereas in experiment 2 the reverse was the case. No feedback regarding test results were provided until after completion of the testing. The principal findings were: (i) when ratings preceded measurements of olfactory function, there was no significant correlation between the two parameters. However, ratings of olfactory function correlated significantly with ratings of nasal airway patency. (ii) In contrast, when measurements of olfactory function preceded the ratings, this constellation switched. Now ratings of olfactory function correlated significantly with measured olfactory function, whereas there was no significant correlation between ratings of nasal airway patency and ratings of olfactory function. In conclusion, these data suggest that ratings of olfactory function are unreliable in healthy, untrained subjects. The ratings seem to reflect changes of nasal airway patency to a larger degree than measurable olfactory function. The results further indicate that this is mainly due to the limited attention the sense of smell receives in daily life.", "author" : [ { "dropping-particle" : "", "family" : "Landis", "given" : "Basile N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hugentobler", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giger", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lacroix", "given" : "J. S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemical Senses", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "691-694", "title" : "Ratings of overall olfactory function", "type" : "article-journal", "volume" : "28" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "27", "plainTextFormattedCitation" : "27", "previouslyFormattedCitation" : "27" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }27). Therefore, in order to increase the accuracy of epidemiological estimates, more objective assessment is required in the form of psychophysical testing for odour identification, discrimination or threshold. Odour identification tests may be culturally specific and should therefore be validated for the target population (for more detail, see ‘psychophysical testing’ in ‘olfactory assessment’ section).In Germany, Landis and colleagues assessed olfactory function in 1,240 non-rhinological patients (mean age 41.7 years) presenting to an otorhinolaryngology outpatient clinic. Using the odour identification component of the “Sniffin’ Sticks” test battery, they demonstrated functional anosmia in 4.7% and hyposmia in 15% of those tested (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/00005537-200410000-00017", "ISBN" : "1531-4995", "ISSN" : "0023-852X", "PMID" : "15454769", "abstract" : "Goals of the study were to evaluate the frequency of olfactory dysfunction in a large representative population without sinonasal complaints and to investigate the extent to which general pathological conditions, medications, and aging influence olfaction.", "author" : [ { "dropping-particle" : "", "family" : "Landis", "given" : "B N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Konnerth", "given" : "C G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Laryngoscope", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "1764-9", "title" : "A study on the frequency of olfactory dysfunction.", "type" : "article-journal", "volume" : "114" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "28", "plainTextFormattedCitation" : "28", "previouslyFormattedCitation" : "28" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }28). Later, in 2008, Vennemann and colleagues performed odour identification testing in a random sample of 1,312 adults (aged 25-75), as part of the Dortmund Health Study. Based on their 12-item screening test an estimated prevalence of 21.6% had impaired olfaction (score of <10), with 3.6% of these being classified as functionally anosmic (score of ≤ 6) (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00415-008-0807-9", "ISBN" : "0041500808079", "ISSN" : "03405354", "PMID" : "18677645", "abstract" : "BACKGROUND: The aim of this study was to evaluate the effect of smoking on taste and smell impairment in a large population- based study.\\n\\nSTUDY DESIGN: Cross-sectional survey in Dortmund, Germany.\\n\\nMETHODS: The population sample was randomly drawn from the city's central registration office. Following a standardized interview, validated taste and smell tests were performed. Descriptive statistics and logistic regression was used in the analysis.\\n\\nRESULTS: Among the 1312 study participants, 3.6 % were functionally anosmic, and 18 % had olfactory dysfunction. Approximately 20 % recognized only three or less of the four tastes when presented at suprathreshold concentrations, indicating signs of taste impairment. Current smoking in general increased the risk for impairment of olfactory function (odds ratio 1.71, 95 % CI 1.19-2.47), but not the risk for taste impairment. Heavy smokers of 20 or more cigarettes/day had significant increased risks for impairment in both senses.\\n\\nCONCLUSIONS: Our results reveal that both olfactory and gustatory function are compromised in a significant proportion of the general population. Smoking increases significantly the risk of impairment of olfactory function. Our findings add an important detail to the large body of evidence that describes adverse health effects of smoking.", "author" : [ { "dropping-particle" : "", "family" : "Vennemann", "given" : "M. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berger", "given" : "K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Neurology", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "1121-1126", "title" : "The association between smoking and smell and taste impairment in the general population", "type" : "article-journal", "volume" : "255" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "29", "plainTextFormattedCitation" : "29", "previouslyFormattedCitation" : "29" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }29). This prevalence increased with age and cigarette smoking.The Sk?vde population-based study used the Scandinavian Odor Identification Test (SOIT) in addition to subjective patient reported measures to determine the rate of olfactory dysfunction in Sweden. Their original study population was 1,387 participants (aged ≥ 20 years), following which additional adolescent participants were added to produce a sample of 1,713. In their original study, the prevalence of self-reported ‘worse-than-normal’ olfactory function was 15.3% (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/00016480410017468", "ISSN" : "0001-6489", "PMID" : "15768812", "abstract" : "OBJECTIVE: To enable adequate planning of ENT healthcare it is important to know the prevalence of olfactory dysfunction in the general population. Whether an individual will actually seek medical attention for olfactory dysfunction is likely to depend predominantly on his/her self-evaluation of the sense of smell. This motivated an investigation of the prevalences of self-reported poorer- and better-than-normal odor detection sensitivity in the general population.\\n\\nMATERIAL AND METHODS: A random sample of 1900 adult inhabitants, stratified for age and gender, was drawn from the municipal population register of Sk\u00f6vde, Sweden. Subjects were asked to attend a structured interview concerning their self-evaluation of their odor detection sensitivity.\\n\\nRESULTS: In total, 1387 volunteers (73% of the sample) were investigated. The overall prevalences of self-reported poorer- and better-than normal odor detection sensitivity were 15.3% and 17.4%, respectively. The prevalence of poorer sensitivity was found to increase with age, and the prevalence of better sensitivity was lower in men than women.\\n\\nCONCLUSIONS: Considering the fairly high participation rate in this study and the fact that the population of Sk\u00f6vde is representative of the general Swedish population, the obtained prevalences can be considered representative of the general Swedish adult population.", "author" : [ { "dropping-particle" : "", "family" : "Nordin", "given" : "Steven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Br\u00e4merson", "given" : "Annika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bende", "given" : "Mats", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Acta Oto-laryngologica", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "1171-1173", "title" : "Prevalence of self-reported poor odor detection sensitivity: the sk\u00f6vde population-based study", "type" : "article-journal", "volume" : "124" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "30", "plainTextFormattedCitation" : "30", "previouslyFormattedCitation" : "30" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }30). The prevalence of dysfunction based on the SOIT was higher at 19.1%, with 13.3% qualifying as ‘hyposmic’ (defined as a SOIT score of 10-12) and 5.8% ‘anosmic’ (SOIT score of ≤ 9) (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/00005537-200404000-00026", "ISBN" : "0023-852X (Print)\\r0023-852X (Linking)", "ISSN" : "0023-852X", "PMID" : "15064632", "abstract" : "OBJECTIVES/HYPOTHESIS: Patients with olfactory dysfunction appear repeatedly in ear, nose, and throat practices, but the prevalence of such problems in the general adult population is not known. Therefore, the objectives were to investigate the prevalence of olfactory dysfunction in an adult Swedish population and to relate dysfunction to age, gender, diabetes mellitus, nasal polyps, and smoking habits. STUDY DESIGN: Cross-sectional, population-based epidemiological study. METHODS: A random sample of 1900 adult inhabitants, who were stratified for age and gender, was drawn from the municipal population register of Sk\u00f6vde, Sweden. Subjects were called to clinical visits that included questions about olfaction, diabetes, and smoking habits. Examination was performed with a smell identification test and nasal endoscopy. RESULTS: In all, 1387 volunteers (73% of the sample) were investigated. The overall prevalence of olfactory dysfunction was 19.1%, composed of 13.3% with hyposmia and 5.8% with anosmia. A logistic regression analysis showed a significant relationship between impaired olfaction and aging, male gender, and nasal polyps, but not diabetes or smoking. In an analysis of a group composed entirely of individuals with anosmia, diabetes mellitus and nasal polyps were found to be risk factors, and gender and smoking were not. CONCLUSION: The sample size of the population-based study was adequate, with a good fit to the entire population, which suggests that it was representative for the Swedish population. Prevalence data for various types of olfactory dysfunction could be given with reasonable precision, and suggested risk factors analyzed. The lack of a statistically significant relationship between olfactory dysfunction and smoking may be controversial.", "author" : [ { "dropping-particle" : "", "family" : "Br\u00e4merson", "given" : "Annika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johansson", "given" : "Leif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ek", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nordin", "given" : "Steven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bende", "given" : "Mats", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Laryngoscope", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "733-737", "title" : "Prevalence of olfactory dysfunction: the sk\u00f6vde population-based study.", "type" : "article-journal", "volume" : "114" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "31", "plainTextFormattedCitation" : "31", "previouslyFormattedCitation" : "31" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }31). In their later study, the prevalence of parosmia was found to be 3.9% (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "03000729", "PMID" : "17432070", "abstract" : "AIM: Parosmia can be defined as a qualitative odor distortion. Despite the consequences of this condition for quality of life, the scientific literature lacks information about the prevalence of parosmia in the general population, which was the objective of the present study. METHODS: Random samples of 1,900 adult and 401 teenage inhabitants, stratified for age and gender, were drawn from the municipal population register of Sk\u00f6vde, Sweden. In total, 1,713 individuals (74% of the samples) agreed to participate, of which 1,387 (73%) were adults and 326 (81%) were teenagers. They responded to a question about parosmia by means of either a structured interview (adults) or a questionnaire (teenagers). RESULTS: The overall prevalence of parosmia was 3.9% (4.0% in adults and 3.4% in teenagers), which was stable across gender, but differed somewhat between age groups, with highest prevalence in the age group 20-29 years. CONCLUSIONS: The rather high overall prevalence, 3.9%, does indeed suggest that parosmia deserves attention when attempting to better understand olfactory dysfunction in clinical settings and in the general population of both adults and teenagers.", "author" : [ { "dropping-particle" : "", "family" : "Nordin", "given" : "Steven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Br\u00e4merson", "given" : "Annika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Millqvist", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bende", "given" : "Mats", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "50-53", "title" : "Prevalence of parosmia: The Sk\u00f6vde population-based studies", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "32", "plainTextFormattedCitation" : "32", "previouslyFormattedCitation" : "32" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }32). Another Swedish study, based on data from the Betula project, demonstrated a negative correlation between age and olfactory function, as determined through testing with a modified SOIT in 1,906 subjects (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/chemse/bjh059", "ISBN" : "0379-864X (Print)", "ISSN" : "0379864X", "PMID" : "15269128", "abstract" : "This study investigated demographic and cognitive correlates of cued odor identification in a population-based sample from the Betula project: 1906 healthy adults varying in age from 45 to 90 years were assessed in a number of tasks tapping various cognitive domains, including cognitive speed, semantic memory and executive functioning. The results revealed a gradual and linear deterioration in cued odor identification across the adult life span. Overall, females identified more odors than men, although men and women performed at the same level in the oldest age cohort (85-90 years). Hierarchical regression analyses revealed that age, sex, education, cognitive speed and vocabulary were reliable correlates of performance in the odor identification task. In addition, age-related deficits in the included demographic and cognitive variables could not fully account for the observed age-related impairment in identification, suggesting that additional factors are underlying the observed deterioration. Likely candidates here are sensory abilities such as olfactory detection and discrimination.", "author" : [ { "dropping-particle" : "", "family" : "Larsson", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nilsson", "given" : "L. G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olofsson", "given" : "Jonas K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nordin", "given" : "Steven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemical Senses", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "547-554", "title" : "Demographic and cognitive predictors of cued odor identification: Evidence from a population-based study", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "33", "plainTextFormattedCitation" : "33", "previouslyFormattedCitation" : "33" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }33).In Spain, the OLFACAT (Olfaction in Catalonia) survey assessed detection, recognition and identification of 4 self-administered microencapsulated odourants. Responses were obtained from 9,348 persons and normal olfactory function was assigned where the respondent was able to detect, recognise and correctly identify all four odourants. ‘Hyposmia’ was assigned where a person was unable to correctly detect, recognise or identify one or more odour and ‘anosmia’ where they were unable to correctly detect, recognise or identify any odours. According to this classification, the prevalence of smell dysfunction in this cohort was 19.4% for detection (0.3% anosmia, 19.1% hyposmia), 43.5% for recognition (0.2% anosmia, 43.3% hyposmia) and 48.8% for identification (0.8% anosmia, 48% hyposmia). This study was potentially limited by the questionnaire distribution method, which was through a local newspaper, and which may therefore have targeted persons mainly of middle/higher socio-economic and educational status (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/bmjopen-2012-001256", "ISBN" : "2044-6055 (Electronic)", "ISSN" : "2044-6055", "PMID" : "23135536", "abstract" : "OBJECTIVES: To investigate olfaction in general population, prevalence of olfactory dysfunction and related risk factors.\\n\\nDESIGN: Cross-sectional population-based survey, distributing four microencapsulated odorants (rose, banana, musk and gas) and two self-administered questionnaires (odour description; epidemiology/health status).\\n\\nSETTING: The survey was distributed to general population through a bilingual (Catalan, Spanish) newspaper in Catalonia (Spain), on December 2003.\\n\\nPARTICIPANTS: Newspaper readers of all ages and gender; 9348 surveys were analysed from the 10 783 returned.\\n\\nMAIN OUTCOME MEASURES: Characteristics of surveyed population, olfaction by age and gender, smell self-perception and smell impairment risk factors. Terms normosmia, hyposmia and anosmia were used when participants detected, recognised or identified all four, one to three or none of the odours, respectively.\\n\\nRESULTS: Survey profile was a 43-year-old woman with medium-high educational level, living in a city. Olfaction was considered normal in 80.6% (detection), 56% (recognition/memory) and 50.7% (identification). Prevalence of smell dysfunction was 19.4% for detection (0.3% anosmia, 19.1% hyposmia), 43.5% for recognition (0.2% anosmia, 43.3% hyposmia) and 48.8% for identification (0.8% anosmia, 48% hyposmia). Olfaction was worse (p<0.0001) in men than in women through all ages. There was a significant age-related smell detection decline however smell recognition and identification increased up to fourth decade and declined after the sixth decade of life. Risk factors for anosmia were: male gender, loss of smell history and poor olfactory self-perception for detection; low educational level, poor self-perception and pregnancy for recognition; and older age, poor self-perception and history of head trauma and loss of smell for identification. Smoking and exposure to noxious substances were mild protective factors for smell recognition.\\n\\nCONCLUSIONS: Sense of smell in women is better than in men suggesting a learning process during life with deterioration in older ages. Poor self-perception, history of smell loss, head trauma and pregnancy are potential risk factors for olfactory disorders.", "author" : [ { "dropping-particle" : "", "family" : "Mullol", "given" : "Joaquim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alobid", "given" : "Isam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mari\u00f1o-S\u00e1nchez", "given" : "Franklin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Quint\u00f3", "given" : "Lloren\u00e7", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haro", "given" : "Josep", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bernal-Sprekelsen", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valero", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Picado", "given" : "C\u00e8sar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marin", "given" : "Concepci\u00f3", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMJ open", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "title" : "Furthering the understanding of olfaction, prevalence of loss of smell and risk factors: a population-based survey (OLFACAT study).", "type" : "article-journal", "volume" : "2:e001256" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "34", "plainTextFormattedCitation" : "34", "previouslyFormattedCitation" : "34" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }34).Several epidemiological studies utilising psychophysical testing methods have been reported from the United States of America. In 2002, results were published from the Epidemiology of Hearing Loss Study. Olfaction was tested in 2,491 older adults (aged 53-97) living in Beaver Dam, Wisconsin, using the San Diego Odor Identification Test (SDOIT) and subjective patient reporting. Using the former method, overall mean prevalence of olfactory dysfunction (defined as a SDOIT score of <6 out of 8) was 24.5%, rising to 62.5% for subjects over 80 years. Self-reported olfactory dysfunction was less common, at only 9.5%, with the ability to accurately self-assess olfactory function decreasing with age (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1001/jama.288.18.2307", "ISBN" : "0098-7484 (Print)\\n0098-7484 (Linking)", "ISSN" : "00987484", "PMID" : "12425708", "abstract" : "CONTEXT: Older adults represent the fastest-growing segment of the US population, and prevalences of vision and hearing impairment have been extensively evaluated. However, despite the importance of sense of smell for nutrition and safety, the prevalence of olfactory impairment in older US adults has not been studied. OBJECTIVE: To determine the prevalence of olfactory impairment in older adults. DESIGN, SETTING, AND PARTICIPANTS: A total of 2491 Beaver Dam, Wis, residents aged 53 to 97 years participating in the 5-year follow-up examination (1998-2000) for the Epidemiology of Hearing Loss Study, a population-based, cross-sectional study. MAIN OUTCOME MEASURES: Olfactory impairment, assessed by the San Diego Odor Identification Test and self-report. RESULTS: The mean (SD) prevalence of impaired olfaction was 24.5% (1.7%). The prevalence increased with age; 62.5% (95% confidence interval [CI], 57.4%-67.7%) of 80- to 97-year-olds had olfactory impairment. Olfactory impairment was more prevalent among men (adjusted prevalence ratio, 1.92; 95% CI, 1.65-2.19). Current smoking, stroke, epilepsy, and nasal congestion or upper respiratory tract infection were also associated with increased prevalence of olfactory impairment. Self-reported olfactory impairment was low (9.5%) and this measure became less accurate with age. In the oldest group, aged 80 to 97 years, sensitivity of self-report was 12% for women and 18% for men. CONCLUSIONS: This study demonstrates that prevalence of olfactory impairment among older adults is high and increases with age. Self-report significantly underestimated prevalence rates obtained by olfaction testing. Physicians and caregivers should be particularly alert to the potential for olfactory impairment in the elderly population.", "author" : [ { "dropping-particle" : "", "family" : "Murphy", "given" : "Claire", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schubert", "given" : "Carla R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cruickshanks", "given" : "Karen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klein", "given" : "Barbara E K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klein", "given" : "Ronald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nondahl", "given" : "David M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "JAMA : the journal of the American Medical Association", "id" : "ITEM-1", "issue" : "18", "issued" : { "date-parts" : [ [ "2002" ] ] }, "page" : "2307-2312", "title" : "Prevalence of olfactory impairment in older adults.", "type" : "article-journal", "volume" : "288" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "35", "plainTextFormattedCitation" : "35", "previouslyFormattedCitation" : "35" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }35). The National Social Life, Health and Aging Project (NSHAP) assessed olfaction in a nationally representative sample of older adults in the United States during two waves. Odour identification was tested in wave one, whilst both identification and threshold scores were tested in wave two. During the former, severe olfactory dysfunction was demonstrated in 2.7% of 3,005 adults aged 57 to 85 years (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "02684926", "author" : [ { "dropping-particle" : "", "family" : "Boesveldt", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tessler Lindau", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McClintock", "given" : "MK", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lundstr\u00f6m", "given" : "Johan N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "324-330", "title" : "Gustatory and olfactory dysfunction in older adults: a national probability study", "type" : "article-journal", "volume" : "49" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "36", "plainTextFormattedCitation" : "36", "previouslyFormattedCitation" : "36" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }36). During wave two, olfactory function was shown to deteriorate significantly with advancing age, in a cohort of 2,212 subjects aged 62 to 90 years (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/geronb/gbu093", "abstract" : "Objective. To investigate the sense of smell, including sensitivity and odor identification, and characterize the U.S. national prevalence of olfactory dysfunction in older adults, thereby facilitating further investigation of the substantial risks for older adults associated with this basic sensory ability.Method. The sense of smell was evaluated using the Olfactory Function Field Exam (OFFE), a measure designed specifically for field research, which assesses 3 components of olfaction: sensitivity to n-butanol (a standard testing odorant) and androstadienone (AND, a key social odor produced by humans), as well as the ability to identify odors. Respondents were randomly selected from the National Social Life, Health, and Aging Project Wave 2 sample to receive the OFFE (n = 2,304), and 2,212 consented to participate.Results. In the U.S. population aged 62\u201390, n-butanol detection ability was significantly worse at older ages (ordinal logistic regression, p < .001); however, there was no difference in detection ability between genders (p = .60). AND detection ability was also significantly worse at older ages (p = .003), but in contrast to n-butanol, women outperformed men (p = .001). As expected, odor identification ability was worse in older people than in younger (p < .001), and women were more accurate than men (p = .001).Discussion. We report for the first time 3 facets of olfactory function and its association with age and gender in a representative sample of U.S. older adults. Future analyses of these data are needed to elucidate the sense of smell\u2019s role in physical, social, and mental health with aging. ", "author" : [ { "dropping-particle" : "", "family" : "Kern", "given" : "David W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wroblewski", "given" : "Kristen E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schumm", "given" : "L Philip", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinto", "given" : "Jayant M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Rachel C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McClintock", "given" : "Martha K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journals of Gerontology Series B: Psychological Sciences and Social Sciences ", "id" : "ITEM-1", "issue" : "Suppl 2 ", "issued" : { "date-parts" : [ [ "2014", "11", "1" ] ] }, "note" : "10.1093/geronb/gbu093", "page" : "S134-S143", "title" : "Olfactory Function in Wave 2 of the National Social Life, Health, and Aging Project", "type" : "article-journal", "volume" : "69 " }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "37", "plainTextFormattedCitation" : "37", "previouslyFormattedCitation" : "37" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }37). Of note, this is the only epidemiological study where tests were not only performed for screening tests based on odour identification, but also for odour thresholds. Prevalence of olfactory dysfunction has also been reported from the US based Honolulu-Asia Aging Study (HAAS) (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/ana.21291", "ISBN" : "1531-8249", "ISSN" : "03645134", "PMID" : "18067173", "abstract" : "Objective\\nAlthough olfactory dysfunction is commonly associated with Parkinson's disease (PD), it is not known whether such dysfunction can predate the onset of clinical PD in a community-based population. This study examines the association of olfactory dysfunction with future development of PD in Honolulu-Asia Aging Study cohort members\\nMethods\\nOlfaction was assessed from 1991 to 1996 in 2,267 men in the Honolulu-Asia Aging Study aged 71 to 95 years who were free of clinical PD and dementia at the time of olfaction testing. Participants were followed for up to 8 years for incident PD\\nResults\\nIn the course of follow-up, 35 men were diagnosed with PD (24.6/10,000 person-years). The average age at the time of diagnosis was 82.9 \u00b1 3.8 (range, 76\u201393) years, and the average time to a diagnosis was 4.0 \u00b1 1.9 (range, 1\u20138) years. During the first 4 years of follow-up, age-adjusted incidence of PD declined from 54.5/10,000 person-years in the lowest quartile of odor identification to 26.6, 8.2, and 8.4/10,000 person-years in the second, third, and fourth quartiles, respectively (p < 0.001 for trend). After adjustment for age and other potential confounders, the odds ratios for PD in the lowest quartile was 5.2 (95% confidence interval, 1.5\u201325.6) compared with the top two quartiles. This relation was not evident beyond 4 years of follow-up\\nInterpretation\\nImpaired olfaction can predate clinical PD in men by at least 4 years and may be a useful screening tool to detect those at high risk for development of PD in later life. Ann Neurol 2007", "author" : [ { "dropping-particle" : "", "family" : "Ross", "given" : "G. Webster", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Petrovitch", "given" : "Helen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abbott", "given" : "Robert D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tanner", "given" : "Caroline M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Popper", "given" : "Jordan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Masaki", "given" : "Kamal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Launer", "given" : "Lenore", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "White", "given" : "Lon R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of Neurology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "167-173", "title" : "Association of olfactory dysfunction with risk for future Parkinson's disease", "type" : "article-journal", "volume" : "63" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "38", "plainTextFormattedCitation" : "38", "previouslyFormattedCitation" : "38" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }38) and the Memory and Aging Project (MAP) (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1159/000090250", "ISBN" : "0251-5350", "ISSN" : "02515350", "PMID" : "16352908", "abstract" : "The authors examined the association of odor identification with rate of decline in different cognitive systems. Participants are 481 older persons from the Rush Memory and Aging Project. At baseline, the Brief Smell Identification Test was administered. At annual intervals for up to 3 years, a battery of 19 cognitive tests was administered from which previously established composite measures of 5 cognitive domains were derived. In mixed-effects models adjusted for age, sex, and education, lower odor identification score was associated with lower function at baseline in each cognitive domain. Lower score was also associated with more rapid decline in perceptual speed (estimate=0.015, SE=0.006, p=0.013) and episodic memory (estimate=0.012, SE=0.006, p=0.030) but not with rate of decline in semantic memory, working memory, or visuospatial ability. Thus, on average, a person with a low odor identification score (6, 10th percentile) declined more than twice as rapidly in perceptual speed and episodic memory as a person with a high score (11, 90th percentile). Results were unchanged in subsequent analyses that controlled for cigarette smoking or clinically diagnosed stroke. The results indicate that impaired odor identification in old age is associated with impaired global cognition and more rapid decline in perceptual processing speed and episodic memory.", "author" : [ { "dropping-particle" : "", "family" : "Wilson", "given" : "Robert S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arnold", "given" : "Steven E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tang", "given" : "Yuxiao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bennett", "given" : "David A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Neuroepidemiology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "61-67", "title" : "Odor identification and decline in different cognitive domains in old age", "type" : "article-journal", "volume" : "26" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "39", "plainTextFormattedCitation" : "39", "previouslyFormattedCitation" : "39" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }39). Using the Cross-Cultural Smell Identification Test, the HAAS study demonstrated impaired odour identification in around three quarters of adult men over 71 years. Using the same psychophysical test, the MAP study reported a prevalence of 55.3% in their cohort of mean age 80.6 years. Devanand and colleagues reported data from the Washington Heights/Inwood Columbia Aging Project cohort, in which odour identification was tested in 1,169 older adults (mean age 80 years) (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/ana.24447", "ISBN" : "0364-5134", "ISSN" : "15318249", "PMID" : "26031760", "abstract" : "OBJECTIVE: To examine the association between odor identification deficits and future mortality in a multiethnic community cohort of older adults.\\n\\nMETHODS: Participants were evaluated with the 40-item University of Pennsylvania Smell Identification Test (UPSIT). Follow-up occurred at 2-year intervals with information on death obtained from informant interviews and the National Death Index.\\n\\nRESULTS: During follow-up (mean 4.1 SD 2.6 years), 349 of 1169 (29.9%) participants died. Participants who died were more likely to be older (p\u2009<\u20090.001), male (p\u2009<\u20090.001), have lower UPSIT scores (p\u2009<\u20090.001), and have a diagnosis of dementia (p\u2009<\u20090.001). In a Cox model, the association between lower UPSIT score and mortality (Hazard Ratio 1.07 per point interval, 95%CI 1.05 to 1.08, p<0.001) persisted after controlling for age, gender, education, ethnicity, language, modified Charlson medical comorbidity index, dementia, depression, alcohol abuse, head injury, smoking, Body Mass Index, vision and hearing impairment (Hazard Ratio=1.05, 95%CI 1.03 to 1.07, p<0.001). Compared to the fourth quartile with the highest UPSIT scores, hazard ratios for mortality for the first, second, and third quartiles of UPSIT scores were 3.81 (95%CI 2.71 to 5.34), 1.75 (95%CI 1.23 to 2.50), and 1.58 (95%CI 1.09 to 2.30), respectively. Participant mortality rate was 45% in the lowest quartile of UPSIT scores (anosmia) and 18% in the highest quartile of UPSIT scores.\\n\\nINTERPRETATION: Impaired odor identification, particularly in the anosmic range, is associated with increased mortality in older adults even after controlling for dementia and medical comorbidity. This article is protected by copyright. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Devanand", "given" : "Davangere P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Seonjoo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Manly", "given" : "Jennifer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andrews", "given" : "Howard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schupf", "given" : "Nicole", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Masurkar", "given" : "Arjun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stern", "given" : "Yaakov", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mayeux", "given" : "Richard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doty", "given" : "Richard L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of Neurology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "401-411", "title" : "Olfactory identification deficits and increased mortality in the community", "type" : "article-journal", "volume" : "78" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "40", "plainTextFormattedCitation" : "40", "previouslyFormattedCitation" : "40" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }40). Using the University of Pennsylvania Smell Identification Test, the average identification score across the entire cohort was 25.18 ± 7.26, therefore falling at the border between ‘severe microsmia’ and ‘microsmia’. During their follow up period, this study went on to demonstrate a statistically significant, independent association between olfactory dysfunction (particularly anosmia) and increased risk of mortality. Finally, the Blue Mountains Eye Study assessed olfactory function in 1,636 older adults (aged 60 and over) in Australia. Using the SDOIT, the authors demonstrated olfactory impairment in 27% of their cohort. In addition to demonstrating deterioration in olfactory function with age, the authors demonstrated a negative correlation with body mass index, clinically supporting the concept that olfaction enhances appetite and food enjoyment (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1177/0898264309353066", "ISBN" : "0898-2643", "ISSN" : "0898-2643", "PMID" : "20133956", "abstract" : "To determine the prevalence of olfactory impairment and its associations with neurodegenerative and other conditions in older adults.", "author" : [ { "dropping-particle" : "", "family" : "Karpa", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gopinath", "given" : "Bamini", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rochtchina", "given" : "Elena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jie Jin Wang", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cumming", "given" : "Robert G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sue", "given" : "Carolyn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mitchell", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of aging and health", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "154-168", "title" : "Prevalence and neurodegenerative or other associations with olfactory impairment in an older community.", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "41", "plainTextFormattedCitation" : "41", "previouslyFormattedCitation" : "41" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }41). Conclusion:‘Functional anosmia has a prevalence of approximately 5% of the general population. Normal aging significantly contributes to this disease burden.Anatomy and Physiology of OlfactionExcept in rare circumstances, the perception of odour requires a functional peripheral sensory organ and central pathways.Approximately 6-30 million bipolar receptor cells, or olfactory sensory neurons (OSN), can be found in the olfactory neuroepithelium of young adult humans, whose axons collectively constitute the olfactory nerve (cranial nerve 1) (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1288/00005537-198312000-00011", "ISBN" : "1531-4995", "ISSN" : "0023-852X", "abstract" : "This thesis describes the ultrastructure of human nasal mucosa, based upon surgical biopsy specimens. The intent of the study is to characterize the normal ultrastructure of human nasal mucosa with emphasis upon the difference between olfactory and respiratory epithelia. Other nasal epithelia (anterior, sinus, and posterior) are reviewed briefly for comparison only. Several pathological examples of the olfactory and respiratory epithelia are also briefly presented for contrast.", "author" : [ { "dropping-particle" : "", "family" : "Jafek", "given" : "Bruce W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Laryngoscope", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "1983" ] ] }, "page" : "1576-1599", "title" : "Ultrastructure of human nasal mucosa", "type" : "article-journal", "volume" : "93" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "42", "plainTextFormattedCitation" : "42", "previouslyFormattedCitation" : "42" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }42). The cell bodies of these bipolar cells are found within the nasal olfactory epithelium. Though traditionally thought to be limited to the olfactory cleft, there is uncertainty about the extent of the olfactory neuroepithelium within the nasal cavity, especially in younger people (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/lary.21856", "ISSN" : "1531-4995", "PMID" : "21792956", "abstract" : "The pathophysiology underlying human olfactory disorders is poorly understood because biopsying the olfactory epithelium (OE) can be unrepresentative and extensive immunohistochemical analysis is lacking. Autopsy tissue enriches our grasp of normal and abnormal olfactory immunohistology and guides the sampling of the OE by biopsy. Furthermore, a comparison of the molecular phenotype of olfactory epithelial cells between rodents and humans will improve our ability to correlate human histopathology with olfactory dysfunction.", "author" : [ { "dropping-particle" : "", "family" : "Holbrook", "given" : "Eric H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Enming", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Curry", "given" : "William T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lin", "given" : "Derrick T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwob", "given" : "James E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Laryngoscope", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "1687-1701", "title" : "Immunohistochemical characterization of human olfactory tissue.", "type" : "article-journal", "volume" : "121" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "43", "plainTextFormattedCitation" : "43", "previouslyFormattedCitation" : "43" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }43), but mature and functional OSN can be found in humans at the insertion of the middle turbinate (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Brunn", "given" : "A", "non-dropping-particle" : "von", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arch Mikr Anat", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "1892" ] ] }, "page" : "632-651", "title" : "Beitrage zur mikroskopischen Anatomie menschlichen Nasenhohle .", "type" : "article-journal", "volume" : "39" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/aja.1000080103", "ISSN" : "1553-0795", "author" : [ { "dropping-particle" : "", "family" : "Read", "given" : "Effie A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Anatomy", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "1908" ] ] }, "page" : "17-47", "title" : "A contribution to the knowledge of the olfactory apparatus in dog, cat and man", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Lang", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "1989" ] ] }, "publisher" : "Thieme Medical Publishers", "publisher-place" : "New York", "title" : "Clinical Anatomy of the Nose, Nasal Cavity and Paranasal Sinuses (3rd ed)", "type" : "chapter" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1097/00005537-200003000-00016", "ISBN" : "0023-852X (Print)\\r0023-852X (Linking)", "ISSN" : "0023-852X", "PMID" : "10718430", "abstract" : "OBJECTIVES/HYPOTHESIS: To functionally investigate the distribution of the olfactory epithelium in humans by means of the electro-olfactogram (EOG) and anatomically located biopsy specimens. STUDY DESIGN: Prospective, nonrandomized, investigational. METHODS: Supra-threshold EOG recordings were made on 12 healthy, trained volunteers (6 women, 6 men; age range, 21-48 y). Vanillin was used as the stimulus, since it exclusively excites olfactory receptor neurons. The EOG was recorded with tubular electrodes that were placed using thin-fiber endoscopic guidance. Biopsy specimens were obtained of anterosuperior nasal cavity mucosa in the same regions as the positive EOGs in 15 smell-tested patients (7 women, 8 men; age range, 22-60 y) during routine nasal and sinus surgery. This biopsied tissue was histologically processed and stained for olfactory and neural proteins. RESULTS: Viable responses to EOG testing were obtained in 7 of 12 subjects. In these seven subjects it was possible to identify nine sites above or below the anterior middle turbinate insertion where EOGs were obtained. The biopsy results showed mature olfactory receptor neurons in this same area. CONCLUSIONS: Human olfactory epithelium appears to be distributed more anteriorly than previously assumed.", "author" : [ { "dropping-particle" : "", "family" : "Leopold", "given" : "D A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwob", "given" : "J E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hong", "given" : "S C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Knecht", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kobal", "given" : "Gerd", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Laryngoscope", "id" : "ITEM-4", "issue" : "3 Pt 1", "issued" : { "date-parts" : [ [ "2000" ] ] }, "page" : "417-421", "title" : "Anterior distribution of human olfactory epithelium.", "type" : "article-journal", "volume" : "110" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Feron", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perry", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McGrath", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mackay-Sim", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arch Otolaryngol Head Neck Surg", "id" : "ITEM-5", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "861-866", "title" : "New Techniques for Biopsy and Culture of Human Olfactory Epithelial Neurons", "type" : "article-journal", "volume" : "124" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "44\u201348", "plainTextFormattedCitation" : "44\u201348", "previouslyFormattedCitation" : "44\u201348" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }44–48).Olfactory sensory neurons extend multiple dendritic cilia into an overlying olfactory mucus layer, so creating a large surface area for odourant binding. Basally, OSN extend axons in bundles (olfactory fila) through the foramina of the cribriform plate towards the olfactory bulb. The olfactory bulb is the first relay in the olfactory system and is found immediately superior (dorsal) to the cribriform plate and inferior (ventral) to the orbitofrontal cortex. Within the olfactory bulb, OSN axons form their first synapse with bulbar glomerular cells. It is therefore interesting that OSN are first order excitatory sensory neurons, which extend directly from the mucosa of the olfactory cleft into the brain. OSN are also interesting in that they are capable of regeneration from the basal cells found within the olfactory neuroepithelium although the turn-over time in humans is unclear (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3389/fnins.2014.00182", "ISSN" : "1662453X", "PMID" : "25018692", "abstract" : "Neurogenesis continues well beyond embryonic and early postnatal ages in three areas of the nervous system. The subgranular zone supplies new neurons to the dentate gyrus of the hippocampus. The subventricular zone supplies new interneurons to the olfactory bulb, and the olfactory neuroepithelia generate new excitatory sensory neurons that send their axons to the olfactory bulb. The latter two areas are of particular interest as they contribute new neurons to both ends of a first-level circuit governing olfactory perception. The vomeronasal organ and the main olfactory epithelium comprise the primary peripheral olfactory epithelia. These anatomically distinct areas share common features, as each exhibits extensive neurogenesis well beyond the juvenile phase of development. Here we will discuss the effect of age on the structural and functional significance of neurogenesis in the vomeronasal and olfactory epithelia, from juvenile to advanced adult ages, in several common model systems. We will next discuss how age affects the regenerative capacity of these neural stem cells in response to injury. Finally, we will consider the integration of newborn neurons into an existing circuit as it is modified by the age of the animal.", "author" : [ { "dropping-particle" : "", "family" : "Brann", "given" : "Jessica H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Firestein", "given" : "Stuart J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Frontiers in Neuroscience", "id" : "ITEM-1", "issue" : "8 JUN", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "1-11", "title" : "A lifetime of neurogenesis in the olfactory system", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "49", "plainTextFormattedCitation" : "49", "previouslyFormattedCitation" : "49" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }49). Olfactory ensheathing cells (OEC) are supporting glial cells, which are present in the peripheral and central olfactory systems (neuroepithelium and olfactory bulb respectively). OECs play a facilitative role in the regeneration of OSNs and may putatively be used in future treatment of nerve lesions (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3109/02688697.2010.522744", "ISBN" : "1360-046X (Electronic)\\r0268-8697 (Linking)", "ISSN" : "0268-8697", "PMID" : "20979435", "abstract" : "Clinical trials in spinal cord injury (SCI) can be affected by many confounding variables including spontaneous recovery, variation in the lesion type and extend. However, the clinical need and the paucity of effective therapies has spawned a large number of animal studies and clinical trials for SCI. In this review, we suggest that brachial plexus avulsion injury, a longitudinal spinal cord lesion, is a simpler model to test methods of spinal cord repair. We explore reconstructive techniques currently explored for the repair of brachial plexus avulsion and focus on the use of olfactory ensheathing cell transplantation as an adjunct treatment in brachial plexus repair.", "author" : [ { "dropping-particle" : "", "family" : "Kachramanoglou", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andrews", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "East", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carlstedt", "given" : "T P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raisman", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Choi", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "British journal of neurosurgery", "id" : "ITEM-1", "issue" : "September 2010", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "16-27", "title" : "Novel strategies in brachial plexus repair after traumatic avulsion.", "type" : "article-journal", "volume" : "25" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1055/s-0033-1361837", "ISSN" : "2193-6331", "PMID" : "25302141", "abstract" : "Studies using animal models have recently suggested that the olfactory mucosa may be a source of cells capable of stimulating and contributing to complex neurologic regeneration. Several groups have already transplanted cell derivatives from the olfactory mucosa into injury models, and the results so far have been promising. To fully appreciate the meaning of these experiments, a better understanding of the cellular biology and physiology of the olfactory system is necessary. It is therefore of utmost importance for us to first identify and understand its constituents.", "author" : [ { "dropping-particle" : "", "family" : "Chen", "given" : "C Russell", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kachramanoglou", "given" : "Carolina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Daqing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andrews", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Choi", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of neurological surgery. Part B, Skull base", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "293-300", "title" : "Anatomy and cellular constituents of the human olfactory mucosa: a review.", "type" : "article-journal", "volume" : "75" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "50,51", "plainTextFormattedCitation" : "50,51", "previouslyFormattedCitation" : "50,51" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }50,51). The superior turbinate has been demonstrated to be a safe area to harvest olfactory mucosa for OEC cell culture (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.4193/Rhin15.365", "ISSN" : "03000729", "PMID" : "27107010", "author" : [ { "dropping-particle" : "", "family" : "Andrews", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Poirrier", "given" : "Anne-lise", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lund", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Choi", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "183-91", "title" : "Safety of human olfactory mucosal biopsy for the purpose of olfactory ensheathing cell harvest and nerve repair: a prospective controlled study in patients undergoing endoscopic sinus surgery", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "52", "plainTextFormattedCitation" : "52", "previouslyFormattedCitation" : "52" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }52) and interestingly there is limited evidence that OEC yield rates are higher in young compared to old patients or in patients with less compared to those with more nasal inflammation (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1227/NEU.0b013e31827b99be", "ISBN" : "1524-4040 (Electronic)\\r0148-396X (Linking)", "ISSN" : "0148396X", "PMID" : "23149968", "abstract" : "BACKGROUND: Autotransplantation of olfactory ensheathing cells (OECs) into the damaged central nervous system is a potential therapeutic strategy for spinal cord and root cord injuries. One limiting factor has been the poor OEC yields from human mucosal biopsies. Previous studies have only commented on their success in obtaining mucosal specimens containing olfactory mucosa, but have not commented on the yield of OECs from those specimens. OBJECTIVE: To describe a reproducible and safe surgical technique for obtaining human olfactory mucosa and identify patient factors that possibly affect the yield of OEC cultures from the human olfactory mucosa. METHODS: We obtained mucosal biopsies from 43 consecutive patients by using a novel reproducible surgical technique and our laboratory culture protocol. The Spearman rank correlation coefficient was used to assess the relationship between OECs and fibroblast yield with patient characteristics and specimen factors. RESULTS: A greater yield of OECs was obtained from patients of younger age. In addition, patients with worse mucosal disease yielded poorer cell cultures. Greatest yields were found in patients with absence of mucosal disease. Furthermore, a higher yield of OECs was obtained from specimens harvested from the more caudal portions of the superior turbinate, and OEC yield did not correlate with the ventroposterior location of the biopsy. CONCLUSION: We have provided evidence that biopsies closer to the cribriform plate can produce larger yields of OECs, and that patient factors like age and mucosal disease adversely affect the culture yield.", "author" : [ { "dropping-particle" : "", "family" : "Kachramanoglou", "given" : "Carolina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Law", "given" : "Stuart", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andrews", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Daqing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Choi", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Neurosurgery", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "170-178", "title" : "Culture of olfactory ensheathing cells for central nerve repair: The limitations and potential of endoscopic olfactory mucosal biopsy", "type" : "article-journal", "volume" : "72" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "53", "plainTextFormattedCitation" : "53", "previouslyFormattedCitation" : "53" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }53).The second order output neurons from the olfactory bulb are the mitral and tufted cells. Following signal integration, these neurons extend their axons along the lateral olfactory tract towards the structures of the primary olfactory cortex. These structures include: the anterior olfactory nucleus, the piriform cortex, the periamygdaloid cortex, the anterior cortical nucleus of the amygdala and the rostral entorhinal cortex. Odour processing may also involve ‘secondary’ and ‘tertiary’ brain areas, including structures such as the hippocampus, parahippocampal gyrus, insular cortex, and orbitofrontal cortex (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1017/CBO9781107415324.004", "ISBN" : "9788578110796", "ISSN" : "1098-6596", "PMID" : "25246403", "abstract" : "Predicting the binding mode of flexible polypeptides to proteins is an important task that falls outside the domain of applicability of most small molecule and protein\u2212protein docking tools. Here, we test the small molecule flexible ligand docking program Glide on a set of 19 non-\u03b1-helical peptides and systematically improve pose prediction accuracy by enhancing Glide sampling for flexible polypeptides. In addition, scoring of the poses was improved by post-processing with physics-based implicit solvent MM- GBSA calculations. Using the best RMSD among the top 10 scoring poses as a metric, the success rate (RMSD \u2264 2.0 \u00c5 for the interface backbone atoms) increased from 21% with default Glide SP settings to 58% with the enhanced peptide sampling and scoring protocol in the case of redocking to the native protein structure. This approaches the accuracy of the recently developed Rosetta FlexPepDock method (63% success for these 19 peptides) while being over 100 times faster. Cross-docking was performed for a subset of cases where an unbound receptor structure was available, and in that case, 40% of peptides were docked successfully. We analyze the results and find that the optimized polypeptide protocol is most accurate for extended peptides of limited size and number of formal charges, defining a domain of applicability for this approach.", "author" : [ { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Welge-L\u00fcssen", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Chemical Information and Modeling", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2006" ] ] }, "number-of-pages" : "1689-1699", "title" : "Taste and Smell: An Update", "type" : "book", "volume" : "53" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "54", "plainTextFormattedCitation" : "54", "previouslyFormattedCitation" : "54" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }54). In order to initiate olfactory processing, odourants must first reach the olfactory neuroepithelium. Here, they become dissolved in the mucus layer and bind with olfactory receptors (OR), which are found on the dendritic cilia of the OSN. Olfactory receptors are G-coupled receptors and binding of the odourant ligand leads to downstream signalling cascades involving activation of adenylyl cyclase and subsequent opening of cAMP-dependent cation channels (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/0092-8674(91)90418-X", "ISBN" : "0092-8674", "ISSN" : "00928674", "PMID" : "1840504", "abstract" : "The mammalian olfactory system can recognize and discriminate a large number of different odorant molecules. The detection of chemically distinct odorants presumably results from the association of odorous ligands with specific receptors on olfactory sensory neurons. To address the problem of olfactory perception at a molecular level, we have cloned and characterized 18 different members of an extremely large multigene family that encodes seven transmembrane domain proteins whose expression is restricted to the olfactory epithelium. The members of this novel gene family are likely to encode a diverse family of odorant receptors.", "author" : [ { "dropping-particle" : "", "family" : "Buck", "given" : "Linda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Axel", "given" : "Richard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cell", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "1991" ] ] }, "page" : "175-187", "title" : "A novel multigene family may encode odorant receptors: A molecular basis for odor recognition", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "55", "plainTextFormattedCitation" : "55", "previouslyFormattedCitation" : "55" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }55). Resultant action potential generation is then propagated to the structures outlined above. Human gene studies have demonstrated up to 400 active OR genes, though humans are able to detect thousands of distinct odours ((ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/molbev/msg013", "ISBN" : "0737-4038", "ISSN" : "07374038", "PMID" : "12644552", "abstract" : "Olfactory receptors (OR) constitute the molecular basis for the sense of smell. They are encoded by a large multigene family that in humans includes approximately 400 functional genes and approximately 600 putative pseudogenes, distributed on all but two chromosomes. To examine the ethnogeographic variability in the functional chemosensory repertoire, we resequenced 32 OR loci reported to contain a single coding region disruption in seven Caucasians and seven Pygmies. Thirteen of the 32 OR loci were found to have an interrupted coding region in all 28 alleles sampled, seven had an intact form in all the individuals examined, and 12 were polymorphic, segregating both the intact and the null variants. Among the latter loci, the frequency of the null allele was higher in Caucasians than in Pygmies, suggesting that African populations may have a larger repertoire of functional OR genes. Interestingly, when analyzing the entire OR coding regions, we find an excess of high-frequency derived alleles at many loci in the Caucasian sample but less so in the Pygmy sample. Our observations are unlikely to be accounted for by simple demographic models but may be explained by positive selection acting on OR loci in Caucasians.", "author" : [ { "dropping-particle" : "", "family" : "Gilad", "given" : "Yoav", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lancet", "given" : "Doron", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Molecular Biology and Evolution", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "307-314", "title" : "Population differences in the human functional olfactory repertoire", "type" : "article-journal", "volume" : "20" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1371/journal.pone.0096333", "ISBN" : "1932-6203", "ISSN" : "19326203", "PMID" : "24800820", "abstract" : "Olfactory perception is mediated by a large array of olfactory receptor genes. The human genome contains 851 olfactory receptor gene loci. More than 50% of the loci are annotated as nonfunctional due to frame-disrupting mutations. Furthermore haplotypic missense alleles can be nonfunctional resulting from substitution of key amino acids governing protein folding or interactions with signal transduction components. Beyond their role in odor recognition, functional olfactory receptors are also required for a proper targeting of olfactory neuron axons to their corresponding glomeruli in the olfactory bulb. Therefore, we anticipate that profiling of olfactory receptor gene expression in whole human olfactory mucosa and analysis in the human population of their expression should provide an opportunity to select the frequently expressed and potentially functional olfactory receptors in view of a systematic deorphanization. To address this issue, we designed a TaqMan Low Density Array (Applied Biosystems), containing probes for 356 predicted human olfactory receptor loci to investigate their expression in whole human olfactory mucosa tissues from 26 individuals (13 women, 13 men; aged from 39 to 81 years, with an average of 67\u00b111 years for women and 63\u00b112 years for men). Total RNA isolation, DNase treatment, RNA integrity evaluation and reverse transcription were performed for these 26 samples. Then 384 targeted genes (including endogenous control genes and reference genes specifically expressed in olfactory epithelium for normalization purpose) were analyzed using the same real-time reverse transcription PCR platform. On average, the expression of 273 human olfactory receptor genes was observed in the 26 selected whole human olfactory mucosa analyzed, of which 90 were expressed in all 26 individuals. Most of the olfactory receptors deorphanized to date on the basis of sensitivity to known odorant molecules, which are described in the literature, were found in the expressed olfactory receptors gene set.", "author" : [ { "dropping-particle" : "", "family" : "Verbeurgt", "given" : "Christophe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilkin", "given" : "Fran??oise", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tarabichi", "given" : "Maxime", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gregoire", "given" : "Fran??oise", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dumont", "given" : "Jacques E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chatelain", "given" : "Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "21-26", "title" : "Profiling of olfactory receptor gene expression in whole human olfactory mucosa", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "56,57", "plainTextFormattedCitation" : "56,57", "previouslyFormattedCitation" : "56,57" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }56,57) but see also: ref ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/anie.201309508", "ISBN" : "1521-3773 (Electronic)\\r1433-7851 (Linking)", "ISSN" : "15213773", "PMID" : "24939725", "abstract" : "The biocatalytic production of flavor naturals that determine chemosensory percepts of foods and beverages is an ever challenging target for academic and industrial research. Advances in chemical trace analysis and post-genomic progress at the chemistry-biology interface revealed odor qualities of nature's chemosensory entities to be defined by odorant-induced olfactory receptor activity patterns. Beyond traditional views, this review and meta-analysis now shows characteristic ratios of only about 3 to 40 genuine key odorants for each food, from a group of about 230 out of circa 10\u2009000 food volatiles. This suggests the foodborn stimulus space has co-evolved with, and roughly match our circa 400 olfactory receptors as best natural agonists. This perspective gives insight into nature's chemical signatures of smell, provides the chemical odor codes of more than 220 food samples, and beyond addresses industrial implications for producing recombinants that fully reconstruct the natural odor signatures for use in flavors and fragrances, fully immersive interactive virtual environments, or humanoid bioelectronic noses.", "author" : [ { "dropping-particle" : "", "family" : "Dunkel", "given" : "Andreas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinhaus", "given" : "Martin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kotthoff", "given" : "Matthias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nowak", "given" : "Bettina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Krautwurst", "given" : "Dietmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schieberle", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hofmann", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Angewandte Chemie - International Edition", "id" : "ITEM-1", "issue" : "28", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "7124-7143", "title" : "Nature's chemical signatures in human olfaction: A foodborne perspective for future biotechnology", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "58", "plainTextFormattedCitation" : "58", "previouslyFormattedCitation" : "58" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }58). This is made possible through complex combinatorial encoding, whereby each odourant ligand is recognised by varying combinations of OR (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/35093026", "ISBN" : "0028-0836", "ISSN" : "0028-0836", "PMID" : "11557990", "abstract" : "The human nose is often considered something of a luxury, but in the rest of the animal world, from bacteria to mammals, detecting chemicals in the environment has been critical to the successful organism. An indication of the importance of olfactory systems is the significant proportion - as much as 4% - of the genomes of many higher eukaryotes that is devoted to encoding the proteins of smell. Growing interest in the detection of diverse compounds at single-molecule levels has made the olfactory system an important system for biological modelling.", "author" : [ { "dropping-particle" : "", "family" : "Firestein", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature", "id" : "ITEM-1", "issue" : "6852", "issued" : { "date-parts" : [ [ "2001" ] ] }, "page" : "211-218", "title" : "How the olfactory system makes sense of scents.", "type" : "article-journal", "volume" : "413" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/scientificamerican1095-154", "ISBN" : "0036-8733 (Print)\\r0036-8733 (Linking)", "ISSN" : "0036-8733", "PMID" : "7481719", "abstract" : "Mammals can recognize thousands of odors, some of which prompt powerful responses. Recent experiments illuminate how the nose and brain may perceive scents.", "author" : [ { "dropping-particle" : "", "family" : "Axel", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scientific American", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "1995" ] ] }, "page" : "154-9", "title" : "The molecular logic of smell.", "type" : "article-journal", "volume" : "273" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1111/j.1749-6632.1974.tb49847.x", "ISSN" : "0077-8923", "PMID" : "4529253", "author" : [ { "dropping-particle" : "", "family" : "Holley", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duchamp", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Revial", "given" : "M F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Juge", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the New York Academy of Sciences", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "1974" ] ] }, "page" : "102-14", "title" : "Qualitative and quantitative discrimination in the frog olfactory receptors: analysis from electrophysiological data.", "type" : "article-journal", "volume" : "237" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "59\u201361", "plainTextFormattedCitation" : "59\u201361", "previouslyFormattedCitation" : "59\u201361" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }59–61). In addition, other types of chemoreceptors have been identified which are likely to be involved in human chemoreception (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1523/JNEUROSCI.1779-14.2014", "ISSN" : "1529-2401", "PMID" : "25209267", "abstract" : "The mammalian olfactory system detects a plethora of environmental chemicals that are perceived as odors or stimulate instinctive behaviors. Studies using odorant receptor (OR) genes have provided insight into the molecular and organizational strategies underlying olfaction in mice. One important unanswered question, however, is whether these strategies are conserved in primates. To explore this question, we examined the macaque, a higher primate phylogenetically close to humans. Here we report that the organization of sensory inputs in the macaque nose resembles that in mouse in some respects, but not others. As in mouse, neurons with different ORs are interspersed in the macaque nose, and there are spatial zones that differ in their complement of ORs and extend axons to different domains in the olfactory bulb of the brain. However, whereas the mouse has multiple discrete band-like zones, the macaque appears to have only two broad zones. It is unclear whether the organization of OR inputs in a rodent/primate common ancestor degenerated in primates or, alternatively became more sophisticated in rodents. The mouse nose has an additional small family of chemosensory receptors, called trace amine-associated receptors (TAARs), which may detect social cues. Here we find that TAARs are also expressed in the macaque nose, suggesting that TAARs may also play a role in human olfactory perception. We further find that one human TAAR responds to rotten fish, suggesting a possible role as a sentinel to discourage ingestion of food harboring pathogenic microorganisms.", "author" : [ { "dropping-particle" : "", "family" : "Horowitz", "given" : "Lisa F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saraiva", "given" : "Luis R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuang", "given" : "Donghui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yoon", "given" : "Kyoung-hye", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buck", "given" : "Linda B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of neuroscience : the official journal of the Society for Neuroscience", "id" : "ITEM-1", "issue" : "37", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "12241-52", "title" : "Olfactory receptor patterning in a higher primate.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/nature05066", "ISBN" : "1476-4687 (Electronic)\\r0028-0836 (Linking)", "ISSN" : "0028-0836", "PMID" : "16878137", "abstract" : "The mammalian olfactory system detects chemicals sensed as odours as well as social cues that stimulate innate responses. Odorants are detected in the nasal olfactory epithelium by the odorant receptor family, whose approximately 1,000 members allow the discrimination of a myriad of odorants. Here we report the discovery of a second family of receptors in the mouse olfactory epithelium. Genes encoding these receptors, called 'trace amine-associated receptors' (TAARs), are present in human, mouse and fish. Like odorant receptors, individual mouse TAARs are expressed in unique subsets of neurons dispersed in the epithelium. Notably, at least three mouse TAARs recognize volatile amines found in urine: one detects a compound linked to stress, whereas the other two detect compounds enriched in male versus female urine-one of which is reportedly a pheromone. The evolutionary conservation of the TAAR family suggests a chemosensory function distinct from odorant receptors. Ligands identified for TAARs thus far suggest a function associated with the detection of social cues.", "author" : [ { "dropping-particle" : "", "family" : "Liberles", "given" : "Stephen D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buck", "given" : "Linda B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature", "id" : "ITEM-2", "issue" : "7103", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "645-650", "title" : "A second class of chemosensory receptors in the olfactory epithelium.", "type" : "article-journal", "volume" : "442" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1371/journal.pone.0054950", "ISSN" : "19326203", "PMID" : "23393561", "abstract" : "In addition to the canonical olfactory receptors, TAARs were currently suggested to be a second class of chemosensory receptors in the olfactory epithelium of vertebrates. In contrast to several deorphanized murine TAARs, agonists for the intact human TAAR genes 2, 5, 6, 8 and 9 that are potentially expressed in the human olfactory epithelium have not been determined so far. Moreover, the physiological relevance of TAARs still remains elusive. We present the first successful functional expression of a human TAAR and agonists of human TAAR5. We performed a ligand screening using recombinantly expressed human TAAR5 in HANA3A cells and Xenopus laevis oocytes. In order to measure receptor activity, we used a cAMP-dependent reporter gene assay and two-electrode voltage clamp technique. As a result, human TAAR5 can be activated in a concentration-dependent manner by trimethylamine and with less efficacy by dimethylethylamine. It could neither be activated by any other of the tested single amines with a related chemical structure (42 in total), nor by any of the tested odorant mixtures. The hypothesis that Single Nucleotide Polymorphisms (SNP) within the reading frame of an olfactory receptor gene can cause a specific anosmia, formed the basis for clarifying the question, if anosmia for trimethylamine is caused by a SNP in a TAAR coding sequence. All functional human TAAR gene reading frames of subjects with specific anosmia for trimethylamine were amplified and products analyzed regarding SNP distribution. We demonstrated that the observed specific anosmia for trimethylamine is not correlated with a SNP in the coding sequence of one of the putatively functional human TAAR genes.", "author" : [ { "dropping-particle" : "", "family" : "Wallrabenstein", "given" : "Ivonne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuklan", "given" : "Jonas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weber", "given" : "Lea", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zborala", "given" : "Sandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Werner", "given" : "Markus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altm\u00fcller", "given" : "Janine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Becker", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schmidt", "given" : "Anna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hatt", "given" : "Hanns", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gisselmann", "given" : "G\u00fcnter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2013" ] ] }, "title" : "Human Trace Amine-Associated Receptor TAAR5 Can Be Activated by Trimethylamine", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "62\u201364", "plainTextFormattedCitation" : "62\u201364", "previouslyFormattedCitation" : "62\u201364" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }62–64).Finally, it is important to remember that the sensation of smell is also influenced by the somatosensory and chemesthetic sensations of the nose: for example the cooling sensation of menthol or the prickle of carbon dioxide from carbonated drinks. These sensations are mediated in the nose by the trigeminal nerve (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaehling", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grosse", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "27-31", "title" : "Automated assessment of intranasal trigeminal function", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "65", "plainTextFormattedCitation" : "65", "previouslyFormattedCitation" : "65" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }65), and there is increasing evidence that trigeminal and olfactory functions are closely linked and potentially interdependent (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1749-6632.2009.03910.x", "ISBN" : "9781573317382", "ISSN" : "00778923", "PMID" : "19686136", "abstract" : "Although numerous fMRI studies have been performed on the processing of olfactory information, the intranasal trigeminal system so far has not received much attention. In a pilot study stimulants were presented within a constantly flowing airstream birhinally to activate the olfactory (phenylethyl alcohol, H(2)S) or the trigeminal (CO(2)) nerves. Both olfactory and trigeminal stimulation activated the ventral insular cortex. Intranasal trigeminal stimulation additionally led to an activation of the midbrain, superior temporal gyrus, anterior caudate nucleus, and the dorsolateral orbitofrontal cortex. Cerebellar activation was reduced relative to odorous stimuli. For all stimuli, right-sided activity was more pronounced. These results suggested that processing of intranasal activation follows a pattern which is, at least to some degree, similar for both trigeminal and olfactory stimulation. This and results from several other studies emphasize the fact that there is a high degree of interaction between the different aspects of the chemical senses, also in the sense that chemosensory-induced activation in the nasal cavity is processed in similar cortical networks. Interactions between the olfactory and trigeminal system can also be seen in patients with acquired olfactory loss, who exhibit reduced trigeminal sensitivity, possibly due to the lack of a central-nervous interaction. Both the orbitofrontal cortex and the rostral insula appear to be of significance in the amplification of trigeminal input, which is missing in patients with olfactory loss.", "author" : [ { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iannilli", "given" : "E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frasnelli", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boyle", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerber", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the New York Academy of Sciences", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "190-195", "title" : "Central processing of trigeminal activation in humans", "type" : "article-journal", "volume" : "1170" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1111/ejn.12066", "ISBN" : "1460-9568", "ISSN" : "0953816X", "PMID" : "23205840", "abstract" : "The mammalian olfactory epithelium contains olfactory receptor neurons and trigeminal sensory endings. The former mediate odor detection, the latter the detection of irritants. The two apparently parallel chemosensory systems are in reality interdependent in various well-documented ways. Psychophysical studies have shown that virtually all odorants can act as irritants, and that most irritants have an odor. Thus, the sensory perception of odorants and irritants is based on simultaneous input from the two systems. Moreover, functional interactions between the olfactory system and the trigeminal system exist on both peripheral and central levels. Here we examine the impact of trigeminal stimulation on the odor response of olfactory receptor neurons. Using an odorant with low trigeminal potency (phenylethyl alcohol) and a non-odorous irritant (CO(2) ), we have explored this interaction in psychophysical experiments with human subjects and in electroolfactogram (EOG) recordings from rats. We have demonstrated that simultaneous activation of the trigeminal system attenuates the perception of odor intensity and distorts the EOG response. On the molecular level, we have identified a route for this cross-modal interaction. The neuropeptide calcitonin-gene related peptide (CGRP), which is released from trigeminal sensory fibres upon irritant stimulation, inhibits the odor response of olfactory receptor neurons. CGRP receptors expressed by these neurons mediate this neuromodulatory effect. This study demonstrates a site of trigeminal-olfactory interaction in the periphery. It reveals a pathway for trigeminal impact on olfactory signal processing that influences odor perception.", "author" : [ { "dropping-particle" : "", "family" : "Daiber", "given" : "Philipp", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Genovese", "given" : "Federica", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schriever", "given" : "Valentin A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "M??hrlen", "given" : "Frank", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frings", "given" : "Stephan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Journal of Neuroscience", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "572-582", "title" : "Neuropeptide receptors provide a signalling pathway for trigeminal modulation of olfactory transduction", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/0031-9384(78)90070-7", "ISBN" : "0031-9384", "ISSN" : "00319384", "PMID" : "662939", "abstract" : "Psychometric ratings of the perceived intensity, pleasantness, coolness, warmth, and presumptive safety of high concentrations of 47 nasally-inhaled chemicals commonly used in olfactory research were established for three groups of human observers (n = 15/group): (1) anosmics lacking olfactory (CN I), but not trigeminal (CN V), nerve function; (2) normals asked to rate only intranasal trigeminal (CN V) sensations (trigeminal focus group); and (3) normals asked to rate the overall odor experience in the traditional fashion. Forty-five of the 47 compounds were detected by at least some proportion of the anosmics in a forced-chice test. Although differences in the rated intensities of the stimuli were present between the three experimental groups, the relative rankings of the intensity responses were quite similar (rs ranging from 0.92 to 0.97). The pleasantness and presumed safety of the chemicals varied inversely with the perceived intensity in all three groups. The use of 11 to 13 readily-available and computer-derived molecular descriptors in linear learning machine pattern recognition analyses separated the 47 stimuli correctly into four discrete intensity classes. A multiple linear regression equation based upon such molecular descriptors (multiple R = .88) proved successful in predicting the perceived trigeminal intensities of 12 chemical stimuli similar in general structure to members of the original stimulus set (r = .80 between predicted and observed intensities). These results emphasize the importance of trigeminal input in human nasal chemoreception and support the notion that the perceived intensities of nasally-inhaled stimulants can be mathematically predicted from relatively simple physicochemical and molecular structural parameters. ?? 1978.", "author" : [ { "dropping-particle" : "", "family" : "Doty", "given" : "Richard L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brugger", "given" : "William E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jurs", "given" : "Peter C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Orndorff", "given" : "Michael A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Snyder", "given" : "Peter J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lowry", "given" : "L. Dale", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Physiology and Behavior", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "1978" ] ] }, "page" : "175-185", "title" : "Intranasal trigeminal stimulation from odorous volatiles: Psychometric responses from anosmic and normal humans", "type" : "article-journal", "volume" : "20" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1186/s13223-015-0074-0", "ISSN" : "1710-1484", "PMID" : "25897313", "abstract" : "TRPA1 has been proposed to be associated with diverse sensory allergic reactions, including thermal (cold) nociception, hearing and allergic inflammatory conditions. Some naturally occurring compounds are known to activate TRPA1 by forming a Michael addition product with a cysteine residue of TRPA1 through covalent protein modification and, in consequence, to cause allergic reactions. The anti-allergic property of TRPA1 agonists may be due to the activation and subsequent desensitization of TRPA1 expressed in sensory neurons. In this review, naturally occurring TRPA1 antagonists, such as camphor, 1,8-cineole, menthol, borneol, fenchyl alcohol and 2-methylisoborneol, and TRPA1 agonists, including thymol, carvacrol, 1'S-1'- acetoxychavicol acetate, cinnamaldehyde, \u03b1-n-hexyl cinnamic aldehyde and thymoquinone as well as isothiocyanates and sulfides are discussed.", "author" : [ { "dropping-particle" : "", "family" : "Mihara", "given" : "Satoru", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shibamoto", "given" : "Takayuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology", "id" : "ITEM-4", "issue" : "1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "11", "title" : "The role of flavor and fragrance chemicals in TRPA1 (transient receptor potential cation channel, member A1) activity associated with allergies.", "type" : "article-journal", "volume" : "11" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "66\u201369", "plainTextFormattedCitation" : "66\u201369", "previouslyFormattedCitation" : "66\u201369" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }66–69). In addition, trigeminal activation is crucial to the perception of nasal airflow (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00405-013-2466-4", "ISSN" : "09374477", "PMID" : "23568039", "abstract" : "Nasal surgeries constitute an extensive manipulation of the nasal mucosa and therefore of structures related to trigeminal and olfactory sensitivity. While olfactory changes due to nasal surgery are relatively well investigated, there are only very few studies regarding trigeminal sensitivity. Aim of the present study was to investigate sensory changes after nasal surgery with special regard to the trigeminal sensitivity. In 38 patients prior to and around 12\u00a0weeks after nasal surgery the following psychophysical measures were performed: odor identification, odor discrimination, phenyl ethyl alcohol odor threshold, sensitivity to trigeminal stimuli, trigeminal detection thresholds and trigeminal pain thresholds. These results were compared to those of a control group (43 healthy volunteers). Psychophysical olfactory and trigeminal testing showed no major changes in patients after surgery compared to the control group. Independent from the time of measurement higher trigeminal detection thresholds were found in patients compared to healthy subjects, meaning that trigeminal thresholds were already increased before surgery. The present study revealed a decreased trigeminal sensitivity in patients already before surgery. It may be hypothesized that patients also exhibit a decreased sensitivity for nasal airflow, which may also contribute to the patients' impression of impaired nasal breathing.", "author" : [ { "dropping-particle" : "", "family" : "Scheibe", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schulze", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mueller", "given" : "C. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schuster", "given" : "B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Archives of Oto-Rhino-Laryngology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "87-92", "title" : "Intranasal trigeminal sensitivity: Measurements before and after nasal surgery", "type" : "article-journal", "volume" : "271" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "70", "plainTextFormattedCitation" : "70", "previouslyFormattedCitation" : "70" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }70). Conclusion:OSN are interesting in that they are capable of regeneration from the basal cells found within the olfactory neuroepithelium.Causes and Classification of Olfactory LossPrevious attempts have been made to classify olfactory dysfunction according to the location of presumed pathology, in a similar way to classification used in the auditory system. In this way, definitions have included those as in Table 2, below:[Table 2]However, anatomical classification in this way may be restrictive. The above categories are not mutually exclusive and their use as such may lead to incomplete appreciation of the underlying pathophysiology. This is particularly evident with regards to several conditions known to cause olfactory dysfunction. Chronic rhinosinusitis (CRS) is a common inflammatory condition affecting the mucosa of the nose and one or more of the paranasal sinuses. It has several distinct phenotypic subtypes including CRS with or without polyps. It has been suggested that hyposmia and anosmia associated with CRS is caused by mechanical obstruction of odourant transmission to the olfactory cleft due to mucosal oedema or polyps (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/lary.24330", "ISBN" : "0023-852x", "ISSN" : "15314995", "PMID" : "23901043", "abstract" : "OBJECTIVES/HYPOTHESIS: To assess the effect of oral plus intranasal corticosteroids on subjective outcomes (smell and nasal congestion) and objective outcomes (tissue eosinophilia and nitric oxide) in severe nasal polyposis (NP).\\n\\nSTUDY DESIGN: After a 4-week steroid washout period (w0), severe NP were randomized into a treatment group (n = 67) that receive oral prednisone for 2 weeks (w2) plus intranasal budesonide for 12 weeks (w12), and a control group (n = 22) that received no steroid treatment.\\n\\nMETHODS: Barcelona Smell Test 24 (BAST-24), nasal congestion, tissue eosinophilia, and nasal nitric oxide (nNO) were assessed.\\n\\nRESULTS: Before treatment, patients showed a significant impairment of smell detection (30.7 \u00b1 39.5%), identification (7.1 \u00b1 16.1%), and forced choice (13.8 \u00b1 23.3%) in BAST-24 compared to healthy population. At w2, the treatment group showed a significant improvement in detection, identification, and forced choice. Positive effect was also seen after 12 weeks of intranasal corticosteroids. A significant reduction of nasal congestion (1.17 \u00b1 1.0 vs. 2.73 \u00b1 0.5) and polyp tissue eosinophilia (10.9 \u00b1 4.2 vs. 41.2 \u00b1 12.2) with an increase of nNO (650 \u00b1 317 vs. 420 \u00b1 221 ppb) were observed at w2 compared to w0 and to the control group. These effects were also seen at w12.\\n\\nCONCLUSIONS: Combined oral and intranasal corticosteroids improve smell and nasal congestion and decrease nasal inflammation, as measured by reduced tissue eosinophilia and increased detection of nNO. Severity of smell loss correlates with degree of nasal congestion but not with inflammation, as measured by tissue eosinophilia or nasally exhaled nNO. Our findings suggest that improvement in smell may be related to improved conduction of odorants to the olfactory neuroepithelium.", "author" : [ { "dropping-particle" : "", "family" : "Alobid", "given" : "Isam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benitez", "given" : "Pedro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cardelus", "given" : "Sara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borja Callejas", "given" : "Francisco", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lehrer-Coriat", "given" : "Eduardo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pujols", "given" : "Laura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Picado", "given" : "Cesar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mullol", "given" : "Joaquim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Laryngoscope", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "50-56", "title" : "Oral plus nasal corticosteroids improve smell, nasal congestion, and inflammation in sino-nasal polyposis", "type" : "article-journal", "volume" : "124" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "71", "plainTextFormattedCitation" : "71", "previouslyFormattedCitation" : "71" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }71). Accordingly, opacification of the olfactory cleft on CT has been correlated with olfactory function (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.4193/Rhino14.160", "ISBN" : "0300-0729 (Print)\\r0300-0729", "ISSN" : "03000729", "PMID" : "25756075", "abstract" : "OBJECTIVES: To assess subjective improvement of olfactory function following endoscopic sinus surgery (ESS) in chronic rhinosinusitis associated with nasal polyps (CRSwNP) and to analyse factors of recovery with the European Test of Olfactory Capabilities (ETOC). METHODS: We carried out a prospective study of 30 patients with CRSwNP from November 2011 to April 2013. The ETOC was filled the day before surgery and in the short term follow-up. Sixteen suprathreshold odorants with a detection task and a forced choice verbal identification task were tested. RESULTS: The mean composite score (MCS) improved at 3 and 6 months. The preoperative MCS was correlated to the Lund-Mackay score and to the olfactory cleft opacification on preoperative computed tomography (CT) scan. Multivariate linear regression modelling of patients with preoperative anosmia showed that the olfactory recovery at 3 months was predicted by the preoperative Lund-Mackay score and the age, and at 6 months by the preoperative Lund-Mackay score. CONCLUSION: With a convenient psychophysical test, we showed that olfactory cleft opacification and CT scan score could be predictive factors of olfaction disorder severity and improvement after ESS in CRSwNP. These results need to be strengthened in the long term with a larger panel of patients.", "author" : [ { "dropping-particle" : "", "family" : "Vandenhende-Szymanski", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hochet", "given" : "B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chevalier", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mortuaire", "given" : "G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "29-34", "title" : "Olfactory cleft opacity and ct score are predictive factors of smell recovery after surgery in nasal polyposis", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "72", "plainTextFormattedCitation" : "72", "previouslyFormattedCitation" : "72" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }72). Alone, this would make CRS a conductive olfactory dysfunction. However, the link between eosinophilia and olfactory dysfunction has been well demonstrated (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/MLG.0b013e318170b5cb", "ISBN" : "1531-4995 (Electronic)", "ISSN" : "1531-4995", "PMID" : "18438263", "abstract" : "OBJECTIVE/HYPOTHESIS: This prospective study aimed to investigate predictors of nasal surgery in terms of olfactory function. STUDY DESIGN: Prospective study. METHODS: A total of 775 patients were included in this prospective study (482 men, 293 women; age range 10-81 years, mean age 41 years, standard deviation = 15.3 y). Prior to surgery, patients received a detailed otorhinolaryngologic examination including nasal endoscopy. Olfactory function was assessed with a standardized odor identification test (\"Sniffin' Sticks\"). In 356 patients, olfactory function was retested 4 months after surgery (63-339 days after surgery; mean 128 days, standard deviation = 29 days); 206 of these patients received sinus surgery, while 150 received surgery involving the septum. RESULTS: Using a conservative definition of change of olfactory function, following sinus surgery, improvement of the sense of smell was found in 23%, no change was seen in 68%, and decreased function was seen in 9% of the patients; in patients with septum surgery, improvement was seen in 13%, no change in 81%, and decreased function in 7%. Patients exhibiting a postoperative decrease of olfactory function had significantly higher preoperative olfactory scores than patients who experienced improvement. In terms of the sense of smell, nasal surgery produced the highest success rates in patients with eosinophilia and a high degree of polyposis. Neither age nor sex had a major impact on the outcome of surgery in terms of olfactory function. CONCLUSIONS: These results in a large group of patients confirm previous work. Apart from apparent success in 13 to 23% of patients, there is also a small but significant group of patients (7 to 9%) in whom olfactory function decreases after surgery. Because this decrease was mostly found in patients with relatively good preoperative olfactory function, this group should receive specific attention when counseling patients about the potential risks of nasal surgery.", "author" : [ { "dropping-particle" : "", "family" : "Pade", "given" : "J\u00fcrgen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Laryngoscope", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2008" ] ] }, "note" : "Only septoplasty/SMR +/- turbinates and FESS. NO SRP", "page" : "1260-1264", "title" : "Olfactory function following nasal surgery.", "type" : "article-journal", "volume" : "118" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Klimek", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klimek", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eggers", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eggers", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J. Allergy Clin. Immunol.", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "1997" ] ] }, "page" : "159-164", "title" : "Olfactory dysfunction in allergic rhinitis is related to nasal eosinophilc inflammation", "type" : "article-journal", "volume" : "100" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.otohns.2009.06.085", "ISSN" : "1097-6817", "PMID" : "19786212", "abstract" : "OBJECTIVE: Describe detailed histopathologic findings from a cohort of patients with chronic rhinosinusitis and evaluate whether histologic measures correlate with baseline clinical factors.\\nSTUDY DESIGN: Cross-sectional study with planned data collection.\\nSETTING: Tertiary medical center.\\nSUBJECTS AND METHODS: Adult patients with chronic rhinosinusitis were prospectively enrolled and demographic data and medical comorbidities recorded. Disease severity was measured by computed tomography (CT), endoscopy, Smell Identification Test (SIT), the Chronic Sinusitis Survey, Rhinosinusitis Disability Index, and SF-36 General Health Survey. Mucosal specimens were assessed for the presence of mucosal inflammation, including cellular (eosinophils, neutrophils, lymphocytes, mast cells, plasma cells, macrophages), epithelial (squamous metaplasia, basement membrane thickening, goblet cells), and stromal markers (subepithelial edema, fibrosis). Histopathologic findings were correlated to baseline clinical factors.\\nRESULTS: A total of 147 subjects were enrolled with histologic samples available for review. Presence of inflammatory markers was diverse, with lymphocytes present in 100 percent of subjects, eosinophils in 49.7 percent, and neutrophils found in 0.7 percent. Total eosinophil counts correlated with the presence of nasal polyposis (r = -0.367; P < 0.001), asthma (r = 0.264; P = 0.001), and aspirin intolerance (r = 0.279; P = 0.001). Mucosal eosinophilia correlated with worse disease severity on CT (r = 0.414; P < 0.001), endoscopy (r = 0.376; P < 0.001), and SIT (r = -0.253; P = 0.002), with the highest correlations seen in subgroups without nasal polyps. Histopathologic findings did not significantly correlate with any quality-of-life measure.\\nCONCLUSION: Mucosal eosinophilia correlates with objective disease severity as defined by CT, endoscopy, and SIT scores. Although other histologic markers of inflammation are present, none show similar correlations. The presence of mucosal eosinophils does not correlate with quality-of-life scores.", "author" : [ { "dropping-particle" : "", "family" : "Soler", "given" : "Zachary M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sauer", "given" : "David A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mace", "given" : "Jess", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Timothy L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Otolaryngology--Head and Neck Surgery: Official Journal of American Academy of Otolaryngology-Head and Neck Surgery", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "454-461", "publisher" : "Elsevier Inc.", "title" : "Relationship between clinical measures and histopathologic findings in chronic rhinosinusitis", "type" : "article-journal", "volume" : "141" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1016/j.anl.2012.12.001", "ISBN" : "1879-1476 (Electronic)\\r0385-8146 (Linking)", "ISSN" : "03858146", "PMID" : "23312885", "abstract" : "Objective: To address the controversy over whether olfactory function is improved or not after endoscopic sinus surgery (ESS) in patients with eosinophilic (ECRS) and non-eosinophilic chronic rhinosinusitis (non-ECRS). Methods: Between June 2006 and March 2012, 89 adult patients with CRS underwent ESS at Hyogo College of Medicine. There were 55 men and 34 women with a mean age of 53 years old, ranging from 23 to 79 years. The average follow-up period was 10.7 months (3-24) after ESS. Peripheral blood examination, sinonasal CT imaging, and four kinds of olfaction tests [self-administered olfaction test (SAOQ), visual analog scale (VAS), T&T recognition threshold tests (T&T) and intravenous olfaction test using prosultiamine] were performed. We diagnosed ECRS when (i) symptoms of nasal congestion and olfactory disorder, (ii) bilateral chronic rhinosinusitis with nasal polyps (CRSwNPs), (iii) peripheral blood eosinophilia (>7.0%), and (iv) ethmoid sinus dominant opacification in preoperative CT findings (i.e. ethmoid sinuses (E) were more bilaterally occupied than those of maxillary sinuses (M), E/M \u2265 1), were completely fulfilled. We divided the patients into two groups of ECRS (group A) and non-ECRS (group B). Olfaction tests before operation, and at the 3rd, 6th, 12th, and 24th month postoperation were analyzed. The severity and therapeutic evaluation of olfaction were based on criteria of T&T recognition thresholds. Results: The mean SAOQ and VAS scores showed significant improvement within 6 months after ESS in both group A and group B. In total, the improvement rates were 52.0% (26/50) at 3 months, 58.5% (24/41) at 6 months, 40.5% (15/37) at 12 months, and 41.2% (7/17) at 24 months. The significant improvement of T&T recognition thresholds in group B was maintained for 24 months, whereas those in group A, showing transient improvement, deteriorated after 12 months or more. A significant difference in postoperative T&T recognition between groups A and B was found at the 12th postoperative month. In both A and B, 84% of patients had a response to prosultiamine (positive group) in the preoperative stage. T&T thresholds in the positive group were significantly better that those in the negative groups in the postoperative stage. Conclusion: Olfactory disorders due to ECRS showed transient improvement that deteriorated as time passed after surgery. The olfaction in the non-ECRS patients recovered comparatively well. Postoperative olfactory results were unf\u2026", "author" : [ { "dropping-particle" : "", "family" : "Oka", "given" : "Hideki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsuzuki", "given" : "Kenzo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takebayashi", "given" : "Hironori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kojima", "given" : "Yusuke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daimon", "given" : "Takashi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sakagami", "given" : "Masafumi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Auris Nasus Larynx", "id" : "ITEM-4", "issue" : "5", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "452-457", "publisher" : "Elsevier Ireland Ltd", "title" : "Olfactory changes after endoscopic sinus surgery in patients with chronic rhinosinusitis", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "73\u201376", "plainTextFormattedCitation" : "73\u201376", "previouslyFormattedCitation" : "73\u201376" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }73–76), and increasing evidence from both animal models and human research has suggested that inflammation within the neuroepithelium can lead to temporary, reversible interference with odourant binding/olfactory perception (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/alr.21187", "ISBN" : "2122633255", "ISSN" : "20426976", "PMID" : "23733314", "abstract" : "BACKGROUND: Olfactory loss is a debilitating symptom of chronic rhinosinusitis. To study the impact of inflammation on the olfactory system, the inducible olfactory inflammation (IOI) transgenic mouse was created in which inflammation can be turned on and off within the olfactory epithelium. In this study, the type II tumor necrosis factor (TNF) receptor (TNFR2) was knocked out, and the effect on the olfactory loss phenotype was assessed. METHODS: IOI mice were bred to TNFR2 knockout mice to yield progeny IOI mice lacking the TNFR2 receptor (TNFR2(-/-) ). TNF-alpha expression was induced within the olfactory epithelium for 6 weeks to generate chronic inflammation. Olfactory function was assayed by electro-olfactogram (EOG), and olfactory tissue was processed for histology and immunohistochemical staining. RESULTS: Compared to IOI mice with wild-type TNFR2, IOI mice lacking the TNFR2 demonstrated similar levels of inflammatory infiltration and enlargement of the subepithelial layer. However, IOI-TNFR2(-/-) mice differed markedly in that the neuronal layer was largely preserved and active progenitor cell proliferation was present. Odorant responses were maintained in the IOI-TNFR2(-/-) mice, in contrast to IOI mice. CONCLUSION: TNFR2 is the minor receptor for TNF-alpha, but appears to play an important role in mediating TNF-induced disruption of the olfactory system. This finding suggests that neuronal death and inhibition of proliferation in CRS may be mediated by TNFR2 on olfactory neurons and progenitor cells. Further studies are needed to elucidate the subcellular pathways involved and develop novel therapies for treating olfactory loss in the setting of CRS.", "author" : [ { "dropping-particle" : "", "family" : "Pozharskaya", "given" : "Tatyana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liang", "given" : "Jonathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lane", "given" : "Andrew P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Forum of Allergy and Rhinology", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2013" ] ] }, "note" : "4, 5", "page" : "740-747", "title" : "Regulation of inflammation-associated olfactory neuronal death and regeneration by the type II tumor necrosis factor receptor", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1523/JNEUROSCI.4507-09.2010", "ISSN" : "0270-6474", "author" : [ { "dropping-particle" : "", "family" : "Lane", "given" : "A. P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turner", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "May", "given" : "L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reed", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Neuroscience", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "2324-2329", "title" : "A Genetic Model of Chronic Rhinosinusitis-Associated Olfactory Inflammation Reveals Reversible Functional Impairment and Dramatic Neuroepithelial Reorganization", "type" : "article-journal", "volume" : "30" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "77,78", "plainTextFormattedCitation" : "77,78", "previouslyFormattedCitation" : "77,78" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }77,78). Furthermore, long term inflammation is believed to cause neuroepithelial remodelling and replacement with respiratory type epithelium (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/00005537-200103000-00008", "ISBN" : "0023-852X (Print)\\r0023-852X (Linking)", "ISSN" : "0023-852X", "PMID" : "11224769", "abstract" : "The sense of smell has been largely ignored by otorhinolaryngologists, even though 1) its medical stewardship falls within their specialty's purview, 2) olfactory dysfunction is not uncommon in the general population, and 3) disorders of olfaction have significant quality of life, nutritional, and safety consequences. This report provides a succinct overview of the major intranasal neural systems present in humans (namely, cranial nerves O, I, and V, and the nonfunctional accessory [vomeronasal] organ system), along with a summary of notable findings resulting from the application of modern olfactory tests to patient populations, emphasizing diseases of the nose. Such tests have led to the discovery of significant influences of age, gender, smoking, toxic exposure, and genetics on the ability to smell. Within the field of otorhinolaryngology, they have revealed that 1) surgical and medical interventions in patients with rhinosinusitis do not, on average, lead to complete recovery of olfactory function, despite common beliefs to the contrary, and 2) associations are generally lacking between measures of airway patency and olfactory function in such cases. These findings have thrown into question the dogma that olfactory loss in rhinosinusitis is attributable primarily to blockage of airflow to the receptors and have led to histopathological studies demonstrating significant olfactory epithelial compromise in sinonasal syndromes.", "author" : [ { "dropping-particle" : "", "family" : "Doty", "given" : "R L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mishra", "given" : "a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Laryngoscope", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2001" ] ] }, "page" : "409-423", "title" : "Olfaction and its alteration by nasal obstruction, rhinitis, and rhinosinusitis.", "type" : "article-journal", "volume" : "111" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "79", "plainTextFormattedCitation" : "79", "previouslyFormattedCitation" : "79" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }79,ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/chemse/27.7.623", "ISSN" : "0379-864X", "PMID" : "12200342", "abstract" : "It has been shown that olfactory epithelium can be safely biopsied from the living, intact human being. Observations of the ultrastructure of this epithelium shows changes that can then be correlated with the etiology and degree of olfactory loss, allowing a greater understanding of both normal transduction and of the pathology of dysfunction. Examples of the common forms of olfactory dysfunction are presented and discussed. Additionally, the technique will allow additional immuno-histochemical and molecular study of the tissue, will increase the understanding of both normal and pathological function and should translate to new therapeutic regimens.", "author" : [ { "dropping-particle" : "", "family" : "Jafek", "given" : "B W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Murrow", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Michaels", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Restrepo", "given" : "Diego", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Linschoten", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemical Senses", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2002" ] ] }, "page" : "623-628", "title" : "Biopsies of Human Olfactory Epithelium", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "80", "plainTextFormattedCitation" : "80", "previouslyFormattedCitation" : "80" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }80). Additionally, olfactory bulb volumes are decreased in patients with CRS (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2500/ajr.2008.22.3237", "ISSN" : "10506586", "PMID" : "19178796", "abstract" : "BACKGROUND: The aim of this study was to assess the volume of the olfactory bulb (OB) in patients with chronic rhinosinusitis (without nasal polyposis at the endoscopic evaluation) and to evaluate the correlation between this measure and the degree of sinonasal inflammation. METHODS: Patients with sinonasal disease (SND; n = 22) were compared with healthy controls (n = 16) using orthonasal and retronasal olfactory test results and OB volumes measurement calculated by planimetric manual contouring using standardized methods. The Lund-Mackay score (originally described for CT scan) was also used to gauge sinonasal inflammation (SND score). RESULTS: The two groups were not significantly different in terms of age or distribution of sex. Patients had significantly higher right- and left-sided SND scores than controls. There was no significant group difference between patients and controls with regard to OB volume. However, patients with an SND score < or =12 had larger OB volumes than patients with higher SND scores (p < 0.001). Even when controlling for the subjects' age, a significant correlation was present between OB volume and SND score (r = -0.52; p = 0.001) with smaller OB volumes being associated with a higher degree of sinonasal pathology. CONCLUSION: OB volume correlated with the SND score, which is an indicator of the degree of sinonasal inflammation. SND patients with a slight decrease or even normal olfactory function may already exhibit changes in their OB volume. This study also seems to emphasize the idea that OB volume changes are more sensitive to subtle changes in the olfactory system than results from psychophysical testing.", "author" : [ { "dropping-particle" : "", "family" : "Rombaux", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Potier", "given" : "Helene", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bertrand", "given" : "Bernard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duprez", "given" : "Thierry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of rhinology", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "598-601", "title" : "Olfactory bulb volume in patients with sinonasal disease.", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "81", "plainTextFormattedCitation" : "81", "previouslyFormattedCitation" : "81" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }81). Indeed, Gudziol and colleagues have shown that olfactory bulb volume can increase significantly after treatment in patients with CRS, compared with controls (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/brain/awp243", "ISBN" : "1460-2156", "ISSN" : "00068950", "PMID" : "19773353", "abstract" : "Differentiation of progenitor cells into neurons in the olfactory bulb depends on olfactory stimulation that can lead to an increase in olfactory bulb volume. In this study, we investigated whether the human olfactory bulb volume increases with increasing olfactory function due to treatment of chronic rhinosinusitis. Nineteen patients with chronic rhinosinusitis were investigated before and after treatment. For comparison, additional measurements were performed in 18 healthy volunteers. Volumetric measurements of the olfactory bulb were based on planimetric manual contouring of magnetic resonance scans. Olfactory function was evaluated separately for each nostril using tests for odour threshold, odour discrimination and odour identification. Measurements were performed on two occasions, 3 months apart. In healthy controls, the olfactory bulb volume did not change significantly between the two measurements. In contrast, the olfactory bulb volume in patients increased significantly from the initial 64.5 +/- 3.2 to 70.0 +/- 3.5 mm(3) on the left side (P = 0.02) and from 60.9 +/- 3.5 to 72.4 +/- 2.8 mm(3) on the right side (P < 0.001). The increase in olfactory bulb volume correlated significantly with an increase in odour thresholds (r = 0.60, P = 0.006, left side; r = 0.49, P = 0.03, right side), but not with changes in odour discrimination or odour identification. Results of this study support the idea that stimulation of olfactory receptor neurons impacts on the cell death in the olfactory bulb, not only in rodents but also in humans. To our knowledge, this is the first longitudinal study that describes an enlargement of the human olfactory bulb due to improvement of peripheral olfactory function.", "author" : [ { "dropping-particle" : "", "family" : "Gudziol", "given" : "V.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buschh\u00fcter", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abolmaali", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerber", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rombaux", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Brain", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "3096-3101", "title" : "Increasing olfactory bulb volume due to treatment of chronic rhinosinusitis-a longitudinal study", "type" : "article-journal", "volume" : "132" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "82", "plainTextFormattedCitation" : "82", "previouslyFormattedCitation" : "82" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }82). Therefore, it would appear that olfactory dysfunction due to CRS is likely a combination of both conductive, sensorineural and even central components in established disease. This argues against the anatomical classification of olfactory disorders. Similar anatomical overlap might be described in posttraumatic olfactory loss. The causative pathology in these cases has traditionally been described as severing of the olfactory nerve filaments as they cross the cribriform plate to reach olfactory bulb (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "09358943", "author" : [ { "dropping-particle" : "", "family" : "Delank", "given" : "K W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fechner", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Laryngol. Rhinol. Otol.", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "1996" ] ] }, "page" : "154-159", "title" : "Zur Pathophysiologie der posttraumatischen Riechst\u00f6rungen", "type" : "article-journal", "volume" : "75" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "83", "plainTextFormattedCitation" : "83", "previouslyFormattedCitation" : "83" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }83). However, the temporal course in such patients often does not fit with such dramatic and complete damage, but rather with delayed central damage, for example through cortical oedema (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.4193/Rhino15.010", "ISBN" : "4969630143", "ISSN" : "03000729", "author" : [ { "dropping-particle" : "", "family" : "Lotsch", "given" : "Jorn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reither", "given" : "Nicole", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bogdanov", "given" : "Vasyl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haehner", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ultsch", "given" : "Alfred", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hill", "given" : "Konstanze", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "365-370", "title" : "A brain-lesion pattern based algorithm for the diagnosis of posttraumatic olfactory loss", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "84", "plainTextFormattedCitation" : "84", "previouslyFormattedCitation" : "84" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }84). In addition, the degree of posttraumatic olfactory loss can be correlated with central lesions, demonstrated with magnetic resonance imaging of the brain (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.4193/Rhino15.010", "ISBN" : "4969630143", "ISSN" : "03000729", "author" : [ { "dropping-particle" : "", "family" : "Lotsch", "given" : "Jorn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reither", "given" : "Nicole", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bogdanov", "given" : "Vasyl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haehner", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ultsch", "given" : "Alfred", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hill", "given" : "Konstanze", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "365-370", "title" : "A brain-lesion pattern based algorithm for the diagnosis of posttraumatic olfactory loss", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "84", "plainTextFormattedCitation" : "84", "previouslyFormattedCitation" : "84" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }84). In this way, the anatomical site of the lesion might either be sensorineural, central or both. One should also bear in mind that facial lesions obtained during head injury may cause obstruction of airflow to the olfactory cleft, thereby contributing a conductive element to any olfactory dysfunction. In order to bypass these limitations in classification, chemosensory research has evolved to describe olfactory dysfunction according to putative underlying aetiology. Whilst an extensive number of underlying aetiological conditions have been linked to olfactory dysfunction, the main causes are as follows:Olfactory dysfunction secondary to sinonasal diseasePost-infectious olfactory dysfunctionPosttraumatic olfactory dysfunctionOlfactory dysfunction associated with neurological diseaseOlfactory dysfunction associated with exposure to drugs/toxinsCongenital olfactory dysfunctionOlfactory dysfunction associated with agingOther possible causes: iatrogenic damage (sinonasal and skull base surgery, laryngectomy), tumours, multiple systemic co-morbiditiesIdiopathic olfactory dysfunctionThe following section will briefly describe the current pathophysiological evidence for the above classifications.Olfactory dysfunction secondary to sinonasal diseaseRhinosinusitis is the main cause of olfactory loss due to sinonasal disease. This may be either acute (lasting less than 12 weeks, with complete resolution of symptoms) or chronic rhinosinusitis (lasting 12 weeks or longer). A variety of phenotypic subtypes exist, with olfaction being most affected by chronic rhinosinusitis with nasal polyposis (CRSwNP), followed by chronic rhinosinusitis without polyps (CRSsNP), non-allergic rhinitis, atrophic rhinitis and allergic rhinitis (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s11882-016-0617-6", "ISSN" : "1529-7322", "author" : [ { "dropping-particle" : "", "family" : "Rombaux", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huart", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Levie", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cingi", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Allergy and Asthma Reports", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "41", "publisher" : "Current Allergy and Asthma Reports", "title" : "Olfaction in Chronic Rhinosinusitis", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "85", "plainTextFormattedCitation" : "85", "previouslyFormattedCitation" : "85" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }85). According to the European Position Paper on Rhinosinusitis and Nasal Polyps, as well as the American Academy of Otolaryngology-Head and Neck Surgery Guidelines, quantitative olfactory dysfunction (in the form of hyposmia or anosmia) is one of the key diagnostic symptoms (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1013-0047", "PMID" : "22764607", "abstract" : "The European Position Paper on Rhinosinusitis and Nasal Polyps 2012 is the update of similar evidence based position papers published in 2005 and 2007.The document contains chapters on definitions and classification, we now also proposed definitions for difficult to treat rhinosinusitis, control of disease and better definitions for rhinosinusitis in children. More emphasis is placed on the diagnosis and treatment of acute rhinosinusitis. Throughout the document the terms chronic rhinosinusitis without nasal polyps and chronic rhinosinusitis with nasal polyps are used to further point out differences in pathophysiology and treatment of these two entities. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. Last but not least all available evidence for management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is analyzed and presented and management schemes based on the evidence are proposed.", "author" : [ { "dropping-particle" : "", "family" : "Fokkens", "given" : "Wytske J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lund", "given" : "Valerie J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mullol", "given" : "Joachim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bachert", "given" : "Claus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alobid", "given" : "Isam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baroody", "given" : "Fuad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cohen", "given" : "Noam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cervin", "given" : "Anders", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Douglas", "given" : "Richard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gevaert", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Georgalas", "given" : "Christos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goossens", "given" : "Herman", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harvey", "given" : "Richard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hellings", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hopkins", "given" : "Claire", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jones", "given" : "Nick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Joos", "given" : "Guy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kalogjera", "given" : "Livije", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kern", "given" : "Bob", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kowalski", "given" : "Marek", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Price", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Riechelmann", "given" : "Herbert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schlosser", "given" : "Rodney", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Senior", "given" : "Brent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thomas", "given" : "Mike", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Toskala", "given" : "Elina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voegels", "given" : "Richard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "De Yun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wormald", "given" : "Peter John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology. Supplement", "id" : "ITEM-1", "issue" : "23", "issued" : { "date-parts" : [ [ "2012", "3" ] ] }, "page" : "1-298", "title" : "European Position Paper on Rhinosinusitis and Nasal Polyps 2012.", "type" : "article-journal", "volume" : "50" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1177/0194599815572097", "ISBN" : "0194-5998", "ISSN" : "1097-6817", "PMID" : "25832968", "abstract" : "OBJECTIVE: This update of a 2007 guideline from the American Academy of Otolaryngology-Head and Neck Surgery Foundation provides evidence-based recommendations to manage adult rhinosinusitis, defined as symptomatic inflammation of the paranasal sinuses and nasal cavity. Changes from the prior guideline include a consumer added to the update group, evidence from 42 new systematic reviews, enhanced information on patient education and counseling, a new algorithm to clarify action statement relationships, expanded opportunities for watchful waiting (without antibiotic therapy) as initial therapy of acute bacterial rhinosinusitis (ABRS), and 3 new recommendations for managing chronic rhinosinusitis (CRS). PURPOSE: The purpose of this multidisciplinary guideline is to identify quality improvement opportunities in managing adult rhinosinusitis and to create explicit and actionable recommendations to implement these opportunities in clinical practice. Specifically, the goals are to improve diagnostic accuracy for adult rhinosinusitis, promote appropriate use of ancillary tests to confirm diagnosis and guide management, and promote judicious use of systemic and topical therapy, which includes radiography, nasal endoscopy, computed tomography, and testing for allergy and immune function. Emphasis was also placed on identifying multiple chronic conditions that would modify management of rhinosinusitis, including asthma, cystic fibrosis, immunocompromised state, and ciliary dyskinesia. ACTION STATEMENTS: The update group made strong recommendations that clinicians (1) should distinguish presumed ABRS from acute rhinosinusitis (ARS) caused by viral upper respiratory infections and noninfectious conditions and (2) should confirm a clinical diagnosis of CRS with objective documentation of sinonasal inflammation, which may be accomplished using anterior rhinoscopy, nasal endoscopy, or computed tomography. The update group made recommendations that clinicians (1) should either offer watchful waiting (without antibiotics) or prescribe initial antibiotic therapy for adults with uncomplicated ABRS; (2) should prescribe amoxicillin with or without clavulanate as \ufb01rst-line therapy for 5 to 10 days (if a decision is made to treat ABRS with an antibiotic); (3) should reassess the patient to confirm ABRS, exclude other causes of illness, and detect complications if the patient worsens or fails to improve with the initial management option by 7 days after diagnosis or worsens d\u2026", "author" : [ { "dropping-particle" : "", "family" : "Rosenfeld", "given" : "Richard M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Piccirillo", "given" : "Jay F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chandrasekhar", "given" : "Sujana S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brook", "given" : "Itzhak", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ashok Kumar", "given" : "Kaparaboyna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kramper", "given" : "Maggie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Orlandi", "given" : "Richard R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "James N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Patel", "given" : "Zara M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peters", "given" : "Anju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walsh", "given" : "Sandra a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Corrigan", "given" : "Maureen D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Otolaryngology\u2013 Head and Neck Surgery", "id" : "ITEM-2", "issue" : "2 suppl", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "S1-S39", "title" : "Clinical Practice Guideline (Update): Adult Sinusitis.", "type" : "article-journal", "volume" : "152" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "86,87", "plainTextFormattedCitation" : "86,87", "previouslyFormattedCitation" : "86,87" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }86,87).As outlined in the above section, olfactory dysfunction due to CRS is likely caused by a combination of factors. These include: obstructed transmission of odourants to the olfactory neuroepithelium caused by oedema, discharge ± polyps; short term reversible ligand-OR inflammatory-mediated binding dysfunction (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/alr.21187", "ISBN" : "2122633255", "ISSN" : "20426976", "PMID" : "23733314", "abstract" : "BACKGROUND: Olfactory loss is a debilitating symptom of chronic rhinosinusitis. To study the impact of inflammation on the olfactory system, the inducible olfactory inflammation (IOI) transgenic mouse was created in which inflammation can be turned on and off within the olfactory epithelium. In this study, the type II tumor necrosis factor (TNF) receptor (TNFR2) was knocked out, and the effect on the olfactory loss phenotype was assessed. METHODS: IOI mice were bred to TNFR2 knockout mice to yield progeny IOI mice lacking the TNFR2 receptor (TNFR2(-/-) ). TNF-alpha expression was induced within the olfactory epithelium for 6 weeks to generate chronic inflammation. Olfactory function was assayed by electro-olfactogram (EOG), and olfactory tissue was processed for histology and immunohistochemical staining. RESULTS: Compared to IOI mice with wild-type TNFR2, IOI mice lacking the TNFR2 demonstrated similar levels of inflammatory infiltration and enlargement of the subepithelial layer. However, IOI-TNFR2(-/-) mice differed markedly in that the neuronal layer was largely preserved and active progenitor cell proliferation was present. Odorant responses were maintained in the IOI-TNFR2(-/-) mice, in contrast to IOI mice. CONCLUSION: TNFR2 is the minor receptor for TNF-alpha, but appears to play an important role in mediating TNF-induced disruption of the olfactory system. This finding suggests that neuronal death and inhibition of proliferation in CRS may be mediated by TNFR2 on olfactory neurons and progenitor cells. Further studies are needed to elucidate the subcellular pathways involved and develop novel therapies for treating olfactory loss in the setting of CRS.", "author" : [ { "dropping-particle" : "", "family" : "Pozharskaya", "given" : "Tatyana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liang", "given" : "Jonathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lane", "given" : "Andrew P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Forum of Allergy and Rhinology", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2013" ] ] }, "note" : "4, 5", "page" : "740-747", "title" : "Regulation of inflammation-associated olfactory neuronal death and regeneration by the type II tumor necrosis factor receptor", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1523/JNEUROSCI.4507-09.2010", "ISSN" : "0270-6474", "author" : [ { "dropping-particle" : "", "family" : "Lane", "given" : "A. P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turner", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "May", "given" : "L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reed", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Neuroscience", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "2324-2329", "title" : "A Genetic Model of Chronic Rhinosinusitis-Associated Olfactory Inflammation Reveals Reversible Functional Impairment and Dramatic Neuroepithelial Reorganization", "type" : "article-journal", "volume" : "30" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "77,78", "plainTextFormattedCitation" : "77,78", "previouslyFormattedCitation" : "77,78" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }77,78); longer term neuroepithelium remodelling (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/chemse/27.7.623", "ISSN" : "0379-864X", "PMID" : "12200342", "abstract" : "It has been shown that olfactory epithelium can be safely biopsied from the living, intact human being. Observations of the ultrastructure of this epithelium shows changes that can then be correlated with the etiology and degree of olfactory loss, allowing a greater understanding of both normal transduction and of the pathology of dysfunction. Examples of the common forms of olfactory dysfunction are presented and discussed. Additionally, the technique will allow additional immuno-histochemical and molecular study of the tissue, will increase the understanding of both normal and pathological function and should translate to new therapeutic regimens.", "author" : [ { "dropping-particle" : "", "family" : "Jafek", "given" : "B W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Murrow", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Michaels", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Restrepo", "given" : "Diego", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Linschoten", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemical Senses", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2002" ] ] }, "page" : "623-628", "title" : "Biopsies of Human Olfactory Epithelium", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "80", "plainTextFormattedCitation" : "80", "previouslyFormattedCitation" : "80" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }80) and finally olfactory bulb remodelling. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2500/ajr.2008.22.3237", "ISSN" : "10506586", "PMID" : "19178796", "abstract" : "BACKGROUND: The aim of this study was to assess the volume of the olfactory bulb (OB) in patients with chronic rhinosinusitis (without nasal polyposis at the endoscopic evaluation) and to evaluate the correlation between this measure and the degree of sinonasal inflammation. METHODS: Patients with sinonasal disease (SND; n = 22) were compared with healthy controls (n = 16) using orthonasal and retronasal olfactory test results and OB volumes measurement calculated by planimetric manual contouring using standardized methods. The Lund-Mackay score (originally described for CT scan) was also used to gauge sinonasal inflammation (SND score). RESULTS: The two groups were not significantly different in terms of age or distribution of sex. Patients had significantly higher right- and left-sided SND scores than controls. There was no significant group difference between patients and controls with regard to OB volume. However, patients with an SND score < or =12 had larger OB volumes than patients with higher SND scores (p < 0.001). Even when controlling for the subjects' age, a significant correlation was present between OB volume and SND score (r = -0.52; p = 0.001) with smaller OB volumes being associated with a higher degree of sinonasal pathology. CONCLUSION: OB volume correlated with the SND score, which is an indicator of the degree of sinonasal inflammation. SND patients with a slight decrease or even normal olfactory function may already exhibit changes in their OB volume. This study also seems to emphasize the idea that OB volume changes are more sensitive to subtle changes in the olfactory system than results from psychophysical testing.", "author" : [ { "dropping-particle" : "", "family" : "Rombaux", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Potier", "given" : "Helene", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bertrand", "given" : "Bernard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duprez", "given" : "Thierry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of rhinology", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "598-601", "title" : "Olfactory bulb volume in patients with sinonasal disease.", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "81", "plainTextFormattedCitation" : "81", "previouslyFormattedCitation" : "81" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }81,ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/brain/awp243", "ISBN" : "1460-2156", "ISSN" : "00068950", "PMID" : "19773353", "abstract" : "Differentiation of progenitor cells into neurons in the olfactory bulb depends on olfactory stimulation that can lead to an increase in olfactory bulb volume. In this study, we investigated whether the human olfactory bulb volume increases with increasing olfactory function due to treatment of chronic rhinosinusitis. Nineteen patients with chronic rhinosinusitis were investigated before and after treatment. For comparison, additional measurements were performed in 18 healthy volunteers. Volumetric measurements of the olfactory bulb were based on planimetric manual contouring of magnetic resonance scans. Olfactory function was evaluated separately for each nostril using tests for odour threshold, odour discrimination and odour identification. Measurements were performed on two occasions, 3 months apart. In healthy controls, the olfactory bulb volume did not change significantly between the two measurements. In contrast, the olfactory bulb volume in patients increased significantly from the initial 64.5 +/- 3.2 to 70.0 +/- 3.5 mm(3) on the left side (P = 0.02) and from 60.9 +/- 3.5 to 72.4 +/- 2.8 mm(3) on the right side (P < 0.001). The increase in olfactory bulb volume correlated significantly with an increase in odour thresholds (r = 0.60, P = 0.006, left side; r = 0.49, P = 0.03, right side), but not with changes in odour discrimination or odour identification. Results of this study support the idea that stimulation of olfactory receptor neurons impacts on the cell death in the olfactory bulb, not only in rodents but also in humans. To our knowledge, this is the first longitudinal study that describes an enlargement of the human olfactory bulb due to improvement of peripheral olfactory function.", "author" : [ { "dropping-particle" : "", "family" : "Gudziol", "given" : "V.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buschh\u00fcter", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abolmaali", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerber", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rombaux", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Brain", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "3096-3101", "title" : "Increasing olfactory bulb volume due to treatment of chronic rhinosinusitis-a longitudinal study", "type" : "article-journal", "volume" : "132" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "82", "plainTextFormattedCitation" : "82", "previouslyFormattedCitation" : "82" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }82) Olfactory dysfunction associated with sinonasal disease tends to occur gradually, and fluctuates over time (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/MOO.0000000000000013", "ISBN" : "0000000000000", "ISSN" : "1531-6998", "PMID" : "24370953", "abstract" : "PURPOSE OF REVIEW: The aim of this review is to provide an overview of the causes of olfactory dysfunction, their evaluation and management, with a main focus on the gradual/progressive loss of smell.\\n\\nRECENT FINDINGS: As the sense of smell gives us essential information about our environment, its loss can cause nutritional and social problems while threatening an individual's safety. Recent surveys have shown quite a substantial prevalence of hyposmia (one out of four people) and anosmia (one out of 200 people) in a variety of populations.\\n\\nSUMMARY: Nasal inflammatory diseases such as allergic rhinitis and predominantly chronic rhinosinusitis account for the major and common causes of gradual/progressive loss of smell. However, they are also among the most successfully treated forms of olfactory dysfunction. The management of gradual/progressive smell deficit must always address its etiological causes. In most cases, a detailed medical history and nasal examination, smell testing, and imaging will help to establish an appropriate diagnosis. In addition to anti-inflammatory therapy, mainly nasal and systemic corticosteroids, recent investigations on smell training suggest that the controlled exposure to selected odors may increase olfactory performance.\\n\\nVIDEO ABSTRACT AVAILABLE: See the Video Supplementary Digital Content 1 ().", "author" : [ { "dropping-particle" : "", "family" : "Enriquez", "given" : "Karla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lehrer", "given" : "Eduardo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mullol", "given" : "Joaquim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current opinion in otolaryngology & head and neck surgery", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "34-41", "title" : "The optimal evaluation and management of patients with a gradual onset of olfactory loss.", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "88", "plainTextFormattedCitation" : "88", "previouslyFormattedCitation" : "88" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }88). It infrequently improves without treatment and is not commonly associated with parosmias (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/lary.26229", "author" : [ { "dropping-particle" : "", "family" : "Whitcroft", "given" : "Katherine L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cuevas", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haehner", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "1-5", "title" : "Patterns of olfactory impairment reflect underlying disease etiology", "type" : "article-journal", "volume" : "00000" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Seiden", "given" : "AM", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Taste and smell disorders", "editor" : [ { "dropping-particle" : "", "family" : "Seiden", "given" : "AM", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "1997" ] ] }, "page" : "52-71", "publisher" : "Thieme Medical Publishers", "title" : "Olfactory loss secondary to nasal and sinus pathology. In: Taste and smell disorders", "type" : "chapter" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Jafek", "given" : "BW", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moran", "given" : "DT", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eller", "given" : "PM", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rowley", "given" : "JC", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jafek", "given" : "TB", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arch Otolaryngol Head Neck Surg", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "1987" ] ] }, "page" : "547-9", "title" : "Steroid-dependent anosmia", "type" : "article-journal", "volume" : "113" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "89\u201391", "plainTextFormattedCitation" : "89\u201391", "previouslyFormattedCitation" : "89\u201391" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }89–91).Given the high prevalence of CRS within the general population (10.9% in Europe (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1398-9995.2011.02646.x", "ISBN" : "1398-9995 (Electronic)\\n0105-4538 (Linking)", "ISSN" : "01054538", "PMID" : "21605125", "abstract" : "Background: Chronic rhinosinusitis (CRS) is a common health problem, with significant medical costs and impact on general health. Even so, prevalence figures for Europe are unavailable. In this study, conducted by the GA 2LEN network of excellence, the European Position Paper on Rhinosinusitis and nasal Polyps (EP 3OS) diagnostic criteria are applied to estimate variation in the prevalence of Chronic rhinosinusitis (CRS) for Europe. Method: A postal questionnaire was sent to a random sample of adults aged 15-75 years in 19 centres in Europe. Participants reported symptoms of CRS, and doctor diagnosed CRS, allergic rhinitis, age, gender and smoking history. Definition of CRS was based on the EP 3OS diagnostic criteria: the presence of more than two of the symptoms: (i) nasal blockage, (ii) nasal discharge, (iii) facial pain/pressure or (iv) reduction in sense of smell, for >12 weeks in the past year - with at least one symptom being nasal blockage or discharge. Results: Information was obtained from 57 128 responders living in 19 centres in 12 countries. The overall prevalence of CRS by EP 3OS criteria was 10.9% (range 6.9-27.1). CRS was more common in smokers than in nonsmokers (OR 1.7: 95% CI 1.6-1.9). The prevalence of self-reported physician-diagnosed CRS within centres was highly correlated with the prevalence of EP 3OS-diagnosed CRS. Conclusion: This is the first European international multicentre prevalence study of CRS. In this multicentre survey of adults in Europe, about one in ten participants had CRS with marked geographical variation. Smoking was associated with having CRS in all parts of Europe. \u00a9 2011 John Wiley & Sons A/S.", "author" : [ { "dropping-particle" : "", "family" : "Hastan", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fokkens", "given" : "W. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bachert", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Newson", "given" : "R. B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bislimovska", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bockelbrink", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bousquet", "given" : "P. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brozek", "given" : "G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruno", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dahl??n", "given" : "S. E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forsberg", "given" : "B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gunnbj??rnsd??ttir", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kasper", "given" : "L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kr??mer", "given" : "U.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kowalski", "given" : "M. L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lange", "given" : "B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lundb??ck", "given" : "B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salagean", "given" : "E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Todo-Bom", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tomassen", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Toskala", "given" : "E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drunen", "given" : "C. M.", "non-dropping-particle" : "Van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bousquet", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zuberbier", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jarvis", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burney", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Allergy: European Journal of Allergy and Clinical Immunology", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "1216-1223", "title" : "Chronic rhinosinusitis in Europe - An underestimated disease. A GA 2LEN study", "type" : "article-journal", "volume" : "66" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "25", "plainTextFormattedCitation" : "25", "previouslyFormattedCitation" : "25" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }25)), it is likely that sinonasal diseases constitute the most frequent cause of olfactory dysfunction (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00106-003-0877-z", "ISSN" : "0017-6192", "author" : [ { "dropping-particle" : "", "family" : "Damm", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Temmel", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Welge-Lussen", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eckel", "given" : "H. 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However, such patients are often managed by their general practitioner or general ENT surgeons, and are therefore less commonly encountered in specialist smell and taste clinics. Post-infectious olfactory dysfunctionUpper respiratory tract infections are a frequent cause of olfactory dysfunction. Indeed, post-infectious loss is one of the most common presentations seen in specialist clinics (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "ooa00128 [pii]", "ISBN" : "0886-4470 (Print)\\n0886-4470 (Linking)", "ISSN" : "0886-4470", "PMID" : "12049556", "abstract" : "OBJECTIVE: To investigate the consequences of olfactory loss and explore specific questions related to the effect of duration of olfactory loss, degree of olfactory sensitivity, and cause of the olfactory loss. PATIENTS: A total of 278 consecutive patients with hyposmia or anosmia were examined. RESULTS: Causes of olfactory loss were categorized as follows: trauma (17%), upper respiratory tract infection (URI) (39%), sinonasal disease (21%), congenital anosmia (3%), idiopathic causes (18%), or other causes (3%). Our data suggest that (1) recovery rate was higher in URI olfactory loss than in olfactory loss from other causes; (2) likelihood of recovery seemed to decrease with increased duration of olfactory loss; and (3) the elderly are more prone to URI olfactory loss than younger patients. Regarding changes in quality of life (QoL), we found that (1) in most patients olfactory loss caused food-related problems; (2) loss in QoL did not change with duration of olfactory loss; (3) younger patients had more complaints than older ones, and women had more complaints than men; (4) complaint scores were higher in hyposmic patients than in anosmic patients; and (5) self-rated depression did not relate to measured olfactory function. CONCLUSIONS: Among many complaints of olfactory loss, the predominant ones were food related. This loss in QoL seemed to be of greater importance in younger than in older people, and women seem to be affected more strongly than men.", "author" : [ { "dropping-particle" : "", "family" : "Temmel", "given" : "Andreas F P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Quint", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schickinger-Fischer", "given" : "Bettina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klimek", "given" : "Ludger", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stoller", "given" : "Elisabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of otolaryngology--head & neck surgery", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2002" ] ] }, "page" : "635-641", "title" : "Characteristics of olfactory disorders in relation to major causes of olfactory loss.", "type" : "article-journal", "volume" : "128" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Deems", "given" : "DA", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doty", "given" : "RL", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Settle", "given" : "RG", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arch Otolaryngol Head Neck Surg", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "1991" ] ] }, "page" : "519-521", "title" : "Smell and taste disorders, a study of 750 patients from the University of Pennsylvania Smell and Taste Center", "type" : "article-journal", "volume" : "117" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "94,95", "plainTextFormattedCitation" : "94,95", "previouslyFormattedCitation" : "94,95" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }94,95). Typically, women are affected more frequently than men, and are middle aged or older at presentation (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/chemse/27.7.623", "ISSN" : "0379-864X", "PMID" : "12200342", "abstract" : "It has been shown that olfactory epithelium can be safely biopsied from the living, intact human being. Observations of the ultrastructure of this epithelium shows changes that can then be correlated with the etiology and degree of olfactory loss, allowing a greater understanding of both normal transduction and of the pathology of dysfunction. Examples of the common forms of olfactory dysfunction are presented and discussed. Additionally, the technique will allow additional immuno-histochemical and molecular study of the tissue, will increase the understanding of both normal and pathological function and should translate to new therapeutic regimens.", "author" : [ { "dropping-particle" : "", "family" : "Jafek", "given" : "B W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Murrow", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Michaels", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Restrepo", "given" : "Diego", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Linschoten", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemical Senses", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2002" ] ] }, "page" : "623-628", "title" : "Biopsies of Human Olfactory Epithelium", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "80", "plainTextFormattedCitation" : "80", "previouslyFormattedCitation" : "80" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }80). The latter may be due to the reduced regenerative ability of the olfactory system with advancing age and the accumulation of previous insults (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0736-5748(96)00046-9", "ISBN" : "0736-5748", "ISSN" : "07365748", "PMID" : "9010732", "abstract" : "Olfactory epithelium retains the capacity to recover anatomically after damage well into adult life and perhaps throughout its duration. None the less, olfactory dysfunctions have been reported widely for elderly humans. The present study investigates the effects of aging on the neurophysiological and anatomical status of the olfactory epithelium in barrier-raised Fischer 344X Brown Norway F1 hybrid rats at 7, 10, 25 and 32/35 months old. The posterior part of the olfactory epithelium in 32/35-month-old rats is well preserved. Globose basal cells are dividing, and new neurons are being born even at this advanced age. None the less, the numbers of proliferating basal cells and immature, GAP-43 (+) neurons are significantly decreased. Neurophysiological status was evaluated using voltage-sensitive dye techniques to assess inherent patterns of odorant-induced activity in the epithelium lining the septum and the medial surface of the turbinates. In middle and posterior zones of the epithelium, there were neither age-related changes in overall responsivity of this part of the olfactory epithelium to any of five odorants, nor shifts in the location of the odorant-induced hotspots. The inherent activity patterns elicited by the different odorants do become more distinct as a function of age, which probably reflects the decline in immature neurons and a slight, but not statistically significant, increase in mature neurons as a function of age. In contrast with the excellent preservation of posterior epithelium, the epithelium lining the anterodorsal septum and the corresponding face of the turbinates is damaged in the 32/35-month-old animals: in this part, horizontal basal cells are reactive, more basal cells and sustentacular cells are proliferating than in younger animals or in posterior epithelium of the same animals, and the neuronal population is less mature on average. Our findings indicate that degeneration of the olfactory epithelium is not an inevitable or preprogrammed consequence of the aging process, since the posterior zone of the epithelium is very well preserved in these barrier-protected animals. However, the deterioration in the anterior epithelium suggests that environmental insults can accumulate or become more severe with age and overwhelm the regenerative capacity of the epithelium. Alternatively, the regenerative capacity of the epithelium may wane somewhat with age. Either of these mechanisms or some combination of them can account for th\u2026", "author" : [ { "dropping-particle" : "", "family" : "Loo", "given" : "Alice T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Youngentob", "given" : "Steven L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kent", "given" : "Paul F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwob", "given" : "James E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Developmental Neuroscience", "id" : "ITEM-1", "issue" : "7-8", "issued" : { "date-parts" : [ [ "1996" ] ] }, "page" : "881-900", "title" : "The aging olfactory epithelium: Neurogenesis, response to damage, and odorant-induced activity", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "96", "plainTextFormattedCitation" : "96", "previouslyFormattedCitation" : "96" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }96). Onset is usually sudden, and though patients may describe an unusually severe infection, some may be unaware of the causative episode. Such cases may therefore be incorrectly labelled as idiopathic. Often, patients are affected by parosmia and there is little fluctuation in olfactory ability over time (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/lary.26229", "author" : [ { "dropping-particle" : "", "family" : "Whitcroft", "given" : "Katherine L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cuevas", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haehner", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "1-5", "title" : "Patterns of olfactory impairment reflect underlying disease etiology", "type" : "article-journal", "volume" : "00000" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "89", "plainTextFormattedCitation" : "89", "previouslyFormattedCitation" : "89" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }89). Whilst post-infectious olfactory impairment can be permanent, this is often not the case. Indeed, it has been suggested that post-infectious olfactory loss improves more frequently than in other common aetiological subgroups (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "ooa00128 [pii]", "ISBN" : "0886-4470 (Print)\\n0886-4470 (Linking)", "ISSN" : "0886-4470", "PMID" : "12049556", "abstract" : "OBJECTIVE: To investigate the consequences of olfactory loss and explore specific questions related to the effect of duration of olfactory loss, degree of olfactory sensitivity, and cause of the olfactory loss. PATIENTS: A total of 278 consecutive patients with hyposmia or anosmia were examined. RESULTS: Causes of olfactory loss were categorized as follows: trauma (17%), upper respiratory tract infection (URI) (39%), sinonasal disease (21%), congenital anosmia (3%), idiopathic causes (18%), or other causes (3%). Our data suggest that (1) recovery rate was higher in URI olfactory loss than in olfactory loss from other causes; (2) likelihood of recovery seemed to decrease with increased duration of olfactory loss; and (3) the elderly are more prone to URI olfactory loss than younger patients. Regarding changes in quality of life (QoL), we found that (1) in most patients olfactory loss caused food-related problems; (2) loss in QoL did not change with duration of olfactory loss; (3) younger patients had more complaints than older ones, and women had more complaints than men; (4) complaint scores were higher in hyposmic patients than in anosmic patients; and (5) self-rated depression did not relate to measured olfactory function. CONCLUSIONS: Among many complaints of olfactory loss, the predominant ones were food related. This loss in QoL seemed to be of greater importance in younger than in older people, and women seem to be affected more strongly than men.", "author" : [ { "dropping-particle" : "", "family" : "Temmel", "given" : "Andreas F P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Quint", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schickinger-Fischer", "given" : "Bettina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klimek", "given" : "Ludger", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stoller", "given" : "Elisabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of otolaryngology--head & neck surgery", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2002" ] ] }, "page" : "635-641", "title" : "Characteristics of olfactory disorders in relation to major causes of olfactory loss.", "type" : "article-journal", "volume" : "128" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "94", "plainTextFormattedCitation" : "94", "previouslyFormattedCitation" : "94" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }94). In their 2006 prospective cohort study, Reden and colleagues demonstrated an improvement in the psychophysical test scores of approximately one third of 262 patients with post-infectious olfactory dysfunction over an observation period of 14 months (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0886-4470", "abstract" : "Objective: To investigate the outcome of olfactory function in patients with olfactory loss following infections of the upper respiratory tract (post-URTI) or head trauma. Design: Retrospective patient-based study. Setting: Smell and Taste Outpatient Clinic at a university hospital. Patients: A total of 361 patients (228 women, 133 men) were included. Main Outcome Measures: Olfactory function was assessed using the \"Sniffin' Sticks\" test battery, which result in a threshold, discrimination, and identification score. The mean interval between first and last visit was 14 months. Results: In comparing the overall threshold, discrimination, and identification scores between the last and first visit, olfactory function improved in 26% of the patients whereas it decreased in 6%. The cause of olfactory impairment had a significant effect on the recovery rate of olfactory function. Within the post-URTI group (n=262), 32% of the patients improved, but in the posttraumatic group (n=99) only 10% improved. In patients with post-URTI olfactory loss, a negative correlation was found between age and recovery of olfactory function. In general, the factor \"sex\" had no significant effect on recovery of smell function. Conclusions: To our knowledge, the series of patients presented herein is the largest in the literature to date in which standardized testing methods were used to assess the progression of impaired olfaction. It showed that the rate of improvement of olfactory function was significantly higher in patients with post-URTI dysosmia compared with patients with posttraumatic dysosmia. During an observation period of approximately 1 year, more than 30% of patients with post-URTI olfactory loss experienced improvement, whereas only 10% of patients with posttraumatic olfactory loss experienced improvement. Furthermore, age plays a significant role in the recovery of olfactory function. \u00a92006 American Medical Association. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Reden", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mueller", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mueller", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Konstantinidis", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frasnelli", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Landis", "given" : "BN", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of Otolaryngology - Head and Neck Surgery", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "265-269", "title" : "Recovery of olfactory function following closed head injury or infections of the upper respiratory tract", "type" : "article-journal", "volume" : "132" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "97", "plainTextFormattedCitation" : "97", "previouslyFormattedCitation" : "97" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }97). Whilst higher estimates of recovery have been quoted elsewhere in the literature (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Hendricks", "given" : "AP", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "1988" ] ] }, "page" : "229-251", "title" : "Olfactory dysfunction", "type" : "article-journal", "volume" : "26" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "98", "plainTextFormattedCitation" : "98", "previouslyFormattedCitation" : "98" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }98), care should be taken in interpreting data based on patient self-reporting (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.5631/jibirin.104.703", "ISBN" : "0001648985018", "ISSN" : "1884-4545", "author" : [ { "dropping-particle" : "", "family" : "Mori", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aiba", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sugiura", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matsumoto", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tomiyama", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okuda", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okihaki", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakai", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Acta oto-laryngologica", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "1998" ] ] }, "page" : "197-201", "title" : "Clinical Study of Olfactory Disturbance", "type" : "article-journal", "volume" : "583" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "99", "plainTextFormattedCitation" : "99", "previouslyFormattedCitation" : "99" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }99), or where patient numbers are limited (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Duncan", "given" : "HJ", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seiden", "given" : "AM", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arch Otolaryngol Head Neck Surg", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "1995" ] ] }, "page" : "1183-1187", "title" : "Long-term follow-up of olfactory loss secondary to head trauma and upper respiratory tract infection.", "type" : "article-journal", "volume" : "121" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "100", "plainTextFormattedCitation" : "100", "previouslyFormattedCitation" : "100" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }100). A variety of pathogens may cause post-infectious olfactory dysfunction, including viruses, bacteria, fungi, or rare organisms such as microfilaria (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0-8247-0719-2", "author" : [ { "dropping-particle" : "", "family" : "Murphy", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doty", "given" : "Richard L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duncan", "given" : "H J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "chapter-number" : "22", "container-title" : "Handbook of Olfaction and Gustation", "edition" : "3rd", "editor" : [ { "dropping-particle" : "", "family" : "Doty", "given" : "Richard L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "461-478", "publisher" : "Marcel Dekker", "publisher-place" : "New York", "title" : "Clinical disorders of olfaction", "type" : "chapter" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "16", "plainTextFormattedCitation" : "16", "previouslyFormattedCitation" : "16" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }16). The most common of these are viruses, of which a wide variety have been linked with olfactory dysfunction, including those causing the common cold, influenza and HIV (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Philpott", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "DeVere", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Management of Smell and Taste Disorders: A Practical Guide for Clinicians", "editor" : [ { "dropping-particle" : "", "family" : "Welge-L\u00fcssen", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "91-105", "publisher" : "Thieme Medical Publishers", "title" : "Post-infectious and post-traumatic olfactory disorders", "type" : "chapter" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1097/01.mlg.0000249922.37381.1e\\r00005537-200702000-00016 [pii]", "ISBN" : "0023-852X (Print)\\r0023-852X (Linking)", "ISSN" : "0023-852X", "PMID" : "17277621", "abstract" : "OBJECTIVE: Causative viruses of postviral olfactory dysfunction (PVOD) have not yet been identified. The aim of this study was to investigate causative viruses in patients with PVOD. STUDY DESIGN AND METHODS: Nasal discharge was collected from 24 patients with PVOD. We investigated the presence of 10 viruses in nasal discharge and examined the time course, with regard to changes in olfactory dysfunction and nasal obstruction in patients with PVOD, using questionnaires, acoustic rhinometry, and olfactory tests. RESULTS: Rhinoviruses were detected in 10 patients by electrophoresis. Rhinoviruses were also confirmed in four patients by nucleotide sequences. Viral serotypes were identified to be human rhinovirus (HRV)-40, HRV-75, HRV-78, and HRV-80. One of the four patients complained of anosmia, whereas another complained of dysosmia. Olfactory testing did not show significant improvement at 4, 8, 11, and 24 weeks after the first visit in the four patients, although results of acoustic rhinometry significantly improved. Two of the four patients complained of olfactory dysfunction even 6 months after the first visit. Coronavirus and parainfluenza virus were detected in one patient each, and Epstein-Barr viruses were detected in three patients. CONCLUSIONS: This study for the first time detected rhinovirus, coronavirus, parainfluenza virus, and Epstein-Barr virus in nasal discharge of patients with PVOD. Furthermore, the present study suggests that rhinoviruses can cause olfactory dysfunction through mechanisms other than nasal obstruction and that rhinoviruses can induce various severities and different time courses of olfactory dysfunction.", "author" : [ { "dropping-particle" : "", "family" : "Suzuki", "given" : "Motohiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saito", "given" : "Koichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Min", "given" : "Wei-Ping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vladau", "given" : "Costin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Toida", "given" : "Kazunori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Itoh", "given" : "Hirotaka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Murakami", "given" : "Shingo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Laryngoscope", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "272-277", "title" : "Identification of viruses in patients with postviral olfactory dysfunction.", "type" : "article-journal", "volume" : "117" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "101,102", "plainTextFormattedCitation" : "101,102", "previouslyFormattedCitation" : "101,102" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }101,102). However, the terminology post-infectious should be used preferentially to post-viral olfactory dysfunction in order to acknowledge the various causative pathogens within this group. The pathophysiology of post-infectious olfactory loss remains poorly delineated, but is thought to involve either damage to the olfactory neuroepithelium or central olfactory processing pathways (mediated via direct transmission of pathogens to the brain through the olfactory nerve) (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Baker", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Genter", "given" : "MB", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "chapter-number" : "26", "container-title" : "Handbook of Olfaction and Gustation", "edition" : "2nd", "editor" : [ { "dropping-particle" : "", "family" : "Doty", "given" : "Richard L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "549-574", "publisher" : "Marcel Dekker", "publisher-place" : "New York", "title" : "The Olfactory System and the Nasal Mucosa as Portals of Entry of Viruses, Drugs, and Other Exogenous Agents into the Brain.", "type" : "chapter" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISBN" : "0379-864X (Print)\\r0379-864X (Linking)", "ISSN" : "0379-864X", "PMID" : "11595672", "abstract" : "The present study assessed the functional consequences of viral infection with a neurotropic coronavirus, designated MHV OBLV, that specifically targets central olfactory structures. Using standard operant techniques and a 'go, no-go' successive discrimination paradigm, six BALB/c mice were trained to discriminate between the presentation of an air or odor stimulus (three mice for each of the odorants propanol and propyl acetate). Two additional BALB/c mice were trained to discriminate between the presentation of air and the presentation of either vanillin or propionic acid. Following criterion performance, each mouse received an additional 2000 trials of overtraining. At completion of overtraining one mouse from the propanol and propyl acetate groups were allocated as untreated. The remaining six mice were inoculated with 300 microl of the OBLV stock per nostril for a total of 1.5 x 10(6) p.f.u. in 600 microl. Following a 1 month rest, untreated and inoculated animals were again tested on their respective air versus odor discrimination task. Untreated animals immediately performed at criterion levels. In contrast, inoculated animals varied in their capacity to discriminate between air and odorant. Five of the six inoculated mice showed massive disruption of the olfactory bulb, including death of mitral cells; the other was more modestly affected. In addition, the density of innervation of the olfactory mucosa by substance P-containing trigeminal fibers is also affected by inoculation. Those mice that remained anosmic to the training odorants had the most severe reduction in mitral cell number and substance P fiber density among the inoculated animals.", "author" : [ { "dropping-particle" : "", "family" : "Youngentob", "given" : "S L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwob", "given" : "J E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saha", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Manglapus", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jubelt", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemical senses", "id" : "ITEM-2", "issue" : "8", "issued" : { "date-parts" : [ [ "2001" ] ] }, "page" : "953-63", "title" : "Functional consequences following infection of the olfactory system by intranasal infusion of the olfactory bulb line variant (OBLV) of mouse hepatitis strain JHM.", "type" : "article-journal", "volume" : "26" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "103,104", "plainTextFormattedCitation" : "103,104", "previouslyFormattedCitation" : "103,104" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }103,104) . With regards to the former, histological analysis in patients with post-infectious olfactory loss shows neuroepithelial remodelling and replacement with respiratory type epithelium or occasionally metaplastic squamous epithelium (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0300-0729 (Print)\r0300-0729 (Linking)", "ISSN" : "03000729", "PMID" : "7530857", "abstract" : "Seventy patients with olfactory disorders following upper respiratory viral infection (URVI) were studied clinically, and the olfactory mucosa of 13 patients was biopsied using special biopsy forceps. The specimens were examined using immunohistochemical staining for neuron-specific enolase (NSE), S-100 protein (S-100), cytokeratin (CK), and proliferating cell nuclear antigen (PCNA). Although the clinical course of URVI-olfactory disorders was not very good, overall a high proportion of Alinamin intravenous injection test-positive patient's recovered their sense of smell. Immunohistochemical study of the biopsy specimens revealed a decrease in the number of olfactory receptor cells and nerve bundles. In a few cases the olfactory neuroepithelium was replaced by metaplastic squamous epithelium. Sometimes different types of degeneration were found in the same specimen. No PCNA-immunoreactivity was detected in the olfactory epithelium. The result generally correlated with the degree of degeneration of the olfactory mucosa, because regeneration of the olfactory receptor cells is suspected to be extremely slow or rare in humans. Alinamin test-positive patients had many olfactory receptor cells. These findings suggest that olfactory mucosal biopsy and the Alinamin intravenous injection test are useful methods of determining the prognosis in post-URVI olfactory disorders.", "author" : [ { "dropping-particle" : "", "family" : "Yamagishi", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fujiwara", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakamura", "given" : "H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "1994" ] ] }, "page" : "113-118", "title" : "Olfactory mucosal findings and clinical course in patients with olfactory disorders following upper respiratory viral infection", "type" : "article-journal", "volume" : "32" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1093/chemse/27.7.623", "ISSN" : "0379-864X", "PMID" : "12200342", "abstract" : "It has been shown that olfactory epithelium can be safely biopsied from the living, intact human being. Observations of the ultrastructure of this epithelium shows changes that can then be correlated with the etiology and degree of olfactory loss, allowing a greater understanding of both normal transduction and of the pathology of dysfunction. Examples of the common forms of olfactory dysfunction are presented and discussed. Additionally, the technique will allow additional immuno-histochemical and molecular study of the tissue, will increase the understanding of both normal and pathological function and should translate to new therapeutic regimens.", "author" : [ { "dropping-particle" : "", "family" : "Jafek", "given" : "B W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Murrow", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Michaels", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Restrepo", "given" : "Diego", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Linschoten", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemical Senses", "id" : "ITEM-2", "issue" : "7", "issued" : { "date-parts" : [ [ "2002" ] ] }, "page" : "623-628", "title" : "Biopsies of Human Olfactory Epithelium", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "80,105", "plainTextFormattedCitation" : "80,105", "previouslyFormattedCitation" : "80,105" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }80,105). The number of OSN cells is reduced, they are found in patchy distribution and their morphology may be altered: for example they may be shrunken in size with dendrites that do not reach the mucosal layer. The associated number of receptors is also reduced (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/chemse/27.7.623", "ISSN" : "0379-864X", "PMID" : "12200342", "abstract" : "It has been shown that olfactory epithelium can be safely biopsied from the living, intact human being. Observations of the ultrastructure of this epithelium shows changes that can then be correlated with the etiology and degree of olfactory loss, allowing a greater understanding of both normal transduction and of the pathology of dysfunction. Examples of the common forms of olfactory dysfunction are presented and discussed. Additionally, the technique will allow additional immuno-histochemical and molecular study of the tissue, will increase the understanding of both normal and pathological function and should translate to new therapeutic regimens.", "author" : [ { "dropping-particle" : "", "family" : "Jafek", "given" : "B W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Murrow", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Michaels", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Restrepo", "given" : "Diego", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Linschoten", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemical Senses", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2002" ] ] }, "page" : "623-628", "title" : "Biopsies of Human Olfactory Epithelium", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "80", "plainTextFormattedCitation" : "80", "previouslyFormattedCitation" : "80" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }80). Furthermore, olfactory bulb volumes are reduced in patients with post-infectious loss and correlate with residual olfactory function (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "00001756-200504040-00011 [pii]", "ISBN" : "0959-4965 (Print)\\r0959-4965 (Linking)", "ISSN" : "0959-4965", "PMID" : "15770154", "abstract" : "The olfactory bulb is a highly plastic structure the volume of which partly reflects the degree of afferent neural activity. In this study, 22 patients with post-infectious olfactory deficit, nine participants with post-traumatic olfactory deficit, and 17 healthy controls underwent magnetic resonance volumetry of the olfactory bulb. Patients presented with significantly smaller olfactory bulb volumes than controls; significant correlations between olfactory function and bulb volume were observed. Patients with parosmia exhibited smaller olfactory bulb volumes than those without parosmia. Findings indicate that smell deficits leading to a reduced sensory input to the olfactory bulb result in structural changes at the level of the bulb. Reduced olfactory bulb volumes may also be considered to be characteristic of parosmia.", "author" : [ { "dropping-particle" : "", "family" : "Mueller", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rodewald", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reden", "given" : "Jens", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerber", "given" : "Johannes", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kummer", "given" : "Ruediger", "non-dropping-particle" : "von", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Neuroreport", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "475-478", "title" : "Reduced olfactory bulb volume in post-traumatic and post-infectious olfactory dysfunction", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.neuroimage.2008.05.004", "ISSN" : "10538119", "abstract" : "The olfactory bulb (OB) is considered to be the most important relay station in odor processing. Involving 125 randomly selected subjects (58 men, 67 women; age range: 19 to 79 years), the present study aimed to investigate a possible correlation between OB volume and specific olfactory functions including odor threshold, odor discrimination, and odor identification. The history of all participants was taken in great detail to exclude possible causes of smell dysfunction. All participants received an otolaryngological investigation including a volumetric scan of the brain (MRI), lateralized olfactory tests and a screen for cognitive impairment. Volumetric measurements of the right and left OB were performed by manual segmentation of the coronal slices through the OB. Significant correlations between OB volumes in relation to olfactory function were observed, independent of the subjects' age. Additionally, OB volumes decreased with age. In agreement with previous research the present study confirmed the correlation between OB volume and specific olfactory functions. Furthermore, the correlation between OB volume and olfactory functionwas not mediated by the subjects' age. In conclusion, the present data obtained from a relatively large group of subjects forms the basis for age-related normative values of OB volumes. \u00a9", "author" : [ { "dropping-particle" : "", "family" : "Buschh\u00fcter", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smitka", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Puschmann", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerber", "given" : "J.C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Witt", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abolmaali", "given" : "N.D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "NeuroImage", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2008", "8" ] ] }, "page" : "498-502", "title" : "Correlation between olfactory bulb volume and olfactory function", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "106,107", "plainTextFormattedCitation" : "106,107", "previouslyFormattedCitation" : "106,107" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }106,107). This likely reflects bulb plasticity, partly in response to reduced afferent input from the OSN of the neuroepithelium. Posttraumatic olfactory dysfunctionOlfactory dysfunction secondary to traumatic injury is a major cause of permanent olfactory impairment, and can be ascribed to one or more mechanisms. First, injuries affecting the nose may result in mechanical obstruction of odourants to the olfactory neuroepithelium, through distorting nasal bone or septal fractures, direct neuroepithelial injury, blood clots, oedema or alteration in mucous characteristics (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Costanzo", "given" : "R M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "DiNardo", "given" : "L J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reiter", "given" : "E R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "chapter-number" : "30", "container-title" : "Handbook of Olfaction and Gustation", "edition" : "2nd", "editor" : [ { "dropping-particle" : "", "family" : "Doty", "given" : "Richard L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "pp. 629-638", "publisher" : "Marcel Dekker", "publisher-place" : "New York", "title" : "Head injury and olfaction", "type" : "chapter" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "108", "plainTextFormattedCitation" : "108", "previouslyFormattedCitation" : "108" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }108). The second mechanism involves transection, or shearing of the olfactory fila as they traverse the cribriform plate (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "09358943", "author" : [ { "dropping-particle" : "", "family" : "Delank", "given" : "K W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fechner", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Laryngol. Rhinol. Otol.", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "1996" ] ] }, "page" : "154-159", "title" : "Zur Pathophysiologie der posttraumatischen Riechst\u00f6rungen", "type" : "article-journal", "volume" : "75" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "83", "plainTextFormattedCitation" : "83", "previouslyFormattedCitation" : "83" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }83). Such transection may occur with more severe coup/contra-coup type injuries, or with fractures of the midface/anterior skull base, with possible subsequent scarring that may limit axonal regeneration and targeting (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1001/archneur.1989.00520390066018", "ISSN" : "0003-9942", "author" : [ { "dropping-particle" : "", "family" : "Jafek", "given" : "Bruce W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of Neurology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "1989", "3", "1" ] ] }, "page" : "300", "title" : "Post-traumatic Anosmia", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1097/01.MLG.0000181493.83661.CE", "ISBN" : "0023-852X (Print)\\r0023-852X (Linking)", "ISSN" : "0023-852X", "PMID" : "16369158", "abstract" : "Random biopsies of the human adult olfactory mucosa often demonstrate degenerative changes in the olfactory epithelium (OE) in both dysosmic and normosmic patients and, consequently, have limited diagnostic usefulness. However, detailed analysis of the subepithelial tissue with specific attention to the fascicles of the olfactory nerve and abnormalities of axonal growth may improve the correlation of histopathology with sensory function.", "author" : [ { "dropping-particle" : "", "family" : "Holbrook", "given" : "Eric H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leopold", "given" : "Donald a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwob", "given" : "James E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Laryngoscope", "id" : "ITEM-2", "issue" : "12", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "2144-54", "title" : "Abnormalities of axon growth in human olfactory mucosa.", "type" : "article-journal", "volume" : "115" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "109,110", "plainTextFormattedCitation" : "109,110", "previouslyFormattedCitation" : "109,110" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }109,110). Finally, contusions, intraparenchymal haemorrhage or resultant gliosis may lead to dysfunction of the central structures involved in olfactory processing (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.4193/Rhino15.010", "ISBN" : "4969630143", "ISSN" : "03000729", "author" : [ { "dropping-particle" : "", "family" : "Lotsch", "given" : "Jorn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reither", "given" : "Nicole", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bogdanov", "given" : "Vasyl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haehner", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ultsch", "given" : "Alfred", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hill", "given" : "Konstanze", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "365-370", "title" : "A brain-lesion pattern based algorithm for the diagnosis of posttraumatic olfactory loss", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "84", "plainTextFormattedCitation" : "84", "previouslyFormattedCitation" : "84" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }84,ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3389/fneur.2014.00005", "ISSN" : "16642295", "PMID" : "24478752", "abstract" : "Traumatic brain injury (TBI) is a common condition that is often complicated by neuropsychiatric sequelae that can have major impacts on function and quality of life. An alteration in the sense of smell is recognized as a relatively common complication of TBI; however in clinical practice, this complication may not be sought or adequately characterized. We conducted a systematic review of studies concerned with olfactory functioning following TBI. Our predetermined criteria led to the identification of 25 studies published in English, which we examined in detail. We have tabulated the data from these studies in eight separate tables, beginning with Table 1, which highlights each study's key findings, and we provide a summary/synthesis of the findings in the accompanying results and discussion sections. Despite widely differing methodologies, the studies attest to a high frequency of post-TBI olfactory dysfunction and indicate that its presence can serve as a potential marker of additional structural or functional morbidities.", "author" : [ { "dropping-particle" : "", "family" : "Schofield", "given" : "Peter William", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moore", "given" : "Tammie Maree", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gardner", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Frontiers in Neurology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "1-22", "title" : "Traumatic brain injury and olfaction: A systematic review", "type" : "article-journal", "volume" : "5" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "111", "plainTextFormattedCitation" : "111", "previouslyFormattedCitation" : "111" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }111). For example, localised contusion of the olfactory bulbs following injury has been previously documented (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/00001199-199203000-00005", "ISSN" : "0885-9701", "author" : [ { "dropping-particle" : "", "family" : "Costanzo", "given" : "Richard M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zasler", "given" : "Nathan D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Head Trauma Rehabilitation", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "1992" ] ] }, "page" : "15-24", "title" : "Epidemiology and Pathophysiology of Olfactory and Gustatory Dysfunction in Head Trauma", "type" : "article" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "112", "plainTextFormattedCitation" : "112", "previouslyFormattedCitation" : "112" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }112). However, posttraumatic olfactory loss can occur without any visible signs of trauma on imaging studies (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.4193/Rhino15.010", "ISBN" : "4969630143", "ISSN" : "03000729", "author" : [ { "dropping-particle" : "", "family" : "Lotsch", "given" : "Jorn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reither", "given" : "Nicole", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bogdanov", "given" : "Vasyl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haehner", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ultsch", "given" : "Alfred", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hill", "given" : "Konstanze", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "365-370", "title" : "A brain-lesion pattern based algorithm for the diagnosis of posttraumatic olfactory loss", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "84", "plainTextFormattedCitation" : "84", "previouslyFormattedCitation" : "84" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }84).Patients with posttraumatic olfactory dysfunction may describe sudden onset loss following their injury, however, presentation may also be delayed. Such delay may be in line with the patient first noticing their impairment when back in their usual environment. Alternatively, delayed presentation may reflect an underlying pathology that does not involve olfactory fila transection, but possibly central damage exacted through progressive mechanisms (e.g. oedema). Following onset, fluctuation in function is infrequent and patients are often affected by phantosmia (and to a lesser degree, by parosmia) (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/lary.26229", "author" : [ { "dropping-particle" : "", "family" : "Whitcroft", "given" : "Katherine L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cuevas", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haehner", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "1-5", "title" : "Patterns of olfactory impairment reflect underlying disease etiology", "type" : "article-journal", "volume" : "00000" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1093/chemse/23.5.513", "ISBN" : "0379-864X (Print)\\r0379-864X (Linking)", "ISSN" : "0379864X", "PMID" : "9805635", "abstract" : "Following recovery from olfactory nerve transection, animals regain their ability to discriminate between odors. Odor discrimination is restored after new neurons establish connections with the olfactory bulb. However, it is not known if the new connections alter odor quality perception. To address this question, 20 adult hamsters were first trained to discriminate between cinnamon and strawberry odors. After reaching criterion (> or = 90% correct response), half of the animals received a bilateral nerve transection (BTX) and half a surgical sham procedure. Animals were not tested again until day 40, a point in recovery when connections are re-established with the bulb. When BTX animals were tested without food reinforcement, they could not perform the odor discrimination task. Sham animals, however, could discriminate, demonstrating that the behavioral response had not been extinguished during the 40 day period. When reinforcement was resumed, BTX animals were able to discriminate between cinnamon and strawberry after four test sessions. In addition, their ability to discriminate between these two familiar odors was no different than that of BTX and sham animals tested with two novel odors, baby powder and coffee. These findings suggest that, after recovery from nerve transection, there are alterations in sensory perception and that restoration of odor quality discrimination requires that the animal must again learn to associate individual odor sensations with a behavioral response.", "author" : [ { "dropping-particle" : "", "family" : "Yee", "given" : "Karen K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Costanzo", "given" : "Richard M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemical Senses", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "1998" ] ] }, "page" : "513-519", "title" : "Changes in odor quality discrimination following recovery from olfactory nerve transection", "type" : "article-journal", "volume" : "23" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISBN" : "0379-864X (Print)\\r0379-864X (Linking)", "ISSN" : "0379-864X", "PMID" : "11369671", "abstract" : "Re-innervation of the olfactory bulb was investigated after transection of the olfactory nerve using monoclonal antibody RB-8 to assess whether rhinotopy of the primary olfactory projection is restored. In normal animals RB-8 heavily stains the axons, and their terminals, that project from the ventrolateral olfactory epithelium onto glomeruli of the ventrolateral bulb (termed RB-8(+)). In contrast, axons from dorsomedial epithelium are unlabeled (RB-8(-)) and normally terminate in the dorsomedial bulb. Sprague-Dawley rats underwent unilateral olfactory nerve transection and survived for 6 weeks prior to perfusion, sectioning and immunostaining with RB-8. Nerve lesion does not shift the position of the boundary between RB-8(+) and RB-8(-) regions of the epithelium. However, following transection and bulb re-innervation, the distribution of RB-8(+) and RB-8(-) axons is markedly abnormal. First, in all 10 experimental animals RB-8(-) axons displace RB-8(+) axons from anterior glomeruli. Furthermore, the usual target of the RB-8(-) fibers, i.e. the dorsomedial bulb at more posterior levels of the bulb, remains denervated, judging by the lack of staining with antibodies that label axons derived from all epithelial zones. Finally, RB-8(+) fibers invade foreign territory in the dorsolateral bulb on the lesioned side in some cases. The shifts in terminal territory in the bulb after transection contrast with the restoration of the normal zonal patterning of the projection after recovery from methyl bromide lesion, but is consistent with reports of mistargeting by a receptor-defined subset of neurons after transection.", "author" : [ { "dropping-particle" : "", "family" : "Christensen", "given" : "M D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holbrook", "given" : "E H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Costanzo", "given" : "R M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwob", "given" : "J E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemical senses", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2001" ] ] }, "page" : "359-69", "title" : "Rhinotopy is disrupted during the re-innervation of the olfactory bulb that follows transection of the olfactory nerve.", "type" : "article-journal", "volume" : "26" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "89,113,114", "plainTextFormattedCitation" : "89,113,114", "previouslyFormattedCitation" : "89,113,114" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }89,113,114). Evidence from several studies suggests that recovery is less frequent than in post-infectious loss and whilst prognosis is often poor, recovery may occur in approximately 30% of cases over time depending on the severity of the insult (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "ooa00128 [pii]", "ISBN" : "0886-4470 (Print)\\n0886-4470 (Linking)", "ISSN" : "0886-4470", "PMID" : "12049556", "abstract" : "OBJECTIVE: To investigate the consequences of olfactory loss and explore specific questions related to the effect of duration of olfactory loss, degree of olfactory sensitivity, and cause of the olfactory loss. PATIENTS: A total of 278 consecutive patients with hyposmia or anosmia were examined. RESULTS: Causes of olfactory loss were categorized as follows: trauma (17%), upper respiratory tract infection (URI) (39%), sinonasal disease (21%), congenital anosmia (3%), idiopathic causes (18%), or other causes (3%). Our data suggest that (1) recovery rate was higher in URI olfactory loss than in olfactory loss from other causes; (2) likelihood of recovery seemed to decrease with increased duration of olfactory loss; and (3) the elderly are more prone to URI olfactory loss than younger patients. Regarding changes in quality of life (QoL), we found that (1) in most patients olfactory loss caused food-related problems; (2) loss in QoL did not change with duration of olfactory loss; (3) younger patients had more complaints than older ones, and women had more complaints than men; (4) complaint scores were higher in hyposmic patients than in anosmic patients; and (5) self-rated depression did not relate to measured olfactory function. CONCLUSIONS: Among many complaints of olfactory loss, the predominant ones were food related. This loss in QoL seemed to be of greater importance in younger than in older people, and women seem to be affected more strongly than men.", "author" : [ { "dropping-particle" : "", "family" : "Temmel", "given" : "Andreas F P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Quint", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schickinger-Fischer", "given" : "Bettina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klimek", "given" : "Ludger", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stoller", "given" : "Elisabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of otolaryngology--head & neck surgery", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2002" ] ] }, "page" : "635-641", "title" : "Characteristics of olfactory disorders in relation to major causes of olfactory loss.", "type" : "article-journal", "volume" : "128" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0886-4470", "abstract" : "Objective: To investigate the outcome of olfactory function in patients with olfactory loss following infections of the upper respiratory tract (post-URTI) or head trauma. Design: Retrospective patient-based study. Setting: Smell and Taste Outpatient Clinic at a university hospital. Patients: A total of 361 patients (228 women, 133 men) were included. Main Outcome Measures: Olfactory function was assessed using the \"Sniffin' Sticks\" test battery, which result in a threshold, discrimination, and identification score. The mean interval between first and last visit was 14 months. Results: In comparing the overall threshold, discrimination, and identification scores between the last and first visit, olfactory function improved in 26% of the patients whereas it decreased in 6%. The cause of olfactory impairment had a significant effect on the recovery rate of olfactory function. Within the post-URTI group (n=262), 32% of the patients improved, but in the posttraumatic group (n=99) only 10% improved. In patients with post-URTI olfactory loss, a negative correlation was found between age and recovery of olfactory function. In general, the factor \"sex\" had no significant effect on recovery of smell function. Conclusions: To our knowledge, the series of patients presented herein is the largest in the literature to date in which standardized testing methods were used to assess the progression of impaired olfaction. It showed that the rate of improvement of olfactory function was significantly higher in patients with post-URTI dysosmia compared with patients with posttraumatic dysosmia. During an observation period of approximately 1 year, more than 30% of patients with post-URTI olfactory loss experienced improvement, whereas only 10% of patients with posttraumatic olfactory loss experienced improvement. Furthermore, age plays a significant role in the recovery of olfactory function. \u00a92006 American Medical Association. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Reden", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mueller", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mueller", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Konstantinidis", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frasnelli", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Landis", "given" : "BN", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of Otolaryngology - Head and Neck Surgery", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "265-269", "title" : "Recovery of olfactory function following closed head injury or infections of the upper respiratory tract", "type" : "article-journal", "volume" : "132" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.jcma.2014.11.009", "ISSN" : "17287731", "PMID" : "25801491", "abstract" : "Background: Post-traumatic olfactory dysfunction is common but has a poor prognosis. The purpose of this study was to analyze the effect of clinical features on improvements in post-traumatic olfactory dysfunction. Methods: From 2007 to 2013, patients with post-traumatic olfactory dysfunction were enrolled. Olfactory function was assessed using the Sniffin' Sticks test at the first and final visits. Olfactory improvement was defined as a change in olfactory state to an improved level. Variables with a potential effect on improvements in olfactory dysfunction, including age, sex, time from trauma to first visit, initial olfactory function, observation time, and olfactory bulb integrity, were entered into logistic regression analysis. Results: In total, 107 patients were included, with a mean age of 40 years. The mean follow-up period was 9.4 months. Eighteen patients (16.8%) had improvements with regard to olfactory function. No clinical factors were found to influence olfactory recovery in univariate and multivariate analyses (all p > 0.05). In addition, there were no differences in clinical features between the patients with and without olfactory recovery (all p > 0.05). Conclusion: No significantly favorable prognostic factors for post-traumatic olfactory recovery were identified, reflecting, to some extent, the poor prognosis of post-traumatic olfactory damage. The results of this study provide useful information that clinical physicians can use when counseling patients with post-traumatic olfactory disorder regarding the prognosis, observation choice, and possible treatment strategy.", "author" : [ { "dropping-particle" : "", "family" : "Fan", "given" : "La Yuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuo", "given" : "Chin Lung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lirng", "given" : "Jiing Feng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shu", "given" : "Chih Hung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of the Chinese Medical Association", "id" : "ITEM-3", "issue" : "5", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "299-303", "publisher" : "Elsevier Taiwan LLC and the Chinese Medical Association", "title" : "Investigation of prognostic factors for post-traumatic olfactory dysfunction", "type" : "article-journal", "volume" : "78" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Sumner", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Brain", "id" : "ITEM-4", "issue" : "87", "issued" : { "date-parts" : [ [ "1964" ] ] }, "page" : "107-120", "title" : "Post-traumatic anosmia", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Doty", "given" : "RL", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yousem", "given" : "DM", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pham", "given" : "LT", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kreshak", "given" : "AA", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geckle", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "WW", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arch Neurol", "id" : "ITEM-5", "issued" : { "date-parts" : [ [ "1997" ] ] }, "page" : "1131-1140", "title" : "Olfactory dysfunction in patients with head trauma", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.4076/1752-1947-3-9283", "ISSN" : "1752-1947", "PMID" : "19918296", "abstract" : "Olfactory loss due to head trauma is a common condition. Depending on the severity of the head trauma, anosmia might occur in up to 30% of patients. The period of time until recovery has been reported to be a couple of months in most cases. However, recovery from post-traumatic olfactory loss might occur much later. We present a rare case of recovery from anosmia nine years after the initial trauma.", "author" : [ { "dropping-particle" : "", "family" : "Mueller", "given" : "Christian A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of medical case reports", "id" : "ITEM-6", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "9283", "title" : "Recovery of olfactory function after nine years of post-traumatic anosmia: a case report.", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "94,97,115\u2013118", "plainTextFormattedCitation" : "94,97,115\u2013118", "previouslyFormattedCitation" : "94,97,115\u2013118" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }94,97,115–118). Olfactory dysfunction associated with neurological diseaseOver recent years, the link between olfactory dysfunction and neurological disease has been increasingly recognised. Whilst such dysfunction has been associated with epilepsy (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jocn.2015.03.035", "ISSN" : "15322653", "abstract" : "We studied olfactory function in a cohort of 25 temporal lobe epilepsy (TLE) patients and 25 healthy controls. Our objectives were to measure olfactory acuity in patients with right, left or bilateral TLE and compare them with age and sex matched controls, and to correlate olfactory acuity with duration of seizure, baseline seizure control and the number of drugs used. Olfactory impairment is common in neurological disorders and dysfunction of the temporo-limbic neural substrates involved in olfactory perception is noted in TLE. We measured olfactory acuity in 25 patients with TLE, nine with right, 10 with left and six with bilateral temporal lobe seizure activity, and compared them to the controls. Odor identification was assessed using the University of Pennsylvania Smell Identification Test (UPSIT) which is a 40 item olfactory test used to diagnose olfactory deficits. Our results showed that patients with TLE exhibited significant impairment in UPSIT performance compared to the controls. There was no significant difference in scores between the right and left TLE patients. The severity of olfactory impairment did not correlate with the duration of seizures, baseline seizure control and number of drugs used. We concluded that significant olfactory impairment is seen in both right and left TLE patients, unrelated to the duration and baseline frequency of seizures or drugs used.", "author" : [ { "dropping-particle" : "", "family" : "Desai", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Agadi", "given" : "J. B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karthik", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Praveenkumar", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Netto", "given" : "A. B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Neuroscience", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1614-1618", "publisher" : "Elsevier Ltd", "title" : "Olfactory abnormalities in temporal lobe epilepsy", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1007/s00415-012-6741-x", "ISSN" : "03405354", "PMID" : "23135292", "abstract" : "The study aimed to investigate the volume of the olfactory bulb (OB) in patients with temporal lobe epilepsy (TLE). Specifically, we wanted to see whether the olfactory deficit typically found in TLE patients also exerts a top-down influence on the OB. Twenty patients, and 20 age- and sex-matched healthy controls underwent olfactory testing by means of the Sniffin' Sticks testing device (measurement of odor threshold, and identification abilities). In addition, they underwent an MR scan with 2-mm-thick T2-weighted fast spin-echo images without interslice gap in the coronal plane covering the anterior and middle segments of the base of the skull. Olfactory function was significantly impaired in TLE patients compared to healthy controls both at threshold level and for odor identification (p < 0.001); in addition, OB volumes were smaller than in controls (p = 0.013). The deficit seen at the level of the OB did not correlate with the side of the epileptic focus. Assuming that the olfactory deficit in TLE patients is due to the central nervous epileptic focus it appears that the OB volume is not only subject to changes in the periphery of the olfactory system, but also changes as a consequence to changes at a cortical level.", "author" : [ { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henkel", "given" : "Sophia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Negoias", "given" : "Simona", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Galv??n", "given" : "Jos?? R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bogdanov", "given" : "Vasyl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hopp", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hallmeyer-Elgner", "given" : "Susanne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerber", "given" : "Johannes", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reuner", "given" : "Ulrike", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haehner", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Neurology", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1004-1008", "title" : "Olfactory bulb volume in patients with temporal lobe epilepsy", "type" : "article-journal", "volume" : "260" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "119,120", "plainTextFormattedCitation" : "119,120", "previouslyFormattedCitation" : "119,120" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }119,120), myasthenia gravis (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Leon-Sarmiento", "given" : "FE", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leon-Ariza", "given" : "DS", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doty", "given" : "RL", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Clin Neuromuscul Dis", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1-6", "title" : "Dysfunctional chemosensation in myasthenia gravis: a systematic review", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "121", "plainTextFormattedCitation" : "121", "previouslyFormattedCitation" : "121" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }121) and stroke (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/s12883-015-0463-5", "ISBN" : "1288301504635", "ISSN" : "1471-2377", "PMID" : "26459234", "abstract" : "BACKGROUND: The aim of the study was to investigate odor identification performance in patients one year after hospital admittance due to stroke. Predictors for olfactory dysfunction were investigated as well as self-reported olfactory function and pleasantness of olfactory items.\\n\\nMETHODS: A 1-year prospective study was performed. Stroke location, classification and comorbidities were registered at hospital admission. One year after admission, olfactory function was assessed using standardized olfactory methods (screening for loss of detection sensitivity and an odor identification test). A group of matched controls was derived from a population-based study to compare odor identification performance between groups. Patients were asked for their personal judgment regarding their olfactory function and pleasantness of odorous items. In addition, global cognitive function and symptoms of depression were assessed.\\n\\nRESULTS: A total of 78 patients were enrolled (46 males, 32 females; mean age 68 years) of which 28.2% exhibited reduced olfactory function (hyposmia) and 15.4% exhibited loss of olfactory function (10.3% functional anosmia, 5.1% complete anosmia). Patients showed significantly lower olfactory performance compared to age- and sex-mated matched controls. Predictors of impaired olfactory function were age and NIHSS score. Self-reports indicated no significant differences between patients with normal olfactory function and those with reduced function. Yet, patients having an olfactory dysfunction rated odorous items as significantly less pleasant compared to patients without dysfunction.\\n\\nCONCLUSIONS: Olfactory dysfunction seems to occur frequently after stoke even one year after initial admission. The deficits seem to relate to hyposmia and functional anosmia, and less to a complete loss of smell sensitivity.", "author" : [ { "dropping-particle" : "", "family" : "Wehling", "given" : "Eike", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Naess", "given" : "Halvor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wollschlaeger", "given" : "Daniel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hofstad", "given" : "Hakon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bramerson", "given" : "Annika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bende", "given" : "Mats", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nordin", "given" : "Steven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC neurology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "199", "publisher" : "BMC Neurology", "title" : "Olfactory dysfunction in chronic stroke patients.", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "122", "plainTextFormattedCitation" : "122", "previouslyFormattedCitation" : "122" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }122) it is most commonly seen in neurodegenerative conditions such as Parkinson’s disease and Alzheimer’s disease (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00401-014-1261-7", "ISBN" : "0001-6322", "ISSN" : "14320533", "PMID" : "24554308", "abstract" : "Olfactory dysfunction is a common and early symptom of many neurodegenerative diseases, particularly of Parkinson's disease and other synucleinopathies, Alzheimer's disease (AD), and mild cognitive impairment heralding its progression to dementia. The neuropathologic changes of olfactory dysfunction in neurodegenerative diseases may involve the olfactory epithelium, olfactory bulb/tract, primary olfactory cortices, and their secondary targets. Olfactory dysfunction is related to deposition of pathological proteins, \u03b1-synuclein, hyperphosphorylated tau protein, and neurofilament protein in these areas, featured by neurofibrillary tangles, Lewy bodies and neurites inducing a complex cascade of molecular processes including oxidative damage, neuroinflammation, and cytosolic disruption of cellular processes leading to cell death. Damage to cholinergic, serotonergic, and noradrenergic systems is likely involved, since such damage is most marked in those diseases with severe anosmia. Recent studies of olfactory dysfunction have focused its potential as an early biomarker for the diagnosis of neurodegenerative disorders and their disease progression. Here, we summarize the current knowledge on neuropathological and pathophysiological changes of the olfactory system in the most frequent neurodegenerative diseases, in particular AD and synucleinopathies. We also present neuropathological findings in the olfactory bulb and tract in a large autopsy cohort (n = 536, 57.8 % female, mean age 81.3 years). The severity of olfactory bulb HP\u03c4, A\u03b2, and \u03b1Syn pathology correlated and increased significantly (P < 0.001) with increasing neuritic Braak stages, Thal A\u03b2 phases, and cerebral Lewy body pathology, respectively. Hence, further studies are warranted to investigate the potential role of olfactory biopsies (possibly restricted to the olfactory epithelium) in the diagnostic process of neurodegenerative diseases in particular in clinical drug trials to identify subjects showing early, preclinical stages of neurodegeneration and to stratify clinically impaired cohorts according to the underlying cerebral neuropathology.", "author" : [ { "dropping-particle" : "", "family" : "Attems", "given" : "Johannes", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walker", "given" : "Lauren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jellinger", "given" : "Kurt A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Acta Neuropathologica", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "459-475", "title" : "Olfactory bulb involvement in neurodegenerative diseases", "type" : "article-journal", "volume" : "127" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.7860/JCDR/2012/3408.2382", "ISSN" : "2249782X", "PMID" : "23205370", "abstract" : "Olfactory disorders are noted in a majority of neurodegenerative diseases, but they are often misjudged and are rarely rated in the clinical setting. Severe changes in the olfactory tests are observed in Parkinson's disease. Olfactory deficits are an early feature in Alzheimer's disease and they worsen with the disease progression. Alterations in the olfactory function are also noted after severe head injuries, temporal lobe epilepsy, multiple sclerosis, and migraine. The purpose of the present review was to discuss the available scientific knowledge on the olfactory memory and to relate its impairment with neurodegenerative diseases.", "author" : [ { "dropping-particle" : "", "family" : "Bahuleyan", "given" : "Biju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Satendra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical and Diagnostic Research", "id" : "ITEM-2", "issue" : "8", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "1437-1441", "title" : "Olfactory memory impairment in neurodegenerative diseases", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.nbd.2011.10.026", "ISBN" : "0969-9961", "ISSN" : "09699961", "PMID" : "22192366", "abstract" : "Olfactory dysfunction is an early 'pre-clinical' sign of Parkinson's disease (PD). The present review is a comprehensive and up-to-date assessment of such dysfunction in PD and related disorders. The olfactory bulb is implicated in the dysfunction, since only those syndromes with olfactory bulb pathology exhibit significant smell loss. The role of dopamine in the production of olfactory system pathology is enigmatic, as overexpression of dopaminergic cells within the bulb's glomerular layer is a common feature of PD and most animal models of PD. Damage to cholinergic, serotonergic, and noradrenergic systems is likely involved, since such damage is most marked in those diseases with the most smell loss. When compromised, these systems, which regulate microglial activity, can influence the induction of localized brain inflammation, oxidative damage, and cytosolic disruption of cellular processes. In monogenetic forms of PD, olfactory dysfunction is rarely observed in asymptomatic gene carriers, but is present in many of those that exhibit the motor phenotype. This suggests that such gene-related influences on olfaction, when present, take time to develop and depend upon additional factors, such as those from aging, other genes, formation of ??-synuclein- and tau-related pathology, or lowered thresholds to oxidative stress from toxic insults. The limited data available suggest that the physiological determinants of the early changes in PD-related olfactory function are likely multifactorial and may include the same determinants as those responsible for a number of other non-motor symptoms of PD, such as dysautonomia and sleep disturbances. ?? 2011 Elsevier Inc.", "author" : [ { "dropping-particle" : "", "family" : "Doty", "given" : "Richard L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Neurobiology of Disease", "id" : "ITEM-3", "issue" : "3", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "527-552", "publisher" : "Elsevier Inc.", "title" : "Olfaction in Parkinson's disease and related disorders", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "123\u2013125", "plainTextFormattedCitation" : "123\u2013125", "previouslyFormattedCitation" : "123\u2013125" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }123–125). Indeed, evidence suggests that olfactory dysfunction in Parkinson’s disease (PD) is more common than the resting tremor and predates motor symptoms by many years (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00415-008-5004-3", "ISBN" : "9780444519009", "ISSN" : "03405354", "PMID" : "18787879", "abstract" : "Epidemiological research aims to provide information on the development, prevalence and progression of diseases, and their associated risk factors. Epidemiological research is thus the basis of increasing our understanding on the aetiology of diseases and as a consequence the starting point for identifying at risk groups in the population, development for novel prevention and treatment strategies, and health care planning. This review provides an overview of the epidemiology of Parkinson's disease, the second most common neurodegenerative disorder, with special emphasis on population-based data on the clinical progression of motor and non-motor features of the disease.", "author" : [ { "dropping-particle" : "", "family" : "Alves", "given" : "Guido", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forsaa", "given" : "Elin Bjelland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Kenn Freddy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dreetz Gjerstad", "given" : "Michaela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Larsen", "given" : "Jan Petter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Neurology", "id" : "ITEM-1", "issue" : "SUPPL. 5", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "18-32", "title" : "Epidemiology of Parkinson's disease", "type" : "article-journal", "volume" : "255" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/ana.20160", "ISBN" : "0364-5134 (Print)\\r0364-5134 (Linking)", "ISSN" : "03645134", "PMID" : "15293269", "abstract" : "Olfactory dysfunction is an early and common symptom in Parkinson's disease (PD). In an effort to determine whether otherwise unexplained (idiopathic) olfactory dysfunction is associated with an increased risk of developing PD, we designed a prospective study in a cohort of 361 asymptomatic relatives (parents, siblings, or children) of PD patients. A combination of olfactory detection, identification, and discrimination tasks was used to select groups of hyposmic (n = 40) and normosmic (n = 38) individuals for a 2-year clinical follow-up evaluation and sequential single-photon emission computed tomography (SPECT), using [123I]beta-CIT as a dopamine transporter ligand, to assess nigrostriatal dopaminergic function at baseline and 2 years from baseline. A validated questionnaire, sensitive to the presence of parkinsonism, was used in the follow-up of the remaining 283 relatives. Two years from baseline, 10% of the individuals with idiopathic hyposmia, who also had strongly reduced [123I]beta-CIT binding at baseline, had developed clinical PD as opposed to none of the other relatives in the cohort. In the remaining nonparkinsonian hyposmic relatives, the average rate of decline in dopamine transporter binding was significantly higher than in the normosmic relatives. These results indicate that idiopathic olfactory dysfunction is associated with an increased risk of developing PD of at least 10%.", "author" : [ { "dropping-particle" : "", "family" : "Ponsen", "given" : "Mirthe M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stoffers", "given" : "Diederick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Booij", "given" : "Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eck-Smit", "given" : "B. L F", "non-dropping-particle" : "Van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wolters", "given" : "Erik Ch", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berendse", "given" : "Henk W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of Neurology", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "173-181", "title" : "Idiopathic hyposmia as a preclinical sign of Parkinson's disease", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1002/ana.21291", "ISBN" : "1531-8249", "ISSN" : "03645134", "PMID" : "18067173", "abstract" : "Objective\\nAlthough olfactory dysfunction is commonly associated with Parkinson's disease (PD), it is not known whether such dysfunction can predate the onset of clinical PD in a community-based population. This study examines the association of olfactory dysfunction with future development of PD in Honolulu-Asia Aging Study cohort members\\nMethods\\nOlfaction was assessed from 1991 to 1996 in 2,267 men in the Honolulu-Asia Aging Study aged 71 to 95 years who were free of clinical PD and dementia at the time of olfaction testing. Participants were followed for up to 8 years for incident PD\\nResults\\nIn the course of follow-up, 35 men were diagnosed with PD (24.6/10,000 person-years). The average age at the time of diagnosis was 82.9 \u00b1 3.8 (range, 76\u201393) years, and the average time to a diagnosis was 4.0 \u00b1 1.9 (range, 1\u20138) years. During the first 4 years of follow-up, age-adjusted incidence of PD declined from 54.5/10,000 person-years in the lowest quartile of odor identification to 26.6, 8.2, and 8.4/10,000 person-years in the second, third, and fourth quartiles, respectively (p < 0.001 for trend). After adjustment for age and other potential confounders, the odds ratios for PD in the lowest quartile was 5.2 (95% confidence interval, 1.5\u201325.6) compared with the top two quartiles. This relation was not evident beyond 4 years of follow-up\\nInterpretation\\nImpaired olfaction can predate clinical PD in men by at least 4 years and may be a useful screening tool to detect those at high risk for development of PD in later life. Ann Neurol 2007", "author" : [ { "dropping-particle" : "", "family" : "Ross", "given" : "G. Webster", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Petrovitch", "given" : "Helen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abbott", "given" : "Robert D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tanner", "given" : "Caroline M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Popper", "given" : "Jordan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Masaki", "given" : "Kamal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Launer", "given" : "Lenore", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "White", "given" : "Lon R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of Neurology", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "167-173", "title" : "Association of olfactory dysfunction with risk for future Parkinson's disease", "type" : "article-journal", "volume" : "63" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1016/j.parkreldis.2008.12.005", "ISBN" : "1873-5126 (Electronic)", "ISSN" : "13538020", "PMID" : "19138875", "abstract" : "Previous data on the prevalence of olfactory dysfunction in Parkinson's disease (PD) range from 45% to 90%. The present multicenter study aimed to provide data on the prevalence of smell loss in a large sample of PD patients from three independent populations. Olfactory sensitivity was tested in 400 patients from Australia, Germany, and The Netherlands by means of a psychophysical olfactory test, the \"Sniffin' Sticks\", which is comprised of 3 subtests of olfactory function. Out of the total number of patients 45.0% presented as functionally anosmic, 51.7% were hyposmic, whereas only 3.3% were normosmic. This indicates that 96.7% of PD patients present with significant olfactory loss when compared to young normosmic subjects. This figure falls to 74.5%, however, when adjusted to age-related norms. Thus, olfactory dysfunction should be considered as a reliable marker of the disease. \u00a9 2008 Elsevier Ltd. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Haehner", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boesveldt", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berendse", "given" : "H. W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mackay-Sim", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fleischmann", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silburn", "given" : "P. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnston", "given" : "A. N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mellick", "given" : "G. D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herting", "given" : "B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reichmann", "given" : "H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Parkinsonism and Related Disorders", "id" : "ITEM-4", "issue" : "7", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "490-494", "publisher" : "Elsevier Ltd", "title" : "Prevalence of smell loss in Parkinson's disease - A multicenter study", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "38,126\u2013128", "plainTextFormattedCitation" : "38,126\u2013128", "previouslyFormattedCitation" : "38,126\u2013128" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }38,126–128). Functional imaging studies have demonstrated reduced activity of the hippocampus and amygdala in response to odourous stimuli in patients with PD compared with healthy controls (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/jnnp.2006.113860", "ISBN" : "1468-330X", "ISSN" : "0022-3050", "PMID" : "17519323", "abstract" : "BACKGROUND: Olfactory dysfunction is a frequent non-motor symptom in Parkinson's disease (PD) and is considered to be an early manifestation of the disease. OBJECTIVE: To establish the cortical basis of olfactory function in patients with PD. METHOD: Functional magnetic resonance imaging (fMRI) was used to investigate brain activity related to olfactory processing in patients with hyposmic PD at mild to moderate stages of the disease (n = 12, median Hoehn and Yahr stage 2.0) and in healthy, age-matched controls (n = 16) while passively perceiving a positively valenced (rose-like) odorant. RESULTS: In both patients with PD and healthy controls, olfactory stimulation activated brain regions relevant for olfactory processing (ie the amygdaloid complex, lateral orbitofrontal cortex, striatum, thalamus, midbrain and the hippocampal formation). In controls, a bilateral activation of the amygdala and hippocampus was observed, whereas patients with PD involved these structures in the left hemisphere only. Group comparison showed that regions of higher activation in patients with PD were located bilaterally in the inferior frontal gyrus (BA 44/45) and anterior cingulate gyrus (BA 24/32), and the left dorsal and right ventral striatum. CONCLUSIONS: In patients with PD, results obtained under the specific conditions used suggest that neuronal activity in the amygdala and hippocampus is reduced. Assuming an impact on olfactory-related regions early in PD, our findings support the idea that selective impairment of these brain regions contributes to olfactory dysfunction. Furthermore, neuronal activity in components of the dopaminergic, cortico-striatal loops appears to be upregulated, indicating that compensatory processes are involved. This mechanism has not yet been demonstrated during olfactory processing in PD.", "author" : [ { "dropping-particle" : "", "family" : "Westermann", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wattendorf", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwerdtfeger", "given" : "U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Husner", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fuhr", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gratzl", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bilecen", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Welge-L\u00fcssen", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Welge-Lussen", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Neurology, Neurosurgery & Psychiatry", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "19-24", "title" : "Functional imaging of the cerebral olfactory system in patients with Parkinson's disease", "type" : "article-journal", "volume" : "79" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "129", "plainTextFormattedCitation" : "129", "previouslyFormattedCitation" : "129" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }129). Histological studies have shown deposition of pathological Lewy bodies and neurites within the central olfactory system, including the olfactory bulb and tract, as well as decreased neuronal populations within the anterior olfactory nucleus (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00401-014-1261-7", "ISBN" : "0001-6322", "ISSN" : "14320533", "PMID" : "24554308", "abstract" : "Olfactory dysfunction is a common and early symptom of many neurodegenerative diseases, particularly of Parkinson's disease and other synucleinopathies, Alzheimer's disease (AD), and mild cognitive impairment heralding its progression to dementia. The neuropathologic changes of olfactory dysfunction in neurodegenerative diseases may involve the olfactory epithelium, olfactory bulb/tract, primary olfactory cortices, and their secondary targets. Olfactory dysfunction is related to deposition of pathological proteins, \u03b1-synuclein, hyperphosphorylated tau protein, and neurofilament protein in these areas, featured by neurofibrillary tangles, Lewy bodies and neurites inducing a complex cascade of molecular processes including oxidative damage, neuroinflammation, and cytosolic disruption of cellular processes leading to cell death. Damage to cholinergic, serotonergic, and noradrenergic systems is likely involved, since such damage is most marked in those diseases with severe anosmia. Recent studies of olfactory dysfunction have focused its potential as an early biomarker for the diagnosis of neurodegenerative disorders and their disease progression. Here, we summarize the current knowledge on neuropathological and pathophysiological changes of the olfactory system in the most frequent neurodegenerative diseases, in particular AD and synucleinopathies. We also present neuropathological findings in the olfactory bulb and tract in a large autopsy cohort (n = 536, 57.8 % female, mean age 81.3 years). The severity of olfactory bulb HP\u03c4, A\u03b2, and \u03b1Syn pathology correlated and increased significantly (P < 0.001) with increasing neuritic Braak stages, Thal A\u03b2 phases, and cerebral Lewy body pathology, respectively. Hence, further studies are warranted to investigate the potential role of olfactory biopsies (possibly restricted to the olfactory epithelium) in the diagnostic process of neurodegenerative diseases in particular in clinical drug trials to identify subjects showing early, preclinical stages of neurodegeneration and to stratify clinically impaired cohorts according to the underlying cerebral neuropathology.", "author" : [ { "dropping-particle" : "", "family" : "Attems", "given" : "Johannes", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walker", "given" : "Lauren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jellinger", "given" : "Kurt A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Acta Neuropathologica", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "459-475", "title" : "Olfactory bulb involvement in neurodegenerative diseases", "type" : "article-journal", "volume" : "127" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.jns.2009.08.042", "ISBN" : "0022-510X", "ISSN" : "0022510X", "PMID" : "19783257", "abstract" : "Olfactory dysfunction has gained recognition as an early and nearly universal feature of Lewy body Parkinson's disease (PD). Recently, research efforts have focused on the use of early non-motor symptoms of PD as early biomarkers and have suggested that investigating neurodegeneration in the aspects of the nervous system subserving these symptoms may offer important insights into the pathophysiology of Lewy body PD. Therefore, there has been interest in characterizing the pathology observed in the olfactory bulb and system of patients with PD, dementia with Lewy bodies and perhaps more importantly, in subjects with incidental Lewy pathology, defined as people with Lewy pathology without evidence of Parkinsonism or dementia during life. The olfactory bulb may be ideally suited to investigations into the pathophysiology of the Lewy body disorders as it is one of the few areas of the brain wherein the entirety of neurons susceptible to Lewy neurodegeneration, including the dendritic arborization, cell soma, axon and synaptic terminals, can be examined in the same preparation. Interestingly, there is a lack of Lewy neurodegeneration in the dopaminergic neurons of the olfactory bulb and paradoxically, an apparent increase in dopaminergic neurons in some PD patients compared to controls. In this report, the known neuropathology of the olfactory system in PD will be reviewed and the advantages of investigating degeneration of the olfactory bulb as a model of Lewy neurodegeneration will be discussed.", "author" : [ { "dropping-particle" : "", "family" : "Duda", "given" : "John E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of the Neurological Sciences", "id" : "ITEM-2", "issue" : "1-2", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "49-54", "publisher" : "Elsevier B.V.", "title" : "Olfactory system pathology as a model of Lewy neurodegenerative disease", "type" : "article-journal", "volume" : "289" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "123,130", "plainTextFormattedCitation" : "123,130", "previouslyFormattedCitation" : "123,130" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }123,130). However, the significance of such changes with regards to the wider neuropathology of PD remains to be fully elucidated. Whilst it has been suggested that the olfactory neuroepithelium may offer an attractive target for diagnostic biopsies, several studies have shown no significant difference in immunohistochemical markers (including different synuclein subtypes) of olfactory epithelium in PD patients versus controls (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/mds.22464", "ISSN" : "08853185", "abstract" : "Parkinson's disease (PD) is a neurodegenerative disorder involving several neuronal systems. Impaired olfactory function may constitute one of the earliest symptoms of PD. However, it is still unclear to what degree changes of the olfactory epithelium may contribute to dysosmia and if these changes are different from those of other hyposmic or anosmic patients. This study aimed to investigate the hypothesis that olfactory loss in PD is a consequence of specific PD-related damage of olfactory epithelium. Biopsies of 7 patients diagnosed with PD were taken. Six patients with PD were hyposmic, one anosmic. As non-PD controls served 9 patients with hyposmia, 9 with anosmia, and 7 normosmic individuals. Further, nasal mucosa of 4 postmortem individuals was investigated. Immunohistochemical examinations were performed with antibodies against olfactory marker protein (OMP), protein gene product 9.5 (PGP 9.5), beta-tubulin, (BT), proliferation-associated antigen (Ki 67), the stem cell marker nestin, cytokeratin, p75NGFr, and +\ufffd-synuclein. Most of the biopsy specimens exhibited irregular areas of olfactory-like, dysplastic epithelium positive for either PGP 9.5 or BT, but negative for OMP. No major histochemical differences in either the expression or distribution of these proteins were observed in the olfactory epithelium of patients with PD compared with controls. Reverse transcription PCR (RT-PCR) data indicated mRNA for OMP in almost all subjects, independently of their olfactory performance. These data support the idea that olfactory loss in Parkinson's disease is not a consequence of damage to the olfactory epithelium but rather results from distinct central-nervous abnormalities. -R 2009 Movement Disorder Society", "author" : [ { "dropping-particle" : "", "family" : "Witt", "given" : "Martin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bormann", "given" : "Katja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gudziol", "given" : "Volker", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pehlke", "given" : "Kerstin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barth", "given" : "Kathrin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Minovi", "given" : "Amir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "H\u00e4hner", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reichmann", "given" : "Heinz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Movement Disorders", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "906-914", "title" : "Biopsies of olfactory epithelium in patients with Parkinson's disease", "type" : "article-journal", "volume" : "24" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1006/exnr.1999.7228", "ISBN" : "0014-4886 (Print)", "ISSN" : "0014-4886", "PMID" : "10619569", "abstract" : "A family of homologous proteins known as alpha-, beta-, and gamma-synuclein are abundantly expressed in brain, especially in the presynaptic terminal of neurons. Although the precise function of these proteins remains unknown, alpha-synuclein has been implicated in synaptic plasticity associated with avian song learning as well as in the pathogenesis of Parkinson's disease (PD), dementia with LBs (DLB), some forms of Alzheimer's disease (AD), and multiple system atrophy (MSA). Since olfactory dysfunction is a common feature of these disorders and the olfactory receptor neurons (ORNs) of the olfactory epithelium (OE) regenerate throughout the lifespan, we used antibodies specific for alpha-, beta-, and gamma-synucleins to examine the olfactory mucosa of patients with PD, DLB, AD, MSA, and controls without a neurological disorder. Although antibodies to alpha- and beta-synucleins detected abnormal dystrophic neurites in the OE of patients with neurodegenerative disorders, similar pathology was also seen in the OE of controls. More significantly, we show here for the first time that alpha-, beta-, and gamma-synucleins are differentially expressed in cells of the OE and respiratory epithelium and that alpha-synuclein is the most abundant synuclein in the olfactory mucosa, where it is prominently expressed in ORNs. Moreover, alpha- and gamma-synucleins also were prominent in the OE basal cells, which include the progenitor cells of the ORNs in the OE. Thus, our data on synuclein expression within the OE may signify that synuclein plays a role in the regeneration and plasticity of ORNs in the adult human OE.", "author" : [ { "dropping-particle" : "", "family" : "Duda", "given" : "J E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arnold", "given" : "S E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "V M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trojanowski", "given" : "J Q", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Experimental neurology", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "1999" ] ] }, "page" : "515-22", "title" : "The expression of alpha-, beta-, and gamma-synucleins in olfactory mucosa from patients with and without neurodegenerative diseases.", "type" : "article-journal", "volume" : "160" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "131,132", "plainTextFormattedCitation" : "131,132", "previouslyFormattedCitation" : "131,132" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }131,132). In addition, work by Huisman and colleagues indicates that there are an increased number of (inhibitory) dopaminergic neurons in the olfactory bulb which may explain, at least to some degree, hyposmia in PD patients (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/mds.10713", "ISBN" : "0885-3185 (Print)", "ISSN" : "08853185", "PMID" : "15197709", "abstract" : "Hyposmia is one of the most prevalent symptoms of Parkinson's disease. It may occur even before the motor symptoms start. To determine whether the olfactory dysfunctions, like the motor symptoms, are associated with a loss of dopamine, the number of dopaminergic cells in the olfactory bulb of Parkinson's disease patients was studied using tyrosine hydroxylase immunohistochemistry. The quantitative analysis reveals that the total number of tyrosine hydroxylase-immunoreactive neurons in the olfactory bulb is twice as high in Parkinson patients compared to age and gender-matched controls. Because dopamine is known to inhibit olfactory transmission in the olfactory glomeruli, we suggest that the increase of dopaminergic neurons in the olfactory bulb is responsible for the hyposmia in Parkinson patients. The increase of dopamine in the olfactory bulb explains why olfaction does not improve with levodopa therapy.", "author" : [ { "dropping-particle" : "", "family" : "Huisman", "given" : "Evelien", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uylings", "given" : "Harry B M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V.", "family" : "Hoogland", "given" : "Piet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Movement Disorders", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "687-692", "title" : "A 100% increase of dopaminergic cells in the olfactory bulb may explain hyposmia in parkinson's disease", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "133", "plainTextFormattedCitation" : "133", "previouslyFormattedCitation" : "133" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }133) (but see also (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/mds.22009", "ISBN" : "0885-3185", "ISSN" : "08853185", "PMID" : "18581481", "abstract" : "Gender differences in dopaminergic related neurodegenerative diseases have hardly been studied until now. It is generally accepted that more men than women suffer from Parkinson's disease. One of the most prevalent symptoms in Parkinson's patients, hyposmia, does not show gender differences, while normally the sense of smell is better developed in females. Whether the change in dopamine in the olfactory bulb contributes equally to hyposmia in male and female Parkinson's patients is the subject of the present study. In a stereological study the total number of tyrosine hydroxylase immunoreactive neurons in the olfactory bulbs of male and female Parkinson's patients and age-matched controls has been estimated. The present stereological study shows that the number of tyrosine hydroxylase positive cells in control females is significantly lower than those in control males. The number of dopaminergic cells in the olfactory bulbs of both male and female Parkinson's patients equals that of healthy males of the same age group. We therefore conclude that the hyposmia in Parkinson's disease patients cannot simply be ascribed to dopamine in the olfactory bulb.", "author" : [ { "dropping-particle" : "", "family" : "Huisman", "given" : "Evelien", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uylings", "given" : "Harry B M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V.", "family" : "Hoogland", "given" : "Piet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Movement Disorders", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "1407-1413", "title" : "Gender-related changes in increase of dopaminergic neurons in the olfactory bulb of Parkinson's disease patients", "type" : "article-journal", "volume" : "23" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "134", "plainTextFormattedCitation" : "134", "previouslyFormattedCitation" : "134" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }134)). Patients with olfactory dysfunction secondary to PD commonly describe a gradual onset, and may be initially unaware of their deficit. Such patients do not often report parosmia and are unlikely to see any improvement over time (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/lary.26229", "author" : [ { "dropping-particle" : "", "family" : "Whitcroft", "given" : "Katherine L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cuevas", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haehner", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "1-5", "title" : "Patterns of olfactory impairment reflect underlying disease etiology", "type" : "article-journal", "volume" : "00000" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "89", "plainTextFormattedCitation" : "89", "previouslyFormattedCitation" : "89" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }89). Olfactory dysfunction is not affected by treatment with anti-PD medications (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/jnnp.55.2.138", "ISBN" : "0022-3050 (Print)", "ISSN" : "0022-3050", "PMID" : "1538221", "abstract" : "Decreased olfactory function is among the first signs of idiopathic Parkinson's disease (PD). Whether such dysfunction is present to the same degree on both sides of the nose, however, is unknown. Furthermore, whether the deficit results from or is influenced by anti-Parkinsonian medications has not been definitely established. Odour identification ability was evaluated on the left and right sides of the nose in 20 early-stage untreated PD patients, 20 early-stage treated PD patients, and 20 controls. In all cases, the PD related olfactory dysfunction was bilateral and no difference was observed between the test scores of patients taking or not taking drugs for PD. Although asymmetries of unsystematic direction were present in the test scores of some PD patients, similar asymmetries were observed in the controls and the asymmetries were not related to the side of the major motor dysfunction. As in earlier work, no relation was present between the olfactory test scores and the degree of tremor, rigidity, bradykinesia, or gait disturbance at the time of testing. These findings indicate that the olfactory dysfunction of early stage PD is robust, typically of the same general magnitude on both sides of the nose, and uninfluenced by anti-Parkinsonian medications.", "author" : [ { "dropping-particle" : "", "family" : "Doty", "given" : "R L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stern", "given" : "M B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pfeiffer", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gollomp", "given" : "S M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hurtig", "given" : "H I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Neurol Neurosurg Psychiatry", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "1992" ] ] }, "page" : "138-142", "title" : "Bilateral olfactory dysfunction in early stage treated and untreated idiopathic Parkinson's disease", "type" : "article-journal", "volume" : "55" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "135", "plainTextFormattedCitation" : "135", "previouslyFormattedCitation" : "135" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }135). Olfactory dysfunction associated with exposure to toxins or medicationsChronic exposure to toxins can result in olfactory dysfunction. Pathogenic agents include heavy metals such as cadmium and manganese, pesticides, herbicides and solvents. Chemotherapeutic agents and other medications should also be considered in this group. The pathological correlates of olfactory dysfunction associated with toxin exposure may involve either peripheral neuroepithelial or central damage, the latter being facilitated through transport of toxins via the olfactory nerve (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0-8247-0719-2", "author" : [ { "dropping-particle" : "", "family" : "Murphy", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doty", "given" : "Richard L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duncan", "given" : "H J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "chapter-number" : "22", "container-title" : "Handbook of Olfaction and Gustation", "edition" : "3rd", "editor" : [ { "dropping-particle" : "", "family" : "Doty", "given" : "Richard L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "461-478", "publisher" : "Marcel Dekker", "publisher-place" : "New York", "title" : "Clinical disorders of olfaction", "type" : "chapter" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "16", "plainTextFormattedCitation" : "16", "previouslyFormattedCitation" : "16" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }16). Table 3 shows an abbreviated list of agents and medications that have been reported to affect olfaction. Although many medications have been reported to affect olfaction, carefully controlled data for the effects of such drugs on olfaction is limited.[Table 3]Congenital olfactory dysfunctionCertain genetic conditions are known to be associated with congenital dysfunction, most notably the developmental endocrine disorder Kallmann syndrome (hypogonadotropic hypogonadism). Typically, the diagnosis is made at an age between 12 and 16 years. The condition is associated with hypoplastic/aplastic olfactory bulbs and olfactory sulci, and OSN of varying number and maturity (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/chemse/27.7.623", "ISSN" : "0379-864X", "PMID" : "12200342", "abstract" : "It has been shown that olfactory epithelium can be safely biopsied from the living, intact human being. Observations of the ultrastructure of this epithelium shows changes that can then be correlated with the etiology and degree of olfactory loss, allowing a greater understanding of both normal transduction and of the pathology of dysfunction. Examples of the common forms of olfactory dysfunction are presented and discussed. Additionally, the technique will allow additional immuno-histochemical and molecular study of the tissue, will increase the understanding of both normal and pathological function and should translate to new therapeutic regimens.", "author" : [ { "dropping-particle" : "", "family" : "Jafek", "given" : "B W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Murrow", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Michaels", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Restrepo", "given" : "Diego", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Linschoten", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemical Senses", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2002" ] ] }, "page" : "623-628", "title" : "Biopsies of Human Olfactory Epithelium", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/nrendo.2015.112", "ISSN" : "1759-5037", "PMID" : "26194704", "abstract" : "Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder caused by the deficient production, secretion or action of gonadotropin-releasing hormone (GnRH), which is the master hormone regulating the reproductive axis. CHH is clinically and genetically heterogeneous, with >25 different causal genes identified to date. Clinically, the disorder is characterized by an absence of puberty and infertility. The association of CHH with a defective sense of smell (anosmia or hyposmia), which is found in \u223c50% of patients with CHH is termed Kallmann syndrome and results from incomplete embryonic migration of GnRH-synthesizing neurons. CHH can be challenging to diagnose, particularly when attempting to differentiate it from constitutional delay of puberty. A timely diagnosis and treatment to induce puberty can be beneficial for sexual, bone and metabolic health, and might help minimize some of the psychological effects of CHH. In most cases, fertility can be induced using specialized treatment regimens and several predictors of outcome have been identified. Patients typically require lifelong treatment, yet \u223c10-20% of patients exhibit a spontaneous recovery of reproductive function. This Consensus Statement summarizes approaches for the diagnosis and treatment of CHH and discusses important unanswered questions in the field.", "author" : [ { "dropping-particle" : "", "family" : "Boehm", "given" : "Ulrich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouloux", "given" : "Pierre-Marc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dattani", "given" : "Mehul T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roux", "given" : "Nicolas", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dod\u00e9", "given" : "Catherine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dunkel", "given" : "Leo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dwyer", "given" : "Andrew A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giacobini", "given" : "Paolo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hardelin", "given" : "Jean-Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Juul", "given" : "Anders", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maghnie", "given" : "Mohamad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pitteloud", "given" : "Nelly", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prevot", "given" : "Vincent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raivio", "given" : "Taneli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tena-Sempere", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Quinton", "given" : "Richard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Young", "given" : "Jacques", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature reviews. Endocrinology", "id" : "ITEM-2", "issue" : "9", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "547-64", "publisher" : "Nature Publishing Group", "title" : "Expert consensus document: European Consensus Statement on congenital hypogonadotropic hypogonadism-pathogenesis, diagnosis and treatment.", "type" : "article-journal", "volume" : "11" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.2214/ajr.166.2.8553963", "ISBN" : "0361-803X (Print)\\r0361-803X (Linking)", "ISSN" : "0361-803X", "PMID" : "8553963", "abstract" : "OBJECTIVE: The purpose of this study was to evaluate patients with reduced or no sense of smell since birth for sites of abnormality by MR imaging. MATERIALS AND METHODS: Twenty-five patients who reported no olfactory function since birth were evaluated by olfactory testing, sinonasal endoscopy, and MR imaging. Surface coil and head coil images of the olfactory bulbs, olfactory tracts, subfrontal cortex, and temporal lobes in contiguous 3-mm sections were obtained. Two reviewers determined unilateral olfactory bulb and tract volumes and temporal lobe volumes in two separate sessions. Qualitative grading for olfactory bulb, olfactory tract, olfactory sulcus, subfrontal region, hippocampus, and temporal lobe damage also was performed. RESULTS: The absence of olfactory bulbs and tracts (68-84%) or the presence of hypoplasia (16-32%) was noted in all cases. Eight individuals had Kallmann's syndrome (hypogonadotropic hypogonadism with anosmia). Temporal and/or frontal lobe volume loss was noted in five individuals and was mild in all but one individual. CONCLUSION: Congenital anosmia or hyposmia appears to be an olfactory bulb-olfactory tract phenomenon rather than a cerebral process.", "author" : [ { "dropping-particle" : "", "family" : "Yousem", "given" : "David M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geckle", "given" : "Rena J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bilker", "given" : "Warren B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McKeown", "given" : "D A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doty", "given" : "Richard L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "AJR Am J Roentgenol", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "1996" ] ] }, "page" : "439-443", "title" : "MR evaluation of patients with congenital hyposmia or anosmia", "type" : "article-journal", "volume" : "166" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1002/alr.21550", "ISSN" : "20426984", "PMID" : "25951300", "abstract" : "BACKGROUND: The relationship between olfactory function, rhinencephalon and forebrain changes in Kallmann syndrome (KS) have not been adequately investigated. We evaluated a large cohort of male KS patients using Sniffin' Sticks and MRI in order to study olfactory bulb (OB) volume, olfactory sulcus (OS) depth, cortical thickness close to the OS, and olfactory phenotype.\\n\\nMETHODS: Olfaction was assessed administering Sniffin' Sticks\u00ae, in 38 KS patients and 17 controls (by means of Screening 12 test\u00ae). All subjects underwent magnetic resonance imaging (MRI) to study OB volume, sulcus depth, and cortical thickness.\\n\\nRESULTS: Compared to controls, KS patients showed smaller OB volume (p<0.0001), reduced sulcus depth (p<0.0001), and thicker cortex in the region close to the OS (p<0.0001). Anosmic KS patients had smaller OB than controls and hyposmic KS patients; there was no difference between hyposmic KS patients and controls. OB volume correlated with Sniffin' Sticks score (r = 0.64; p < 0.001), OS depth (p<0.0001) and, inversely, with cortical thickness changes (p<0.0001). Sniffin' Sticks showed an inverse correlation with cortical thickness (r = -0.5; p<0.0001) and a trend toward a statistically significant correlation with OS depth.\\n\\nCONCLUSION: The present study provides further evidence of the strict relationship between olfaction and OB volume. The strong correlation between OB volume and the overlying cortical changes highlights the key role of rhinencephalon in forebrain embryogenesis.", "author" : [ { "dropping-particle" : "", "family" : "Ottaviano", "given" : "Giancarlo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cantone", "given" : "Elena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "D'Errico", "given" : "Arianna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salvalaggio", "given" : "Alessandro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Citton", "given" : "Valentina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scarpa", "given" : "Bruno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Favaro", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinisi", "given" : "Antonio Agostino", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liuzzi", "given" : "Raffaele", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonanni", "given" : "Guglielmo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salle", "given" : "Francesco", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elefante", "given" : "Andrea", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Manara", "given" : "Renzo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Staffieri", "given" : "Alberto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Martini", "given" : "Alessandro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brunetti", "given" : "Arturo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Forum of Allergy and Rhinology", "id" : "ITEM-4", "issue" : "9", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "855-861", "title" : "Sniffin' Sticks and olfactory system imaging in patients with Kallmann syndrome", "type" : "article-journal", "volume" : "5" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "80,144\u2013146", "plainTextFormattedCitation" : "80,144\u2013146", "previouslyFormattedCitation" : "80,144\u2013146" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }80,144–146). Such patients usually have functional anosmia, or severe hyposmia from birth. Recent work has also demonstrated olfactory, but not gustatory dysfunction in Turner’s syndrome (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.maturitas.2012.07.012", "ISBN" : "1873-4111 (Electronic)\\r0378-5122 (Linking)", "ISSN" : "03785122", "PMID" : "22889822", "abstract" : "Objectives: To assess the impact of Turner's syndrome (TS) and other congenital hypogonadisms (OCH) on the sense of smell and taste. Design: An analytical study of three independent cohorts was designed: patients affected by TS, OCH, and a control group of healthy women taking contraception. Setting: Gynaecological Endocrinology Unit and Smell Clinic in Rhinology Unit of Hospital Clinic of Barcelona. Participants: Thirty TS patients between 20 and 50 years of age receiving hormone replacement treatment (HT) were included as the exposed cohort; fourteen age-matched women with OCH taking HT were recruited; forty-three age-matched healthy controls receiving hormone contraception treatment were selected as the control group. This group was matched with an historical cohort of forty healthy women without contraception, used to validate BAST-24 in Hospital Clinic of Barcelona. Interventions: Clinical history, presence of nasal symptoms, general physical examination, nasal endoscopy, and Barcelona Smell Test-24 (BAST-24) and gustometry were carried out on all patients. Main measures: TS physical dysmorphology features, intensity of nasal symptoms and signs of nasal obstruction were collected. BAST-24 test included 24 odours to assess both sensory (detection, memory and forced choice) and sensitivity (intensity, irritability, freshness and pleasantness) odour characteristics, as well as 4 tastes to evaluate taste domains (detection and forced choice). Results: Healthy women taking hormone contraception felt odours with more intensity (p = 0.002) and less irritability (p < 0.001) than the historical cohort. TS patients showed a significant impairment in smell memory (p < 0.005) and forced-choice (p < 0.001) compared with controls taking contraception, whereas no differences were found in odour sensitivity. Detection of taste was successful in 100% of patients. When considering only individual tastes, none of them showed statistically significant differences between groups. Conclusion: Patients with TS show the impairment of smell but not of taste, compared to OCH and healthy controls taking contraception. Smell sensitivity was not affected. ?? 2012 Elsevier Ireland Ltd.", "author" : [ { "dropping-particle" : "", "family" : "Ros", "given" : "Cristina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alobid", "given" : "Isam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Centellas", "given" : "Silvia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balasch", "given" : "Juan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mullol", "given" : "Joaquim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Castelo-Branco", "given" : "Camil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Maturitas", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "244-250", "publisher" : "Elsevier Ireland Ltd", "title" : "Loss of smell but not taste in adult women with Turner's syndrome and other congenital hypogonadisms", "type" : "article-journal", "volume" : "73" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "147", "plainTextFormattedCitation" : "147", "previouslyFormattedCitation" : "147" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }147), and the Bardet Biedl Syndrome (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/ajmg.a.30512", "ISBN" : "1552-4825 (Print)\\r1552-4825 (Linking)", "ISSN" : "15524825", "PMID" : "15654695", "abstract" : "Recent discoveries have lead to the hypothesis that ciliary dysfunction is a mechanism underlying the pathogenesis of Bardet-Biedl syndrome (BBS). Here, we describe two individuals with decreased olfaction who are members of an extended family affected with BBS caused by a homozygous deletion (c.77-220del) in the BBS4 gene. These findings correlate with the evidence that several BBS proteins, including BBS4, are expressed in the olfactory epithelium (OE). Although the prevalence and the spectrum of impaired olfaction in BBS are not known, the causal relationship of the BBS4 deletion in this family and the decreased olfaction is corroborated by evidence that Bbs2 and Bbs4 knockout mice have severe olfaction deficits and that also patients with BBS caused by mutations in other BBS genes can have impaired olfaction. This finding broadens the spectrum of clinical manifestations associated with BBS, confirms the role of BBS4 in olfaction, and lends support to the hypothesis that ciliary dysfunction is an important aspect of BBS pathogenesis.", "author" : [ { "dropping-particle" : "", "family" : "Iannaccone", "given" : "Alessandro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mykytyn", "given" : "Kirk", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Persico", "given" : "Antonio M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Searby", "given" : "Charles C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baldi", "given" : "Alfonso", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jablonski", "given" : "Monica M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sheffield", "given" : "Val C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Medical Genetics", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "343-346", "title" : "Clinical evidence of decreased olfaction in Bardet-Biedl syndrome caused by a deletion in the BBS4 gene", "type" : "article-journal", "volume" : "132 A" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "148", "plainTextFormattedCitation" : "148", "previouslyFormattedCitation" : "148" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }148). As MRI scanning becomes more common, non-syndromic hypoplasia/aplasia of the olfactory bulb is increasingly recognised. As such, the most frequent cause of congenital or ‘developmental’ anosmia is now thought to be isolated, non-syndromic, idiopathic congenital anosmia with no known genetic cause (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0195-6108 (Print)\\r0195-6108 (Linking)", "ISSN" : "0195-6108", "PMID" : "11827889", "abstract" : "BACKGROUND AND PURPOSE: Anosmias with chromosomal disorders has been well investigated. However, isolated anosmia (IA) has received less attention, although it occurs more frequently. We compared frontobasal structures in patients with IA since birth or early childhood with those in control subjects. METHODS: Imaging findings obtained in 16 patients with IA were compared with those obtained in eight control subjects. Imaging was performed with a standard quadrature head coil at 1.5 T. T1-weighted spin-echo (coronal plane perpendicular to frontal skull base; section thickness, 3 mm; pixels, 0.43 x 0.39 mm) and sagittal T1-weighted magnetization-prepared rapid gradient-echo (voxels, 1.0 x 1.0 x 1.0 mm) sequences were performed. We assessed the length and depth of the olfactory sulcus, olfactory bulb volume, and olfactory sulcus depth in the plane of the posterior tangent through the eyeballs (PPTE). RESULTS: Five patients with IA had bilateral hypoplastic olfactory bulbs. Three patients with IA had hypoplastic olfactory bulbs on the right and aplastic olfactory bulbs on the left. Eight patients with IA had bilaterally aplastic olfactory bulbs. The depth of the olfactory sulcus at the level of the PPTE was smaller in patients with IA than in control subjects. The depth of the olfactory sulcus was greater on the right than on the left, and there was no overlap. Among patients with IA, the depth of the olfactory sulcus differed significantly between those with and those without visible olfactory tracts. CONCLUSION: The depth of the olfactory sulcus at the level of the PPTE reflects the presence of olfactory tracts. The presence or absence of the olfactory tract may therefore have some association with cortical growth of the olfactory sulcus region. The olfactory sulcus is deeper on the right than on the left, particularly in patients with IA. We speculate that olfaction may be processed predominantly in the right hemisphere.\\n", "author" : [ { "dropping-particle" : "", "family" : "Abolmaali", "given" : "Nasreddin D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hietschold", "given" : "Volker", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vogl", "given" : "Thomas J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huttenbrink", "given" : "Karl-Bernd", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Neuroradiology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2002" ] ] }, "page" : "157-164", "title" : "MR Evaluation in Patients with Isolated Anosmia Since Birth or Early Childhood", "type" : "article-journal", "volume" : "23" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "149", "plainTextFormattedCitation" : "149", "previouslyFormattedCitation" : "149" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }149). To make this diagnosis, the normal olfactory bulb structure should be hypoplastic or absent and the olfactory sulcus should be shortened (the sulcus is seen just above the olfactory bulb on coronal scanning) (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3174/ajnr.A2632", "ISSN" : "01956108", "PMID" : "21868619", "abstract" : "In congenital anosmia, the OB and OT can be aplastic or hypoplastic. In clinical routine, these are sometimes difficult to assess. We thus wanted to investigate morphologic differences of the OS in patients with IA since birth or early childhood in comparison with controls, to investigate whether there is a depth of OS that is predictive of IA.", "author" : [ { "dropping-particle" : "", "family" : "Huart", "given" : "Caroline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meusel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerber", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duprez", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rombaux", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Neuroradiology", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "1911-1914", "title" : "The depth of the olfactory sulcus is an indicator of congenital anosmia", "type" : "article-journal", "volume" : "32" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "150", "plainTextFormattedCitation" : "150", "previouslyFormattedCitation" : "150" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }150) , though there are exceptions to that rule (see (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/cge.12491", "ISSN" : "13990004", "PMID" : "25156905", "abstract" : "Isolated congenital anosmia (ICA) is a rare disorder, where otherwise healthy individuals present with an inability to smell since birth. A list of studies have described the genes involved in syndromic anosmia; however the genetics of ICA is still in its infancy. So far no mutations have been identified in human ICA outside the list. Studies in mice show that the cyclic nucleotide gated channel subunit CNGA2, expressed in the olfactory epithelium has a crucial role in olfactory signal transduction. We have identified a novel X-linked stop mutation in CNGA2 (c.634C>T, p.R212*) in two brothers with ICA using exome sequencing. No additional mutations in CNGA2 were identified in a cohort of 31 non-related ICA individuals. Magnetic resonance brain imaging revealed diminished olfactory bulbs and flattened olfactory sulci. This is the first report of a mutation in the cyclic nucleotide gated gene CNGA2 and supports the critical role of this gene in human olfaction. possibly the first mutation reported in humans with isolated congenital anosmia.", "author" : [ { "dropping-particle" : "", "family" : "Karstensen", "given" : "H. G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mang", "given" : "Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fark", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tommerup", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Genetics", "id" : "ITEM-1", "issue" : "607123", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "293-296", "title" : "The first mutation in CNGA2 in two brothers with anosmia", "type" : "article-journal", "volume" : "2" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "151", "plainTextFormattedCitation" : "151", "previouslyFormattedCitation" : "151" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }151)). Following diagnosis, patients should undergo genetic, endocrinological and paediatric (if appropriate) evaluation in order to delineate the complete phenotype of the congenital dysfunction.Olfactory dysfunction associated with normal agingAs evidenced through epidemiological studies, olfactory function decreases with age. One such study demonstrated olfactory impairment in 62.5% of persons over 80 (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1001/jama.288.18.2307", "ISBN" : "0098-7484 (Print)\\n0098-7484 (Linking)", "ISSN" : "00987484", "PMID" : "12425708", "abstract" : "CONTEXT: Older adults represent the fastest-growing segment of the US population, and prevalences of vision and hearing impairment have been extensively evaluated. However, despite the importance of sense of smell for nutrition and safety, the prevalence of olfactory impairment in older US adults has not been studied. OBJECTIVE: To determine the prevalence of olfactory impairment in older adults. DESIGN, SETTING, AND PARTICIPANTS: A total of 2491 Beaver Dam, Wis, residents aged 53 to 97 years participating in the 5-year follow-up examination (1998-2000) for the Epidemiology of Hearing Loss Study, a population-based, cross-sectional study. MAIN OUTCOME MEASURES: Olfactory impairment, assessed by the San Diego Odor Identification Test and self-report. RESULTS: The mean (SD) prevalence of impaired olfaction was 24.5% (1.7%). The prevalence increased with age; 62.5% (95% confidence interval [CI], 57.4%-67.7%) of 80- to 97-year-olds had olfactory impairment. Olfactory impairment was more prevalent among men (adjusted prevalence ratio, 1.92; 95% CI, 1.65-2.19). Current smoking, stroke, epilepsy, and nasal congestion or upper respiratory tract infection were also associated with increased prevalence of olfactory impairment. Self-reported olfactory impairment was low (9.5%) and this measure became less accurate with age. In the oldest group, aged 80 to 97 years, sensitivity of self-report was 12% for women and 18% for men. CONCLUSIONS: This study demonstrates that prevalence of olfactory impairment among older adults is high and increases with age. Self-report significantly underestimated prevalence rates obtained by olfaction testing. Physicians and caregivers should be particularly alert to the potential for olfactory impairment in the elderly population.", "author" : [ { "dropping-particle" : "", "family" : "Murphy", "given" : "Claire", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schubert", "given" : "Carla R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cruickshanks", "given" : "Karen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klein", "given" : "Barbara E K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klein", "given" : "Ronald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nondahl", "given" : "David M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "JAMA : the journal of the American Medical Association", "id" : "ITEM-1", "issue" : "18", "issued" : { "date-parts" : [ [ "2002" ] ] }, "page" : "2307-2312", "title" : "Prevalence of olfactory impairment in older adults.", "type" : "article-journal", "volume" : "288" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "35", "plainTextFormattedCitation" : "35", "previouslyFormattedCitation" : "35" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }35). Furthermore, logistic regression analysis of data from the NSHAP study (described above) has demonstrated that olfactory dysfunction is a predictor of 5-year mortality, after controlling for confounding factors (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0107541", "ISBN" : "1932-6203 (Electronic)\\r1932-6203 (Linking)", "ISSN" : "19326203", "PMID" : "25271633", "abstract" : "Prediction of mortality has focused on disease and frailty, although antecedent biomarkers may herald broad physiological decline. Olfaction, an ancestral chemical system, is a strong candidate biomarker because it is linked to diverse physiological processes. We sought to determine if olfactory dysfunction is a harbinger of 5-year mortality in the National Social Life, Health and Aging Project [NSHAP], a nationally representative sample of older U.S. adults. 3,005 community-dwelling adults aged 57-85 were studied in 2005-6 (Wave 1) and their mortality determined in 2010-11 (Wave 2). Olfactory dysfunction, determined objectively at Wave 1, was used to estimate the odds of 5-year, all cause mortality via logistic regression, controlling for demographics and health factors. Mortality for anosmic older adults was four times that of normosmic individuals while hyposmic individuals had intermediate mortality (p<0.001), a \"dose-dependent\" effect present across the age range. In a comprehensive model that included potential confounding factors, anosmic older adults had over three times the odds of death compared to normosmic individuals (OR, 3.37 [95%CI 2.04, 5.57]), higher than and independent of known leading causes of death, and did not result from the following mechanisms: nutrition, cognitive function, mental health, smoking and alcohol abuse or frailty. Olfactory function is thus one of the strongest predictors of 5-year mortality and may serve as a bellwether for slowed cellular regeneration or as a marker of cumulative toxic environmental exposures. This finding provides clues for pinpointing an underlying mechanism related to a fundamental component of the aging process.", "author" : [ { "dropping-particle" : "", "family" : "Pinto", "given" : "Jayant M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wroblewski", "given" : "Kristen E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kern", "given" : "David W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schumm", "given" : "L. Philip", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McClintock", "given" : "Martha K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "1-9", "title" : "Olfactory dysfunction predicts 5-year mortality in older adults", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1093/gerona/glw036", "ISSN" : "1758-535X", "PMID" : "26946102", "abstract" : "BACKGROUND Sensory impairments increase with age and the majority of older people will experience a sensory impairment if they live long enough. However, the relationships of hearing, visual, and olfactory impairments with mortality are not well understood. METHODS Epidemiology of Hearing Loss Study participants (n = 2,418) aged 53-97 years (mean = 69 years) were examined in 1998-2000 and hearing, visual acuity, and olfaction were measured. Participants were followed for mortality for up to 17 years (mean = 12.8 years). Cox proportional hazards models were used to assess the association between prevalent sensory impairments and the 15-year cumulative incidence of death. RESULTS A total of 1,099 (45.4%) of participants died during the follow-up period. In age- and sex-adjusted Cox models, the risk of mortality was higher among participants with one (hazard ratio [HR] = 1.40, 95% confidence interval [CI] = 1.19, 1.64) or two or more (HR = 2.12, 95% CI = 1.74, 2.58) sensory impairments than among participants with no sensory impairments. Olfactory impairment at baseline was significantly associated with mortality (HR = 1.28, 95% CI = 1.07, 1.52) after adjusting for age, sex, sensory comorbidities, cardiovascular risk factors and disease, cognitive impairment, frailty, subclinical atherosclerosis, and inflammatory marker levels (n = 1,745). Hearing and visual impairment were not associated with mortality after adjusting for subclinical atherosclerosis and inflammation. CONCLUSION Olfactory impairment, but not hearing or visual impairment, was associated with an increased risk of mortality. These results suggest that olfactory impairment may be a marker of underlying physiologic processes or pathology that is associated with aging and reduced survival in older adults.", "author" : [ { "dropping-particle" : "", "family" : "Schubert", "given" : "Carla R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fischer", "given" : "Mary E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinto", "given" : "A. Alex", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klein", "given" : "Barbara E K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klein", "given" : "Ronald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tweed", "given" : "Ted S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cruickshanks", "given" : "Karen J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The journals of gerontology. Series A, Biological sciences and medical sciences", "id" : "ITEM-2", "issue" : "00", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "1-6", "title" : "Sensory Impairments and Risk of Mortality in Older Adults.", "type" : "article-journal", "volume" : "00" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1093/gerona/glu158", "ISBN" : "1079-5006", "ISSN" : "1758535X", "PMID" : "25182599", "abstract" : "BACKGROUND: The purpose of this study was to determine if subclinical markers of atherosclerosis are associated with a decline in olfactory function. METHODS: The San Diego Odor Identification Test was administered to 2,302 participants (age 21-84 years) at the baseline (2005-2008) and 5-year follow-up (2010-2013) examinations of the Beaver Dam Offspring Study. A decline in odor identification was defined as a decrease in San Diego Odor Identification Test score of 2 or more (range 0-8) from Beaver Dam Offspring Study 1 to Beaver Dam Offspring Study 2. Carotid intima media thickness and plaque, blood pressure, pulse wave velocity, and body mass index were measured and other risk factor data were obtained by interview. RESULTS: Overall 3.2% of participants had a decline in San Diego Odor Identification Test score at 5 years. In age- and sex-adjusted models, mean intima media thickness (odds ratio = 1.17, 95% CI = 1.01, 1.34, per 0.1 mm) and number of sites (range 0-6) with carotid artery plaque (odds ratio = 1.35, 95% CI = 1.11, 1.65, per site) at baseline were associated with an increased risk for decline. Plaque score (odds ratio = 1.24, 95% CI = 1.01, 1.53) remained a significant independent predictor of olfactory decline in a model that included age, sex, hypertension, body mass index, alcohol, and smoking. CONCLUSIONS: Subclinical atherosclerosis was associated with an increased risk for olfactory decline indicating that atherosclerosis may be one of the risk factors for the decline in olfactory function seen with aging. Strategies to improve vascular health may also benefit olfactory health.", "author" : [ { "dropping-particle" : "", "family" : "Schubert", "given" : "Carla R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cruickshanks", "given" : "Karen J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fischer", "given" : "Mary E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huang", "given" : "Guan Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klein", "given" : "Ronald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsai", "given" : "Michael Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinto", "given" : "A. Alex", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journals of Gerontology - Series A Biological Sciences and Medical Sciences", "id" : "ITEM-3", "issue" : "7", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "879-884", "title" : "Carotid intima media thickness, atherosclerosis, and 5-year decline in odor identification: The beaver dam offspring study", "type" : "article-journal", "volume" : "70" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "8,9,152", "plainTextFormattedCitation" : "8,9,152", "previouslyFormattedCitation" : "8,9,152" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }8,9,152). The link between olfactory dysfunction and mortality has also been shown in other studies (please see epidemiology section for more details) (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/ana.24447", "ISBN" : "0364-5134", "ISSN" : "15318249", "PMID" : "26031760", "abstract" : "OBJECTIVE: To examine the association between odor identification deficits and future mortality in a multiethnic community cohort of older adults.\\n\\nMETHODS: Participants were evaluated with the 40-item University of Pennsylvania Smell Identification Test (UPSIT). Follow-up occurred at 2-year intervals with information on death obtained from informant interviews and the National Death Index.\\n\\nRESULTS: During follow-up (mean 4.1 SD 2.6 years), 349 of 1169 (29.9%) participants died. Participants who died were more likely to be older (p\u2009<\u20090.001), male (p\u2009<\u20090.001), have lower UPSIT scores (p\u2009<\u20090.001), and have a diagnosis of dementia (p\u2009<\u20090.001). In a Cox model, the association between lower UPSIT score and mortality (Hazard Ratio 1.07 per point interval, 95%CI 1.05 to 1.08, p<0.001) persisted after controlling for age, gender, education, ethnicity, language, modified Charlson medical comorbidity index, dementia, depression, alcohol abuse, head injury, smoking, Body Mass Index, vision and hearing impairment (Hazard Ratio=1.05, 95%CI 1.03 to 1.07, p<0.001). Compared to the fourth quartile with the highest UPSIT scores, hazard ratios for mortality for the first, second, and third quartiles of UPSIT scores were 3.81 (95%CI 2.71 to 5.34), 1.75 (95%CI 1.23 to 2.50), and 1.58 (95%CI 1.09 to 2.30), respectively. Participant mortality rate was 45% in the lowest quartile of UPSIT scores (anosmia) and 18% in the highest quartile of UPSIT scores.\\n\\nINTERPRETATION: Impaired odor identification, particularly in the anosmic range, is associated with increased mortality in older adults even after controlling for dementia and medical comorbidity. This article is protected by copyright. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Devanand", "given" : "Davangere P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Seonjoo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Manly", "given" : "Jennifer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andrews", "given" : "Howard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schupf", "given" : "Nicole", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Masurkar", "given" : "Arjun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stern", "given" : "Yaakov", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mayeux", "given" : "Richard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doty", "given" : "Richard L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of Neurology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "401-411", "title" : "Olfactory identification deficits and increased mortality in the community", "type" : "article-journal", "volume" : "78" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1093/gerona/glr165", "ISSN" : "10795006", "PMID" : "22080501", "abstract" : "Population-based data on the relationship between impaired olfaction and risk of mortality among older adults are lacking. We used a representative cohort of adults aged 60 years or older to assess whether olfactory loss is a predictor of mortality, independent of potential confounders.", "author" : [ { "dropping-particle" : "", "family" : "Gopinath", "given" : "Bamini", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sue", "given" : "Carolyn M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kifley", "given" : "Annette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mitchell", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journals of Gerontology - Series A Biological Sciences and Medical Sciences", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "204-209", "title" : "The association between olfactory impairment and total mortality in older adults", "type" : "article-journal", "volume" : "67 A" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "40,153", "plainTextFormattedCitation" : "40,153", "previouslyFormattedCitation" : "40,153" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }40,153).Previous work has suggested that olfactory loss with age is not homogeneous across smells: sensitivity towards unpleasant odours are usually preserved longer than pleasant ones, perhaps due to the formers’ role in environmental navigation and defence (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.acn.2006.05.006", "ISBN" : "0887-6177", "ISSN" : "08876177", "PMID" : "16920329", "abstract" : "The purpose of this study was to investigate (a) the relationship between identification proficiency for specific odors and chronological age and (b) to determine whether the relationships were related to perceived quality (i.e., judgments of familiarity, intensity, and hedonics) of the odor item. Data from 472 subjects (227 men, 245 women) ranging in age from 18 to 79 years were assessed in a cued identification test comprising 16 odors. The results indicated a reliable age effect in overall odor identification performance. Further analyses indicated that the observed age-related deficit was odorant-specific, with some odors being equally well identified across age cohorts and others showing sensitivity to the process of aging. Additional examination regarding the observed age-differential effects across the different odor types indicated that these may be understood according to the pleasantness/upleasantness associated with the odor. Specifically, odors perceived as unpleasant showed age invariance whereas odors rated as pleasant exhibited age sensitivity. ?? 2006 National Academy of Neuropsychology.", "author" : [ { "dropping-particle" : "", "family" : "Konstantinidis", "given" : "Iordanis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Larsson", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of Clinical Neuropsychology", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "615-621", "title" : "Identification of unpleasant odors is independent of age", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "154", "plainTextFormattedCitation" : "154", "previouslyFormattedCitation" : "154" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }154). The potential causes of olfactory impairment with advancing age are multiple and varied. A number of generic physiological changes occur within the nose of the aged that may affect olfaction, including parasympathetic/sympathetic dysregulation, reduced mucosal blood flow, fibrosis of the cribriform foramina and possibly also age-related mucociliary dysfunction. Moreover, age related changes in the olfactory neuroepithelium, olfactory bulbs and central olfactory system also occur (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1159/000381619", "ISSN" : "14230003", "PMID" : "25968962", "abstract" : "Decreased olfactory function is very common in the older population, being present in >50% of individuals aged between 65 and 80 years and in 62-80% of those >80 years of age. Smell dysfunction significantly influences physical well-being, quality of life, nutritional status as well as everyday safety and is associated with increased mortality. Multiple factors contribute to age-related olfactory sensory loss, including nasal engorgement, cumulative damage of the olfactory epithelium from environmental insults, a reduction in mucosal metabolizing enzymes, sensory loss of receptor cells to odorants, and changes in neurotransmitter and neuromodulator systems. In addition, structural and functional abnormalities of the olfactory epithelium, olfactory bulb, central olfactory cortex, and basic olfactory circuitry, which are related to the neuronal expression of aberrant proteins in these areas, may result in olfactory sensory impairment in aging and neurodegenerative diseases. Impaired odour identification is associated with a decrease in cognitive abilities and memory decline. A reduction in the sense of smell is considered to potentially represent an early and important warning of neurodegenerative disorders, particularly of Parkinson's disease and Alzheimer's disease, and, in mild cognitive impairment, olfactory impairment may herald progression to dementia. Further investigations of the potential role of olfactory dysfunction in the early diagnosis and treatment of neurodegenerative diseases are warranted. \u00a9 2015 S. Karger AG, Basel.", "author" : [ { "dropping-particle" : "", "family" : "Attems", "given" : "Johannes", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walker", "given" : "Lauren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jellinger", "given" : "Kurt A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gerontology", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "485-490", "title" : "Olfaction and Aging: A Mini-Review", "type" : "article-journal", "volume" : "61" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "155", "plainTextFormattedCitation" : "155", "previouslyFormattedCitation" : "155" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }155). Changes in the neuroepithelium and olfactory bulb may be in part due to the reduced regenerative capacity of the OSN (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0736-5748(96)00046-9", "ISBN" : "0736-5748", "ISSN" : "07365748", "PMID" : "9010732", "abstract" : "Olfactory epithelium retains the capacity to recover anatomically after damage well into adult life and perhaps throughout its duration. None the less, olfactory dysfunctions have been reported widely for elderly humans. The present study investigates the effects of aging on the neurophysiological and anatomical status of the olfactory epithelium in barrier-raised Fischer 344X Brown Norway F1 hybrid rats at 7, 10, 25 and 32/35 months old. The posterior part of the olfactory epithelium in 32/35-month-old rats is well preserved. Globose basal cells are dividing, and new neurons are being born even at this advanced age. None the less, the numbers of proliferating basal cells and immature, GAP-43 (+) neurons are significantly decreased. Neurophysiological status was evaluated using voltage-sensitive dye techniques to assess inherent patterns of odorant-induced activity in the epithelium lining the septum and the medial surface of the turbinates. In middle and posterior zones of the epithelium, there were neither age-related changes in overall responsivity of this part of the olfactory epithelium to any of five odorants, nor shifts in the location of the odorant-induced hotspots. The inherent activity patterns elicited by the different odorants do become more distinct as a function of age, which probably reflects the decline in immature neurons and a slight, but not statistically significant, increase in mature neurons as a function of age. In contrast with the excellent preservation of posterior epithelium, the epithelium lining the anterodorsal septum and the corresponding face of the turbinates is damaged in the 32/35-month-old animals: in this part, horizontal basal cells are reactive, more basal cells and sustentacular cells are proliferating than in younger animals or in posterior epithelium of the same animals, and the neuronal population is less mature on average. Our findings indicate that degeneration of the olfactory epithelium is not an inevitable or preprogrammed consequence of the aging process, since the posterior zone of the epithelium is very well preserved in these barrier-protected animals. However, the deterioration in the anterior epithelium suggests that environmental insults can accumulate or become more severe with age and overwhelm the regenerative capacity of the epithelium. Alternatively, the regenerative capacity of the epithelium may wane somewhat with age. Either of these mechanisms or some combination of them can account for th\u2026", "author" : [ { "dropping-particle" : "", "family" : "Loo", "given" : "Alice T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Youngentob", "given" : "Steven L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kent", "given" : "Paul F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwob", "given" : "James E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Developmental Neuroscience", "id" : "ITEM-1", "issue" : "7-8", "issued" : { "date-parts" : [ [ "1996" ] ] }, "page" : "881-900", "title" : "The aging olfactory epithelium: Neurogenesis, response to damage, and odorant-induced activity", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "96", "plainTextFormattedCitation" : "96", "previouslyFormattedCitation" : "96" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }96). In the absence of efficient OSN regeneration, damage from previous insults (e.g. upper respiratory tract infections and exposure to toxins) may accumulate to form permanent damage. The reduced olfactory bulb volumes seen with advancing age may be partially due to reduced afferent input (and consequent trophic effects) in line with OSN damage (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/brain/awp243", "ISBN" : "1460-2156", "ISSN" : "00068950", "PMID" : "19773353", "abstract" : "Differentiation of progenitor cells into neurons in the olfactory bulb depends on olfactory stimulation that can lead to an increase in olfactory bulb volume. In this study, we investigated whether the human olfactory bulb volume increases with increasing olfactory function due to treatment of chronic rhinosinusitis. Nineteen patients with chronic rhinosinusitis were investigated before and after treatment. For comparison, additional measurements were performed in 18 healthy volunteers. Volumetric measurements of the olfactory bulb were based on planimetric manual contouring of magnetic resonance scans. Olfactory function was evaluated separately for each nostril using tests for odour threshold, odour discrimination and odour identification. Measurements were performed on two occasions, 3 months apart. In healthy controls, the olfactory bulb volume did not change significantly between the two measurements. In contrast, the olfactory bulb volume in patients increased significantly from the initial 64.5 +/- 3.2 to 70.0 +/- 3.5 mm(3) on the left side (P = 0.02) and from 60.9 +/- 3.5 to 72.4 +/- 2.8 mm(3) on the right side (P < 0.001). The increase in olfactory bulb volume correlated significantly with an increase in odour thresholds (r = 0.60, P = 0.006, left side; r = 0.49, P = 0.03, right side), but not with changes in odour discrimination or odour identification. Results of this study support the idea that stimulation of olfactory receptor neurons impacts on the cell death in the olfactory bulb, not only in rodents but also in humans. To our knowledge, this is the first longitudinal study that describes an enlargement of the human olfactory bulb due to improvement of peripheral olfactory function.", "author" : [ { "dropping-particle" : "", "family" : "Gudziol", "given" : "V.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buschh\u00fcter", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abolmaali", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerber", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rombaux", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Brain", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "3096-3101", "title" : "Increasing olfactory bulb volume due to treatment of chronic rhinosinusitis-a longitudinal study", "type" : "article-journal", "volume" : "132" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "82", "plainTextFormattedCitation" : "82", "previouslyFormattedCitation" : "82" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }82,ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/0306-4522(92)90150-Z", "ISBN" : "0306-4522 (Print)\\r0306-4522 (Linking)", "ISSN" : "03064522", "PMID" : "1372114", "abstract" : "The blood supply to the brain has been linked closely to nervous system function and metabolism, thereby possibly playing a direct role in brain maturation. Previously, we demonstrated that closure of an external naris early in life results in large changes within the olfactory bulb, including reductions in laminar volume and cell number and a rapid decline in metabolism and protein synthesis. To understand the role of the blood supply in the dramatic changes following naris closure, the present study examines the development of olfactory bulb vasculature in unilaterally odor-deprived and control rats. On post-partum day 1 (P1; the day after birth), littermate rat pups underwent either unilateral naris occlusion or sham surgery. On P5, P10, P15, P20, P30 and P60, animals were perfused with an india ink-gelatin mixture to assess blood vessel amount and complexity. Densitometric analyses were performed to obtain values of blood vessel area ratios (vessel area/tissue area), branch point number and branch point density. Considerable vessel development in all bulbs occurred over the first two to three weeks post-partum. By P20, large reductions in vessel area ratios were observed in all constituent laminae of deprived bulbs. While similar reductions in number of vessel branch points/tissue area were seen, few changes were noted in the number of branch points/vessel area. The effects were primarily confined to early developmental periods: bulb vasculature in animals deprived at older ages (P40) appeared normal. The results indicate that the vasculature responds to alterations in sensory stimulation early in life, therefore potentially playing an important regulative role in neural development. \u00a9 1991.", "author" : [ { "dropping-particle" : "", "family" : "Korol", "given" : "D. L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brunjes", "given" : "P. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Neuroscience", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "1992" ] ] }, "page" : "631-641", "title" : "Unilateral naris closure and vascular development in the rat olfactory bulb", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "156", "plainTextFormattedCitation" : "156", "previouslyFormattedCitation" : "156" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }156,ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Gudden", "given" : "B", "non-dropping-particle" : "von", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archiv f Psychiatrie u Nervenkrankheiten", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "1870" ] ] }, "page" : "693-723", "title" : "Experimentaluntersuchungen ueber das periphere und zentrale Nervensystem", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "157", "plainTextFormattedCitation" : "157", "previouslyFormattedCitation" : "157" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }157).Other disorders associated with olfactory dysfunctionOther disorders associated with olfactory dysfunction may include intranasal or intracranial neoplasms, nasal surgery (e.g., septoplasty ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "03000729", "PMID" : "15626251", "abstract" : "AIM: Aim of the study was to evaluate septoplasty-related changes of lateralised olfactory function during both early and late postoperative periods in comparison to the preoperative situation. MATERIAL/METHODS: Lateralised olfactory function was assessed in 30 patients using the \"Sniffin' Sticks\" test battery. Measurements were performed preoperatively, and 4 and 9 months postoperatively. RESULTS: Prior to septal surgery measurements revealed significantly higher odor thresholds for the obstructed nostril compared to contralateral thresholds. No such observations were made for suprathreshold measures. Postoperatively, a significant decline of odor discrimination was found in comparison to the preoperative situation. However, there was no significant change of odor thresholds and odor identification function during the 9-month postoperative follow up. On an individual basis, one of the initially normosmic patients became hyposmic following surgery. CONCLUSIONS: The present data indicate that odor thresholds, but not suprathreshold olfactory function, are related to nasal obstruction resulting from septal deviation. In contrast, postoperative changes were only seen for odor discrimination. Apart from psychological explanations of this finding, it may be hypothesized that these observations result from changes in intranasal airflow following surgery.", "author" : [ { "dropping-particle" : "", "family" : "Pfaar", "given" : "O.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "H\u00fcttenbrink", "given" : "K. B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "195-199", "title" : "Assessment of olfactory function after septoplasty: A longitudinal study", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "158", "plainTextFormattedCitation" : "158", "previouslyFormattedCitation" : "158" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }158), endocrine disorders (such as Addison’s Disease, Turner’s Syndrome or hypothyroidism), metabolic disorders such as diabetes mellitus, hypertension, vitamin B12 deficiency, dysfunction as a complication of surgery (for example anterior skull base operations) (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0-8247-0719-2", "author" : [ { "dropping-particle" : "", "family" : "Murphy", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doty", "given" : "Richard L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duncan", "given" : "H J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "chapter-number" : "22", "container-title" : "Handbook of Olfaction and Gustation", "edition" : "3rd", "editor" : [ { "dropping-particle" : "", "family" : "Doty", "given" : "Richard L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "461-478", "publisher" : "Marcel Dekker", "publisher-place" : "New York", "title" : "Clinical disorders of olfaction", "type" : "chapter" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "16", "plainTextFormattedCitation" : "16", "previouslyFormattedCitation" : "16" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }16,ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1177/0003319714520956", "ISBN" : "1940-1574 (Electronic) 0003-3197 (Linking)", "ISSN" : "1940-1574", "PMID" : "24554429", "abstract" : "We evaluated olfactory dysfunction in 154 adults (74 men, mean age 60.9+/-11.9 years), of whom 119 had type 2 diabetes mellitus (T2DM). Olfactory function was assessed with \"Sniffin' Sticks.\" A total Threshold-Discrimination-Identification (TDI) score was calculated. Type 2 diabetes mellitus, hypertension, and hyperlipidemia were associated with lower olfactory scores (all TDI scores<0.001). Age was negatively associated with odor threshold, odor identification, and TDI score (P=.009, <.001, and <.001, respectively). After adjusting for age, gender, body mass index, smoking, alcohol, diabetes, hypertension, hyperlipidemia, and cardiovascular disease, only T2DM and hypertension were associated with TDI score (R square=0.281). Diabetic complications were associated with olfactory dysfunction (P=.006): TDI scores were lower in the presence of diabetic peripheral neuropathy (P=.017) and retinopathy (P=.047). In conclusion, T2DM and hypertension are independently associated with olfactory dysfunction while diabetic peripheral neuropathy and retinopathy are significantly associated with lower olfactory scores. The clinical relevance of these findings needs to be further examined.", "author" : [ { "dropping-particle" : "", "family" : "Gouveri", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katotomichelakis", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gouveris", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Danielides", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maltezos", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papanas", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Angiology", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "869-876", "title" : "Olfactory dysfunction in type 2 diabetes mellitus: an additional manifestation of microvascular disease?", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "159", "plainTextFormattedCitation" : "159", "previouslyFormattedCitation" : "159" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }159,ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1227/NEU.0b013e318282a535", "ISBN" : "1524-4040 (Electronic)\\r0148-396X (Linking)", "ISSN" : "1524-4040", "PMID" : "23246823", "abstract" : "BACKGROUND:: Endoscopic skull base surgery is now the preferred treatment option to remove skull base tumors. OBJECTIVE:: To evaluate the patient's sense of smell and mucociliary clearance time (MCT) after skull base surgery. METHODS:: Patients with pituitary adenoma underwent a Transnasal Transphenoidal Endoscopic Approach (TTEA Group, N=36), while patients with other benign parasellar tumors underwent an Expanded Endonasal Approach (EEA Group, N=14) with a vascularized septal flap (VSF). Assessment of symptoms (Visual Analogue Scale, VAS), olfactometry (Barcelona Smell Test, BAST-24), and MCT (Saccharin test) were performed before and 3 months after surgery. RESULTS:: Before surgery, patients reported poorer BAST-24 scores on detection, identification, and forced choice than the healthy population, while both study groups had similar sinonasal symptoms, BAST-24, and MCT scores. After surgery, no changes in symptom scores (VAS) were observed except for the loss of smell (26.7\u00b130.5 mm, p<0.05) and posterior nasal discharge (29.7\u00b130.3 mm, p<0.05) compared to baseline (5.2\u00b111.3, 19.1\u00b125.3, respectively). EEA patients reported higher loss of smell and posterior nasal discharge compared to TTEA. TTEA and EEA groups had similar scores on post-operative BAST-24. After surgery, however, patients showed prolonged Saccharin test (15.6\u00b110.8 min, p<0.05) compared to baseline (8.4\u00b14.4 min). In addition, EEA reported longer MCT than TTEA patients. CONCLUSION:: EEA but not TTEA has a short-term (3 months) negative impact on patient's olfaction and mucociliary clearance. Patients should be informed about smell loss as a consequence of skull base surgery to prevent legal claims. Likewise, further research and some modifications on reconstruction flaps are encouraged to avoid damaging the olfactory neuroepithelium.", "author" : [ { "dropping-particle" : "", "family" : "Alobid", "given" : "Isam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ense\u00f1at", "given" : "Joaquim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mari\u00f1o-S\u00e1nchez", "given" : "Franklin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Notaris", "given" : "Matteo", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Centellas", "given" : "Silvia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mullol", "given" : "Joaquim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bernal-Sprekelsen", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Neurosurgery", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "540-6", "title" : "Impairment of Olfaction and Mucociliary Clearance After Expanded Endonasal Approach Using Vascularised Septal Flap Reconstruction for Skull Base Tumors.", "type" : "article-journal", "volume" : "72" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "160", "plainTextFormattedCitation" : "160", "previouslyFormattedCitation" : "160" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }160) or surgery resulting in decreased airflow to the olfactory cleft (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1001/archotol.133.7.650", "ISBN" : "0886-4470", "ISSN" : "0886-4470 (Print)", "PMID" : "17638776", "abstract" : "OBJECTIVE: To assess the long-term results of the nasal airflow-inducing maneuver in olfaction rehabilitation in patients who had undergone laryngectomy. DESIGN: Prospective interventional study. SETTING: University hospital. PATIENTS: Twenty-four patients who had undergone laryngectomy (21 men and 3 women; mean age, 68 years) who received olfactory rehabilitation with the nasal airflow-inducing maneuver were reevaluated 6 and 12 months after primary treatment. MAIN OUTCOME MEASURE: Olfactory function was tested by means of a semistructured interview; the Questionnaire on Olfaction, Taste and Appetite; and the Scandinavian Odor-Identification Test. Quality of life was measured with the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-H&N35 questionnaires. Patients were categorized as smellers or nonsmellers based on results of the Scandinavian Odor-Identification Test. RESULTS: Before treatment, 10 of 24 patients (42%) were smellers and 14 (58%) were nonsmellers. At 6-month follow-up, 20 of 23 patients (87%) were smellers, whereas after 12 months, 21 of 24 patients (88%) were smellers. Long-term olfaction rehabilitation was achieved in 11 of 14 patients (79%) with anosmia, and 15 of all 24 patients (63%) could be classified as having normal olfactory capacity at the end of the study. CONCLUSION: The nasal airflow-inducing maneuver is a patient-friendly, inexpensive, and effective method for restoring the sense of smell in patients after laryngectomy, and the results persist in the long term.", "author" : [ { "dropping-particle" : "", "family" : "Risberg-Berlin", "given" : "Birgit", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moller", "given" : "Riitta Ylitalo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Finizia", "given" : "Caterina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of otolaryngology--head & neck surgery", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "650-654", "title" : "Effectiveness of olfactory rehabilitation with the nasal airflow-inducing maneuver after total laryngectomy: one-year follow-up study.", "type" : "article-journal", "volume" : "133" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "161", "plainTextFormattedCitation" : "161", "previouslyFormattedCitation" : "161" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }161). Psychiatric conditions (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.neubiorev.2008.05.003", "ISBN" : "0149-7634", "ISSN" : "01497634", "PMID" : "18555528", "abstract" : "Cognitive deficits are well documented in psychiatric disorders, particularly in schizophrenia and depression. Cognitive activity roots in perceptions. However, research on sensorial alterations in psychiatric conditions has mainly focused on visual or auditory processes and less on olfaction. Here, we examine data on olfactory deficits in psychiatric patients using a systematic review of recent publications. Schizophrenic patients are mainly characterized by no reliable change in odour sensitivity and by a deficit in odour identification, recognition and discrimination. Depressed patients principally exhibit a deficit in the hedonic aspects of this perception, even if, in some case, alterations in sensitivity or identification are also found. Changes in odour perception are also found in dementia and in some neurodegenerative disease, but in this case alterations concern all aspects of the sensorial experience (detection threshold, identification and recognition). Taken together, these data indicate that olfactory abnormalities might be a marker of psychiatric conditions, with a specific pattern for each disease. ?? 2008 Elsevier Ltd. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Atanasova", "given" : "Boriana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graux", "given" : "J??r??me", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hage", "given" : "Wissam", "non-dropping-particle" : "El", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hommet", "given" : "Caroline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Camus", "given" : "Vincent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Belzung", "given" : "Catherine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Neuroscience and Biobehavioral Reviews", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "1315-1325", "title" : "Olfaction: A potential cognitive marker of psychiatric disorders", "type" : "article-journal", "volume" : "32" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.ijpsycho.2013.07.003", "ISBN" : "0167-8760", "ISSN" : "01678760", "PMID" : "23856353", "abstract" : "Smell identification deficits (SIDs) are relatively specific to schizophrenia and its negative symptoms, and may predict transition to psychosis in clinical high-risk (CHR) individuals. Moreover, event-related potentials (ERPs) to odors are reduced in schizophrenia. This study examined whether CHR patients show SIDs and abnormal olfactory N1 and P2 potentials. ERPs (49 channels) were recorded from 21 CHR and 20 healthy participants (13 males/group; ages 13-27years) during an odor detection task using three concentrations of hydrogen sulfide (H2S) or blank air presented unilaterally by a constant-flow olfactometer. Neuronal generator patterns underlying olfactory ERPs were identified and measured by principal components analysis (unrestricted Varimax) of reference-free current source densities (CSD). Replicating previous findings, CSD waveforms to H2S stimuli were characterized by an early N1 sink (345ms, lateral-temporal) and a late P2 source (600ms, mid-frontocentroparietal). N1 and P2 varied monotonically with odor intensity (strong>medium>weak) and did not differ across groups. Patients and controls also showed comparable odor detection and had normal odor identification and thresholds (Sniffin' Sticks). However, olfactory ERPs strongly reflected differences in odor intensity and detection in controls, but these associations were substantially weaker in patients. Moreover, severity of negative symptoms in patients was associated with reduced olfactory ERPs and poorer odor detection, identification and thresholds. Three patients who developed psychosis had poorer odor detection and thresholds, and marked reductions of N1 and P2. Thus, despite the lack of overall group differences, olfactory measures may be of utility in predicting transition to psychosis among CHR patients. ?? 2013 Elsevier B.V.", "author" : [ { "dropping-particle" : "", "family" : "Kayser", "given" : "J??rgen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tenke", "given" : "Craig E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kroppmann", "given" : "Christopher J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alschuler", "given" : "Daniel M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ben-David", "given" : "Shelly", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fekri", "given" : "Shiva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruder", "given" : "Gerard E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Corcoran", "given" : "Cheryl M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Psychophysiology", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "190-206", "title" : "Olfaction in the psychosis prodrome: Electrophysiological and behavioral measures of odor detection", "type" : "article-journal", "volume" : "90" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "162,163", "plainTextFormattedCitation" : "162,163", "previouslyFormattedCitation" : "162,163" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }162,163) and migraine (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/BF00313864", "ISBN" : "0340-5354 (Print)\\r0340-5354 (Linking)", "ISSN" : "0340-5354", "PMID" : "4056833", "abstract" : "Osmophobia or hyperosmia featured in 25 of 50 migraineurs during the headache phase of their attacks. Pleasant or unpleasant odours could precipitate migraines in 11 patients in this series. Other sensory disturbances and precipitants were also studied. Neurological precipitation of attacks provides further support for a primary neural rather than a vascular pathogenesis of migraine.", "author" : [ { "dropping-particle" : "", "family" : "Blau", "given" : "J N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Solomon", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Neurology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1985" ] ] }, "page" : "275-6", "title" : "Smell and other sensory disturbances in migraine.", "type" : "article-journal", "volume" : "232" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1046/j.1468-2982.1997.1707729.x", "ISBN" : "0333-1024", "ISSN" : "03331024", "PMID" : "9399001", "abstract" : "Olfactory thresholds for acetone and vanillin and the unpleasantness rating of concentrated acetone were measured in 20 migraine sufferers and 21 controls. The olfactory threshold for vanillin was lower in migraine sufferers than in controls. In addition, patients who reported that odours frequently seemed stronger during attacks of migraine were able to detect acetone at a lower concentration than most other patients. No differences were found between migraine sufferers and controls for ratings of the unpleasantness of concentrated acetone. These findings suggest that hyperacuity to odours persists between episodes of migraine. Sensitivity to odours could contribute to the migraine predisposition.", "author" : [ { "dropping-particle" : "", "family" : "Snyder", "given" : "R. D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drummond", "given" : "P. D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cephalalgia", "id" : "ITEM-2", "issue" : "7", "issued" : { "date-parts" : [ [ "1997" ] ] }, "page" : "729-732", "title" : "Olfaction in migraine", "type" : "article-journal", "volume" : "17" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "13,164", "plainTextFormattedCitation" : "13,164", "previouslyFormattedCitation" : "13,164" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }13,164) have also been linked to dysfunction as has radiotherapy (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.radonc.2005.09.015", "ISBN" : "0167-8140", "ISSN" : "01678140", "PMID" : "2005533415", "abstract" : "Background and Purpose: Changes in olfactory function have been reported in patients receiving significant doses of radiation to the olfactory epithelium. Aim of this study was to investigate severity and time course of changes in olfactory function in patients irradiated for tumours of the head and neck region. Material and Methods: Forty-four patients receiving radiotherapy (RT) for tumours in the area of the head and neck participated (16 women, 28 men; age 11-81 y; mean 55 y). Olfactory function was measured before and bi-weekly during RT for 6 weeks. A subgroup (25 patients) was followed for 12 months. Patients were divided into two groups according to the dose to the olfactory epithelium. Twenty-two patients ('OLF group') had radiation doses to the olfactory epithelium between 23.7 and 79.5 Gy (median 62.2 Gy). In the 22 patients of the 'non-OLF group' the dose applied to the olfactory epithelium was significantly lower (2.9-11.1 Gy, median 5.9 Gy). Total tumour dose (30-76.8 Gy), age, sex distribution, and baseline chemosensory function were not significantly different between groups. Testing was performed for odour identification, odour discrimination, and olfactory thresholds. Results: Odour discrimination, but not odour identification or odour threshold, was significantly decreased 2-6 weeks after begin of therapy in the OLF group. In addition, a significant effect of the radiation dose was observed for odour discrimination. More than 6 months after therapy, OLF group patients had significantly lower odour identification scores compared to the non-OLF group. Conclusion: As indicated through the non-significant change of olfactory thresholds, the olfactory epithelium is relatively resistant against effects of radiation. It is hypothesized that RT has additional effects on the olfactory bulb/orbitofrontal cortex responsible for the observed changes of suprathreshold olfactory function. ?? 2005 Elsevier Ireland Ltd. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Holscher", "given" : "Tobias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seibt", "given" : "Annedore", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Appold", "given" : "Steffen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dorr", "given" : "Wolfgang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herrmann", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huttenbrink", "given" : "Karl Bernd", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Radiotherapy and Oncology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "157-163", "title" : "Effects of radiotherapy on olfactory function", "type" : "article-journal", "volume" : "77" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "165", "plainTextFormattedCitation" : "165", "previouslyFormattedCitation" : "165" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }165) or alcohol dependence (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/01.ALC.0000057945.57330.2C", "ISBN" : "1530-0277", "ISSN" : "0145-6008", "PMID" : "12658108", "abstract" : "BACKGROUND: Various olfactory deficits have been reported in the alcohol-induced amnestic syndrome (Korsakoff's syndrome). Less is known about olfactory functioning in nonamnesic and nondemented alcoholic patients. METHODS: Olfactory performance of 30 alcohol-dependent patients was assessed unirhinally using the Sniffin' Sticks (threshold, discrimination, identification, composite TDI score) and compared with that of 30 healthy controls, matched for sex, age, and smoking status. RESULTS: Patients showed significantly reduced olfactory sensitivity (higher threshold), discrimination, and identification compared with controls. No group differences were observed in laterality. Identification and discrimination group differences remained significant after controlling for differences in sensitivity. Olfactory deficits in patients were present independent of age, gender, and duration of abstinence (<3 months) and were not attributable to smoking or general cognitive abilities. More than half of the patients (56.7%) could be classified as hyposmic. Lower overall olfactory functioning (TDI) was associated with longer duration of a regular alcohol intake and higher values of gamma-glutamyltransferase (GGT). CONCLUSIONS: Olfactory dysfunction is common in nonamnesic and nondemented patients with alcohol dependence. Results suggest a detrimental effect of alcohol on central olfactory processing.", "author" : [ { "dropping-particle" : "", "family" : "Rupp", "given" : "Claudia I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kurz", "given" : "Martin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kemmler", "given" : "Georg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mair", "given" : "Dolores", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hausmann", "given" : "Armand", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hinterhuber", "given" : "Hartmann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fleischhacker", "given" : "W Wolfgang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Alcoholism, clinical and experimental research", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "432-9", "title" : "Reduced olfactory sensitivity, discrimination, and identification in patients with alcohol dependence.", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1371/journal.pone.0023190", "ISBN" : "1932-6203", "ISSN" : "19326203", "PMID" : "21858026", "abstract" : "BACKGROUND: Olfactory abilities are now a flourishing field in psychiatry research. As the orbitofrontal cortex appears to be simultaneously implicated in odour processing and executive impairments, it has been proposed that olfaction could constitute a cognitive marker of psychiatric states. While this assumption appears promising, very few studies have been conducted on this topic among psychopathological populations. The present study thus aimed at exploring the links between olfaction and executive functions. These links were evaluated using two tasks of comparable difficulty, one known to rely on orbitofrontal cortex processing (i.e., a confabulation task), and one not associated with this area (i.e., Stop-Signal task).\\n\\nMETHODOLOGY/PRINCIPAL FINDINGS: Twenty recently detoxified alcoholic individuals and twenty paired controls took part in an experiment evaluating olfactory abilities and executive functioning (i.e., Stop-Signal task and confabulation task). Comorbidities and potential biasing variables were also controlled for. Alcoholic individuals exhibited impaired performance for high-level olfactory processing and significant confabulation problems as compared to controls (but no deficit in Stop-Signal task), even when the influence of comorbidities was taken into account. Most importantly, olfactory abilities and confabulation rates were significantly correlated in both groups.\\n\\nCONCLUSIONS/SIGNIFICANCE: Alcoholism jointly leads to olfactory and memory source impairments, and these two categories of deficits are associated. These results strongly support the proposition that olfactory and confabulation measures both index orbitofrontal functioning, and suggest that olfaction could become a reliable cognitive marker in psychiatric disorders. Moreover, it underlines the need to take into account these olfactory and source memory impairments in a clinical context.", "author" : [ { "dropping-particle" : "", "family" : "Maurage", "given" : "Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Callot", "given" : "Christophe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chang", "given" : "Betty", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Philippot", "given" : "Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rombaux", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Timary", "given" : "Philippe", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "id" : "ITEM-2", "issue" : "8", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "2-8", "title" : "Olfactory impairment is correlated with confabulation in alcoholism: Towards a multimodal testing of orbitofrontal cortex", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.biopsycho.2011.06.004", "ISSN" : "03010511", "PMID" : "21718751", "abstract" : "Olfactory abilities are crucial in the development and maintenance of alcoholism, but while they have been widely explored in other psychiatric states, little is known concerning this sensorial modality among alcoholics. The present study explored the brain correlates of the olfaction deficit in alcoholism. Ten alcoholics and ten matched controls took part in psychophysical and electrophysiological olfactory testing. At behavioural level, we showed odor identification deficits in alcoholism, for orthonasal and retronasal testing. Electrophysiological data showed abnormalities (in latency and amplitude) for N1 and P2 olfactory components among alcoholics, which constitutes the first description of the cerebral correlates of olfactory impairments in alcoholism. This deficit appears associated with alterations in the brain structures responsible for the secondary, \"cognitive\" processing of odors. These results underline the need to take into account olfactory deficits in clinical practice and in studies exploring brain correlates of craving by means of alcohol odors. ?? 2011 Elsevier B.V.", "author" : [ { "dropping-particle" : "", "family" : "Maurage", "given" : "Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Callot", "given" : "Christophe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Philippot", "given" : "Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rombaux", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Timary", "given" : "Philippe", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biological Psychology", "id" : "ITEM-3", "issue" : "1", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "28-36", "publisher" : "Elsevier B.V.", "title" : "Chemosensory event-related potentials in alcoholism: A specific impairment for olfactory function", "type" : "article-journal", "volume" : "88" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "166\u2013168", "plainTextFormattedCitation" : "166\u2013168", "previouslyFormattedCitation" : "166\u2013168" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }166–168). The role of smoking/nicotine in olfactory loss remains controversial. Several previous studies have demonstrated a dose-dependent, negative effect of smoking on olfactory function (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00415-008-0807-9", "ISBN" : "0041500808079", "ISSN" : "03405354", "PMID" : "18677645", "abstract" : "BACKGROUND: The aim of this study was to evaluate the effect of smoking on taste and smell impairment in a large population- based study.\\n\\nSTUDY DESIGN: Cross-sectional survey in Dortmund, Germany.\\n\\nMETHODS: The population sample was randomly drawn from the city's central registration office. Following a standardized interview, validated taste and smell tests were performed. Descriptive statistics and logistic regression was used in the analysis.\\n\\nRESULTS: Among the 1312 study participants, 3.6 % were functionally anosmic, and 18 % had olfactory dysfunction. Approximately 20 % recognized only three or less of the four tastes when presented at suprathreshold concentrations, indicating signs of taste impairment. Current smoking in general increased the risk for impairment of olfactory function (odds ratio 1.71, 95 % CI 1.19-2.47), but not the risk for taste impairment. Heavy smokers of 20 or more cigarettes/day had significant increased risks for impairment in both senses.\\n\\nCONCLUSIONS: Our results reveal that both olfactory and gustatory function are compromised in a significant proportion of the general population. Smoking increases significantly the risk of impairment of olfactory function. Our findings add an important detail to the large body of evidence that describes adverse health effects of smoking.", "author" : [ { "dropping-particle" : "", "family" : "Vennemann", "given" : "M. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berger", "given" : "K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Neurology", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "1121-1126", "title" : "The association between smoking and smell and taste impairment in the general population", "type" : "article-journal", "volume" : "255" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0098-7484", "PMID" : "2304239", "abstract" : "Little is known about the influence of cigarette smoking on the ability to smell; previous studies on this topic have led to contradictory findings and have failed to take into account smoking dose and duration. In the present study, the 40-odorant University of Pennsylvania Smell Identification Test was administered to 638 subjects for whom detailed smoking histories were available. Smoking was found to be adversely associated with odor identification ability in a dose-related manner in both current and previous cigarette smokers. Among previous smokers, improvement in olfactory function was related to the time elapsed since the cessation of smoking. Logistic regression analysis found current smokers to be nearly twice as likely to evidence an olfactory deficit than persons who have never smoked. Overall, the data suggest that (1) smoking causes long-term but reversible adverse effects on the ability to smell and (2) the failure of some studies to demonstrate smoking effects may be caused by the inclusion of persons with a history of smoking in the nonsmoking groups.", "author" : [ { "dropping-particle" : "", "family" : "Frye", "given" : "R E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwartz", "given" : "B S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doty", "given" : "R L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "JAMA", "id" : "ITEM-2", "issue" : "9", "issued" : { "date-parts" : [ [ "1990", "3", "2" ] ] }, "page" : "1233-6", "title" : "Dose-related effects of cigarette smoking on olfactory function.", "type" : "article-journal", "volume" : "263" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISBN" : "0300-0729 (Print)\\r0300-0729 (Linking)", "ISSN" : "03000729", "PMID" : "18085020", "abstract" : "Although smoking is a widely spread habit, its effect on olfaction has not been clearly established. The aim of this study was to investigate the effect of cigarette smoking on the olfactory function, using the \"Sniffin' Sticks\" test. Sixty-five smokers were studied, with a median period of smoking of 10 years (range: 1-45 years) and a median number of 15 cigarettes smoked per day (range: 5-20). Forty-nine non-smokers were used as controls. Olfactory function was evaluated using the \"Sniffin' Sticks\" test, which consists of odour threshold (OT), odour discrimination (OD) and odour identification (OI) and its overall results may be presented as a composite threshold-discrimination-identification (TDI) score. Multivariate linear and logistic regression analyses were performed. All OT, OD, OI and TDI scores were statistically significantly lower in smokers compared to non-smokers, even when controlled for gender and age. Low OT, OD, OI and TDI scores were more prevalent among smokers than non-smokers. Multivariate logistic regression analysis, adjusted for gender and age, revealed that smoking remained a strong independent risk factor for low OT, OD, OI and TDI scores. Among smokers, statistically significant negative relationships were found between pack-years and OT, OD, OI and TDI, controlling for age. In conclusion, smoking was found to be adversely associated with the olfactory ability in a dose-related manner. Smokers were found to be nearly six times as likely to evidence an olfactory deficit as non smokers, depending on the duration and the amount of cigarettes smoked.", "author" : [ { "dropping-particle" : "", "family" : "Katotomichelakis", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balatsouras", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tripsianis", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davris", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maroudias", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Danielides", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Simopoulos", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "273-280", "title" : "The effect of smoking on the olfactory function", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "29,169,170", "plainTextFormattedCitation" : "29,169,170", "previouslyFormattedCitation" : "29,169,170" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }29,169,170). The underlying pathophysiology of this loss has been suggested to involve increased apoptosis of OSN (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/00005537-200408000-00012", "ISBN" : "0023-852X (Print)", "ISSN" : "0023852X", "abstract" : "OBJECTIVE: To investigate the effects of tobacco smoke on the olfactory epithelium. Cigarette smoking has been associated with hyposmia; however, the pathophysiology is poorly understood. The sense of smell is mediated by olfactory sensory neurons (OSNs) exposed to the nasal airway, rendering them vulnerable to environmental injury and death. As a consequence, a baseline level of apoptotic OSN death has been demonstrated even in the absence of obvious disease. Dead OSNs are replaced by the mitosis and maturation of progenitors to maintain sufficient numbers of neurons into adult life. Disruption of this balance has been suggested as a common cause for clinical smell loss. This current study will evaluate the effects of tobacco smoke on the olfactory mucosa, with emphasis on changes in the degree of OSN apoptosis. STUDY DESIGN: A rat model was used to assess the olfactory epithelium after exposure to tobacco smoke. METHODS: Rats were exposed to tobacco smoke alone (for 12 weeks), smoke plus dietary ethanol (for the final 5 weeks), or to neither (control). Immunohistochemical analysis of the olfactory epithelium was performed using an antibody to the active form of caspase-3. Positive staining for this form of the caspase-3 enzyme indicates a cell undergoing apoptotic proteolysis. RESULTS: Control rats demonstrated a low baseline level of caspase-3 activity in the olfactory epithelium. In contrast, tobacco smoke exposure triggered a dramatic increase in the degree of OSN apoptosis that affected all stages of the neuronal lineage. CONCLUSIONS: These results support the following hypothesis: smell loss in smokers is triggered by increased OSN death, which eventually overwhelms the regenerative capacity of the epithelium.", "author" : [ { "dropping-particle" : "", "family" : "Vent", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Robinson", "given" : "A M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gentry-Nielsen", "given" : "M J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Conley", "given" : "D B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hallworth", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leopold", "given" : "D A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kern", "given" : "R C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Laryngoscope", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "1383-1388", "title" : "Pathology of the olfactory epithelium: smoking and ethanol exposure", "type" : "article-journal", "volume" : "114" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "171", "plainTextFormattedCitation" : "171", "previouslyFormattedCitation" : "171" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }171) and/or replacement of the olfactory neuroepithelium with squamous metaplasia (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1177/0192623309338055", "ISBN" : "1533-1601 (Electronic)\r0192-6233 (Linking)", "ISSN" : "1533-1601", "PMID" : "19487255", "abstract" : "Few studies have examined the induction of squamous metaplasia in human olfactory nasal tissue caused by tobacco use and the implications it may have for olfaction, particularly when there are pre-existing insults, such as chronic rhinosinusitis (CRS). Quantitative histopathological analyses were performed on Alcian blue- and H&E-stained sections of nasal biopsies taken from the upper aspect of the middle turbinate of CRS patients. Chronic rhinosinusitis patients who were current smokers had a predominance of squamous metaplasia in the olfactory sensory epithelium, whereas CRS patients who were nonsmokers and were not exposed to secondhand cigarette smoke had a prevalence of goblet cell hyperplasia. In spite of this difference, the groups did not differ significantly in olfactory threshold sensitivity. The impact of primary cigarette smoke on olfaction and a possible role of squamous metaplasia in preserving olfactory neurogenesis are discussed.", "author" : [ { "dropping-particle" : "", "family" : "Yee", "given" : "Karen K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pribitkin", "given" : "Edmund a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cowart", "given" : "Beverly J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vainius", "given" : "Aldona a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klock", "given" : "Christopher T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rosen", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hahn", "given" : "Chang-Gyu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rawson", "given" : "Nancy E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Toxicologic pathology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "594-598", "title" : "Smoking-associated squamous metaplasia in olfactory mucosa of patients with chronic rhinosinusitis.", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "172", "plainTextFormattedCitation" : "172", "previouslyFormattedCitation" : "172" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }172). However, other work has shown either negligible (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1365-2621.1968.tb01364.x", "ISBN" : "1750-3841", "ISSN" : "1750-3841", "PMID" : "3899", "abstract" : "SUMMARY\u2014 The individual olfactory thresholds of 97 persons toward 18 odorants were analyzed statistically. There is a significant logarithmic deterioration with age, the average loss of sensitivity being 50% in 22 years. Any influence of sex or smoking is negligible.", "author" : [ { "dropping-particle" : "", "family" : "Venstrom", "given" : "Delpha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Amoore", "given" : "John E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Food Science", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "1968" ] ] }, "page" : "264-265", "title" : "Olfactory Threshold, in Relation to Age, Sex or Smoking", "type" : "article-journal", "volume" : "33" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "173", "plainTextFormattedCitation" : "173", "previouslyFormattedCitation" : "173" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }173), or indeed protective effects (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/bmjopen-2012-001256", "ISBN" : "2044-6055 (Electronic)", "ISSN" : "2044-6055", "PMID" : "23135536", "abstract" : "OBJECTIVES: To investigate olfaction in general population, prevalence of olfactory dysfunction and related risk factors.\\n\\nDESIGN: Cross-sectional population-based survey, distributing four microencapsulated odorants (rose, banana, musk and gas) and two self-administered questionnaires (odour description; epidemiology/health status).\\n\\nSETTING: The survey was distributed to general population through a bilingual (Catalan, Spanish) newspaper in Catalonia (Spain), on December 2003.\\n\\nPARTICIPANTS: Newspaper readers of all ages and gender; 9348 surveys were analysed from the 10 783 returned.\\n\\nMAIN OUTCOME MEASURES: Characteristics of surveyed population, olfaction by age and gender, smell self-perception and smell impairment risk factors. Terms normosmia, hyposmia and anosmia were used when participants detected, recognised or identified all four, one to three or none of the odours, respectively.\\n\\nRESULTS: Survey profile was a 43-year-old woman with medium-high educational level, living in a city. Olfaction was considered normal in 80.6% (detection), 56% (recognition/memory) and 50.7% (identification). Prevalence of smell dysfunction was 19.4% for detection (0.3% anosmia, 19.1% hyposmia), 43.5% for recognition (0.2% anosmia, 43.3% hyposmia) and 48.8% for identification (0.8% anosmia, 48% hyposmia). Olfaction was worse (p<0.0001) in men than in women through all ages. There was a significant age-related smell detection decline however smell recognition and identification increased up to fourth decade and declined after the sixth decade of life. Risk factors for anosmia were: male gender, loss of smell history and poor olfactory self-perception for detection; low educational level, poor self-perception and pregnancy for recognition; and older age, poor self-perception and history of head trauma and loss of smell for identification. Smoking and exposure to noxious substances were mild protective factors for smell recognition.\\n\\nCONCLUSIONS: Sense of smell in women is better than in men suggesting a learning process during life with deterioration in older ages. Poor self-perception, history of smell loss, head trauma and pregnancy are potential risk factors for olfactory disorders.", "author" : [ { "dropping-particle" : "", "family" : "Mullol", "given" : "Joaquim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alobid", "given" : "Isam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mari\u00f1o-S\u00e1nchez", "given" : "Franklin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Quint\u00f3", "given" : "Lloren\u00e7", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haro", "given" : "Josep", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bernal-Sprekelsen", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valero", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Picado", "given" : "C\u00e8sar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marin", "given" : "Concepci\u00f3", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMJ open", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "title" : "Furthering the understanding of olfaction, prevalence of loss of smell and risk factors: a population-based survey (OLFACAT study).", "type" : "article-journal", "volume" : "2:e001256" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "34", "plainTextFormattedCitation" : "34", "previouslyFormattedCitation" : "34" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }34) of smoking on olfaction. Work in rats has shown increased odour memory following treatment with nicotine agonists (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.neulet.2010.01.022", "ISSN" : "03043940", "PMID" : "20083163", "abstract" : "Nicotinic agonists have been shown to enhance performance in cognitive tasks based on attention and memory. The aim of this study was to use a test of olfactory working memory; the odour span task (OST) in rodents, to investigate the effects of subtype-specific nicotinic agonists on working memory in normal rats. Rats were trained in a non-matching to sample (NMTS) rule and then the full OST, which involved identifying a novel odour from an increasing number of presented odours. Male hooded Lister rats were treated with nicotine, selective nicotinic agonists or vehicle (saline). In order to validate the task, muscarinic and nicotinic receptor antagonists were also examined. Nicotine at both 0.05 and 0.1 mg/kg significantly increased mean span length in the OST. The selective ??4??2 nicotinic receptor agonist metanicotine (0.1 mg/kg s.c.) and the selective ??7 nicotinic receptor agonist (R)-N-(1-azabicyclo[2.2.2]oct-3-yl)(5-(2-pyridyl)thiophene-2-carboxamide) (compound A, 10 mg/kg i.p.) also improved performance. In contrast, mecamylamine and scopolamine significantly decreased mean span length. These findings suggest a role for the activation of both ??4??2 and ??7 subtypes of neuronal nicotinic receptor in mediating enhancements of olfactory working memory capacity in normal, non-compromised rats. These nicotinic receptor subtypes may therefore prove to be useful targets for the development of novel treatments for neuropsychiatric disorders that involve cognitive dysfunction. ?? 2010 Elsevier Ireland Ltd. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Rushforth", "given" : "Samantha L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Allison", "given" : "Claire", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wonnacott", "given" : "Susan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shoaib", "given" : "Mohammed", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Neuroscience Letters", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "114-118", "title" : "Subtype-selective nicotinic agonists enhance olfactory working memory in normal rats: A novel use of the odour span task", "type" : "article-journal", "volume" : "471" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "174", "plainTextFormattedCitation" : "174", "previouslyFormattedCitation" : "174" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }174), and it has been postulated that this may contribute to the aforementioned protective effects (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/bmjopen-2012-001256", "ISBN" : "2044-6055 (Electronic)", "ISSN" : "2044-6055", "PMID" : "23135536", "abstract" : "OBJECTIVES: To investigate olfaction in general population, prevalence of olfactory dysfunction and related risk factors.\\n\\nDESIGN: Cross-sectional population-based survey, distributing four microencapsulated odorants (rose, banana, musk and gas) and two self-administered questionnaires (odour description; epidemiology/health status).\\n\\nSETTING: The survey was distributed to general population through a bilingual (Catalan, Spanish) newspaper in Catalonia (Spain), on December 2003.\\n\\nPARTICIPANTS: Newspaper readers of all ages and gender; 9348 surveys were analysed from the 10 783 returned.\\n\\nMAIN OUTCOME MEASURES: Characteristics of surveyed population, olfaction by age and gender, smell self-perception and smell impairment risk factors. Terms normosmia, hyposmia and anosmia were used when participants detected, recognised or identified all four, one to three or none of the odours, respectively.\\n\\nRESULTS: Survey profile was a 43-year-old woman with medium-high educational level, living in a city. Olfaction was considered normal in 80.6% (detection), 56% (recognition/memory) and 50.7% (identification). Prevalence of smell dysfunction was 19.4% for detection (0.3% anosmia, 19.1% hyposmia), 43.5% for recognition (0.2% anosmia, 43.3% hyposmia) and 48.8% for identification (0.8% anosmia, 48% hyposmia). Olfaction was worse (p<0.0001) in men than in women through all ages. There was a significant age-related smell detection decline however smell recognition and identification increased up to fourth decade and declined after the sixth decade of life. Risk factors for anosmia were: male gender, loss of smell history and poor olfactory self-perception for detection; low educational level, poor self-perception and pregnancy for recognition; and older age, poor self-perception and history of head trauma and loss of smell for identification. Smoking and exposure to noxious substances were mild protective factors for smell recognition.\\n\\nCONCLUSIONS: Sense of smell in women is better than in men suggesting a learning process during life with deterioration in older ages. Poor self-perception, history of smell loss, head trauma and pregnancy are potential risk factors for olfactory disorders.", "author" : [ { "dropping-particle" : "", "family" : "Mullol", "given" : "Joaquim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alobid", "given" : "Isam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mari\u00f1o-S\u00e1nchez", "given" : "Franklin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Quint\u00f3", "given" : "Lloren\u00e7", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haro", "given" : "Josep", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bernal-Sprekelsen", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valero", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Picado", "given" : "C\u00e8sar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marin", "given" : "Concepci\u00f3", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMJ open", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "title" : "Furthering the understanding of olfaction, prevalence of loss of smell and risk factors: a population-based survey (OLFACAT study).", "type" : "article-journal", "volume" : "2:e001256" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "34", "plainTextFormattedCitation" : "34", "previouslyFormattedCitation" : "34" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }34). Smoking also likely causes nasal inflammation, providing another mechanism for olfactory dysfunction. Therefore, although it seems to be clear that smoking causes olfactory dysfunction in certain cases, at least for some aspects more research is needed. Idiopathic olfactory dysfunctionWhere an exhaustive assessment has revealed no clear underlying aetiology, olfactory dysfunction may be classified as idiopathic. Studies suggest that up to 16% of patients screened at smell and taste centres fall into this category (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.anorl.2013.03.006", "ISSN" : "1879730X", "PMID" : "24679542", "abstract" : "Introduction and aim There is a high prevalence of olfactory dysfunction in the general population. Several causes of olfactory dysfunction have been reported and this disorder is classically divided into sinonasal and non-sinonasal-related olfactory dysfunction. The aims of this study were firstly, to evaluate the frequency of the various aetiologies of olfactory dysfunction in a population of patients with non-sinonasal-related olfactory dysfunction and secondly, to evaluate the degree of olfactory impairment associated with these various aetiologies. Material and methods We retrospectively reviewed a cohort of 496 patients with non-sinonasal-related olfactory dysfunction. The aetiology of the olfactory dysfunction was recorded for each patient. The aetiology was determined by a complete clinical assessment, including medical history, complete otorhinolaryngological examination, psychophysical testing of olfactory function, recording of olfactory event-related potentials and brain magnetic resonance imaging. Six groups of patients were defined on the basis of the aetiology of the disease and orthonasal and retronasal psychophysical olfactory performances were evaluated in each group. Results Post-infectious and post-traumatic aetiologies were the most common causes, representing 37.9% and 33.1% of patients, respectively, followed by idiopathic (16.3%), congenital (5.9%), toxic (3.4%) and neurological (3.4%) olfactory dysfunction. Anosmia was significantly more frequent in congenital (93.1%) and post-traumatic (62.8%) olfactory dysfunction, whereas hyposmia was more frequent in the post-infectious group (59.6%). Orthonasal and retronasal olfactory function tests were significantly correlated in all groups except for the congenital group. Conclusions The data of this study confirm that the most common causes of non-sinonasal-related olfactory dysfunction are post-infectious and post-traumatic. Post-infectious olfactory dysfunction is mainly observed in middle-aged women and is mainly associated with hyposmia, whereas post-traumatic olfactory dysfunction is mainly observed in young men and is associated with a high rate of anosmia. ?? 2013 Elsevier Masson SAS.", "author" : [ { "dropping-particle" : "", "family" : "Fonteyn", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huart", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deggouj", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collet", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eloy", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rombaux", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Annals of Otorhinolaryngology, Head and Neck Diseases", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "87-91", "publisher" : "Elsevier Masson SAS", "title" : "Non-sinonasal-related olfactory dysfunction: A cohort of 496 patients", "type" : "article-journal", "volume" : "131" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "175", "plainTextFormattedCitation" : "175", "previouslyFormattedCitation" : "175" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }175). However, care should be employed when making this diagnosis, as some such cases may be due to asymptomatic upper respiratory infections, or in older patients early neurodegeneration. With respect to the latter, a multidisciplinary approach should be considered (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Sendon", "given" : "AM", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Olfato y Gusto. Enfoque multidisciplinario", "editor" : [ { "dropping-particle" : "", "family" : "Soler", "given" : "GM", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "223-230", "publisher" : "Acadia Editorial", "publisher-place" : "Buenos Aires", "title" : "Olfato, psicolog\u00eda y psicoan\u00e1lisis", "type" : "chapter" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "176", "plainTextFormattedCitation" : "176", "previouslyFormattedCitation" : "176" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }176). Further studies are needed in this area. Clinical Assessment The initial clinical assessment of the olfactory patient is of vital importance: from the history alone a diagnosis can usually be made. Accurate diagnosis is required not just to guide management but also to give prognostic information. This is particularly important in medico-legal cases. When assessing patients with chemosensory impairment, one should bear in mind the close association of smell and taste (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/joor.12395", "ISSN" : "13652842", "PMID" : "27061099", "abstract" : "Eating is an essential activity to get energy and necessary nutrients for living. While chewing, the food is broken down by the teeth and dissolved by saliva. Taste, flavour and texture are perceived during chewing and will contribute to the appreciation of the food. The senses of taste and smell play an important role in selecting nutritive food instead of toxic substances. Also visual information of a food product is essential in the choice and the acceptance of food products, whereas auditory information obtained during the chewing of crispy products will provide information on whether a product is fresh or stale. Food perception does not just depend on one individual sense, but appears to be the result from multisensory integration of unimodal signals. Large differences in oral physiology parameters exist among individuals, which may lead to differences in food perception. Knowledge of the interplay between mastication and sensory experience for groups of individuals is important for the food industry to control quality and acceptability of their products. Environment factors during eating, like TV watching or electronic media use, may also play a role in food perception and the amount of food ingested. Distraction during eating a meal may lead to disregard about satiety and fullness feelings and thus to an increased risk of obesity. Genetic and social/cultural aspects seem to play an important role in taste sensitivity and food preference. Males generally show larger bite size, larger chewing power and a faster chewing rhythm than females. The size of swallowed particles seems to be larger for obese individuals, although there is no evidence until now of an 'obese chewing style'. Elderly people tend to have fewer teeth and consequently a less good masticatory performance, which may lead to lower intakes of raw food and dietary fibre. The influence of impaired mastication on food selection is still controversial, but it is likely that it may at least cause adaptation in food choice. Systemic conditions, such as high blood pressure, diabetes and cancer, with or without medicine use, tend to be associated with taste and chewing alterations. However, definite conclusions seem hard to reach, as research protocols vary largely.", "author" : [ { "dropping-particle" : "", "family" : "Pereira", "given" : "L. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bilt", "given" : "A.", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Oral Rehabilitation", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "title" : "The influence of oral processing, food perception and social aspects on food consumption: A review", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "177", "plainTextFormattedCitation" : "177", "previouslyFormattedCitation" : "177" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }177). Where a patient complains of reduced or dysfunctional taste, often they are in fact suffering from olfactory impairment and describing consequent impact on flavour perception (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Deems", "given" : "DA", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doty", "given" : "RL", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Settle", "given" : "RG", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arch Otolaryngol Head Neck Surg", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1991" ] ] }, "page" : "519-521", "title" : "Smell and taste disorders, a study of 750 patients from the University of Pennsylvania Smell and Taste Center", "type" : "article-journal", "volume" : "117" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "95", "plainTextFormattedCitation" : "95", "previouslyFormattedCitation" : "95" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }95). For example, the patient may be complaining of retronasal olfactory dysfunction but unaware that they are also experiencing orthonasal impairment.HistoryThorough history taking should include:Specific impairmentIs the patient describing a problem with their sense of smell, taste with respect to flavour or taste with respect to basic gustatory attributes (sweet/salty/bitter/sour/umami)? Is their dysfunction quantitative, qualitative or both? If they are experiencing qualitative dysfunction, is this parosmia (stimulus present; parosmia absent when nares closed) or phantosmia (stimulus absent) or could there in fact be an internal stimulus, e.g., from the sinuses. If they are experiencing quantitative dysfunction, is this affecting all odours, or only specific odours, and how severe is their dysfunction in terms of frequency (i.e. daily or less) and intensity (i.e. functional anosmia or hyposmia)? What treatment have they had for their dysfunction to date, and has this been successful? OnsetSudden onset loss is more common in post-infectious or posttraumatic olfactory dysfunction, although in posttraumatic olfactory loss often there is a gap of days and weeks between the trauma and recognition of the deficit. Gradual onset is more often seen in sinonasal disease, neurodegenerative causes and aging.DurationDysfunction since childhood is likely to indicate congenital anosmia (and pertinent questions regarding other syndromic attributes should be considered). Longer duration of dysfunction may be a poor prognostic sign, particularly in cases of chronic rhinosinusitis and posttraumatic olfactory dysfunction. FluctuationOlfactory function fluctuates most markedly in cases due to inflammatory disease (CRS or allergy).Other nasal symptoms Common symptoms of sinonasal disease (e.g. CRS, allergy) should be assessed, including nasal obstruction, rhinorrhoea, postnasal drip, facial pain, sneezing and itching. Specific impairments and quality of lifeDoes the patient rely on their sense of smell professionally (e.g. chef, sommelier)? Is their dysfunction causing problems with interpersonal communication (particularly of note in mothers) or nutrition (including quantified weight change)? Does the patient describe anxiety or depression as a result of their dysfunction? If the patient is suffering from significant psychological effects, referral for appropriate assessment and management should be considered as appropriate. Does the patient live alone? If so, have they experienced any home accidents (e.g. fires, gas leaks etc.)? Such patients should be counselled regarding smoke and gas alarms and adherence to ‘use-by’ dates on foods. Past medical historyDirect questioning should include previous head injuries, upper respiratory tract infections, nasal or neurosurgery and any other chronic diseases that might affect olfaction. Specific questions regarding symptoms of undiagnosed neurodegenerative disease should be considered in older patients where there is clinical suspicion. Such patients should be referred to neurological services as appropriate (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s40520-015-0380-x", "ISSN" : "1720-8319", "author" : [ { "dropping-particle" : "", "family" : "Ottaviano", "given" : "Giancarlo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frasson", "given" : "Giuliana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nardello", "given" : "Ennio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Martini", "given" : "Alessandro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Aging Clinical and Experimental Research", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2016", "2", "24" ] ] }, "page" : "37-45", "publisher" : "Springer International Publishing", "title" : "Olfaction deterioration in cognitive disorders in the elderly", "type" : "article-journal", "volume" : "28" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "178", "plainTextFormattedCitation" : "178", "previouslyFormattedCitation" : "178" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }178).MedicationsCurrent and previous medication history (including chemotherapies) should be obtained as well as compliance. The latter may be important where medications are required for control of chronic conditions (such as L-thyroxine in hypothyroidism). Where a patient has previously been treated with corticosteroids with improvement in smell, it is likely that they are suffering from sinonasal disease.AllergiesAllergies to medications, seasonal, perennial and occupational environmental allergens should be assessed as well as treatment for these. Smoking and alcoholCurrent smoking and drinking may be associated with both reduced olfaction and taste. Toxins and occupational exposureExposure to toxins known to cause olfactory dysfunction should be assessed. Additionally, exposure to substances that increase the risk of malignancy should be considered (e.g. soft and hardwood dusts and sinonasal/nasopharyngeal carcinoma). Family history Family history of olfactory dysfunction may aid in a diagnosis of congenital dysfunction. In older patients, a family history of neurodegenerative diseases should be assessed (including PD and Alzheimer’s disease). Recommendations: Thorough clinical histories should be sought from all patients.Clinical ExaminationExamination should include a full ENT examination. In addition to anterior rhinoscopy, nasal endoscopy is desirable, ideally with a 0° Hopkin’s rod lens endoscope (4mm diameter or smaller) to start. A 30° endoscope may then be used to facilitate visualisation of the olfactory cleft, which is found in the superior nasal cavity, and bounded by the superior and middle turbinates laterally and superior nasal septum medially (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/00005537-200003000-00016", "ISBN" : "0023-852X (Print)\\r0023-852X (Linking)", "ISSN" : "0023-852X", "PMID" : "10718430", "abstract" : "OBJECTIVES/HYPOTHESIS: To functionally investigate the distribution of the olfactory epithelium in humans by means of the electro-olfactogram (EOG) and anatomically located biopsy specimens. STUDY DESIGN: Prospective, nonrandomized, investigational. METHODS: Supra-threshold EOG recordings were made on 12 healthy, trained volunteers (6 women, 6 men; age range, 21-48 y). Vanillin was used as the stimulus, since it exclusively excites olfactory receptor neurons. The EOG was recorded with tubular electrodes that were placed using thin-fiber endoscopic guidance. Biopsy specimens were obtained of anterosuperior nasal cavity mucosa in the same regions as the positive EOGs in 15 smell-tested patients (7 women, 8 men; age range, 22-60 y) during routine nasal and sinus surgery. This biopsied tissue was histologically processed and stained for olfactory and neural proteins. RESULTS: Viable responses to EOG testing were obtained in 7 of 12 subjects. In these seven subjects it was possible to identify nine sites above or below the anterior middle turbinate insertion where EOGs were obtained. The biopsy results showed mature olfactory receptor neurons in this same area. CONCLUSIONS: Human olfactory epithelium appears to be distributed more anteriorly than previously assumed.", "author" : [ { "dropping-particle" : "", "family" : "Leopold", "given" : "D A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwob", "given" : "J E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hong", "given" : "S C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Knecht", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kobal", "given" : "Gerd", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Laryngoscope", "id" : "ITEM-1", "issue" : "3 Pt 1", "issued" : { "date-parts" : [ [ "2000" ] ] }, "page" : "417-421", "title" : "Anterior distribution of human olfactory epithelium.", "type" : "article-journal", "volume" : "110" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "47", "plainTextFormattedCitation" : "47", "previouslyFormattedCitation" : "47" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }47). Whilst nasal decongestant may be used (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s002280050507", "ISBN" : "0031-6970 (Print)\\r0031-6970 (Linking)", "ISSN" : "00316970", "PMID" : "9832293", "abstract" : "OBJECTIVE: The placebo-controlled, randomized, double-blind study was performed to investigate dose-related effects of oxymetazoline on olfactory function during the course of the spontaneously occurring cold. METHODS: Drug effects were assessed using olfactory/ trigeminal event-related potentials (ERPs) and psychophysical measures (intensity ratings, odor discrimination, butanol threshold); nasal volume was monitored by means of acoustic rhinometry. The investigation was performed in 36 subjects (mean age 24.6 years). The subjects were assigned to treatment groups A, B or C (three groups with 12 subjects each; six women and six men per group). All the subjects received placebo on the left side; on the right side, group A subjects received placebo and group B and C subjects received 0.25 mg x ml(-1) and 0.5 mg x ml(-1) oxymetazoline, respectively. After onset of the rhinitis (day 0) measurements were performed on days 2, 4, 6 and 35. RESULTS: Oxymetazoline clearly produced an increase in nasal volume. However, during the 2-h observation period, effects produced by the two dosages were not significantly different. Despite the increase in nasal volume, oxymetazoline produced only an increase of the overall intensity of H2S stimuli; it had no systematic effect on other measures of olfactory or trigeminal function. In addition, after all the subjects had recovered from the cold, oxymetazoline had no significant main effect on olfactory/trigeminally mediated sensations. CONCLUSIONS: Oxymetazoline appeared to have neither negative nor major positive effects on intranasal chemosensory function. It is hypothesized that oxymetazoline needs to be applied locally to the area of the olfactory cleft in order to significantly improve olfaction during the course of the common cold.", "author" : [ { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rothbauer", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pauli", "given" : "E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kobal", "given" : "G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Journal of Clinical Pharmacology", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "1998" ] ] }, "page" : "521-528", "title" : "Effects of the nasal decongestant oxymetazoline on human olfactory and intranasal trigeminal function in acute rhinitis", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "179", "plainTextFormattedCitation" : "179", "previouslyFormattedCitation" : "179" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }179), it should be noted that topical anaesthetic may cause temporary olfactory dysfunction (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.clinph.2003.12.028", "ISSN" : "13882457", "PMID" : "15134706", "abstract" : "Objective Olfactory and trigeminal systems interact and contribute to the perception of odorants. This study was aimed at investigating the effect of local anesthesia on olfaction. Methods One percent of tetracaine on a cotton swab was applied intranasally at three different locations in 20 volunteers and 4% of lidocaine was applied to the olfactory cleft in a head-down position. Before and after anesthesia, self-assessment, psychometric testing and olfactory event-related potentials [OERPs, using H2S and phenyl ethyl alcohol (PEA)], and chemosomatosensory event-related potentials (CSSERPs, using CO 2) were examined. Results Anesthesia at all four locations significantly lowered the perceived self-assessment of olfaction, while using the cotton swab only anesthesia in the middle meatus elevated threshold (P=0.020), lowered discrimination (P=0.015) and prolonged OERP (PEA, P=0.008; H2S, P=0.016), as well as CSSERPs latencies (CO2, P=0.020). However, complete temporary anosmia was only achieved after applying 4% lidocaine into the olfactory cleft. Conclusions Intranasal anesthesia applied with a swab reduced self-assessment of olfaction but was unable to produce anosmia. Psychometric test results were concordant with changes in chemosensory event-related potentials. Significance Temporary anosmia is technically difficult to achieve but could be demonstrated for the first time using local anesthesia. Even though anesthesia influences self-assessment, measurable olfactory function can remain unchanged. \u00a9 2004 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Welge-L\u00fcssen", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wille", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Renner", "given" : "Bertold", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kobal", "given" : "Gerd", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Neurophysiology", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "1384-1391", "title" : "Anesthesia affects olfaction and chemosensory event-related potentials", "type" : "article-journal", "volume" : "115" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "180", "plainTextFormattedCitation" : "180", "previouslyFormattedCitation" : "180" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }180) and should therefore be avoided until after olfactory testing is performed.Features to note on endoscopy include:General nasal anatomy including inferior, middle and superior meati.Visibility of olfactory cleft, patency and any abnormalities thereof. Discharge, polyps, oedema, crusting, and scarring may be documented using the recently proposed Olfactory Cleft Endoscopy (OCES) Scale (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/alr.21655", "ISSN" : "20426976", "author" : [ { "dropping-particle" : "", "family" : "Soler", "given" : "Zachary M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hyer", "given" : "J. Madison", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karnezis", "given" : "Tom T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schlosser", "given" : "Rodney J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Forum of Allergy & Rhinology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2016", "3" ] ] }, "page" : "293-298", "title" : "The Olfactory Cleft Endoscopy Scale correlates with olfactory metrics in patients with chronic rhinosinusitis", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "181", "plainTextFormattedCitation" : "181", "previouslyFormattedCitation" : "181" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }181). The use of nasal decongestants may be helpful.Signs of acute or chronic rhinosinusitis (including oedema, discharge (mucopurulent or serous), nasal polyps, crusting, scarring). Traditional endoscopic staging of the paranasal sinuses in CRS can be performed using the Lund-Kennedy scoring system (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0096-8056", "ISSN" : "0096-8056", "PMID" : "7574265", "abstract" : "A method of quantifying the symptoms, radiologic data, and endoscopic findings in extensive sinus disease is proposed. It is intended to enable clinicians to classify patients with extensive sinus disease according to severity of disease and prognostic category. The rubric of extensive sinus disease, for scoring and staging, comprises recurrent acute sinusitis and chronic sinusitis, but not an isolated episode of acute sinusitis. The method assigns simple numeric scores to specific computed tomography findings, elements of surgical history, presence of defining symptoms of sinusitis, and endoscopic appearance. This quantitative system may be rationalized into a staging system.", "author" : [ { "dropping-particle" : "", "family" : "Lund", "given" : "V J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kennedy", "given" : "D W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Annals of otology, rhinology & laryngology. Supplement", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "1995" ] ] }, "page" : "17-21", "title" : "Quantification for staging sinusitis. The Staging and Therapy Group.", "type" : "article-journal", "volume" : "167" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "182", "plainTextFormattedCitation" : "182", "previouslyFormattedCitation" : "182" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }182) (a more recent endoscopic staging system specific to the olfactory cleft in patients with CRS has been developed and correlates with olfactory function (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/alr.21552", "ISSN" : "20426976", "author" : [ { "dropping-particle" : "", "family" : "Soler", "given" : "Zachary M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pallanch", "given" : "John F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sansoni", "given" : "Eugene Ritter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jones", "given" : "Cameron S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lawrence", "given" : "Lauren A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schlosser", "given" : "Rodney J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mace", "given" : "Jess C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Timothy L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Forum of Allergy & Rhinology", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2015", "9" ] ] }, "page" : "846-854", "title" : "Volumetric computed tomography analysis of the olfactory cleft in patients with chronic rhinosinusitis", "type" : "article-journal", "volume" : "5" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "183", "plainTextFormattedCitation" : "183", "previouslyFormattedCitation" : "183" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }183)). Other sinonasal abnormalities such as benign or malignant neoplasms. Where malignancy is suspected a full examination of the mucosal surfaces of the head and neck should be undertaken, so requiring thorough oral, pharyngeal and laryngeal examinations.Where a neurological aetiology is suspected, a full cranial nerve and peripheral nervous system examination should be undertaken. Tests of memory and cognition should be deferred to the appropriate neurological specialists (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Soler", "given" : "GM", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Olfato y Gusto. Enfoque multidisciplinario", "editor" : [ { "dropping-particle" : "", "family" : "Soler", "given" : "GM", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "65-76", "publisher" : "Acadia Editorial", "publisher-place" : "Buenos Aires", "title" : "Evaluaci\u00f3n cl\u00ednica del sentido del olfato: conceptos cl\u00ednicos b\u00e1sicos y explicaci\u00f3n del CCCRC o Test de Connecticut", "type" : "chapter" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "184", "plainTextFormattedCitation" : "184", "previouslyFormattedCitation" : "184" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }184) , although appropriate screening tests may be performed if feasible. Where an asymptomatic patient requires assessment for medico-legal purposes, for example prior to surgery (e.g. anterior skull base (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1227/NEU.0b013e318282a535", "ISBN" : "1524-4040 (Electronic)\\r0148-396X (Linking)", "ISSN" : "1524-4040", "PMID" : "23246823", "abstract" : "BACKGROUND:: Endoscopic skull base surgery is now the preferred treatment option to remove skull base tumors. OBJECTIVE:: To evaluate the patient's sense of smell and mucociliary clearance time (MCT) after skull base surgery. METHODS:: Patients with pituitary adenoma underwent a Transnasal Transphenoidal Endoscopic Approach (TTEA Group, N=36), while patients with other benign parasellar tumors underwent an Expanded Endonasal Approach (EEA Group, N=14) with a vascularized septal flap (VSF). Assessment of symptoms (Visual Analogue Scale, VAS), olfactometry (Barcelona Smell Test, BAST-24), and MCT (Saccharin test) were performed before and 3 months after surgery. RESULTS:: Before surgery, patients reported poorer BAST-24 scores on detection, identification, and forced choice than the healthy population, while both study groups had similar sinonasal symptoms, BAST-24, and MCT scores. After surgery, no changes in symptom scores (VAS) were observed except for the loss of smell (26.7\u00b130.5 mm, p<0.05) and posterior nasal discharge (29.7\u00b130.3 mm, p<0.05) compared to baseline (5.2\u00b111.3, 19.1\u00b125.3, respectively). EEA patients reported higher loss of smell and posterior nasal discharge compared to TTEA. TTEA and EEA groups had similar scores on post-operative BAST-24. After surgery, however, patients showed prolonged Saccharin test (15.6\u00b110.8 min, p<0.05) compared to baseline (8.4\u00b14.4 min). In addition, EEA reported longer MCT than TTEA patients. CONCLUSION:: EEA but not TTEA has a short-term (3 months) negative impact on patient's olfaction and mucociliary clearance. Patients should be informed about smell loss as a consequence of skull base surgery to prevent legal claims. Likewise, further research and some modifications on reconstruction flaps are encouraged to avoid damaging the olfactory neuroepithelium.", "author" : [ { "dropping-particle" : "", "family" : "Alobid", "given" : "Isam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ense\u00f1at", "given" : "Joaquim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mari\u00f1o-S\u00e1nchez", "given" : "Franklin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Notaris", "given" : "Matteo", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Centellas", "given" : "Silvia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mullol", "given" : "Joaquim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bernal-Sprekelsen", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Neurosurgery", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "540-6", "title" : "Impairment of Olfaction and Mucociliary Clearance After Expanded Endonasal Approach Using Vascularised Septal Flap Reconstruction for Skull Base Tumors.", "type" : "article-journal", "volume" : "72" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "160", "plainTextFormattedCitation" : "160", "previouslyFormattedCitation" : "160" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }160)), a full examination of the head and neck should be undertaken, including nasal endoscopy, though neurological examination can be omitted if appropriate. Recommendations:Patients with suspected olfactory loss should undergo a full examination of the head and neck, including rigid nasal endoscopy with small diameter endoscopes. Asymptomatic patients requiring assessment for medico-legal purposes should also undergo a full head and neck examination with endoscopy.Basic neurological examination should be undertaken where there is suspicion of an underlying neurological aetiology, though formal and detailed neurocognitive testing can be deferred to the appropriate specialists. Olfactory TestingThe method used for assessing olfactory function and dysfunction is vitally important with respect to accurate diagnosis, outcome reporting and tracking of olfactory changes over time. A limitation of the current literature base is the heterogeneity of assessment techniques used, with consequent effect on definitions of impairment and improvement. As highlighted in the epidemiology section above, this can lead, for example, to large differences in estimated prevalence rates, and impacts significantly on the generalisability of results, especially where non-standardised and potentially unreliable tests are used. In general, three different types of olfactory testing can be undertaken: Subjective, patient reported olfactory assessment.Psychophysical olfactory assessment.Olfactory assessment using electrophysiological studies or magnetic resonance imaging.Subjective AssessmentSubjective testing can be performed using visual analogue scales, Likert questionnaires, or as part of other outcome assessments. For example, the commonly used Sino-Nasal Outcome Test (SNOT-22) is a validated patient reported outcome measure for CRS, which assesses overall disease burden. However, this contains only one question regarding olfactory dysfunction (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1749-4486.2009.01995.x", "ISBN" : "1749-4478", "ISSN" : "17494478", "PMID" : "19793277", "abstract" : "OBJECTIVES: We set out to determine the psychometric validation of a disease-specific health related quality of life instrument for use in chronic rhinosinusitis, the 22 item Sinonasal Outcome Test (SNOT-22), a modification of a pre-existing instrument, the SNOT-20. DESIGN, SETTING AND PARTICIPANTS: The National Comparative Audit of Surgery for Nasal Polyposis and Chronic Rhinosinusitis was a prospective cohort study collecting data on 3128 adult patients undergoing sinonasal surgery in 87 NHS hospitals in England and Wales. Data were collected preoperatively and at 3 months after surgery, and analysed to determine validity of the SNOT-22. Test-retest reliability was assessed in a separate cohort of patients in a single centre. MAIN OUTCOME MEASURES: The SNOT-22, a derivative of the SNOT-20 was the main outcome measure. Patients were also asked to report whether they felt better, the same or worse following surgery. To evaluate the SNOT-22, the internal consistency, responsiveness, known group differences and validity were analysed. RESULTS: Preoperative SNOT-22 scores were completed by 2803 patients. 3-month postoperative SNOT-22 scores were available for 2284 patients of all patients who completed a preoperative form (81.5% response rate). The Cronbach's alpha scores for the SNOT-22 were 0.91 indicating high internal consistency. The test-retest reliability coefficient was 0.93, indicating high reliability of repeated measures. The SNOT-22 was able to discriminate between patients known to suffer with chronic rhinosinusitis and a group of healthy controls (P < 0.0001, t = 85.3). It was also able to identify statistically significant differences in sub-groups of patients with chronic rhinosinusitis. There was a statistically significant (P < 0.0001, t = 39.94) decrease in patient reported SNOT-22 scores at 3 months. At 3 months the overall effect size in all patients was 0.81, which is considered large. We found the minimally important difference that is the smallest change in SNOT-22 score that can be detected by a patient, to be 8.9 points. CONCLUSIONS: We have found the SNOT-22 to be valid and easy to use. It can be used to facilitate routine clinical practice to highlight the impact of chronic rhinosinusitis on the patient's quality of life, and may also be used to measure the outcome of surgical intervention. The minimally important difference allows us to interpret scores in a clinical context, and may help to improve patient selection for surgery.", "author" : [ { "dropping-particle" : "", "family" : "Hopkins", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gillett", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slack", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lund", "given" : "V. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Browne", "given" : "J. P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Otolaryngology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "447-454", "title" : "Psychometric validity of the 22-item Sinonasal Outcome Test", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "185", "plainTextFormattedCitation" : "185", "previouslyFormattedCitation" : "185" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }185). Olfactory-specific patient reported outcome measures, such as the Questionnaire of Olfactory Disorders (QOD), appear to have a greater ability to differentiate between patients with normosmia versus hyposmia than simple Likert questions analyzed from sinus specific questionnaires such as the SNOT-22 and Rhinosinusitis Disability Index (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/alr.21679", "ISSN" : "20426976", "author" : [ { "dropping-particle" : "", "family" : "Soler", "given" : "Zachary M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Timothy L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alt", "given" : "Jeremiah A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramakrishnan", "given" : "Vijay R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mace", "given" : "Jess C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schlosser", "given" : "Rodney J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Forum of Allergy & Rhinology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2016", "4" ] ] }, "page" : "407-413", "title" : "Olfactory-specific quality of life outcomes after endoscopic sinus surgery", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "186", "plainTextFormattedCitation" : "186", "previouslyFormattedCitation" : "186" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }186).However, as discussed briefly above, olfactory self-assessment tends to be unreliable and it has been shown that people do not perform well when compared with psychophysical testing (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/chemse/bjg061", "ISBN" : "0379-864X (Print)", "ISSN" : "0379864X", "PMID" : "14627537", "abstract" : "The aim of this study was to investigate the accuracy of self-reported ratings of olfactory function in 83 healthy subjects. Such ratings were compared with quantitative measures of olfactory function, as well as with ratings of nasal patency. In experiment 1 subjects rated olfactory function and nasal patency before olfactory testing, whereas in experiment 2 the reverse was the case. No feedback regarding test results were provided until after completion of the testing. The principal findings were: (i) when ratings preceded measurements of olfactory function, there was no significant correlation between the two parameters. However, ratings of olfactory function correlated significantly with ratings of nasal airway patency. (ii) In contrast, when measurements of olfactory function preceded the ratings, this constellation switched. Now ratings of olfactory function correlated significantly with measured olfactory function, whereas there was no significant correlation between ratings of nasal airway patency and ratings of olfactory function. In conclusion, these data suggest that ratings of olfactory function are unreliable in healthy, untrained subjects. The ratings seem to reflect changes of nasal airway patency to a larger degree than measurable olfactory function. The results further indicate that this is mainly due to the limited attention the sense of smell receives in daily life.", "author" : [ { "dropping-particle" : "", "family" : "Landis", "given" : "Basile N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hugentobler", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giger", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lacroix", "given" : "J. S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemical Senses", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "691-694", "title" : "Ratings of overall olfactory function", "type" : "article-journal", "volume" : "28" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1097/MLG.0b013e318170b5cb", "ISBN" : "1531-4995 (Electronic)", "ISSN" : "1531-4995", "PMID" : "18438263", "abstract" : "OBJECTIVE/HYPOTHESIS: This prospective study aimed to investigate predictors of nasal surgery in terms of olfactory function. STUDY DESIGN: Prospective study. METHODS: A total of 775 patients were included in this prospective study (482 men, 293 women; age range 10-81 years, mean age 41 years, standard deviation = 15.3 y). Prior to surgery, patients received a detailed otorhinolaryngologic examination including nasal endoscopy. Olfactory function was assessed with a standardized odor identification test (\"Sniffin' Sticks\"). In 356 patients, olfactory function was retested 4 months after surgery (63-339 days after surgery; mean 128 days, standard deviation = 29 days); 206 of these patients received sinus surgery, while 150 received surgery involving the septum. RESULTS: Using a conservative definition of change of olfactory function, following sinus surgery, improvement of the sense of smell was found in 23%, no change was seen in 68%, and decreased function was seen in 9% of the patients; in patients with septum surgery, improvement was seen in 13%, no change in 81%, and decreased function in 7%. Patients exhibiting a postoperative decrease of olfactory function had significantly higher preoperative olfactory scores than patients who experienced improvement. In terms of the sense of smell, nasal surgery produced the highest success rates in patients with eosinophilia and a high degree of polyposis. Neither age nor sex had a major impact on the outcome of surgery in terms of olfactory function. CONCLUSIONS: These results in a large group of patients confirm previous work. Apart from apparent success in 13 to 23% of patients, there is also a small but significant group of patients (7 to 9%) in whom olfactory function decreases after surgery. Because this decrease was mostly found in patients with relatively good preoperative olfactory function, this group should receive specific attention when counseling patients about the potential risks of nasal surgery.", "author" : [ { "dropping-particle" : "", "family" : "Pade", "given" : "J\u00fcrgen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Laryngoscope", "id" : "ITEM-2", "issue" : "7", "issued" : { "date-parts" : [ [ "2008" ] ] }, "note" : "Only septoplasty/SMR +/- turbinates and FESS. NO SRP", "page" : "1260-1264", "title" : "Olfactory function following nasal surgery.", "type" : "article-journal", "volume" : "118" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISBN" : "0300-0729 (Print)\\r0300-0729 (Linking)", "ISSN" : "03000729", "PMID" : "18444490", "abstract" : "BACKGROUND: Despite the common occurrence of rhinological pathology presenting to the ENT clinic, routine testing of olfactory ability is rarely performed. OBJECTIVES: The aim of this study was to determine the role of routine olfactory testing. METHODS: This was a prospective study conducted in the outpatient clinic of a district general hospital. Patients presenting with rhinological complaints had their olfactory status assessed using the combined olfactory test (COT) before and after rhinological surgery. RESULTS: Eighty patients (56 men, 24 women) had tests completed over a 12-month period. Patients assessed mostly had nasal polyposis, chronic rhinosinusitis or septal deformity. 83% of patients had either a complaint of olfactory disturbance or a COT score of 6 or less, or had both; but correlation between symptoms and scores was poor. Post-operative COT scores showed significant improvement (p = 0.02) with post-septoplasty patients showing the most significant improvement as a group (p = 0.001). CONCLUSIONS: Olfactory disturbance is very common in rhinological pathology and the patient's history alone cannot be relied upon. Simple olfactory assessment, such as with the combined olfactory test, is easy to perform and cheap to use and should be a commonly used resource in the ENT clinic. Formal testing can help to document any pre-existing olfactory loss and any post-operative changes as well as detecting unreported hyposmia.", "author" : [ { "dropping-particle" : "", "family" : "Philpott", "given" : "Carl M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rimal", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tassone", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prinsley", "given" : "P. R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Premachandra", "given" : "D. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-3", "issue" : "1", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "34-39", "title" : "A study of olfactory testing in patients with rhinological pathology in the ENT clinic", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "ISSN" : "0300-0729", "PMID" : "9569436", "abstract" : "One hundred and fifteen patients suffering from chronic sinusitis were observed to analyse the prevalence of olfactory dysfunction and the influence of FESS. Pre-operative questionnaires were supplemented by examination of olfactory thresholds and discrimination. Pre-operatively, 58% of the collective were aware or complained of any olfactory deficit. However, the olfactory tests demonstrated that of the collective 52% were hyposmic and 31% anosmic. Eight per cent of the hyposmic patients presented with an isolated reduction of their ability to discriminate odours. Post-operative improvements were found in 70%. Normosmia was post-operatively achieved in 25% of the hyposmic patients, but only in 5% of the anosmic patients. Olfaction changed to the worse in 8% after FESS. Therefore, the prevalence of olfactory dysfunction in chronic sinusitis is pre-operatively higher, and the rate of improvement is lower than generally assumed. The extent of sinus disease as measured by the degree of intranasal polyposis correlates with olfactory dysfunction. Resections of the middle turbinate may have a negative effect on olfaction, due to damage to the olfactory fila or alteration of the normal aerodynamic pattern within the olfactory cleft. However, this hypothesis is based on a few observations and needs to be verified by further investigations.", "author" : [ { "dropping-particle" : "", "family" : "Delank", "given" : "K W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stoll", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-4", "issued" : { "date-parts" : [ [ "1998" ] ] }, "page" : "15-19", "title" : "Olfactory function after functional endoscopic sinus surgery for chronic sinusitis.", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1093/chemse/20.6.645", "ISBN" : "0379-864X (Print)", "ISSN" : "0379-864X", "PMID" : "8788098", "abstract" : "Ten tests of olfactory function (including tests of odor identification, detection, discrimination, memory, and suprathreshold odor intensity and pleasantness perception) were administered on two test occasions to 57 subjects ranging in age from 18 to 83 years. The stability of the average test scores was determined across the two test sessions for 14 measures derived from these 10 tests and for subcomponents of the Japanese T&T olfactometer threshold test. In addition, the test-retest reliability (Pearson r) of each test measure was established. With the exception of a response bias measure, the average test scores did not differ significantly across the two test sessions. Statistically, the reliability coefficients of the primary test measures fell into three general classes bound by the following r values: 0.43-0.53; 0.67-0.71; 0.76-0.90. Detection threshold values were more reliable than recognition threshold values; those based upon a single ascending presentation series were much less reliable than those based upon a staircase procedure. The relationship between test length and reliability was examined for several of the tests and mathematically modeled. For example, within the staircase series incorporating the odorant phenyl ethyl alcohol, reliability was related (R2 = 0.984) to the number of reversals included in the threshold estimate by a function derived from the Spearman-Brown formula; namely, reliability = 0.455* # reversals/[1 + 0.455 (# reversals - 1)]. Reversal location, per se, had little influence on reliability. Overall, this study suggests that (i) considerable variation is present in the reliability of olfactory tests, (ii) reliability is a function of test length, and (iii) caution is warranted in comparing results from nominally different olfactory tests in applied settings since the findings may, in some instances, simply reflect the differential reliability of the tests.", "author" : [ { "dropping-particle" : "", "family" : "Doty", "given" : "R L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McKeown", "given" : "D A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "W W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shaman", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chem Senses", "id" : "ITEM-5", "issue" : "6", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "645-656", "title" : "A Study of the Test-retest Reliability of Ten Olfactory Tests", "type" : "article-journal", "volume" : "20" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1016/j.otohns.2005.10.041", "ISSN" : "01945998", "PMID" : "16500450", "abstract" : "OBJECTIVE: To see if nasal peak inspiratory flow rate and subjective sense of smell had any correlation with olfactory thresholds. STUDY DESIGN AND SETTING: A cohort study of 186 normal volunteers was recruited from among staff and visitors at a university hospital. Olfactory thresholds were detected for each subject (103 with eucalyptol and 83 with phenethyl alcohol), along with nasal peak inspiratory flow (PIFR). Subjective sense of smell, along with nasal symptoms, mood, and alertness, were recorded on visual analogue scores. RESULTS: Subjective perception of smell had no correlation with olfactory thresholds detected (P = 0.4057) and the other subjective measures also had no correlation. There was a significant relationship of PIFR to thresholds in the group tested with phenethyl alcohol (P = 0.002). CONCLUSION: As with the sensation of nasal patency, the self-assessment of a subject's sense of smell has poor correlation with their actual olfactory ability. SIGNIFICANCE: A patient's history cannot be relied upon when determining their olfactory ability and formal testing should be performed. EBM rating: A-1b \u00a9 2006 American Academy of Otolaryngology-Head and Neck Surgery Foundation, Inc. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Philpott", "given" : "Carl M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wolstenholme", "given" : "Charlotte R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goodenough", "given" : "Paul C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clark", "given" : "Allan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Murty", "given" : "George E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Otolaryngology - Head and Neck Surgery", "id" : "ITEM-6", "issue" : "3", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "488-490", "title" : "Comparison of subjective perception with objective measurement of olfaction", "type" : "article-journal", "volume" : "134" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "DOI" : "10.4193/Rhino14.081", "ISSN" : "03000729", "PMID" : "25756084", "abstract" : "BACKGROUND: Past findings of an impact of cognitive impairment on awareness of olfactory dysfunction, and high prevalence of age-associated cognitive impairment motivated the present study of whether middle-aged and elderly adults are unaware of an olfactory dysfunction despite being carefully screened for cognitive impairment. METHODOLOGY: The sample included 203 Norwegian participants, aged 46-79 years, 134 women and 69 men, who underwent comprehensive neuropsychological assessment for screening of cognitive impairment. Subjective assessment of olfactory function (\"How would you estimate your sense of smell?\") was compared with outcome on objective assessment of olfactory function with the Scandinavian Odor Identification Test, which in the present study was shown to be valid for use on Norwegian populations. RESULTS: We found that 79% of this cognitively healthy sample with objectively assessed olfactory dysfunction reported normal olfactory function (57% of functionally anosmics reported normal function). In contrast, only 9% with objectively assessed normal olfactory function reported olfactory dysfunction. CONCLUSION: A large proportion of cognitively well-functioning middle-aged and elderly adults with an olfactory dysfunction are unaware of their dysfunction. The ENT physician who suspects that the sense of smell may be compromised should, in addition to an anamnesis, assess the patient`s olfactory function objectively.", "author" : [ { "dropping-particle" : "", "family" : "Wehling", "given" : "Eike", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lundervold", "given" : "Astri J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Espeset", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reinvang", "given" : "Ivar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Br\u00e4merson", "given" : "Annika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nordin", "given" : "Steven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-7", "issue" : "1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "89-94", "title" : "Even cognitively well-functioning adults are unaware of their olfactory dysfunction: Implications for ENT clinicians and researchers", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "27,73,187\u2013191", "plainTextFormattedCitation" : "27,73,187\u2013191", "previouslyFormattedCitation" : "27,73,187\u2013191" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }27,73,187–191). In 2003 a group of healthy individuals were assessed for correlation between subjective, self-reported olfactory ability and composite psychophysical olfactory test scores (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/chemse/bjg061", "ISBN" : "0379-864X (Print)", "ISSN" : "0379864X", "PMID" : "14627537", "abstract" : "The aim of this study was to investigate the accuracy of self-reported ratings of olfactory function in 83 healthy subjects. Such ratings were compared with quantitative measures of olfactory function, as well as with ratings of nasal patency. In experiment 1 subjects rated olfactory function and nasal patency before olfactory testing, whereas in experiment 2 the reverse was the case. No feedback regarding test results were provided until after completion of the testing. The principal findings were: (i) when ratings preceded measurements of olfactory function, there was no significant correlation between the two parameters. However, ratings of olfactory function correlated significantly with ratings of nasal airway patency. (ii) In contrast, when measurements of olfactory function preceded the ratings, this constellation switched. Now ratings of olfactory function correlated significantly with measured olfactory function, whereas there was no significant correlation between ratings of nasal airway patency and ratings of olfactory function. In conclusion, these data suggest that ratings of olfactory function are unreliable in healthy, untrained subjects. The ratings seem to reflect changes of nasal airway patency to a larger degree than measurable olfactory function. The results further indicate that this is mainly due to the limited attention the sense of smell receives in daily life.", "author" : [ { "dropping-particle" : "", "family" : "Landis", "given" : "Basile N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hugentobler", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giger", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lacroix", "given" : "J. S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemical Senses", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "691-694", "title" : "Ratings of overall olfactory function", "type" : "article-journal", "volume" : "28" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "27", "plainTextFormattedCitation" : "27", "previouslyFormattedCitation" : "27" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }27). This study found that where subjective rating preceded psychophysical testing (using “Sniffin’ Sticks”- see below), there was no significant correlation between the two. Poor self-rating abilities have also been shown in patient populations. An early study by Delank and colleagues showed that 30-40% of CRS patients with impaired olfactory function rated themselves as unimpaired (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0300-0729", "PMID" : "9569436", "abstract" : "One hundred and fifteen patients suffering from chronic sinusitis were observed to analyse the prevalence of olfactory dysfunction and the influence of FESS. Pre-operative questionnaires were supplemented by examination of olfactory thresholds and discrimination. Pre-operatively, 58% of the collective were aware or complained of any olfactory deficit. However, the olfactory tests demonstrated that of the collective 52% were hyposmic and 31% anosmic. Eight per cent of the hyposmic patients presented with an isolated reduction of their ability to discriminate odours. Post-operative improvements were found in 70%. Normosmia was post-operatively achieved in 25% of the hyposmic patients, but only in 5% of the anosmic patients. Olfaction changed to the worse in 8% after FESS. Therefore, the prevalence of olfactory dysfunction in chronic sinusitis is pre-operatively higher, and the rate of improvement is lower than generally assumed. The extent of sinus disease as measured by the degree of intranasal polyposis correlates with olfactory dysfunction. Resections of the middle turbinate may have a negative effect on olfaction, due to damage to the olfactory fila or alteration of the normal aerodynamic pattern within the olfactory cleft. However, this hypothesis is based on a few observations and needs to be verified by further investigations.", "author" : [ { "dropping-particle" : "", "family" : "Delank", "given" : "K W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stoll", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "1998" ] ] }, "page" : "15-19", "title" : "Olfactory function after functional endoscopic sinus surgery for chronic sinusitis.", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "188", "plainTextFormattedCitation" : "188", "previouslyFormattedCitation" : "188" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }188). In a UK based study of 80 patients presenting to a rhinology clinic, only 27.5% accurately reported their olfactory ability (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0300-0729 (Print)\\r0300-0729 (Linking)", "ISSN" : "03000729", "PMID" : "18444490", "abstract" : "BACKGROUND: Despite the common occurrence of rhinological pathology presenting to the ENT clinic, routine testing of olfactory ability is rarely performed. OBJECTIVES: The aim of this study was to determine the role of routine olfactory testing. METHODS: This was a prospective study conducted in the outpatient clinic of a district general hospital. Patients presenting with rhinological complaints had their olfactory status assessed using the combined olfactory test (COT) before and after rhinological surgery. RESULTS: Eighty patients (56 men, 24 women) had tests completed over a 12-month period. Patients assessed mostly had nasal polyposis, chronic rhinosinusitis or septal deformity. 83% of patients had either a complaint of olfactory disturbance or a COT score of 6 or less, or had both; but correlation between symptoms and scores was poor. Post-operative COT scores showed significant improvement (p = 0.02) with post-septoplasty patients showing the most significant improvement as a group (p = 0.001). CONCLUSIONS: Olfactory disturbance is very common in rhinological pathology and the patient's history alone cannot be relied upon. Simple olfactory assessment, such as with the combined olfactory test, is easy to perform and cheap to use and should be a commonly used resource in the ENT clinic. Formal testing can help to document any pre-existing olfactory loss and any post-operative changes as well as detecting unreported hyposmia.", "author" : [ { "dropping-particle" : "", "family" : "Philpott", "given" : "Carl M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rimal", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tassone", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prinsley", "given" : "P. R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Premachandra", "given" : "D. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "34-39", "title" : "A study of olfactory testing in patients with rhinological pathology in the ENT clinic", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "187", "plainTextFormattedCitation" : "187", "previouslyFormattedCitation" : "187" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }187). Whilst subjective assessment is useful in characterising the clinical effect of interventions, including the ‘minimal clinically important change’ (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1179/jmt.2008.16.4.82E", "ISBN" : "1066-9817 (Print)\\n1066-9817 (Linking)", "ISSN" : "1066-9817", "PMID" : "19771185", "abstract" : "Minimal clinically important differences (MCID) are patient derived scores that reflect changes in a clinical intervention that are meaningful for the patient. At present, there are a number of different methods to obtain an MCID, as there a number of different factors that can influence the MCID value. This clinimetric corner outlines the hidden challenges associated with identifying a viable MCID and possible suggestions to improve the future development of these single scores.", "author" : [ { "dropping-particle" : "", "family" : "Cook", "given" : "Chad E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of manual & manipulative therapy", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "E82-E83", "title" : "Clinimetrics Corner: The Minimal Clinically Important Change Score (MCID): A Necessary Pretense.", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "192", "plainTextFormattedCitation" : "192", "previouslyFormattedCitation" : "192" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }192), given the above issues, these should not be performed in isolation. Rather, when diagnosing olfactory impairment, or assessing the effects of treatment, patient reported outcomes should be used in conjunction with more objective forms of assessment, as outlined below. Recommendations:In patients reporting olfactory dysfunction olfactory assessment should be undertaken in order to fully determine disease burden and clinical impact of interventions.Where possible, validated questionnaires should be used. Where this is not possible, a recognized form of assessment, possibly quantitative and/or anchored, such as a visual analogue scale, should be used.Subjective olfactory assessment should not be undertaken in isolation, given its poor accuracy.Psychophysical TestingPsychophysical tests provide a more reliable assessment of olfactory function than subjective testing. Similar to an audiogram, during such assessment, an olfactory stimulus is provided and the outcome of the test is dependent on the patient’s response. Psychophysical testing therefore requires a cooperative subject who can understand and follow instructions, as well as communicate choices to the clinician/investigator. Orthonasal psychophysical toolsThrough modification of psychophysical test type, different aspects of olfaction can be quantitatively assessed. Broadly, these different aspects can be divided into threshold and suprathreshold olfactory function. Odour threshold is the concentration of an odourant where 50% of the stimuli are detected and 50% remain undetectable to a subject. Odour threshold in itself does not require specific identification of the odourant stimulus, rather a detection of ‘something’, usually in comparison to a blank, odourless stimulus. Where comparison is made between odourant and blank stimuli, some degree of short-term, working memory is required. However, this test does not utilize episodic or semantic memory (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/13803391003683070", "ISBN" : "10.1080/13803391003683070", "ISSN" : "1744-411X", "PMID" : "20437286", "abstract" : "The purpose of this study was to determine cognitive correlates of olfactory performance across three different tasks. A total of 170 men and women (30-87 years of age) were assessed in olfactory sensitivity, discrimination, and identification. Also, participants were tested in a range of cognitive tests covering executive functioning, semantic memory, and episodic memory. Hierarchical regression analyses showed that proficiency in executive functioning and semantic memory contributed significantly to odor discrimination and identification performance, whereas all of the cognitive factors proved unrelated to performance in the odor threshold test. This pattern of outcome suggests that an individual's cognitive profile exerts a reliable influence on performance in higher order olfactory tasks.", "author" : [ { "dropping-particle" : "", "family" : "Hedner", "given" : "Margareta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Larsson", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arnold", "given" : "Nancy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zucco", "given" : "Gesualdo M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of clinical and experimental neuropsychology", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "1062-7", "title" : "Cognitive factors in odor detection, odor discrimination, and odor identification tasks.", "type" : "article-journal", "volume" : "32" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "193", "plainTextFormattedCitation" : "193", "previouslyFormattedCitation" : "193" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }193) and therefore has a lower cognitive burden.Suprathreshold olfactory testing involves presentation of odour stimuli of sufficient concentration such that they should be detectable (i.e. above the threshold level) in an unimpaired person. By varying the odour presented, such tools allow for the testing of odour discrimination and identification abilities. Odour discrimination describes the non-verbal ability to differentiate between different odours. Odour identification involves both recognition of a stimulus and communication of its correct identity (i.e., the ability to name an odour). Unprompted odour identification is difficult (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1126/science.760202", "ISBN" : "0036-8075", "ISSN" : "0036-8075", "PMID" : "760202", "abstract" : "Successful odor identification depends on (i) commonly encountered substances, (ii) a long-standing connection between an odor and its name, and (iii) aid in recalling the name. The absence of any one ingredient impairs performance dramatically, but the presence of all three permits ready identification of scores of substances, with performance seemingly limited only by the inherent confusability of the stimuli.", "author" : [ { "dropping-particle" : "", "family" : "Cain", "given" : "W S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Science (New York, N.Y.)", "id" : "ITEM-1", "issue" : "4379", "issued" : { "date-parts" : [ [ "1979" ] ] }, "page" : "467-470", "title" : "To know with the nose: keys to odor identification.", "type" : "article-journal", "volume" : "203" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "194", "plainTextFormattedCitation" : "194", "previouslyFormattedCitation" : "194" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }194), hence most psychophysical tests incorporate either visual or written cues (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3758/s13414-014-0811-3", "ISSN" : "1943-3921", "PMID" : "25520045", "abstract" : "Verbal labels are potent manipulators for olfactory perception, and verbal descriptors used in a cued olfactory identification test will influence the testing results. The main aim of the present study was to test whether the order of presentation of the odorants and the corresponding set of labels (verbal descriptors with or without pictures) would influence the results of a psychophysical odor identification test in 100 normosmic subjects (49 women and 51 men) and 100 patients with olfactory dysfunction (61 women and 39 men). Additionally, we investigated whether the scores would be different between subjects identifying odors from a list of verbal descriptors and subjects using both pictures and verbal descriptors. The subjects were examined with the extended, 32-item \" Sniffin' Sticks \" identification test. We found that the scores of normosmic subjects were significantly higher when the subjects were presented with label options prior to smell-ing, whereas for patients the scores in the two conditions did not differ. Moreover, in both groups the scores were not significantly different when the subjects were presented either with verbal descriptors only or with verbal descriptors and pictures. Our findings seem to be of importance not only to research involving psychophysical olfactory identification tests or in a clinical context, but also to further experiments investigating human olfaction and cognition.", "author" : [ { "dropping-particle" : "", "family" : "Sorokowska", "given" : "a.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Albrecht", "given" : "E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Attention, Perception, & Psychophysics", "id" : "ITEM-1", "issue" : "April 2016", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "731-736", "title" : "Reading first or smelling first? 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Also, participants were tested in a range of cognitive tests covering executive functioning, semantic memory, and episodic memory. Hierarchical regression analyses showed that proficiency in executive functioning and semantic memory contributed significantly to odor discrimination and identification performance, whereas all of the cognitive factors proved unrelated to performance in the odor threshold test. This pattern of outcome suggests that an individual's cognitive profile exerts a reliable influence on performance in higher order olfactory tasks.", "author" : [ { "dropping-particle" : "", "family" : "Hedner", "given" : "Margareta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Larsson", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arnold", "given" : "Nancy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zucco", "given" : "Gesualdo M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of clinical and experimental neuropsychology", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "1062-7", "title" : "Cognitive factors in odor detection, odor discrimination, and odor identification tasks.", "type" : "article-journal", "volume" : "32" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "193", "plainTextFormattedCitation" : "193", "previouslyFormattedCitation" : "193" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }193). Furthermore, tests of odour identification require previous exposure to odour stimulus, and may therefore be culturally specific (e.g., the well-known smell of wintergreen in the USA which is almost unknown in Germany). This also includes the idea that olfactory tests should be adapted to children (see below). For this reason, such tests must be validated in a local population and associated normative data collected before use. The hedonic value of an odour as well as its relative intensity can also be considered forms of suprathreshold olfactory testing. Hedonic assessment of an odour, or how pleasant or unpleasant an odour is, does not require recognition or identification. However, there is a greater emotional component to these ratings and as such, episodic memory may be of greater importance compared with the other aspects of olfaction described above. Relative intensity can be considered a form of threshold testing. Odour detection threshold is not to be confused with odour recognition threshold, which is the concentration of an odour required for recognition or identification. As this test involves identification of the odourant, it combines elements of both suprathreshold and threshold tasks. Hedonic value, intensity ratings and odour recognition thresholds are infrequently used during clinical diagnosis or outcomes assessment. In addition, there are tests that rely on changes in breathing behavior in relation to olfactory stimulation, e.g., the Sniff Magnitude Test (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1001/archotol.132.5.532", "ISSN" : "0886-4470", "author" : [ { "dropping-particle" : "", "family" : "Frank", "given" : "Robert A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gesteland", "given" : "Robert C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bailie", "given" : "Jason", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rybalsky", "given" : "Konstantin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seiden", "given" : "Allen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { 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(ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1055/s-2004-814369", "ISSN" : "0935-8943", "abstract" : "Hintergrund: Es wird kontrovers diskutiert, ob eine rein olfaktorische Reizung Atem\u00e4nderungen generieren kann. Verschiedene Arbeitsgruppen sind der Ansicht, dass die mehr oder weniger stark ausgepr\u00e4gte irritative Komponente jeder Riechreizung die Atem\u00e4nderungen hervorruft. Andere Arbeitsgruppen sehen im Nachweis von respiratorischen Riechreizfolgereaktionen einen Indikator f\u00fcr die Intaktheit des Riechsystems. Methodik und Probanden: 12 riechgesunde Studenten wurden \u00fcber ein Flussolfaktometer pr\u00e4nasal inspirationssynchron mit schwellennahen H2S-Konzentrationen \u00fcber 2 Sekunden 10-mal mit mindestens 60 Sekunden Abstand wiederholt gereizt. Genauso h\u00e4ufig wurde Neutralluft als blank appliziert. Die Atmung wurde als Druckkurve \u00fcber ein Differenzdruckmanometer registriert, digitalisiert und atemzugbezogen ausgewertet. Anhand von 9 Atemparametern wurde der Atemzug w\u00e4hrend einer H2S-Reizung bzw. Neutralluftapplikation mit einem gemittelten Ruheatemzug verglichen. Parametervergr\u00f6\u00dferungen und Parameterverkleinerungen wurden gleicherma\u00dfen mittels ihres Absolutbetrags bewertet. Die Absolutbetr\u00e4ge aller 9 Atemparameter ergaben in ihrer Summe den Respirationsindex (RI). 11 Versuchspersonen wurden jeweils 15-mal mit H2S und Neutralluft stimuliert. Die Auspr\u00e4gung der RI \u00fcber eine Versuchsdauer von 30 bis 50 Minuten wurde ausgewertet. Ergebnisse: Der mittlere RI der einzelnen Probanden variierte unter H2S-Reizung zwischen 201 und 570 und bei Neutralluftapplikation zwischen 85 und 188. Der Unterschied war signifikant (p < 0,001). Bei jeder der ersten 10 Reizwiederholungen war der RI unter H2S-Reizung signifikant gr\u00f6\u00dfer als unter einer Neutralluftapplikation. Im Verlaufe einer 15-fachen H2S-Reizung kam es zu keiner signifikanten Ab- oder Zunahme der RI. Schlussfolgerung: Mit wahrnehmbaren kurzen H2S-Stimuli lassen sich Atem\u00e4nderungen generieren, die sich mithilfe eines LabVIEW-Programms objektivieren lassen. Die Methodik eignet sich zur Objektivierung einer Riechwahrnehmung. Background: It is controversially discussed whether strictly olfactory stimuli are able to evoke changes of breathing patterns. A number work groups argue that the more or less noticeable irritative component of odors are responsible for a respiratory response. Other work groups regard changes of breathing pattern as an indicator for an intact smell ability during \u201dpure\u201d olfactory stimulation. Methods: 12 normosmic young volunteers were repeatedly challenged with hydrogensulfide (H2S) for two seconds o\u2026", "author" : [ { "dropping-particle" : "", "family" : "Gudziol", "given" : "H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "W\u00e4chter", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Laryngo-Rhino-Otologie", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2004", "6" ] ] }, "page" : "367-373", "publisher" : "\u00a9 Georg Thieme Verlag KG Stuttgart \u00b7 New York", "title" : "Gibt es olfaktorisch evozierte Atem\u00e4nderungen?", "type" : "article-journal", "volume" : "83" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "197", "plainTextFormattedCitation" : "197", "previouslyFormattedCitation" : "197" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }197). The Alcohol Sniff Test (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1001/archotol.1997.01900060033005", "ISSN" : "0886-4470", "author" : [ { "dropping-particle" : "", "family" : "Davidson", "given" : "T. 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Subjects close their eyes and an opened alcohol pad is placed 30 cm below the nose. With each exhalation the odor source is moved 1cm closer until the patient reports smelling alcohol. The utility of testing for multiple psychophysical components of olfaction (e.g. threshold, discrimination and identification) when assessing olfactory dysfunction is debated. Previous work by Doty has suggested that different psychophysical tests measure a common source of variance, meaning that olfactory impairment and improvement may be effectively assessed using, for example odour identification alone (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3758/BF03208363", "ISBN" : "0031-5117 (Print)\\r0031-5117 (Linking)", "ISSN" : "0031-5117", "PMID" : "7816540", "abstract" : "It is not known whether nominally different olfactory tests actually measure dissimilar perceptual attributes. In this study, we administered nine olfactory tests, including tests of odor identification, discrimination, detection, memory, and suprathreshold intensity and pleasantness perception, to 97 healthy subjects. A principal components analysis performed on the intercorrelation matrix revealed four meaningful components. The first was comprised of strong primary loadings from most of the olfactory test measures, whereas the second was comprised of primary loadings from intensity ratings given to a set of suprathreshold odorant concentrations. The third and fourth components had primary loadings that reflected, respectively, mean suprathreshold pleasantness ratings and a response bias measure derived from a yes/no odor identification signal detection task. In an effort to adjust for potential confounding influences of age, gender, smoking, and years of schooling on the component structure, a matrix of residuals from a multiple regression analysis, which included these variables, was also analyzed. A similar component pattern emerged. Overall, these findings suggest, in healthy subjects spanning a wide range, that (1) a number of nominally distinct tests of olfactory function are measuring a common source of variance, and (2) some suprathreshold odor intensity and pleasantness rating tests may be measuring sources of variance different from this common source.", "author" : [ { "dropping-particle" : "", "family" : "Doty", "given" : "R L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McKeown", "given" : "D A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raj", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Perception & psychophysics", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "1994" ] ] }, "page" : "701-707", "title" : "Tests of human olfactory function: principal components analysis suggests that most measure a common source of variance.", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "199", "plainTextFormattedCitation" : "199", "previouslyFormattedCitation" : "199" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }199). However, this theory is contradicted by other work. In 1988 Jones-Gotman and Zatorre described impairment of odour identification but not thresholds after selective cerebral excision (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/0028-3932(88)90093-0", "ISBN" : "0028-3932 (Print)\\n0028-3932", "ISSN" : "00283932", "PMID" : "3374800", "abstract" : "The ability to identify common odors using the University of Pennsylvania Smell Identification Test was investigated in 120 patients with a focal surgical brain lesion and 20 normal control subjects. Results showed significant impairment after right or left temporal lobectomy, right or left frontal lobectomy, and right frontotemporal excision. Patients whose excision was confined to the left central, parietal or posterior area showed no significant deficit. The impairment after frontal lobectomy was demonstrated only in patients whose frontal-lobe removal invaded the orbital cortex; that group also showed a significantly greater impairment than did the temporal lobectomy group. All patient groups showed normal detection thresholds for n-butyl alcohol. ?? 1988.", "author" : [ { "dropping-particle" : "", "family" : "Jones-Gotman", "given" : "Marilyn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zatorre", "given" : "Robert J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Neuropsychologia", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "1988" ] ] }, "page" : "387-400", "title" : "Olfactory identification deficits in patients with focal cerebral excision", "type" : "article-journal", "volume" : "26" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "200", "plainTextFormattedCitation" : "200", "previouslyFormattedCitation" : "200" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }200). Similarly, odour identification is affected by HIV dementia, whereas odour threshold scores are preserved (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0031-9384(98)00112-7", "ISSN" : "00319384", "PMID" : "9761231", "abstract" : "A number of studies have shown that HIV infection is associated with decreased olfactory ability. Additionally, it has been hypothesized that a reduced odorant identification may precede the advent of AIDS Dementia Complex (ADC). However, it is not known whether changes in olfactory ability are a manifestation of neurocognitive decline which may precede the appearance of AIDS Dementia Complex, damage to the peripheral olfactory system from opportunistic infection, or whether olfactory structures have a particular sensitivity to HIV. These issues were addressed in a cross-sectional study examining variability in the neuropsychological, neurological, otolaryngological, auditory, and olfactory status in HIV-positive subjects. A stepwise regression provided evidence that the ability to identify odorants was influenced by age, nasal structure and pathology, neurocognitive ability, and level of AIDS Dementia Complex. On the other hand, only nasal pathologies accounted for the variability in olfactory thresholds. These data suggest that identification and thresholds tests may reflect different olfactory pathologies. Additionally, these data suggest at least part of the decline in olfactory ability accompanying an HIV infection may be secondary to nasal pathologies. Because of their rapidly changing neurocognitive status, HIV-positive patients represent an excellent group in which to study the determinants of olfactory ability. Copyright (C) 1998 Elsevier Science Inc.", "author" : [ { "dropping-particle" : "", "family" : "Hornung", "given" : "David E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kurtz", "given" : "Daniel B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bradshaw", "given" : "Charles B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seipel", "given" : "Doris M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kent", "given" : "Paul F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blair", "given" : "Donald C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Emko", "given" : "Precha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Physiology and Behavior", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "1998" ] ] }, "page" : "549-556", "title" : "The olfactory loss that accompanies an HIV infection", "type" : "article-journal", "volume" : "64" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "201", "plainTextFormattedCitation" : "201", "previouslyFormattedCitation" : "201" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }201). Work by Whitcroft and colleagues demonstrated that the pattern of psychophysical test scores obtained in 1,226 subjects, with olfactory loss of varying cause, reflected underlying disease aetiology (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/lary.26229", "ISSN" : "0023852X", "author" : [ { "dropping-particle" : "", "family" : "Whitcroft", "given" : "Katherine L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cuevas", "given" : "Mandy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haehner", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Laryngoscope", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2016", "8" ] ] }, "title" : "Patterns of olfactory impairment reflect underlying disease etiology", "type" : "article-journal", "volume" : "Epub ahead" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "202", "plainTextFormattedCitation" : "202" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }202). In this study, subjects with olfactory loss due to sinonasal disease were particularly impaired in their odour threshold scores, whereas patients with Parkinson’s disease were preferentially impaired in suprathreshold olfactory tasks (odour discrimination and identification). Taken together, these studies suggest that olfactory threshold preferentially tests peripheral causes of olfactory loss (for example due to sinonasal disease), whereas the suprathreshold tests of discrimination and identification preferentially assess central or cognitive causes of olfactory dysfunction. Therefore, assessing both odour threshold and suprathreshold tasks adds to the diagnostic value of the psychophysical tool.Furthermore, the accuracy of psychophysical tools has been shown to increase when composite scores are used. In a study of 2,178 participants of mixed olfactory ability, the diagnostic sensitivity of the individual tests odour threshold (T), discrimination (D) and identification (I) as compared with composite ‘TDI’ scores, were 64%, 56%, and 47% respectively (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/chemse/bjm058", "ISBN" : "0379-864X", "ISSN" : "0379864X", "PMID" : "17761724", "abstract" : "In a clinical context, the importance of the sense of smell has increasingly been recognized, for example, in terms of the evaluation of neurodegenerative disorders. In this study, 2 strategies of olfactory testing, a simple one and a more complex one, were compared with respect to their suitability to assess olfactory dysfunction. Odor threshold (T), discrimination (D), and identification (I) were assessed in a control sample of 916 males and 1160 females, aged 6-90 years, and in 81 men and 21 women, aged 38-80 years, suffering from idiopathic Parkinson's disease (IPD). Sums of the 3 subtest results T, D, and I yielded threshold discrimination identification (TDI) scores reflecting olfactory function. Sensitivity of any of the 3 subtests to confirm the diagnosis established by the composite TDI score was assessed separately for each test. Principal component analyses were applied to determine any common source of variance among the 3 specific subtests. Sensitivities of the subtests to provide the diagnosis established by the composite TDI score were 64% (T), 56% (D), and 47% (I), respectively. In IPD patients, each of the subtests provided the correct diagnosis (sensitivity >90%), as olfaction was impaired in 99% of the patient group. Two principal components emerged in both controls and IPD patients, with eigenvalues >0.5. The first component received high loadings from all factors. The second component received high loadings from odor threshold, whereas loadings from odor discrimination and identification were much smaller. In conclusion, combined testing of several components of olfaction, especially including assessment of thresholds, provides the most significant approach to the diagnosis of smell loss.", "author" : [ { "dropping-particle" : "", "family" : "L\u00f6tsch", "given" : "J\u00f6rn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reichmann", "given" : "Heinz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemical Senses", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2008" ] ] }, "note" : "55% of the total variance, bore high loadings from all factors (0.71, 0.74, and 0.77 for odor threshold, discrimination, and identification, respectively). The second component, explaining 24% of the total variance, received the main loading from odor threshold", "page" : "17-21", "title" : "Different odor tests contribute differently to the evaluation of olfactory loss", "type" : "article-journal", "volume" : "33" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "203", "plainTextFormattedCitation" : "203", "previouslyFormattedCitation" : "202" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }203). These sensitivities increased where paired test scores were used, but did not reach the diagnostic sensitivity of the full composite ‘TDI’ score. Using principle component analysis, this study further demonstrated that olfactory threshold scores individually explained more of the observed variance than odour discrimination or identification. However, these tests require additional effort and take some time to be administered, so logistical issues may limit their use.A variety of orthonasal, psychophysical olfactory tests have been developed for clinical and research use. Some of these tests assess just one aspect of olfaction, whilst other assess multiple components (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s10072-005-0452-3", "ISSN" : "15901874", "PMID" : "16086127", "abstract" : "The sense of smell significantly contributes to quality of life. In recent years much progress has been made in understanding the biochemistry, physiology and pathology of the human olfactory system. Olfactory disorders may arise not only from upper airway phlogosis but also from neurodegenerative disease. Hyposmia may precede motor signs in Parkinson's disease and cognitive deficit in Alzheimer's disease. These findings suggest the complementary role of olfactory tests in the diagnosis and management of neurodegenerative diseases. In this report we present a review of modern olfactory tests and their clinical applications. Although rarely employed in routine clinical practice, the olfactory test evaluates the ability of odour identification and is a useful diagnostic tool for olfaction evaluation. Olfactory screening tests are also available. In this work we strongly recommend the importance of an ENT evaluation before the test administration and dissuade from a self-administration of an olfactory test.", "author" : [ { "dropping-particle" : "", "family" : "Eibenstein", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fioretti", "given" : "A. B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lena", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rosati", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Amabile", "given" : "G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fusetti", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Neurological Sciences", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "147-155", "title" : "Modern psychophysical tests to assess olfactory function", "type" : "article-journal", "volume" : "26" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "204", "plainTextFormattedCitation" : "204", "previouslyFormattedCitation" : "203" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }204,ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/2045-7022-1-2", "ISSN" : "2045-7022", "PMID" : "22410181", "abstract" : "This EAACI Task Force document aims at providing the readers with a comprehensive and complete overview of the currently available tools for diagnosis of nasal and sino-nasal disease. We have tried to logically order the different important issues related to history taking, clinical examination and additional investigative tools for evaluation of the severity of sinonasal disease into a consensus document. A panel of European experts in the field of Rhinology has contributed to this consensus document on Diagnostic Tools in Rhinology.", "author" : [ { "dropping-particle" : "", "family" : "Scadding", "given" : "Glenis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hellings", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alobid", "given" : "Isam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bachert", "given" : "Claus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fokkens", "given" : "Wytske", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wijk", "given" : "Roy Gerth", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gevaert", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guilemany", "given" : "Josep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kalogjera", "given" : "Livije", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lund", "given" : "Valerie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mullol", "given" : "Joaquim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Passalacqua", "given" : "Giovanni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Toskala", "given" : "Elina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drunen", "given" : "Cornelius", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical and translational allergy", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "2", "title" : "Diagnostic tools in Rhinology EAACI position paper.", "type" : "article-journal", "volume" : "1" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "205", "plainTextFormattedCitation" : "205", "previouslyFormattedCitation" : "204" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }205). For example, the well known ‘University of Pennsylvania Smell Identification Test’ (UPSIT) is a reliable, standardized microencapsulated odour identification test, which has been adapted and validated for use in a number of different countries, as well as in children (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/coa.12212", "ISBN" : "1749-4486", "ISSN" : "17494478", "PMID" : "24373213", "author" : [ { "dropping-particle" : "", "family" : "Picillo", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iavarone", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pellecchia", "given" : "M. T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Amboni", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erro", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moccia", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vitale", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Longo", "given" : "K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Santangelo", "given" : "G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spina", "given" : "E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scannapieco", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Orefice", "given" : "G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barone", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Otolaryngology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "53-57", "title" : "Validation of an Italian version of the 40-item University of Pennsylvania Smell Identification Test that is physician administered: Our experience on one hundred and thirty-eight healthy subjects", "type" : "article-journal", "volume" : "39" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1007/s12078-015-9192-9", "ISSN" : "19365810", "author" : [ { "dropping-particle" : "", "family" : "Taherkhani", "given" : "Safa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moztarzadeh", "given" : "Fathollah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mehdizadeh Seraj", "given" : "Jalal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hashemi Nazari", "given" : "Seyed Saeed", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Taherkhani", "given" : "Farzad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gharehdaghi", "given" : "Jaber", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okazi", "given" : "Arash", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pouraghaei", "given" : "Sevda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemosensory Perception", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "183-191", "publisher" : "Chemosensory Perception", "title" : "Iran Smell Identification Test (Iran-SIT): a Modified Version of the University of Pennsylvania Smell Identification Test (UPSIT) for Iranian Population", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1001/jamaoto.2014.1650", "ISBN" : "2168-619X (Electronic)\r2168-6181 (Linking)", "ISSN" : "2168-6181", "PMID" : "25144751", "abstract" : "IMPORTANCE: Sinonasal disease and, specifically, nasal polyps, occur frequently in children with cystic fibrosis (CF). As survival rates have improved, it has become imperative that otolaryngologists become involved in the care of patients with CF to provide appropriate medical and surgical interventions for sinonasal disease. Despite significant variability in the subjective reporting of clinical symptoms, previous work has suggested there may be a relationship between clinical indicators and sinonasal disease in this population.\\n\\nOBJECTIVE: To determine whether the 22-item Sino-Nasal Outcome Test (SNOT-22), the University of Pennsylvania Smell Identification Test (UPSIT), and other measures of sinonasal disease could be used to predict the presence of subclinical nasal polyps in children with CF.\\n\\nDESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional study performed from May 2012 through April 2013 at a cystic fibrosis clinic at BC Children's Hospital in Vancouver, British Columbia, Canada. There were 72 eligible children with CF for this study (with a confirmed diagnosis of CF based on genetic testing; their ages ranged from 6 to 18 years, and they were not actively being treated by an otolaryngologist). Thirty-seven of these patients (23 males, 14 females) consented to participate in this study. Twenty-three declined participation, and 12 could not be contacted.\\n\\nMAIN OUTCOMES AND MEASURES: Potential clinical predictors for the presence of subclinical nasal polyps were determined a priori. All 37 recruited participants completed a full study assessment. Nasal endoscopy (the gold standard) was performed to determine the presence of nasal polyps. Potential predictors that were assessed included age, sex, genotype, pancreatic function, SNOT-22 and UPSIT scores, oral culture swab result, and severity of forced expiratory volume in 1 second (FEV(1)).\\n\\nRESULTS: A SNOT-22 score of greater than 11 was the only statistically significant predictor of nasal polyps (P\u2009=\u2009.04). The positive predictive value was 68.1%, the negative predictive value was 66.7%, and the positive likelihood ratio was 1.82.\\n\\nCONCLUSIONS AND RELEVANCE: Given that the SNOT-22 is easy to administer and inexpensive, this sinus disease-specific questionnaire seems to be an appropriate tool for routine use by respirologists when assessing patients with CF to help predict subclinical nasal polyps.", "author" : [ { "dropping-particle" : "", "family" : "Thamboo", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Santos", "given" : "Rachelle C. Dar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Naidoo", "given" : "Lalenthra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rahmanian", "given" : "Ronak", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chilvers", "given" : "Mark a.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chadha", "given" : "Neil K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "JAMA Otolaryngology\u2013Head & Neck Surgery", "id" : "ITEM-3", "issue" : "10", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "934", "title" : "Use of the SNOT-22 and UPSIT to Appropriately Select Pediatric Patients With Cystic Fibrosis Who Should Be Referred to an Otolaryngologist", "type" : "article-journal", "volume" : "140" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1016/0031-9384(84)90269-5", "ISBN" : "0031-9384", "ISSN" : "00319384", "PMID" : "6463130", "abstract" : "The development of the first standardized \"scratch'n sniff\" olfactory test is described. Over 1600 subjects participated in five experiments. In Experiment 1, 50 microencapsulated odorants were rated as to their intensity, pleasantness, irritation, coolness, and familiarity, and two procedures for releasing them were compared. In Experiment 2, the results of the first experiment and familiarity, and two procedures for releasing them were compared. In Experiment 2, the results of the first experiment and other data were used in the development of the test, which was administered to a large number of subjects. Using multiple regression analysis, scores on this test were shown to be significantly related to the subjects' gender, ethnic background, and smoking behavior. Average test scores decreased as a function of age, with the greatest decline occurring between the sixth and tenth decades of life. These age-related changes were not correlated with scores on the Wechsler Memory Scale. Women performed better than men within all age categories. In Experiment 3, the test was shown to differentiate between subjects with known olfactory disorders (e.g., Kallmann's syndrome; Korsakoff s syndrome) and normal controls, and to reliably detect persons instructed to feign total anosmia. In Experiment 4, the test-retest reliability was established (6-month interval; r=0.918, p<0.001), and in Experiment 5 the test was shown to correlate thresholds with odor detection (r=-0.794, p<0.001). This self-administratered test now makes it possible to rapidly and accurately assess general olfactory function in the laboratory, clinic, or through the mail without complex equipment or space-consuming stores of chemicals. ?? 1984.", "author" : [ { "dropping-particle" : "", "family" : "Doty", "given" : "Richard L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shaman", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dann", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Physiology and Behavior", "id" : "ITEM-4", "issue" : "3", "issued" : { "date-parts" : [ [ "1984" ] ] }, "page" : "489-502", "title" : "Development of the university of pennsylvania smell identification test: A standardized microencapsulated test of olfactory function", "type" : "article-journal", "volume" : "32" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "206\u2013209", "plainTextFormattedCitation" : "206\u2013209", "previouslyFormattedCitation" : "205\u2013208" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }206–209). The UPSIT does not require clinician supervision and is therefore very convenient. Accordingly, it is frequently used in the clinical setting, as well as in research (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s12070-011-0439-8", "ISBN" : "1207001104", "ISSN" : "22313796", "PMID" : "24427662", "abstract" : "The aim of this research was to verify the effect of functional endoscopic sinus surgery (FESS) on olfactory dysfunction in patients who suffer from chronic rhinosinusitis. We enrolled prospective consecutive patients at a tertiary institution who were undergoing FESS; for these patients prolonged medical therapy for chronic rhinosinusitis had failed. Patients were asked to grade their olfactory dysfunction from 1 to 5 with 1 representing lack of any smell function and 5 representing a completely normal sense of smell. Moreover, the pre- and postoperative smell identification test of the University of Pennsylvania was performed for all participating patients. In addition, data including computed tomography scores, nasal endoscopy, and the presence or absence of asthma as well as smoking habits were recorded and analyzed. Patients were followed at least 1 year after surgery. Data were collected on 89 patients who had undergone sinus surgery. Postoperative olfactory function was 77% improved for all subjects as a group. Higher involvement of sinus in computed tomography correlated with poorer results in olfactory UPSIT40 score. Patients' olfaction was significantly related to polyp pathology, duration of disease, age, smoking habits and history of asthma. A variety of patients' characteristics have impact on olfactory outcome of sinusitis patients after FESS.", "author" : [ { "dropping-particle" : "", "family" : "Saedi", "given" : "Babak", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sadeghi", "given" : "Mohammad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yazdani", "given" : "Nasrin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Afshari", "given" : "Akram", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Indian Journal of Otolaryngology and Head and Neck Surgery", "id" : "ITEM-1", "issue" : "SUPPL2", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "283-287", "title" : "Effectiveness of FESS in Smell Improvement of Sinusitis Patients", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1186/1472-6815-8-6", "ISSN" : "14726815", "PMID" : "18831771", "abstract" : "BACKGROUND: Patients undergoing any type of nasal surgery may experience degrees of postoperative olfactory dysfunction. We sought to investigate \"when\" the olfactory function recovers to its preoperative levels. METHODS: In this cohort design, 40 of 65 esthetic open rhinoplasty candidates with equal gender distribution, who met the inclusion criteria, were assessed for their olfactory function using the Smell Identification Test (SIT) with 40 familiar odors in sniffing bottles. All the patients were evaluated for the SIT scores preoperatively and postoperatively (at week 1, week 6, and month 6). RESULTS: At postoperative week one, 87.5% of the patients had anosmia, and the rest exhibited at least moderate levels of hyposmia. The anosmia, which was the dominant pattern at postoperative week 1, resolved and converted to various levels of hyposmia, so that no one at postoperative week 6 showed any such complain. At postoperative week six, 85% of the subjects experienced degrees of hyposmia, almost all being mild to moderate. At postoperative six month, the olfactory function had already reverted to the preoperative levels: no anosmia or moderate to severe hyposmia. A repeated ANOVA was indicative of significant differences in the olfactory function at the different time points. According to our post hoc Benfronney, the preoperative scores had a significant difference with those at postoperative week 1, week 6, but not with the ones at month 6. CONCLUSION: Esthetic open rhinoplasty may be accompanied by some degrees of postoperative olfactory dysfunction. Patients need a time interval of 6 weeks to 6 months to fully recover their baseline olfactory function.", "author" : [ { "dropping-particle" : "", "family" : "Shemshadi", "given" : "Hashem", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Azimian", "given" : "Mojtaba", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Onsori", "given" : "Mohammad Ali", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Azizabadi Farahani", "given" : "Mahdi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC ear, nose, and throat disorders", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "6", "title" : "Olfactory function following open rhinoplasty: A 6-month follow-up study.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Razmpa", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saedi", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Safavi", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohammadi", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "B-ENT", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "269-275", "title" : "Olfactory function after nasal plastic surgery", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "210\u2013212", "plainTextFormattedCitation" : "210\u2013212", "previouslyFormattedCitation" : "209\u2013211" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }210–212). The “Sniffin’ Sticks” are another popular psychophysical test battery, the classical version of which tests odour threshold (T) and discrimination (D) in addition to identification (I) (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "abstract" : "'Sniffin' Sticks' is a new test of nasal chemosensory performance based on pen-like odor dispensing devices. It comprises three tests of olfactory function, namely tests for odor threshold (n-butanol, testing by means of a single staircase), odor discrimination (16 pairs of odorants, triple forced choice) and odor identification (16 common odorants, multiple forced choice from four verbal items per test odorant). After extensive preliminary investigations the tests were applied to a group of 104 healthy volunteers (52 female, 52 male, mean age 49.5 years, range 18-84 years) in order to establish test-retest reliability and to compare them with an established measure of olfactory performance (the Connecticut Chemosensory Clinical Research Center Test, CCCRC). Performance decreased with increasing age of the subjects (P < 0.001). Coefficients of correlation between sessions 1 and 2 were 0.61 for thresholds, 0.54 for discrimination and 0.73 for identification. Butanol thresholds as obtained with the CCCRC increased as a function of age; this relation to the subjects' age was not found for the CCCRC odor identification task. The test-retest reliability for CCCRC thresholds was 0.36, for odor identification it was 0.60. It is concluded that 'Sniffin' Sticks' may be suited for the routine clinical assessment of olfactory performance. Chem Senses 22: 39-52, 1997.", "author" : [ { "dropping-particle" : "", "family" : "Hummel", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sekinger", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wolf", "given" : "S R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pauli", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kobal", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemical Senses", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "1997" ] ] }, "page" : "39-52", "title" : "'Sniffin' Sticks': Olfactory Performance Assessed by the Combined Testing of Odor Identification, Odor Discrimination and Olfactory Threshold", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "214", "plainTextFormattedCitation" : "214", "previouslyFormattedCitation" : "213" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }214). This tool utilises reusable odourant ‘pens’ which are presented to the subject by an examiner. A three-alternate forced choice paradigm is employed for odour threshold and discrimination, whilst odour identification is tested using four-alternate forced choice written/visual cues. Composite ‘TDI’ scores from the individual subtests are used in diagnosis, and higher scores indicate better olfactory function. Again, this assessment tool is reliable, has been validated in different countries, and normative data are available for children (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00405-006-0173-0", "ISBN" : "0937-4477 (Print)\\n0937-4477 (Linking)", "ISSN" : "09374477", "PMID" : "17021776", "abstract" : "\"Sniffin' Sticks\" is a test of nasal chemosensory function that is based on pen-like odor dispensing devices, introduced some 10 years ago by Kobal and co-workers. It consists of tests for odor threshold, discrimination, and identification. Previous work established its test-retest reliability and validity. Results of the test are presented as \"TDI score\", the sum of results obtained for threshold, discrimination, and identification measures. While normative data have been established they are based on a relatively small number of subjects, especially with regard to subjects older than 55 years where data from only 30 healthy subjects have been used. The present study aimed to remedy this situation. Now data are available from 3,282 subjects as compared to data from 738 subjects published previously. Disregarding sex-related differences, the TDI score at the tenth percentile was 24.9 in subjects younger than 15 years, 30.3 for ages from 16 to 35 years, 27.3 for ages from 36 to 55 years, and 19.6 for subjects older than 55 years. Because the tenth percentile has been defined to separate hyposmia from normosmia, these data can be used as a guide to estimate individual olfactory ability in relation to subject's age. Absolute hyposmia was defined as the tenth percentile score of 16-35 year old subjects. Other than previous reports the present norms are also sex-differentiated with women outperforming men in the three olfactory tests. Further, the present data suggest specific changes of individual olfactory functions in relation to age, with odor thresholds declining most dramatically compared to odor discrimination and odor identification.", "author" : [ { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kobal", "given" : "G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gudziol", "given" : "H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mackay-Sim", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Archives of Oto-Rhino-Laryngology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "237-243", "title" : "Normative data for the \"Sniffin' Sticks\" including tests of odor identification, odor discrimination, and olfactory thresholds: An upgrade based on a group of more than 3,000 subjects", "type" : "article-journal", "volume" : "264" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1111/j.1749-4486.2012.02431.x", "ISBN" : "1749-4486", "ISSN" : "17494478", "PMID" : "22433135", "abstract" : "OBJECTIVE: The 'Sniffin' Sticks' olfactory test contains pen-like odour dispensing devices which are used to assess olfactory threshold, discrimination and identification. Odour identification is strongly dependent on familiarity with the odours and has an important cultural component which has limited the usefulness of other validated tests. The 'Sniffin' Sticks' test was developed in Germany and is validated in other countries but not in the UK. This study aims to validate the applicability of 'Sniffin' Sticks' in a local population.\\n\\nDESIGN: Prospective controlled study.\\n\\nSETTING: Rhinology or olfactory disorder clinic.\\n\\nPARTICIPANTS: About 82 subjects, 33 healthy volunteers with a reported normal sense of smell, and 49 patients with an impaired sense of smell presenting either at a rhinology or an olfactory disorder clinic. Each subject's olfactory function was assessed using the 'Sniffin' Sticks' test with a maximum score of 48.\\n\\nMAIN OUTCOME MEASURES: Threshold, discrimination and identification scores along with the combined olfactory score.\\n\\nRESULTS: The mean age of the subjects tested was 46.7 years; 46 female and 36 male. In the patient group 36 were hyposmic and 13 anosmic. In the healthy volunteers group all subjects were normosmic. In the control group the mean combined olfactory score was 34.5 (\u00b12.5). The mean combined score in the patients group was 20.8 (\u00b17.4). Odour threshold scores were 3.7(\u00b12.8) for patients (hyposmics and anomics) and 8.3(\u00b11.8) for controls. In the identification test the controls mean score was 13.6 (\u00b11.2) for while the patients' mean score was 8.6 (\u00b13.5).\\n\\nCONCLUSIONS: In our sample of the local population the combined olfactory and odour identification scores for healthy volunteers and patients with olfactory disorders are comparable with the normative data published on large samples of European populations. However, modification of a few of the distracters is recommended for British patients based on our findings.", "author" : [ { "dropping-particle" : "", "family" : "Neumann", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsioulos", "given" : "K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Merkonidis", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salam", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clark", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Philpott", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Otolaryngology", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "23-27", "title" : "Validation study of the \"Sniffin' Sticks\" olfactory test in a British population: A preliminary communication", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISBN" : "0300-0729", "ISSN" : "03000729", "PMID" : "19145999", "abstract" : "OBJECTIVE: Sniffin sticks battery is a well-validated olfactory test in German speaking population. However adaptation of this test in the cultural background of a country is mandatory before use. MATERIALS AND METHODS: In total 258 subjects were tested in two stages. The first stage included assessment of 60 healthy subjects with the exact translation of Sniffin' Sticks list and recognition of problematic items. In the second stage a modified list after linguistic changes was tested in a representative for the Greek population study group of 198 healthy subjects. Their results were correlated with a sample of 198 Germans of similar age and sex distribution from the German normative data of Sniffin' Sticks. RESULTS: The use of the initial list showed decreased odour identification (< 70%) of 6 items (anis, turpentine, liquorice, apple, lemon, cinnamon). After the appropriate changes the results of the modified list presented significantly increased identification of all problematic items. Identification ability of Greek population showed significant correlation with the German study group having similar behaviour regarding age and gender differences. CONCLUSION: This study provides cultural adaptation of the Sniffin' Sticks olfactory identification test and normative data for the Greek population.", "author" : [ { "dropping-particle" : "", "family" : "Konstantinidis", "given" : "I.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Printza", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Genetzaki", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mamali", "given" : "K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kekes", "given" : "G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Constantinidis", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "292-296", "title" : "Cultural adaptation of an olfactory identification test: The Greek version of Sniffin' Sticks", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "nicht verf\u00fcgbar?", "ISBN" : "4951176289", "PMID" : "18349094", "author" : [ { "dropping-particle" : "", "family" : "Spronsen", "given" : "E", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ebbens", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fokkens", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Rhinology and Allergy", "id" : "ITEM-4", "issue" : "3", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "197-201", "title" : "Olfactory function in healthy children: normative data for odor identification", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "215\u2013218", "plainTextFormattedCitation" : "215\u2013218", "previouslyFormattedCitation" : "214\u2013217" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }215–218). Accordingly, “Sniffin’ Sticks” are used extensively in research (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "abstract" : "Aim: This prospective study aimed to assess treatment outcome on olfaction in patients undergoing Endoscopic Sinus Surgery (ESS) for nasal polyposis, and to evaluate the role of previous sinus surgery and the duration of olfactory deficit as prognostic factors for olfaction improvement. Methods: In total, 116 patients with nasal polyposis who underwent ESS were studied. Olfactory testing was performed using the Sniffin' Sticks test, preoperatively and 1-, 3- and 6-month postoperatively. Results: The values of the composite threshold discrimination identification score were significantly lower in patients with long duration of olfactory deficit and history of previous sinus surgery in all testing sessions. Adjustment for preoperative olfactory measures and all potential confounders revealed that both parameters remained strong independent predictors of normal olfactory function; a successful outcome was more frequent in patients with short duration of olfactory deficit and in patients who had not undergone previous sinus surgeries. However all patients achieved a significant stepwise increment of all indices of olfactory function over time, after ESS. Conclusions: Duration of olfactory deficit and previous sinus surgery presented highly significant predictive value for the short-term outcome of the olfactory function after ESS. However all patients suffering from nasal polyposis will probably improve olfaction significantly in a period up to six months after surgery.", "author" : [ { "dropping-particle" : "", "family" : "Danielides", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katotomichelakis", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balatsouras", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Riga", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Simopoulou", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kantas", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nikolettos", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2009" ] ] }, "note" : "Improvement after FESS dependent on duration of olf dysfunction -- > smaller OB? would this return with training in these patients\n\nLook at ref:\n2,3,8,19,21-23, 24", "page" : "172-180", "title" : "Evaluation of prognostic factors for olfaction in nasal polyposis treated by Endoscopic Sinus Surgery", "type" : "article-journal", "volume" : "47" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Federspil P, Wilhelm-Schwenk R", "given" : "Constantinidis J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "184-187", "title" : "Kinetics of olfactory function following endonasal sinus surgery for nasal polyposis", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.parkreldis.2008.12.005", "ISBN" : "1873-5126 (Electronic)", "ISSN" : "13538020", "PMID" : "19138875", "abstract" : "Previous data on the prevalence of olfactory dysfunction in Parkinson's disease (PD) range from 45% to 90%. The present multicenter study aimed to provide data on the prevalence of smell loss in a large sample of PD patients from three independent populations. Olfactory sensitivity was tested in 400 patients from Australia, Germany, and The Netherlands by means of a psychophysical olfactory test, the \"Sniffin' Sticks\", which is comprised of 3 subtests of olfactory function. Out of the total number of patients 45.0% presented as functionally anosmic, 51.7% were hyposmic, whereas only 3.3% were normosmic. This indicates that 96.7% of PD patients present with significant olfactory loss when compared to young normosmic subjects. This figure falls to 74.5%, however, when adjusted to age-related norms. Thus, olfactory dysfunction should be considered as a reliable marker of the disease. \u00a9 2008 Elsevier Ltd. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Haehner", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boesveldt", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berendse", "given" : "H. W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mackay-Sim", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fleischmann", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silburn", "given" : "P. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnston", "given" : "A. 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D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herting", "given" : "B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reichmann", "given" : "H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Parkinsonism and Related Disorders", "id" : "ITEM-3", "issue" : "7", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "490-494", "publisher" : "Elsevier Ltd", "title" : "Prevalence of smell loss in Parkinson's disease - A multicenter study", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "128,219,220", "plainTextFormattedCitation" : "128,219,220", "previouslyFormattedCitation" : "128,218,219" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }128,219,220). Other olfactory tests allow for the assessment of some, but not all components of olfaction. For example, the Connecticut Chemosensory Clinical Research Center Test assesses odour threshold and identification (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1288/00005537-198801000-00017", "ISBN" : "1531-4995", "ISSN" : "0023-852X", "PMID" : "3336267", "abstract" : "The olfactory test administered to patients at the Connecticut Chemosensory Clinical Research Center combines stability of outcome with sensitivity to variables known to affect olfaction (age, sex). The test, which pairs an odor threshold component with an odor identification component, readily resolves differences in function between patients and controls. It reveals differences in the distribution of functioning for various probable causes (nasal/sinus disease, postupper respiratory infection, and head trauma), proves sensitive to improvements in function caused by therapeutic intervention (ethmoidectomy, steroid administration for nasal/sinus disease), and correlates with objective signs of nasal/sinus disease (visual exam, x-ray). The two components of the test agree well, though the odor identification component seems somewhat more sensitive than the threshold component as currently designed.", "author" : [ { "dropping-particle" : "", "family" : "Cain", "given" : "W S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gent", "given" : "J F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goodspeed", "given" : "R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leonard", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Laryngoscope", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "1988" ] ] }, "page" : "83-88", "title" : "Evaluation of olfactory dysfunction in the Connecticut Chemosensory Clinical Research Center.", "type" : "article", "volume" : "98" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "221", "plainTextFormattedCitation" : "221", "previouslyFormattedCitation" : "220" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }221). As mentioned previously, odour identification tests are culturally specific. Certain odours may not be familiar to those outside the country where the specific test had been developed. For this reason, normative data should ideally be collected from local populations (e.g., ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "17529360", "author" : [ { "dropping-particle" : "", "family" : "Muirhead", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benjamin", "given" : "E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saleh", "given" : "H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Otorhinolaryngologist", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "99-103", "title" : "Is the University of Pennsylvania Smell Identification Test (UPSIT) valid for the UK population?", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "213", "plainTextFormattedCitation" : "213", "previouslyFormattedCitation" : "212" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }213) or alternatively local versions developed. (e.g., ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/coa.12212", "ISBN" : "1749-4486", "ISSN" : "17494478", "PMID" : "24373213", "author" : [ { "dropping-particle" : "", "family" : "Picillo", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iavarone", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pellecchia", "given" : "M. T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Amboni", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erro", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moccia", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vitale", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Longo", "given" : "K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Santangelo", "given" : "G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spina", "given" : "E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scannapieco", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Orefice", "given" : "G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barone", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Otolaryngology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "53-57", "title" : "Validation of an Italian version of the 40-item University of Pennsylvania Smell Identification Test that is physician administered: Our experience on one hundred and thirty-eight healthy subjects", "type" : "article-journal", "volume" : "39" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1007/s12078-015-9192-9", "ISSN" : "19365810", "author" : [ { "dropping-particle" : "", "family" : "Taherkhani", "given" : "Safa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moztarzadeh", "given" : "Fathollah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mehdizadeh Seraj", "given" : "Jalal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hashemi Nazari", "given" : "Seyed Saeed", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Taherkhani", "given" : "Farzad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gharehdaghi", "given" : "Jaber", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okazi", "given" : "Arash", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pouraghaei", "given" : "Sevda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemosensory Perception", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "183-191", "publisher" : "Chemosensory Perception", "title" : "Iran Smell Identification Test (Iran-SIT): a Modified Version of the University of Pennsylvania Smell Identification Test (UPSIT) for Iranian Population", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "206,207", "plainTextFormattedCitation" : "206,207", "previouslyFormattedCitation" : "205,206" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }206,207).Table 4 provides a list of psychophysical olfactory tests which have been used in research and/or clinical settings.[Table 4]Given the diagnostic utility of assessing multiple aspects of olfaction as described above, in combination with the apparent individual value of threshold testing, we suggest that psychophysical tools used in the comprehensive assessment of olfaction should ideally incorporate threshold testing as well as a test of suprathreshold function, for example identification. Recommendations:Psychophysical assessment tools used in clinical and research settings should include tests of odour threshold, and/or one of odour identification or discrimination. Ideally, however, testing should include two or three of these subcomponents.Psychophysical assessment tools should be reliable and validated for the target population.Olfactory testing in childrenMeasuring olfactory ability in children can be challenging since attention span can be limited and, for example, pairing of odor names with the smells may be age and location dependent (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/s40463-015-0061-y", "ISSN" : "1916-0216", "PMID" : "25890082", "abstract" : "BACKGROUND Detection of olfactory dysfunction is important for fire and food safety. Clinical tests of olfaction have been developed for adults but their use in children has been limited because they were felt to be unreliable in children under six years of age. We therefore administered two olfactory tests to children and compared results across tests. METHODS Two olfactory tests (Sniffin' Sticks and University of Pennsylvania Smell Identification Test (UPSIT)) were administered to 78 healthy children ages 3 to 12\u00a0years. Children were randomized to one of two groups: Group 1 performed the UPSIT first and Sniffin' Sticks second, and Group 2 performed Sniffin' Sticks first and UPSIT second. RESULTS All children were able to complete both olfactory tests. Performance on both tests was similar for children 5 and 6\u00a0years of age. There was an age-dependent increase in score on both tests (p\u2009<\u2009.01). Children performed better on the Sniffin' Sticks than the UPSIT (65.3% versus 59.7%, p\u2009<\u2009.01). There was no difference in performance due to order of test presentation. CONCLUSIONS The Sniffin' Sticks and UPSIT olfactory tests can both be completed by children as young as 5\u00a0years of age. Performance on both tests increased with increasing age. Better performance on the Sniffin' Sticks than the UPSIT may be due to a decreased number of test items, better ability to maintain attention, or decreased olfactory fatigue. The ability to reuse Sniffin' Sticks on multiple children may make it more practical for clinical use.", "author" : [ { "dropping-particle" : "", "family" : "Hugh", "given" : "Sarah C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siu", "given" : "Jennifer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forte", "given" : "Vito", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Campisi", "given" : "Paolo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papsin", "given" : "Blake C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Propst", "given" : "Evan J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of otolaryngology - head & neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "10", "publisher" : "BioMed Central", "title" : "Olfactory testing in children using objective tools: comparison of Sniffin' Sticks and University of Pennsylvania Smell Identification Test (UPSIT).", "type" : "article-journal", "volume" : "44" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "222", "plainTextFormattedCitation" : "222", "previouslyFormattedCitation" : "221" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }222). However, olfactory tests have been successfully used in children as young as five, with successful completion of the test increasing with age. As an alternative, for very young and/or noncompliant children, the ‘Smell Wheel’ has been used successfully in children as young as four (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.ijporl.2012.11.022", "ISSN" : "01655876", "abstract" : "OBJECTIVE\nOlfaction is important for nutrition, safety, and quality of life. Detecting smell loss in young children can be difficult, since many children with olfactory deficits do not recognize their problem and may even pretend to smell. The short attention span of some young children precludes testing with longer standardized olfactory tests. Currently there is a dearth of pediatric smell tests. In this study we evaluated the performance of 152 children and young adults on a game-like rotating \u201cSmell Wheel\u201d odor identification test. This forced-choice test, which can be self-administered, was designed to capture the child's imagination and to provide a standardized test measure with odors known to young children using a minimum number of trials. \n\nMETHOD\nThirty 4-5-year olds (10 female), 62 6-7-year olds (17 female), 30 10-11-year olds (18 female) and 30 18-19-year olds (15 female) were tested. Analysis of variance was used to assess the influences of sex and age on the test scores. \n\nRESULTS\nAll participants completed the simple and rapid test protocol. Test performance and age-related changes analogous to those obtained using longer tests were observed. Test scores of participants who self-administered the test were equivalent to those for whom the test was administered by the experimenter. \n\nCONCLUSION\nGood compliance and olfactory test findings congruent with literature results were obtained using the Smell Wheel, suggesting that this test may be useful in assessing olfactory function in pediatric settings where attentional demands are compromised and test time is limited.", "author" : [ { "dropping-particle" : "", "family" : "Cameron", "given" : "E. Leslie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doty", "given" : "Richard L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Pediatric Otorhinolaryngology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "346-350", "title" : "Odor identification testing in children and young adults using the smell wheel", "type" : "article-journal", "volume" : "77" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "223", "plainTextFormattedCitation" : "223", "previouslyFormattedCitation" : "222" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }223). The smell wheel is an 11-odour game-like test in which odors are identified using words and pictures. A pediatric version of “Sniffin’ Sticks” (a 14 odour identification test) is also available (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0101086", "ISSN" : "1932-6203", "author" : [ { "dropping-particle" : "", "family" : "Schriever", "given" : "Valentin A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mori", "given" : "Eri", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Petters", "given" : "Wenke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boerner", "given" : "Carolin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smitka", "given" : "Martin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" 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"plainTextFormattedCitation" : "224", "previouslyFormattedCitation" : "223" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }224).RecommendationWhen testing olfaction in children, the test should fit the motivation of the child and be culturally appropriate. Use of psychophysical tools to diagnose olfactory impairment When using psychophysical tools to define olfactory impairment and improvement, it is important that reference is made to normative data collected for that test. Hyposmia can be separated from normosmia using the 10th percentile of normal test scores gathered from a population of young, healthy subjects (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "abstract" : "'Sniffin' Sticks' is a new test of nasal chemosensory performance based on pen-like odor dispensing devices. It comprises three tests of olfactory function, namely tests for odor threshold (n-butanol, testing by means of a single staircase), odor discrimination (16 pairs of odorants, triple forced choice) and odor identification (16 common odorants, multiple forced choice from four verbal items per test odorant). After extensive preliminary investigations the tests were applied to a group of 104 healthy volunteers (52 female, 52 male, mean age 49.5 years, range 18-84 years) in order to establish test-retest reliability and to compare them with an established measure of olfactory performance (the Connecticut Chemosensory Clinical Research Center Test, CCCRC). Performance decreased with increasing age of the subjects (P < 0.001). Coefficients of correlation between sessions 1 and 2 were 0.61 for thresholds, 0.54 for discrimination and 0.73 for identification. Butanol thresholds as obtained with the CCCRC increased as a function of age; this relation to the subjects' age was not found for the CCCRC odor identification task. The test-retest reliability for CCCRC thresholds was 0.36, for odor identification it was 0.60. It is concluded that 'Sniffin' Sticks' may be suited for the routine clinical assessment of olfactory performance. Chem Senses 22: 39-52, 1997.", "author" : [ { "dropping-particle" : "", "family" : "Hummel", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sekinger", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wolf", "given" : "S R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pauli", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kobal", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemical Senses", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "1997" ] ] }, "page" : "39-52", "title" : "'Sniffin' Sticks': Olfactory Performance Assessed by the Combined Testing of Odor Identification, Odor Discrimination and Olfactory Threshold", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/0031-9384(84)90269-5", "ISBN" : "0031-9384", "ISSN" : "00319384", "PMID" : "6463130", "abstract" : "The development of the first standardized \"scratch'n sniff\" olfactory test is described. Over 1600 subjects participated in five experiments. In Experiment 1, 50 microencapsulated odorants were rated as to their intensity, pleasantness, irritation, coolness, and familiarity, and two procedures for releasing them were compared. In Experiment 2, the results of the first experiment and familiarity, and two procedures for releasing them were compared. In Experiment 2, the results of the first experiment and other data were used in the development of the test, which was administered to a large number of subjects. Using multiple regression analysis, scores on this test were shown to be significantly related to the subjects' gender, ethnic background, and smoking behavior. Average test scores decreased as a function of age, with the greatest decline occurring between the sixth and tenth decades of life. These age-related changes were not correlated with scores on the Wechsler Memory Scale. Women performed better than men within all age categories. In Experiment 3, the test was shown to differentiate between subjects with known olfactory disorders (e.g., Kallmann's syndrome; Korsakoff s syndrome) and normal controls, and to reliably detect persons instructed to feign total anosmia. In Experiment 4, the test-retest reliability was established (6-month interval; r=0.918, p<0.001), and in Experiment 5 the test was shown to correlate thresholds with odor detection (r=-0.794, p<0.001). This self-administratered test now makes it possible to rapidly and accurately assess general olfactory function in the laboratory, clinic, or through the mail without complex equipment or space-consuming stores of chemicals. ?? 1984.", "author" : [ { "dropping-particle" : "", "family" : "Doty", "given" : "Richard L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shaman", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dann", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Physiology and Behavior", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "1984" ] ] }, "page" : "489-502", "title" : "Development of the university of pennsylvania smell identification test: A standardized microencapsulated test of olfactory function", "type" : "article-journal", "volume" : "32" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "209,214", "plainTextFormattedCitation" : "209,214", "previouslyFormattedCitation" : "208,213" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }209,214). Typically, normosmia is related to young healthy people. In contrast, functional anosmia is defined on the basis of the empirical distribution of scores obtained by anosmic people (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00405-006-0173-0", "ISBN" : "0937-4477 (Print)\\n0937-4477 (Linking)", "ISSN" : "09374477", "PMID" : "17021776", "abstract" : "\"Sniffin' Sticks\" is a test of nasal chemosensory function that is based on pen-like odor dispensing devices, introduced some 10 years ago by Kobal and co-workers. It consists of tests for odor threshold, discrimination, and identification. Previous work established its test-retest reliability and validity. Results of the test are presented as \"TDI score\", the sum of results obtained for threshold, discrimination, and identification measures. While normative data have been established they are based on a relatively small number of subjects, especially with regard to subjects older than 55 years where data from only 30 healthy subjects have been used. The present study aimed to remedy this situation. Now data are available from 3,282 subjects as compared to data from 738 subjects published previously. Disregarding sex-related differences, the TDI score at the tenth percentile was 24.9 in subjects younger than 15 years, 30.3 for ages from 16 to 35 years, 27.3 for ages from 36 to 55 years, and 19.6 for subjects older than 55 years. Because the tenth percentile has been defined to separate hyposmia from normosmia, these data can be used as a guide to estimate individual olfactory ability in relation to subject's age. Absolute hyposmia was defined as the tenth percentile score of 16-35 year old subjects. Other than previous reports the present norms are also sex-differentiated with women outperforming men in the three olfactory tests. Further, the present data suggest specific changes of individual olfactory functions in relation to age, with odor thresholds declining most dramatically compared to odor discrimination and odor identification.", "author" : [ { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kobal", "given" : "G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gudziol", "given" : "H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mackay-Sim", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Archives of Oto-Rhino-Laryngology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "237-243", "title" : "Normative data for the \"Sniffin' Sticks\" including tests of odor identification, odor discrimination, and olfactory thresholds: An upgrade based on a group of more than 3,000 subjects", "type" : "article-journal", "volume" : "264" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "215", "plainTextFormattedCitation" : "215", "previouslyFormattedCitation" : "214" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }215)(ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s004050050223", "ISBN" : "0937-4477 (Print)\\r0937-4477 (Linking)", "ISSN" : "09374477", "PMID" : "10867835", "abstract" : "\"Sniffin' Sticks\" is a test of nasal chemosensory performance that is based on penlike odor-dispensing devices. It is comprised of three tests of olfactory function: tests for odor threshold, discrimination and identification. Previous work has already established its test-retest reliability and validity in comparison to established measures of olfactory sensitivity. The results of this test are presented as a composite TDI score--i.e., the sum of results obtained for threshold, discrimination and identification measures. The present multicenter investigation aimed at providing normative values in relation to different age groups. To this end, 966 patients were investigated in 11 centers. An additional study tried to establish values for the identification of anosmic patients, with 70 anosmics investigated in five specialized centers where the presence of anosmia was confirmed by means of olfactory evoked potentials. For healthy subjects, the TDI score at the 10th percentile was 24.5 in subjects younger than 15 years, 30.3 for ages from 16 to 35 years, 28.8 for ages from 36 to 55 years and 27.5 for subjects older than 55 years. While these data can be used to estimate individual olfactory abilities in relation to a subject's age, hyposmia was defined as the 10th percentile score of 16- to 35-year-old subjects. Our latter study revealed that none of 70 anosmics reached a TDI score higher than 15. This score of 15 is regarded as the cut-off value for functional anosmia. These results provide the basis for the routine clinical evaluation of patients with olfactory disorders using \"Sniffin' Sticks.\"", "author" : [ { "dropping-particle" : "", "family" : "Kobal", "given" : "G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klimek", "given" : "L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wolfensberger", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gudziol", "given" : "H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Temmel", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Owen", "given" : "C. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seeber", "given" : "H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pauli", "given" : "E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Archives of Oto-Rhino-Laryngology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2000" ] ] }, "page" : "205-211", "title" : "Multicenter investigation of 1,036 subjects using a standardized method for the assessment of olfactory function combining tests of odor identification, odor discrimination, and olfactory thresholds", "type" : "article-journal", "volume" : "257" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "225", "plainTextFormattedCitation" : "225", "previouslyFormattedCitation" : "224" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }225). In a clinical setting, psychophysical testing is most commonly performed birhinally, where results represent the better of the two sides (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0023-852X (Print)", "PMID" : "9432078", "abstract" : "Results of this study demonstrated that a new olfactory test, the \"Sniffin' Sticks,\" can be used to distinguish hyposmic patients with chronic sinusitis (n = 63) from control subjects. Dirhinic testing yielded improved olfactory sensitivity compared with monorhinic testing. However, dirhinic results were not significantly different from results obtained for the best nostril.", "author" : [ { "dropping-particle" : "", "family" : "Klimek", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moll", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kobal", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mann", "given" : "W J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Laryngoscope", "id" : "ITEM-1", "issue" : "1 Pt 1", "issued" : { "date-parts" : [ [ "1998" ] ] }, "page" : "111-114", "title" : "Lateralized and bilateral olfactory function in patients with chronic sinusitis compared with healthy control subjects.", "type" : "article-journal", "volume" : "108" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1093/chemse/bjg061", "ISBN" : "0379-864X (Print)", "ISSN" : "0379864X", "PMID" : "14627537", "abstract" : "The aim of this study was to investigate the accuracy of self-reported ratings of olfactory function in 83 healthy subjects. Such ratings were compared with quantitative measures of olfactory function, as well as with ratings of nasal patency. In experiment 1 subjects rated olfactory function and nasal patency before olfactory testing, whereas in experiment 2 the reverse was the case. No feedback regarding test results were provided until after completion of the testing. The principal findings were: (i) when ratings preceded measurements of olfactory function, there was no significant correlation between the two parameters. However, ratings of olfactory function correlated significantly with ratings of nasal airway patency. (ii) In contrast, when measurements of olfactory function preceded the ratings, this constellation switched. Now ratings of olfactory function correlated significantly with measured olfactory function, whereas there was no significant correlation between ratings of nasal airway patency and ratings of olfactory function. In conclusion, these data suggest that ratings of olfactory function are unreliable in healthy, untrained subjects. The ratings seem to reflect changes of nasal airway patency to a larger degree than measurable olfactory function. The results further indicate that this is mainly due to the limited attention the sense of smell receives in daily life.", "author" : [ { "dropping-particle" : "", "family" : "Landis", "given" : "Basile N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hugentobler", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giger", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lacroix", "given" : "J. S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemical Senses", "id" : "ITEM-2", "issue" : "8", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "691-694", "title" : "Ratings of overall olfactory function", "type" : "article-journal", "volume" : "28" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "27,226", "plainTextFormattedCitation" : "27,226", "previouslyFormattedCitation" : "27,225" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }27,226). However, increasing evidence suggests that lateralised olfactory testing may serve both diagnostic and prognostic utility. In 2007, Gudziol et al. reported results of monorhinal olfactory testing in 479 healthy controls, 765 patients with CRS and 53 patients with sinonasal or olfactory bulb neoplasms (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/MLG.0b013e3180330092", "ISBN" : "0023-852X (Print)\\r0023-852X (Linking)", "ISSN" : "0023-852X", "PMID" : "17473673", "abstract" : "BACKGROUND: Birhinal testing of odor identification will not allow the detection of unilateral olfactory loss. The aim of the presented study was to evaluate side differences of odor identification in large groups of healthy subjects and in patients with nasal symptoms.\\n\\nPARTICIPANTS AND METHOD: Self-assessment of olfactory function and evaluation of olfactory function by means of a validated test were performed in 479 healthy subjects, in 765 patients with chronic rhinosinusitis (CRS), and in 53 patients with a tumor. A 12-item odor identification test (\"Sniffin' Sticks\") was used to evaluate olfactory function separately for each nostril.\\n\\nRESULTS: Fifteen percent of the healthy subjects demonstrated side differences in the identification of at least 3 out of 12 odors. Healthy elderly subjects showed larger side differences in identification of odor than younger ones; a general difference between odor identification with the right or left nostril was not found. Both CRS patients and patients with a tumor had larger side differences than healthy subjects. Only 20% of the patients with a tumor complained about impaired olfactory sensitivity, but more than 75% of them showed deficits in olfactory tests.\\n\\nCONCLUSION: Side differences of odor identification of 25% or greater should give reason for further investigation. Future studies are needed to investigate whether side differences in healthy subjects are a predicator of a higher risk for general olfactory loss.", "author" : [ { "dropping-particle" : "", "family" : "Gudziol", "given" : "Volker", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Cornelia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Negoias", "given" : "Simona", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ishimaru", "given" : "Tadashi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Laryngoscope", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "808-11", "title" : "Lateralized differences in olfactory function.", "type" : "article-journal", "volume" : "117" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "227", "plainTextFormattedCitation" : "227", "previouslyFormattedCitation" : "226" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }227). Using a 12-item screening version of the Sniffin’ Sticks odour identification test, they found lateralised differences in function of 3 or more points occurred in 15% of controls, 26% of patients with CRS and 32% of those with neoplasms. In 2010, Welge-Lussen and colleagues performed a similar study in 518 patients with olfactory dysfunction of mixed cause (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.4193/Rhin09.156", "ISSN" : "03000729", "PMID" : "20502752", "abstract" : "In clinical settings, olfactory testing is usually performed bilaterally; thus, unilateral olfactory loss may go unnoticed. The aims of this study were to evaluate 1) whether patients presenting with self-reported olfactory disorders demonstrate significant side differences in odour perception, depending on the prevalance of measured unilateral disorder, and 2) to evaluate the existing testing procedure. In 518 patients presenting with olfactory disorders, olfactory testing was performed using the \"Sniffin' Sticks\" test battery (consisting of a threshold, discrimination, and odour identification test) examining each nostril separately. According to the history and results from the clinical examination, olfactory disorders were classified as related to trauma, sinunasal disease, upper respiratory tract infection (URTI), tumour, congenital, idiopathic, and other. A difference of three or more points in one of the subtests or six or more points in the composite olfactory test score was considered a side difference. In almost one quarter of all presenting patients (23.4%), a side difference was detected. To not to miss lateralized disorders, we recommend testing each nostril separately. Depending on the presence or absence of a significant difference, testing then can be continued birhinally or separately for each nostril.", "author" : [ { "dropping-particle" : "", "family" : "Welge-L\u00fcssen", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gudzio", "given" : "Volker", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wolfensberger", "given" : "Markus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Humme", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "156-159", "title" : "Olfactory testing in clinical settings - is there additional benefit from unilateral testing?", "type" : "article-journal", "volume" : "48" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "228", "plainTextFormattedCitation" : "228", "previouslyFormattedCitation" : "227" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }228). Using the full Sniffin’ Stick test battery they demonstrated significant lateralised differences of between 12.5 and 57.1%, depending on cause, the largest side differences being in patients with neoplasms. This study went on to demonstrate that lateralised differences in threshold score correlated significantly with lateralised differences in discrimination, identification and composite TDI scores. Work from Huart and colleagues demonstrated asymmetrical olfactory function (using the “Sniffin’ Stick” test battery) in patients with mild cognitive impairment, which could be used to efficiently differentiate these patients from those with post-infectious impairment or age-matched controls (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3233/JAD-141494", "ISSN" : "18758908", "PMID" : "26402773", "abstract" : "BACKGROUND: Olfactory dysfunction is associated with Alzheimer's disease (AD), and already present at pre-dementia stage. OBJECTIVES: Based on the assumption that early neurodegeneration in AD is asymmetrical and that olfactory input is primarily processed in the ipsilateral hemisphere, we assessed whether unirhinal psychophysical and electrophysiological assessment of olfactory function can contribute to the diagnostic workup of mild cognitive impairment (MCI). METHODS: Olfactory function of 13 MCI patients with positive amyloid PET, 13 aged-matched controls (AC) with negative amyloid PET and 13 patients with post-infectious olfactory loss (OD) was assessed unirhinally using (1) psychophysical testing of olfactory detection, discrimination and identification performance and (2) the recording of olfactory event-related brain potentials. Time-frequency analysis was used to enhance the signal-to-noise ratio of the electrophysiological responses. Psychophysical and electrophysiological assessment of auditory and trigeminal chemosensory function served as controls. RESULTS: As compared to AC and OD, MCI patients exhibited a significant asymmetry of olfactory performance. This asymmetry efficiently discriminated between MCI and AC (sensitivity: 85% , specificity: 77% ), as well as MCI and OD (sensitivity: 85% , specificity: 70% ). There was also an asymmetry of the electrophysiological responses, but not specific for MCI. In both MCI and OD, olfactory stimulation of the best nostril elicited significantly more activity than stimulation of the worse nostril, between 3-7.5 Hz and 1.2-2.0 s after stimulus onset. Trigeminal and auditory psychophysical testing did not show any difference between groups. CONCLUSION: MCI patients exhibit a marked asymmetry of behavioral olfactory function, which could be useful for the diagnostic workup of MCI.", "author" : [ { "dropping-particle" : "", "family" : "Huart", "given" : "Caroline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rombaux", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "G\u00e9rard", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hanseeuw", "given" : "Bernard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lhommel", "given" : "Renaud", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Quenon", "given" : "Lisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ivanoiu", "given" : "Adrian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mouraux", "given" : "Andr\u00e9", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Alzheimer's Disease", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "253-270", "title" : "Unirhinal Olfactory Testing for the Diagnostic Workup of Mild Cognitive Impairment", "type" : "article-journal", "volume" : "47" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "229", "plainTextFormattedCitation" : "229", "previouslyFormattedCitation" : "228" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }229). Imaging studies have additionally shown correlation between monorhinal test scores and ipsilateral olfactory bulb volume (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.neuroscience.2013.01.044", "ISBN" : "0306-4522", "ISSN" : "03064522", "PMID" : "23376116", "abstract" : "The present study aimed to investigate whether side differences in olfactory bulb (OB) volume correlate to respective differences in olfactory function. In a total of 164 healthy volunteers volumetric measures of the OBs were performed plus lateralized measurements of odor thresholds and odor discrimination. Side differences were defined as 10% difference between the left and right OB. In 39 cases volumes on the right side were larger than on the left side, whereas in 29 cases it was the other way around. Subjects with larger right-sided OB volumes were found to be more sensitive to odorous stimulation of the right as compared to the left nostril in terms of odor thresholds and odor detection; higher sensitivity of the left nostrils (decreased odor threshold) was observed in individuals with larger OB volumes on the left side. These data appear to suggest that OB volume may be partly dependent on lateralized influences on the olfactory system, reflecting its lateralized organization. ?? 2013 IBRO.", "author" : [ { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haehner", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Croy", "given" : "I.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iannilli", "given" : "E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Neuroscience", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "51-55", "title" : "Lateralized differences in olfactory bulb volume relate to lateralized differences in olfactory function", "type" : "article-journal", "volume" : "237" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "230", "plainTextFormattedCitation" : "230", "previouslyFormattedCitation" : "229" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }230). With regards to prognosis, follow-up work by Gudziol et al. showed that patients with lateralised olfactory differences were more likely to develop bilateral dysfunction than those without side differences (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00415-009-5445-3", "ISBN" : "0041500954", "ISSN" : "03405354", "PMID" : "20047056", "abstract" : "It is estimated that 15% of normosmic subjects demonstrate lateralized smell loss. The majority of individuals will not notice this difference between nostrils as long as olfactory function of the better nostril remains in the normal range. We were interested in the question whether subjects demonstrating clinically significant side differences of olfactory function are at risk to develop bilateral olfactory loss. Normosmic individuals with such side differences (\"difference group\", n = 35) were re-tested on average 4.6 years after baseline investigations. Additionally, 58 subjects who did not demonstrate side differences (\"control group\") were also re-investigated. All participants received detailed olfactory testing using the \"Sniffin' Sticks\" involving tests for odor threshold, odor discrimination, and odor identification. Olfactory testing at follow-up indicated lower olfactory function (p = 0.005) in the \"difference group\" than in the \"control group\". The degree of side difference at baseline correlated negatively with the results from olfactory testing at follow-up (r = -0.29; p = 0.01). These results suggest that individuals with side differences of olfactory function are at risk to develop bilateral olfactory loss within 4.5 years. Thus, the degree of lateralized smell function is an indicator for future smell loss.", "author" : [ { "dropping-particle" : "", "family" : "Gudziol", "given" : "Volker", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Paech", "given" : "Irene", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Neurology", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "959-963", "title" : "Unilateral reduced sense of smell is an early indicator for global olfactory loss", "type" : "article-journal", "volume" : "257" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "231", "plainTextFormattedCitation" : "231", "previouslyFormattedCitation" : "230" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }231). Should lateralized olfactory testing be considered, even in a time-pressured clinical setting, psychophysical testing could begin with monorhinal odour threshold testing. Where there is no significant difference in threshold score (for Sniffin’ Sticks, <2.5 points) between the right and left sides, testing can continue birhinally. However, where a lateralised difference is present, full monorhinal testing should be performed.Recommendations:Definitions of olfactory impairment should only be made with reference to normative values for the psychophysical test being used.Psychophysical testing should ideally begin with monorhinal testing, if feasible. Where there is no significant difference in lateralised scores, testing may continue bihrinally. Use of psychophysical tools to define clinically relevant change in olfactory functionThe final consideration when using psychophysical tools to characterise olfactory function is the minimum test score change required to indicate clinical improvement or deterioration. This is particularly important when reporting the results of longitudinal prognostic studies and when assessing interventions: whilst there may be a statistically significant improvement in olfactory test scores following some form of treatment, this will not necessarily reflect an improvement in subjective disease burden, unless the change is of sufficient magnitude to be clinically relevant (i.e. has reached the minimal clinically important difference) (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/01.mlg.0000234915.51189.cb", "ISBN" : "0000234915", "ISSN" : "0023-852X", "PMID" : "17003712", "abstract" : "BACKGROUND: Although widely used in healthy subjects and patients with olfactory loss, the significance of changes of scores from validated olfactory tests is unknown. AIM AND METHODS: The aim of the present study was to relate the self-assigned changes of olfactory function in terms of \"better,\" \"unchanged,\" and \"worse\" in patients with smell disorders with the results from olfactory testing by means of a validated test set. Olfactory function of 83 anosmic or hyposmic patients (40 women, 43 men; age 12-84 yr) was tested on two occasions (mean interval 136 days, minimum 7 days, maximum 6.7 yr). Olfactory function was assessed using a validated technique (\"Sniffin' Sticks\"). This test consists of three subtests, one for odor threshold (T), odor discrimination (D), and odor identification (I), with possible results ranging up to 16 points each. From the sum of the results from the three subtests a composite \"TDI\" score was obtained. RESULTS: Forty-four patients indicated an improvement of olfactory function, whereas 39 patients reported no change. No subject reported deterioration of olfactory sensitivity. Subjects assigned to group BETTER had higher TDI scores in the second olfactory tests than subjects assigned to the group UNCHANGED, both in absolute terms and as compared with the first olfactory test (effect \"test occasion\" by \"self-assessed improvement,\" P < .001). There was no significant difference between groups with respect to age and sex (P = .99 and .84, respectively). Logistic regression showed that more than 60% of the subjects reported an improvement of olfactory sensitivity when the TDI score increased by 5.5 points. CONCLUSION: We show that there is a statistically significant relation between measured and perceived improvement of olfactory function in patients who first presented with the diagnosis of anosmia or hyposmia. The results indicate that improved olfactory function in patients with olfactory deficiency is perceived as such in everyday life and is quantitatively related to an improvement in the composite TDI score of the \"Sniffin' Sticks\" olfactory test battery. This is the basis for the application of a specific therapy for olfactory loss because of a possible gain in quality of life for the patients.", "author" : [ { "dropping-particle" : "", "family" : "Gudziol", "given" : "Volker", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "L\u00f6tsch", "given" : "J\u00f6rn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "H\u00e4hner", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zahnert", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Laryngoscope", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2006" ] ] }, "note" : "Clinically significant improvement in olfaction when:\nTDI >/= 5.5\nT >/= 2.5\nI/D >/= 3", "page" : "1858-1863", "title" : "Clinical significance of results from olfactory testing.", "type" : "article-journal", "volume" : "116" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "232", "plainTextFormattedCitation" : "232", "previouslyFormattedCitation" : "231" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }232) (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Doty", "given" : "RL", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yousem", "given" : "DM", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pham", "given" : "LT", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kreshak", "given" : "AA", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geckle", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "WW", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arch Neurol", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "1997" ] ] }, "page" : "1131-1140", "title" : "Olfactory dysfunction in patients with head trauma", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "117", "plainTextFormattedCitation" : "117", "previouslyFormattedCitation" : "117" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }117).Recommendations:When reporting changes in psychophysical test scores, improvement or deterioration in olfactory function should be defined according to established clinical correlates for that test.Psychophysical tests used in screeningIn a clinical context, olfactory screening tests are often required for identification of potential impairment in asymptomatic subjects (for example during pre-operative assessment for medico-legal reasons). Where screening is required, validated tools have been developed which allow for rapid differentiation between normosmia and impaired olfactory function. Such tests include the 12 item Cross-Cultural Smell Identification Test (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/00005537-199603000-00021", "ISSN" : "0023852X", "author" : [ { "dropping-particle" : "", "family" : "Doty", "given" : "Richard L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marcus", "given" : "Avron", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "William Lee", "given" : "W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Laryngoscope", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "1996", "3" ] ] }, "page" : "353-356", "publisher" : "John Wiley & Sons, Inc.", "title" : "Development of the 12-Item Cross-Cultural Smell Identification Test(CC-SIT)", "type" : "article-journal", "volume" : "106" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "233", "plainTextFormattedCitation" : "233", "previouslyFormattedCitation" : "232" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }233) or the 12-item identification adaptation of the “Sniffin’ Sticks” test (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1177/000348940111001015", "ISBN" : "0003-4894 (Print)\\r0003-4894 (Linking)", "ISSN" : "00034894", "PMID" : "11642433", "abstract" : "The study aimed to create a screening test on the basis of the odor identification test as used in the \"Sniffin' Sticks\" olfactory test kit. It should appeal to the practitioner in terms of 1) time required for testing, 2) reliability, 3) separation of \"normal\" from \"abnormal,\" and 4) the fact that it allows lateralized screening. Experiments should provide a normative database (number of subjects > 1,000), establish test-retest reliability (n > 100), and compare results from patients with olfactory loss (n > 200). The correlation between results on 2 repetitive tests was .78. The test differentiated anosmics, hyposmics, and normosmics (p < .001). None of the 112 anosmics reached a score higher than 8; the 90th percentile was at a score of 6. When only 6 odors were used for calculating scores, for anosmics the 95th percentile was at a score of 4. These data provide a basis for the screening of patients by means of \"Sniffin' Sticks.\"", "author" : [ { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Konnerth", "given" : "C. G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rosenheim", "given" : "K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kobal", "given" : "G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of Otology, Rhinology and Laryngology", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2001" ] ] }, "note" : "12 item screening\n11-12 = normosmia\n7-10 = hyposmia\n<7 = anosmia", "page" : "976-981", "title" : "Screening of olfactory function with a four-minute odor identification test: Reliability, normative data, and investigations in patients with olfactory loss", "type" : "article-journal", "volume" : "110" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "234", "plainTextFormattedCitation" : "234", "previouslyFormattedCitation" : "233" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }234). Where abnormalities are identified through screening, patients should then undergo full olfactory testing. Olfactory screening using dedicated psychophysical tools is felt to be preferable to subjective assessment alone, as self-reported symptom questionnaires are not as sensitive or specific as screening odour identification testing, particularly for mild hyposmia (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s12078-014-9170-7", "ISSN" : "1936-5802", "author" : [ { "dropping-particle" : "", "family" : "Rawal", "given" : "Shristi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoffman", "given" : "Howard J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chapo", "given" : "Audrey K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duffy", "given" : "Valerie B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemosensory Perception", "id" : "ITEM-1", "issue" : "3-4", "issued" : { "date-parts" : [ [ "2014", "12", "27" ] ] }, "page" : "108-116", "publisher" : "Springer US", "title" : "Sensitivity and Specificity of Self-Reported Olfactory Function in a Home-Based Study of Independent-Living, Healthy Older Women", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "235", "plainTextFormattedCitation" : "235", "previouslyFormattedCitation" : "234" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }235).Recommendations:Screening for abnormal olfactory function in asymptomatic patients should be undertaken using validated psychophysical tools. Patients with abnormal screening results should undergo full olfactory testing.Gustatory testingGustatory dysfunction occurs less frequently than olfactory impairment. The ability to distinguish subtleties of food flavor relies heavily on retronasal olfaction, including features unique to the human oropharynx and inspiratory airflow (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1073/pnas.1511495112", "ISSN" : "0027-8424", "author" : [ { "dropping-particle" : "", "family" : "Ni", "given" : "Rui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Michalski", "given" : "Mark H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brown", "given" : "Elliott", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doan", "given" : "Ngoc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zinter", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ouellette", "given" : "Nicholas T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shepherd", "given" : "Gordon M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Proceedings of the National Academy of Sciences", "id" : "ITEM-1", "issue" : "47", "issued" : { "date-parts" : [ [ "2015", "11", "24" ] ] }, "page" : "14700-14704", "publisher" : "National Academy of Sciences", "title" : "Optimal directional volatile transport in retronasal olfaction", "type" : "article-journal", "volume" : "112" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "236", "plainTextFormattedCitation" : "236", "previouslyFormattedCitation" : "235" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }236). Accordingly, when patients complain of “abnormal taste”, they are usually suffering from retronasal olfactory dysfunction (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Deems", "given" : "DA", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doty", "given" : "RL", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Settle", "given" : "RG", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arch Otolaryngol Head Neck Surg", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1991" ] ] }, "page" : "519-521", "title" : "Smell and taste disorders, a study of 750 patients from the University of Pennsylvania Smell and Taste Center", "type" : "article-journal", "volume" : "117" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "95", "plainTextFormattedCitation" : "95", "previouslyFormattedCitation" : "95" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }95). Retronasal olfaction can be tested by asking patients to identify flavoured powders. Such tests are useful where there is diagnostic uncertainty. For example, it has been demonstrated that in cases of sudden onset olfactory dysfunction, such as posttraumatic loss, both orthonasal and retronasal functions decline concurrently. However, more progressive dysfunction, such as is seen in sinonasal disease, may preferentially affect the orthonasal route whilst retronasal olfaction may be preserved (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "ooa10079 [pii]", "ISBN" : "0886-4470 (Print)", "ISSN" : "0886-4470", "PMID" : "11926917", "abstract" : "OBJECTIVES: To develop a test kit for the simple assessment of retronasal olfactory function and to compare orthonasal and retronasal olfactory function in healthy subjects and patients with olfactory disorders. DESIGN AND PATIENTS: We tested 230 individuals with normosmia, hyposmia, and anosmia using grocery-available powders. Initially, 30 different substances were investigated. Subjects identified each substance using a list with 4 verbal items (forced choice). After preliminary experiments, 20 items were selected according to the degree to which they were identified by normosmic and anosmic subjects. Orthonasal olfactory function was assessed psychophysically using \"sniffin' sticks,\" which includes tests for odor identification, discrimination, and butanol odor thresholds. In addition, anosmia was confirmed electrophysiologically by means of olfactory-evoked potentials. RESULTS: In healthy subjects, there was a test-retest reliability correlation of r(27) = 0.76 for retronasal olfactory function, which is similar to other odor identification tests. Retronasal testing in normosmic subjects allowed for the discrimination of sex-related differences, with women scoring higher than men (P =.007), and the identification of a slight decrease with age (r(120) = -0.20; P =.03). Orthonasal and retronasal identification of odors was found to correlate (r(86) = 0.78; P<.001). Retronasal testing allowed for the discrimination between normosmia, hyposmia, and anosmia (P<.001). In addition, retronasal performance of anosmic patients appeared to improve with duration of anosmia (P =.03). No difference was found between patients with anosmia of different origin. CONCLUSION: Results of the present investigation indicate that the assessment of retronasal olfactory function is possible using oral stimulus presentation.", "author" : [ { "dropping-particle" : "", "family" : "Heilmann", "given" : "Stefan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strehle", "given" : "Gundel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rosenheim", "given" : "Kati", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Damm", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of otolaryngology--head & neck surgery", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2002" ] ] }, "page" : "414-418", "title" : "Clinical assessment of retronasal olfactory function.", "type" : "article-journal", "volume" : "128" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "237", "plainTextFormattedCitation" : "237", "previouslyFormattedCitation" : "236" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }237,ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/lary.20123", "ISBN" : "0023-852X", "ISSN" : "0023852X", "PMID" : "19235738", "abstract" : "OBJECTIVES: To develop and validate an olfactory test kit suitable for children and adults based on retronasal smelling of aromas combined with a sweet taste. Moreover, to explore the age limit at which olfactory testing is feasible and to extend the normative database for the validated \"Sniffin' Sticks\" test regarding children of younger ages. STUDY DESIGN: Randomized three-way crossover study in healthy children and adults. METHODS:: The newly developed Candy Smell Test (CST, 23 aromatized sorbitol candies) was presented using a four-alternative, forced-choice procedure. First, 353 healthy subjects (230 children and 123 adults) were investigated in three separate sessions with the CST and the validated \"Sniffin' Sticks\" (composed of odor threshold, discrimination, and identification tasks). Both tests were then compared in 124 patients with olfactory disorders. RESULTS: Test-retest reliability showed good reproducibility of the data obtained with the CST on 2 days (r(287) = 0.75, P < .001). Test results correlated significantly with the \"Sniffin' Sticks\" score (r(366) = 0.84, P < .001), although the CST proves to be much easier. The age limit for obtaining valid data was 7 years for both tests. The cutoff limit for the CST scores to separate normosmics from dysosmics was a score of 16 or less out of 23. Anosmia (cutoff score <or=13) was detected with a sensitivity of 94% and a specificity of 83%. CONCLUSIONS: The CST is an easy-to-use, reliable, and fast test of retronasal olfactory performance suitable for the screening of smell function in children above the age of 6 years and adults.", "author" : [ { "dropping-particle" : "", "family" : "Renner", "given" : "Bertold", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mueller", "given" : "Christian A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dreier", "given" : "Juergen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Faulhaber", "given" : "Stefanie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rascher", "given" : "Wolfgang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kobal", "given" : "Gerd", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Laryngoscope", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "487-495", "title" : "The Candy smell test: A new test for retronasal olfactory performance", "type" : "article-journal", "volume" : "119" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "238", "plainTextFormattedCitation" : "238", "previouslyFormattedCitation" : "237" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }238) As part of a full olfactory assessment, screening of gustatory function should be undertaken. This can be achieved using liquids applied to the tongue for sweet, salty, sour or bitter (umami is not commonly screened for as it is poorly identified) (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.fsc.2011.10.011", "ISBN" : "1064-7406", "ISSN" : "10647406", "PMID" : "22558054", "abstract" : "Olfaction and taste promote satisfaction and protection in daily life. The astute facial plastic surgeon recognizes the importance of a baseline smell test to document the patients' olfactory status before surgery. After surgery, the surgeon must be alert to the possible mechanisms of hyposmia and anosmia and the pertinent treatment strategies. The surgeon must also understand the importance of counseling the patient and family regarding the cause of the dysfunction and the proper treatments. This article updates the facial plastic surgeon on the importance of smell and taste and associated disorders with a current review of the literature. ?? 2012 Elsevier Inc.", "author" : [ { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Landis", "given" : "Basile", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huttenbrink", "given" : "Karl-Bernd", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Topics in Otorhinolaryngology- Head and Neck Surgery", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "1-15", "title" : "Smell and Taste Disorders", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "239", "plainTextFormattedCitation" : "239", "previouslyFormattedCitation" : "238" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }239). Where any abnormalities are identified, full gustatory testing should be undertaken using validated tests with normative data (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.4193/Rhin14.266", "ISSN" : "03000729", "PMID" : "26462295", "abstract" : "OBJECTIVE: Assessment of gustatory function in human subjects using the 'taste strips' test is an easy and validated procedure. The aim of this study was to extend this test in order to detect subjects with superior gustatory sensitivity.\\n\\nMETHODS: The investigation included 134 subjects (29.5\u00b112.6 years, range 18-84 years) with normal gustatory function. Four concentrations of sweet, sour, salty, and bitter were augmented with additional low concentrations (sweet: 25/12.5mg/ml sucrose; sour: 27/15mg/ml citric acid; salty: 6.4/2.6mg/ml sodium chloride, bitter: 0.15/0.06mg/ml quinine hydrochloride), resulting in a maximum extended taste score (ETS) of 24.\\n\\nRESULTS: The mean ETS was 14.5 \u00b1 3.2. Specifically, it was 4.5 \u00b1 1.2 for sweet, 2.8 \u00b1 1.0 for sour, 4.0 \u00b1 1.3 for salty, and 3.2 \u00b1 1.2 for bitter. In contrast to the original version of the taste strips test, no ceiling effect was observed. Cluster analysis separated three groups of subjects by ETS, whereas test scores derived from the original four concentrations were insufficient to discriminate the subgroup with higher gustatory sensitivity.\\n\\nCONCLUSIONS: The extended taste strips test seems to be a useful tool for the detection of patients with low gustatory thresholds for sweet, sour, salty, or bitter taste.", "author" : [ { "dropping-particle" : "", "family" : "Wolf", "given" : "Axel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Illini", "given" : "Oliver", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uy", "given" : "Daniel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Renner", "given" : "Bertold", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mueller", "given" : "Christian A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "45-50", "title" : "A new extension to the Taste Strips test", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1007/s00415-009-0088-y", "ISBN" : "1432-1459 (Electronic)\\n0340-5354 (Linking)", "ISSN" : "03405354", "PMID" : "19221845", "abstract" : "OBJECTIVE: To elaborate normative values for a clinical psychophysical taste test (\"Taste Strips\").\\n\\nBACKGROUND: The \"Taste Strips\" are a psychophysical chemical taste test. So far, no definitive normative data had been published and only a fairly small sample size has been investigated. In light of this shortcoming for this easy, reliable and quick taste testing device, we attempted to provide normative values suitable for the clinical use.\\n\\nSETTING: Normative value acquisition study, multicenter study.\\n\\nMETHODS: The investigation involved 537 participants reporting a normal sense of smell and taste (318 female, 219 male, mean age 44 years, age range 18-87 years). The taste test was based on spoon-shaped filter paper strips (\"Taste Strips\") impregnated with the four (sweet, sour, salty, and bitter) taste qualities in four different concentrations. The strips were placed on the left or right side of the anterior third of the extended tongue, resulting in a total of 32 trials. With their tongue still extended, patients had to identify the taste from a list of four descriptors, i. e., sweet, sour, salty, and bitter (multiple forced-choice). To obtain an impression of overall gustatory function, the number of correctly identified tastes was summed up for a \"taste score\".\\n\\nRESULTS: Taste function decreased significantly with age. Women exhibited significantly higher taste scores than men which was true for all age groups. The taste score at the 10(th) percentile was selected as a cut-off value to distinguish normogeusia from hypogeusia. Results from a small series of patients with ageusia confirmed the clinical usefulness of the proposed normative values.\\n\\nCONCLUSION: The present data provide normative values for the \"Taste Strips\" based on over 500 subjects tested.", "author" : [ { "dropping-particle" : "", "family" : "Landis", "given" : "B. N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Welge-Luessen", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bramerson", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bende", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mueller", "given" : "C. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nordin", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Neurology", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "242-248", "title" : "\"taste Strips\" - A rapid, lateralized, gustatory bedside identification test based on impregnated filter papers", "type" : "article-journal", "volume" : "256" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISBN" : "0300-0729 (Print)\\r0300-0729 (Linking)", "ISSN" : "03000729", "PMID" : "12677732", "abstract" : "Assessment of gustatory sensitivity in a clinical setting is the prerequisite for correct diagnosis and adequate treatment of taste dysfunction. Despite of this, no taste test has been established for the routine clinical testing. The aim of the present study was to create a protocol which is easy to administer. The presently used technique is based on strips made from filter paper which were impregnated with different taste solutions (four concentrations each for sweet, sour, salty and bitter). These strips are placed on the tongue and subjects are asked to identify the taste quality. After establishing the concentration range of the taste solutions, the test was tried in 69 subjects. Each subject received eighteen taste strips (four concentrations of each taste quality plus two blanks) in a pseudo-randomized sequence. Results from this new procedure correlated significantly with the results of the well established extensive three-drop-technique (r69 = 0.67). Repeated measures indicated good reproducibility of the results for the taste strips (r69 = 0.68). These data suggest the usefulness of this new technique in routine clinical practice. Major advantages are long shelf-life, convenience of administration, short time needed for testing (approximately 8 min), and the possibility to test each side of the tongue separately.", "author" : [ { "dropping-particle" : "", "family" : "Mueller", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kallert", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Renner", "given" : "B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stiassny", "given" : "K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Temmel", "given" : "A. F P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kobal", "given" : "G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-3", "issue" : "1", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "2-6", "title" : "Quantitative assessment of gustatory function in a clinical context using impregnated \"taste strips\"", "type" : "article-journal", "volume" : "41" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "abstract" : "BACKGROUND: Approximately 5% of the general population is affected by functional anosmia. An additional 15% exhibit decreased olfactory function. Many of these individuals ask ENT-doctors or neurologists for help. A cornerstone of the counselling process is the assessment of olfactory function. The aim of this work is to give a differentiated overview about the administration of commonly used psychophysical tests for olfactory and gustatory function including their normative data. METHODS: Numerous tests are available for the assessment of olfactory function. CONCLUSIONS: The use of standardized, reliable and validated tools is mandatory to provide patients with state-of the-art counseling on treatment options.", "author" : [ { "dropping-particle" : "", "family" : "Walliczek", "given" : "U.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Negoias", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "H\u00e4hner", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Curr Pharm Des", "id" : "ITEM-4", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "1-8", "title" : "Assessment of chemosensory function using \"Sniffin' Sticks\", taste strips, taste sprays, and retronasal olfactory tests.", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1093/chemse/bju060", "ISSN" : "0379-864X", "author" : [ { "dropping-particle" : "", "family" : "Pavlidis", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gouveris", "given" : "H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gorgulla", "given" : "H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hast", "given" : "H.-J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maurer", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemical Senses", "id" : "ITEM-5", "issue" : "3", "issued" : { "date-parts" : [ [ "2015", "3", "1" ] ] }, "page" : "165-171", "title" : "Electrogustometry and Contact Endoscopy Findings in Patients With Head and Neck Malignancies Treated With Chemotherapy, Radiotherapy, or Radiochemotherapy", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1016/j.bjorl.2014.04.002", "ISSN" : "18088694", "abstract" : "INTRODUCTION\nTaste is of great importance for the feeding process. Seen in this light, it is essential to investigate this sense in children as developing human beings. However, despite little variation in the use of tests that measure the gustatory capacity, there are still questions about the applicability and effective use of tools for quantitative assessment in children. \n\nOBJECTIVE\nTo search the literature on quantitative instruments used for the evaluation of taste used in studies with children. \n\nMETHODS\nA search was conducted in the PUBMED and Web of Science platforms, and subsequently, the identified articles were selected and reviewed. The descriptors and terms used were \u201ctaste,\u201d \u201cchild,\u201d \u201cassessment,\u201d \u201cdiagnosis,\u201d and \u201cdysgeusia\u201d. Original articles related to the theme in English, restricted to children and with no year limitation, were selected. Studies conducted in other stages of human development, exclusively or concurrently with the pediatric population; animal studies; literature review articles; dissertations and book chapters; and case studies and editorials were excluded. The data analysis was performed through a cataloging protocol created for this study, including the following points: author, research department, year, location, population/sample, age, purpose of the study, methods, and primary results. \n\nRESULTS\n5613 items were found. 5307 were excluded based on title, 248 by abstract analysis, and 43 by full text evaluation. Fifteen articles were selected for analysis; of these, six were repeated articles, and thus nine articles were selected for review. \n\nCONCLUSION\nThe tests aiming at evaluation of taste were judiciously used, ensuring reliability for future research, which may employ methods similar to previous studies. \n\nINTRODU\u00c7\u00c3O\nO paladar \u00e9 de grande import\u00e2ncia para o processo de alimenta\u00e7\u00e3o. Visto dessa forma, torna-se fundamental a averigua\u00e7\u00e3o deste sentido junto \u00e0s crian\u00e7as, que s\u00e3o seres em desenvolvimento. Por\u00e9m, apesar da pouca varia\u00e7\u00e3o na utiliza\u00e7\u00e3o de testes que mensuram a capacidade gustat\u00f3ria, ainda existe questionamento acerca da aplicabilidade e do uso eficaz dos instrumentos de avalia\u00e7\u00e3o quantitativa, especificamente na popula\u00e7\u00e3o infantil. \n\nOBJETIVO\nLevantar na literatura os instrumentos quantitativos para a avalia\u00e7\u00e3o do paladar utilizados em estudos com crian\u00e7as. \n\nM\u00c9TODO\nBusca dos artigos realizada nas plataformas PUBMED e Web of Science, seguindo etapas de sele\u00e7\u00e3o e an\u00e1lise cr\u00edtica dos peri\u00f3dicos encontr\u2026", "author" : [ { "dropping-particle" : "", "family" : "Moura", "given" : "Raissa Gomes Fonseca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cunha", "given" : "Daniele Andrade", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caldas", "given" : "Ada Salvetti Cavalcanti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silva", "given" : "Hilton Justino", "non-dropping-particle" : "da", "parse-names" : false, "suffix" : "" } ], "container-title" : "Brazilian Journal of Otorhinolaryngology", "id" : "ITEM-6", "issue" : "1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "97-106", "title" : "Quantitative evaluation of taste in childhood populations: a systematic review", "type" : "article-journal", "volume" : "81" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "DOI" : "10.1016/S0031-9384(00)00223-7", "ISSN" : "00319384", "abstract" : "Hyperemesis gravidarum or severe vomiting during pregnancy is a condition of elusive etiology that can harm both mother and fetus. This study examined the association between increased bitter-taste perception and history of hyperemesis gravidarum. Bitter-taste perception varies genetically and can be altered with conditions that damage taste-related cranial nerves. Sixty women were divided into high- (n = 21) and low-vomit (n = 39) groups based on vomiting exposure across all pregnancies and were screened for genetic variation in taste with bitterness of saturated 6-n-propylthiouracil (PROP) delivered on filter paper. Supertasters perceive PROP as intensely bitter; nontasters, as only weakly. Each reported their history of dysgeusia (persistent taste) and taste-related pathology (otitis media and head trauma). The vomit groups did not differ in the frequency of supertasters, but the high-vomit group had fewest nontasters. The high-vomit group also reported dysgeusia most frequently. A subsample (13 high-vomit and 18 low-vomit women) rated the taste intensity of sodium chloride (1 mol), sucrose (1 mol), citric acid (0.0032 mol), and quinine hydrochloride (0.001 mol) applied to areas innervated by cranial nerves VII and IX. The groups only varied significantly in bitterness of quinine hydrochloride. High-vomit women tasted least bitterness on the anterior tongue (chorda tympani branch of VII) and highest bitterness on the posterior tongue (cranial nerve IX) and palate (superficial petrosal branch of VII). In high-vomit women, elevated bitterness on the posterior tongue and palate does not appear related to hydrochloric acid exposure in vomitus; it may explain the occurrence of dysgeusia. This pattern of spatial taste perception may indicate altered oral sensations that if present during pregnancy, could increase the risk of hyperemesis.", "author" : [ { "dropping-particle" : "", "family" : "Sipiora", "given" : "M.L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Murtaugh", "given" : "M.A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gregoire", "given" : "M.B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duffy", "given" : "V.B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Physiology & Behavior", "id" : "ITEM-7", "issue" : "3", "issued" : { "date-parts" : [ [ "2000" ] ] }, "page" : "259-267", "title" : "Bitter taste perception and severe vomiting in pregnancy", "type" : "article-journal", "volume" : "69" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "240\u2013246", "plainTextFormattedCitation" : "240\u2013246", "previouslyFormattedCitation" : "239\u2013245" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }240–246). Recommendations:Comprehensive chemosensory assessment should include gustatory screening for sweet, salty, sour and bitter tastes.Full gustatory testing should be performed where abnormalities are identified on screening. Ideally, this should include discrimination between retronasal olfaction (flavours) and gustatory (taste) abnormalities.Electrophysiology and Functional ImagingWhilst subjective and psychophysical tools are sufficient for most clinical and research based testing, olfaction can also be assessed in a less subjective way using electrophysiological and imaging studies. Electrophysiological studies include electroencephalography (EEG) and electro-olfactography (EOG - the recording of generator potential via an electrode in contact with the olfactory neuroepithelium) (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.4193/Rhino11.126", "ISSN" : "03000729", "PMID" : "22469600", "abstract" : "Electroencephalographic techniques are widely used to provide an objective evaluation of the chemosensory function and to explore neural mechanisms related to the processing of chemosensory events. The most popular technique to evaluate brain responses to chemosensory stimuli is across trial time-domain averaging to reveal chemosensory event-related potentials (CSERP) embedded within the ongoing EEG. Nevertheless, this technique has a poor signal-to-noise ratio and cancels out stimulus-induced changes in the EEG signal that are not strictly phased-locked to stimulus onset. The fact that consistent CSERP are not systematically identifiable in healthy subjects currently constitutes a major limitation to the use of this technique for the diagnosis of chemosensory dysfunction. In this review, we will review the different techniques related to the recording and identification of CSERP, discuss some of their limitations, and propose some novel signal processing methods which could be used to enhance the signal-to-noise ratio of chemosensory event-related brain responses.", "author" : [ { "dropping-particle" : "", "family" : "Rombaux", "given" : "Ph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huart", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mouraux", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "13-21", "title" : "Assessment of chemosensory function using electroencephalographic techniques", "type" : "article-journal", "volume" : "50" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/0168-5597(88)90023-8", "ISBN" : "0168-5597", "ISSN" : "01685597", "PMID" : "2454788", "abstract" : "A stimulation method was employed by which chemosensory evoked potentials were recorded without tactile somatosensory contamination. The purpose of the study was to determine whether potential components evoked by stimulation of the chemoreceptors of the trigeminal nerve can be distinguished from those of the olfactory nerve. The stimulants (vanillin, phenylethyl alcohol, limonene, menthol, anethol, benzaldehyde, carbon dioxide and a mixture of vanilin and carbon dioxide) were presented in a randomized order to 13 volunteers. Chemosensory evoked potentials to substances which anosmics are unable to perceive (vanillin, phenylethyl alcohol) were termed olfactory evoked potentials; potentials to CO2, which effected no olfactory sensations were termed chemo-somatosensory potentials. Analysis of variance revealed that the different substances resulted in statistically significant changes in the amplitudes and latencies of the evoked potentials, and also in the subjective estimates of intensity. An increased excitation of the somatosensory system resulted in reduced latencies and enhanced amplitudes of the evoked potentials. Responses to the mixture of carbon dioxide and vanillin appeared significantly earlier (50\u2013150 msec) than responses to either substance alone.", "author" : [ { "dropping-particle" : "", "family" : "Kobal", "given" : "Gerd", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Cornelia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Electroencephalography and Clinical Neurophysiology/Evoked Potentials Section", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "1988" ] ] }, "page" : "241-250", "title" : "Cerebral chemosensory evoked potentials elicited by chemical stimulation of the human olfactory and respiratory nasal mucosa", "type" : "article-journal", "volume" : "71" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/0006-8993(96)00094-7", "ISBN" : "0006-8993", "ISSN" : "00068993", "PMID" : "8738266", "abstract" : "After chemical stimulation of the human olfactory epithelium it is possible to record a negative response (electro-olfactogram, EOG) which is interpreted as the summated receptor potentials of the olfactory nerve. The aim of the present investigation was to test the EOG's changes in relation to pairs of stimuli. Stimulation was performed with vanillin (0.8 ppm) regarded to exclusively excite fibers of the olfactory nerve. Ten healthy volunteers participated in the experiments. Pairs of stimuli were applied at different interstimulus intervals ISIs (2-8 s). EOG could be recorded in 6 out of 10 subjects. After olfactory stimulation the responses' peak amplitude was found to range from 0.15 to 1.8 mV. When pairs of olfactory stimuli were applied responses obtained at an ISI of 8 s were clearly separated whereas at an ISI of 2 s responses were superimposed on each other. As with an ISI of 8 s, the amplitude produced by the second stimulus was nearly as great as the first responses' amplitude (decrease by approximately 20%). In contrast, intensity estimates obtained in an additional experiment (n = 10) decreased by 40-60%. Based on the present data peripheral encoding in the olfactory system appears to be less subject to desensitization compared to the decrease of intensity estimates.", "author" : [ { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Knecht", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kobal", "given" : "G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Brain Research", "id" : "ITEM-3", "issue" : "1-2", "issued" : { "date-parts" : [ [ "1996" ] ] }, "page" : "160-164", "title" : "Peripherally obtained electrophysiological responses to olfactory stimulation in man: Electro-olfactograms exhibit a smaller degree of desensitization compared with subjective intensity estimates", "type" : "article-journal", "volume" : "717" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1016/j.physbeh.2004.07.024", "ISBN" : "0031-9384 (Print)", "ISSN" : "00319384", "PMID" : "15501486", "abstract" : "Electro-olfactograms (EOG) are electrical potentials of the olfactory epithelium that occur in response to olfactory stimulation. The EOG represents the sum of generator potentials of olfactory receptor neurons. While this response has been used extensively in animal research, there are only a handful of papers describing the properties of the human EOG. In addition to a discussion of methodological issues related to the EOG, this review summarizes the characteristics and uses of these recordings. Among other results, EOGs have been used to provide evidence for the dominant role of the central nervous system in olfactory desensitization, for the functional characterization of the olfactory epithelium, the specific topographical distribution of olfactory receptors, or the expression of olfactory receptor neurons in response to exposure to odorants, and the characterization of certain odorants as olfactory receptor antagonists. In conclusion, in combination with nasal endoscopy and air-dilution olfactometry, the EOG is a unique part of a large array of techniques used to provide a complete picture of the processing of olfactory information in humans. \u00a9 2004 Elsevier Inc. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Knecht", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Physiology and Behavior", "id" : "ITEM-4", "issue" : "1 SPEC. ISS.", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "13-19", "title" : "Recording of the human electro-olfactogram", "type" : "article-journal", "volume" : "83" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.4193/Rhino14.204", "author" : [ { "dropping-particle" : "", "family" : "Gottschlich", "given" : "Marie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-5", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "149-153", "title" : "Effects of handedness on olfactory event-related potentials in a simple olfactory task", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "247\u2013251", "plainTextFormattedCitation" : "247\u2013251", "previouslyFormattedCitation" : "246\u2013250" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }247–251). As EEG and EOG are both event-related, delivery of a known concentration of odorant must be precisely controlled using an olfactometer, which therefore limits the use of such testing for clinical purposes (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.ijpsycho.2010.07.007", "ISBN" : "2122633255", "ISSN" : "01678760", "PMID" : "20688109", "abstract" : "Many human olfactory experiments call for fast and stable stimulus-rise times as well as exact and stable stimulus-onset times. Due to these temporal demands, an olfactometer is often needed. However, an olfactometer is a piece of equipment that either comes with a high price tag or requires a high degree of technical expertise to build and/or to run. Here, we detail the construction of an olfactometer that is constructed almost exclusively with \"off-the-shelf\" parts, requires little technical knowledge to build, has relatively low price tags, and is controlled by E-Prime, a turnkey-ready and easily-programmable software commonly used in psychological experiments. The olfactometer can present either solid or liquid odor sources, and it exhibits a fast stimulus-rise time and a fast and stable stimulus-onset time. We provide a detailed description of the olfactometer construction, a list of its individual parts and prices, as well as potential modifications to the design. In addition, we present odor onset and concentration curves as measured with a photo-ionization detector, together with corresponding GC/MS analyses of signal-intensity drop (5.9%) over a longer period of use. Finally, we present data from behavioral and psychophysiological recordings demonstrating that the olfactometer is suitable for use during event-related EEG experiments. \u00a9 2010 Elsevier B.V.", "author" : [ { "dropping-particle" : "", "family" : "Lundstr\u00f6m", "given" : "Johan N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gordon", "given" : "Amy R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alden", "given" : "Eva C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boesveldt", "given" : "Sanne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Albrecht", "given" : "Jessica", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Psychophysiology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "179-189", "publisher" : "Elsevier B.V.", "title" : "Methods for building an inexpensive computer-controlled olfactometer for temporally-precise experiments", "type" : "article-journal", "volume" : "78" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "252", "plainTextFormattedCitation" : "252", "previouslyFormattedCitation" : "251" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }252). Instead, EEG is useful in medico-legal assessment as well as in patients who might not be able to comply with psychophysical testing. EOG testing is limited to the research setting.Functional imaging allows for the identification of brain activity in response to odourous stimuli, and includes positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0959-4388(02)00346-X", "ISBN" : "0959-4388 (Print)\\r0959-4388 (Linking)", "ISSN" : "09594388", "PMID" : "12139995", "abstract" : "Application of positron emission tomography and magnetic resonance imaging has provided several new insights into various olfactory functions. One is that sniffing and smelling engage separate subsystems in the human olfactory cortex. Another is that perception of odorous compounds (odorants) is mediated by a set of core regions, which are partly different for pure olfactory than for olfactory plus trigeminal odorants. Depending on the task associated with odor perception, the core regions are recruited together with other circuits, in a parallel and hierarchical manner. The sense of smell seems, therefore, to be organized similarly to other sensory modalities, and the specific psychophysical characteristics of olfaction should be attributed to an early involvement of the limbic system rather than to a conceptually different mode of processing.", "author" : [ { "dropping-particle" : "", "family" : "Savic", "given" : "Ivanka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Opinion in Neurobiology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2002" ] ] }, "note" : "Review", "page" : "455-461", "title" : "Imaging of brain activation by odorants in humans", "type" : "article-journal", "volume" : "12" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "253", "plainTextFormattedCitation" : "253", "previouslyFormattedCitation" : "252" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }253). Both techniques utilise changes in cerebral blood flow in order to map brain activity changes in response to stimuli (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1021/cn1000843", "ISBN" : "1948-7193 (Electronic) 1948-7193 (Linking)", "ISSN" : "19487193", "PMID" : "21503268", "abstract" : "Our knowledge regarding the neural processing of the three chemical senses has been lagging behind that of our other senses considerably. It is only during the last 25 years that significant advances have been made in our understanding of where in the human brain odors, tastants, and trigeminal stimuli are processed. Here we provide an overview of the current knowledge of how the human brain processes chemical stimuli based on findings in neuroimaging studies using positron emission tomography and functional magnetic resonance imaging. Additionally, we provide new insights from recent meta-analyses, based on all published neuroimaging studies of the chemical senses, of where the chemical senses converge in the brain.", "author" : [ { "dropping-particle" : "", "family" : "Lundstrom", "given" : "Johan N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boesveldt", "given" : "Sanne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Albrecht", "given" : "Jessica", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "ACS Chemical Neuroscience", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2011" ] ] }, "note" : "Very brief overview of the anatomical locations and functional activation re olfaction/gustation/chemesthesis....as of 2011", "page" : "5-16", "title" : "Central processing of the chemical senses: An overview", "type" : "article-journal", "volume" : "2" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "254", "plainTextFormattedCitation" : "254", "previouslyFormattedCitation" : "253" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }254). However, the use of radioactive isotopes for PET makes this a less attractive technique, and fMRI has become more common. The use of olfactory functional imaging is again typically limited to the research setting. Recommendations:Whilst electrophysiological and imaging studies are often reserved for research purposes, EEG based olfactory testing can be useful for medico-legal purposes. Other InvestigationsWhere olfactory dysfunction has been established, but no cause identified, or further information is needed, structural MRI scanning may be helpful (although there is an unresolved argument, e.g.: (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/alr.21066", "ISSN" : "20426976", "author" : [ { "dropping-particle" : "", "family" : "Decker", "given" : "Jennifer R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meen", "given" : "Eric K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kern", "given" : "Robert C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chandra", "given" : "Rakesh K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Forum of Allergy & Rhinology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "page" : "56-61", "publisher" : "Wiley Subscription Services, Inc., A Wiley Company", "title" : "Cost effectiveness of magnetic resonance imaging in the workup of the dysosmia patient", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "255", "plainTextFormattedCitation" : "255", "previouslyFormattedCitation" : "254" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }255) and (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/lary.23892", "ISSN" : "0023852X", "author" : [ { "dropping-particle" : "", "family" : "Higgins", "given" : "Thomas S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lane", "given" : "Andrew P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Laryngoscope", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2014", "1" ] ] }, "page" : "4-5", "title" : "What is the best imaging modality to investigate olfactory dysfunction in the setting of normal endoscopy?", "type" : "article-journal", "volume" : "124" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "256", "plainTextFormattedCitation" : "256", "previouslyFormattedCitation" : "255" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }256)). In doing so, the olfactory apparatus (olfactory neuroepithelium, the olfactory bulb and higher pathways) can be assessed, intracranial neoplasms (benign or malignant) excluded, undetected neoplasms in the nasal cavity or paranasal sinuses and asymptomatic chronic inflammation of the paranasal sinuses excluded, and traumatic brain injury characterised. It is of note that in head trauma the degree of olfactory loss can be predicted from brain lesion patterns (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.4193/Rhino15.010", "ISBN" : "4969630143", "ISSN" : "03000729", "author" : [ { "dropping-particle" : "", "family" : "Lotsch", "given" : "Jorn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reither", "given" : "Nicole", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bogdanov", "given" : "Vasyl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haehner", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ultsch", "given" : "Alfred", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hill", "given" : "Konstanze", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "365-370", "title" : "A brain-lesion pattern based algorithm for the diagnosis of posttraumatic olfactory loss", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "84", "plainTextFormattedCitation" : "84", "previouslyFormattedCitation" : "84" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }84). MRI scanning additionally allows for calculation of olfactory bulb volume, as well as olfactory sulcus depth. These structures are affected in a number of conditions, namely: post-infectious olfactory loss, neurodegenerative diseases, exposure to toxins and congenital olfactory dysfunction (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2214/ajr.166.2.8553963", "ISBN" : "0361-803X (Print)\\r0361-803X (Linking)", "ISSN" : "0361-803X", "PMID" : "8553963", "abstract" : "OBJECTIVE: The purpose of this study was to evaluate patients with reduced or no sense of smell since birth for sites of abnormality by MR imaging. MATERIALS AND METHODS: Twenty-five patients who reported no olfactory function since birth were evaluated by olfactory testing, sinonasal endoscopy, and MR imaging. Surface coil and head coil images of the olfactory bulbs, olfactory tracts, subfrontal cortex, and temporal lobes in contiguous 3-mm sections were obtained. Two reviewers determined unilateral olfactory bulb and tract volumes and temporal lobe volumes in two separate sessions. Qualitative grading for olfactory bulb, olfactory tract, olfactory sulcus, subfrontal region, hippocampus, and temporal lobe damage also was performed. RESULTS: The absence of olfactory bulbs and tracts (68-84%) or the presence of hypoplasia (16-32%) was noted in all cases. Eight individuals had Kallmann's syndrome (hypogonadotropic hypogonadism with anosmia). Temporal and/or frontal lobe volume loss was noted in five individuals and was mild in all but one individual. CONCLUSION: Congenital anosmia or hyposmia appears to be an olfactory bulb-olfactory tract phenomenon rather than a cerebral process.", "author" : [ { "dropping-particle" : "", "family" : "Yousem", "given" : "David M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geckle", "given" : "Rena J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bilker", "given" : "Warren B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McKeown", "given" : "D A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doty", "given" : "Richard L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "AJR Am J Roentgenol", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "1996" ] ] }, "page" : "439-443", "title" : "MR evaluation of patients with congenital hyposmia or anosmia", "type" : "article-journal", "volume" : "166" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISBN" : "0195-6108 (Print)\\r0195-6108 (Linking)", "ISSN" : "0195-6108", "PMID" : "11827889", "abstract" : "BACKGROUND AND PURPOSE: Anosmias with chromosomal disorders has been well investigated. However, isolated anosmia (IA) has received less attention, although it occurs more frequently. We compared frontobasal structures in patients with IA since birth or early childhood with those in control subjects. METHODS: Imaging findings obtained in 16 patients with IA were compared with those obtained in eight control subjects. Imaging was performed with a standard quadrature head coil at 1.5 T. T1-weighted spin-echo (coronal plane perpendicular to frontal skull base; section thickness, 3 mm; pixels, 0.43 x 0.39 mm) and sagittal T1-weighted magnetization-prepared rapid gradient-echo (voxels, 1.0 x 1.0 x 1.0 mm) sequences were performed. We assessed the length and depth of the olfactory sulcus, olfactory bulb volume, and olfactory sulcus depth in the plane of the posterior tangent through the eyeballs (PPTE). RESULTS: Five patients with IA had bilateral hypoplastic olfactory bulbs. Three patients with IA had hypoplastic olfactory bulbs on the right and aplastic olfactory bulbs on the left. Eight patients with IA had bilaterally aplastic olfactory bulbs. The depth of the olfactory sulcus at the level of the PPTE was smaller in patients with IA than in control subjects. The depth of the olfactory sulcus was greater on the right than on the left, and there was no overlap. Among patients with IA, the depth of the olfactory sulcus differed significantly between those with and those without visible olfactory tracts. CONCLUSION: The depth of the olfactory sulcus at the level of the PPTE reflects the presence of olfactory tracts. The presence or absence of the olfactory tract may therefore have some association with cortical growth of the olfactory sulcus region. The olfactory sulcus is deeper on the right than on the left, particularly in patients with IA. We speculate that olfaction may be processed predominantly in the right hemisphere.\\n", "author" : [ { "dropping-particle" : "", "family" : "Abolmaali", "given" : "Nasreddin D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hietschold", "given" : "Volker", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vogl", "given" : "Thomas J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huttenbrink", "given" : "Karl-Bernd", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Neuroradiology", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2002" ] ] }, "page" : "157-164", "title" : "MR Evaluation in Patients with Isolated Anosmia Since Birth or Early Childhood", "type" : "article-journal", "volume" : "23" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "145,149", "plainTextFormattedCitation" : "145,149", "previouslyFormattedCitation" : "145,149" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }145,149).Adjusted for age and gender, the olfactory bulb volume can be considered as normal, hypoplastic or aplastic. If the olfactory bulb volume is taken at the 10th percentile of the distribution, one can consider that an abnormal OB volume for a man <45 years is less than 58mm3 and for a man >45 years is less than 46mm3. A large number of studies have demonstrated that olfactory bulb volume is correlated to decreased olfactory perception in many disparate diseases (for review see: (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3390/molecules180911586", "ISSN" : "1420-3049", "abstract" : "In the last years, an increasing interest has been paid to the olfactory system, particularly to its abilities of plasticity and its potential continuous neurogenesis throughout adult life. Although mechanisms underlying adult neurogenesis have been largely investigated in animals, to some degree they remain unclear in humans. Based on human research findings, the present review will focus on the olfactory bulb as an evidence of the astonishing plasticity of the human olfactory system.", "author" : [ { "dropping-particle" : "", "family" : "Huart", "given" : "Caroline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rombaux", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Molecules", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2013", "9", "17" ] ] }, "page" : "11586-11600", "publisher" : "Multidisciplinary Digital Publishing Institute", "title" : "Plasticity of the Human Olfactory System: The Olfactory Bulb", "type" : "article-journal", "volume" : "18" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "257", "plainTextFormattedCitation" : "257", "previouslyFormattedCitation" : "256" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }257) ).In patients with CRS, traditional CT staging focused upon the paranasal sinuses correlates weakly with olfactory function, however, it appears that volumetric techniques to assess opacification of the olfactory cleft may provide additional information regarding olfactory function in certain subsets of patients (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/alr.21552", "ISSN" : "20426976", "author" : [ { "dropping-particle" : "", "family" : "Soler", "given" : "Zachary M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pallanch", "given" : "John F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sansoni", "given" : "Eugene Ritter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jones", "given" : "Cameron S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lawrence", "given" : "Lauren A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schlosser", "given" : "Rodney J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mace", "given" : "Jess C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Timothy L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Forum of Allergy & Rhinology", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2015", "9" ] ] }, "page" : "846-854", "title" : "Volumetric computed tomography analysis of the olfactory cleft in patients with chronic rhinosinusitis", "type" : "article-journal", "volume" : "5" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "183", "plainTextFormattedCitation" : "183", "previouslyFormattedCitation" : "183" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }183).Treatment of olfactory dysfunctionDespite considerable efforts within both the clinical and research communities, long-term, effective treatments for olfactory dysfunction largely remain elusive. In the following sections we will outline the more common, or more successful interventions currently available and their evidence base. Medications Currently, medication is the mainstay of treatment in olfactory dysfunction, with 89% of clinicians in a previous European survey preferring topical steroids irrespective of aetiology (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00106-003-0877-z", "ISSN" : "0017-6192", "author" : [ { "dropping-particle" : "", "family" : "Damm", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Temmel", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Welge-Lussen", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eckel", "given" : "H. E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kreft", "given" : "M.-P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klussmann", "given" : "J. P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gudziol", "given" : "H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "H\ufffdttenbrink", "given" : "K.-B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Hno", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "112-120", "title" : "Riechstorungen: Epidemiologie und Therapie in Deutschland, \u00d6sterreich und der Schweiz", "type" : "article-journal", "volume" : "52" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "92", "plainTextFormattedCitation" : "92", "previouslyFormattedCitation" : "92" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }92) (Table 5). CorticosteroidsWith regards to olfactory loss secondary to chronic rhinosinusitis ± nasal polyposis, evidence exists to support use of both topical and systemic steroids (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Federspil P, Wilhelm-Schwenk R", "given" : "Constantinidis J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "184-187", "title" : "Kinetics of olfactory function following endonasal sinus surgery for nasal polyposis", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1111/j.1398-9995.2008.01870.x", "ISSN" : "01054538", "PMID" : "19191775", "abstract" : "BACKGROUND: Nasal polyposis is a disease known to be associated with asthma. The management is anti-inflammatory, with topical and oral corticosteroids as the first-line treatment. The effect of surgical treatment on lower airway inflammation has not been sufficiently studied.\\n\\nAIM: The aim of this study is to investigate the effects of functional endoscopic sinus surgery (FESS) as well as fluticasone proprionate nasal drops (FPND) 400 microg b.i.d. on nasal and lower airway parameters in asthmatics with nasal polyposis.\\n\\nMETHODS: This was a prospective 21-week study of 68 patients with asthma and nasal polyposis, on the benefits of FESS on nasal '(butanol test, subjective olfaction, peak nasal inspiratory flow, congestion, rhinorrhoea, and polyp score)', and on the lower airway parameters (dyspnea, cough, mean daily peak expiratory flow rate (PEFR), and lung function tests). It also included a randomized, double-blind, placebo-controlled 14 weeks phase on FPND.\\n\\nRESULTS: Functional endoscopic sinus surgery significantly improved mean asthma symptom scores and daily PEFR and all nasal parameters including subjective and objective olfaction tests. This is the first study that shows the benefits of FESS on butanol tests in patients with nasal polyposis. We found no significant difference between topical treatment with FPND or placebo in the nasal or lower airway variables.\\n\\nCONCLUSION: Functional endoscopic sinus surgery improved nasal and asthma symptoms in patients with nasal polyposis. Functional endoscopic sinus surgery could be considered early in the natural course of nasal polyposis with concomitant asthma, as well as a second-line treatment in nasal polyposis patients with a reduced sense of smell. The potential benefits of FPND 400 microg b.i.d. were probably overshadowed by FESS.", "author" : [ { "dropping-particle" : "", "family" : "Ehnhage", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olsson", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kolbeck", "given" : "K. G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Skedinger", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dahl??n", "given" : "B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "??lenius", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stj??rne", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Allergy: European Journal of Allergy and Clinical Immunology", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "2009" ] ] }, "note" : "Ref for steroids and olfaction", "page" : "762-769", "title" : "Functional endoscopic sinus surgery improved asthma symptoms as well as PEFR and olfaction in patients with nasal polyposis", "type" : "article-journal", "volume" : "64" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISSN" : "00222151", "author" : [ { "dropping-particle" : "", "family" : "Golding-Wood", "given" : "D G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holmstrom", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Darby", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scadding", "given" : "G K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lund", "given" : "V J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J. Laryngol. Otol .", "id" : "ITEM-3", "issue" : "February", "issued" : { "date-parts" : [ [ "1996" ] ] }, "page" : "132-135", "title" : "The treatment of hyposmia with intranasal steroids", "type" : "article-journal", "volume" : "110" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "ISBN" : "0300-0729 (Print)\\r0300-0729", "ISSN" : "03000729", "PMID" : "14750349", "abstract" : "AIM: In this prospective study the effect of medical and surgical treatment on subjective olfaction was studied in patients with nasal polyposis (NPS). The effects on nasal obstruction, anterior and posterior rhinorrhea, sneezing and itching are reported in another article in this issue. PATIENTS AND METHODS: Protocol 1. Twenty-four patients with NPS who complained about anosmia were treated with a 7-days course of systemic steroids. Their subjective overall sense of smell was determined with a visual analog scale (VAS) before treatment, immediately after treatment, and two months later. Subsequently all patients underwent surgery bilaterally according to the nasalization principles. The sense of smell was re-evaluated at 1, 3, 6, 9, and 12 months postoperatively. Protocol 2. Thirty-two patients with NPS not responding to medical therapy who, for different reasons, did not receive oral steroid treatment, received surgery only and were followed up during one year after nasalization. Of these patients, 25 were anosmic and 7 normosmic. RESULTS: Protocol 1. Following the 7-day treatment with systemic steroids the olfactory score increased significantly. During the waiting time for surgery (64 +/- 39 days) this score deteriorated again in a significant way. One month after nasalization which included a depot injection of triamcinolone 80 mg the day after surgery, the olfactory score ameliorated again and remained stable at 3, 6, 9, and 12 months. None of the patients reported any intake of systemic steroids during the one-year of follow-up. Statistically, there was a trend suggesting that the 12 month post-nasalization score was better than the immediate post-oral steroid score. A good correlation between the improvement of the sense of smell after 7 days of systemic steroids and one year after nasalization was found. Protocol 2 One month after the nasalization protocol, olfaction in patients of the hypo-anosmic group had improved considerably. Scores at 3, 6, 9, and 12 remained very stable. The sense of smell in the normosmic group did not change after surgery and remained stable during the year of follow-up. In total, 49 patients with a severe loss of smell showed a significant improvement at 12 months after surgery. CONCLUSION: The present study shows that 1) long-lasting correction of olfactory dysfunction produced by nasal polyposis can be achieved through the combination of nasalization and low dose of nasal steroids, 2) middle turbinate resection does\u2026", "author" : [ { "dropping-particle" : "", "family" : "Jankowski", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bodino", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-4", "issue" : "4", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "220-230", "title" : "Olfaction in patients with nasal polyposis: Effects of systemic steroids and radical ethmoidectomy with middle turbinate resection (nasalisation)", "type" : "article-journal", "volume" : "41" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1002/lary.24330", "ISBN" : "0023-852x", "ISSN" : "15314995", "PMID" : "23901043", "abstract" : "OBJECTIVES/HYPOTHESIS: To assess the effect of oral plus intranasal corticosteroids on subjective outcomes (smell and nasal congestion) and objective outcomes (tissue eosinophilia and nitric oxide) in severe nasal polyposis (NP). STUDY DESIGN: After a 4-week steroid washout period (w0), severe NP were randomized into a treatment group (n = 67) that receive oral prednisone for 2 weeks (w2) plus intranasal budesonide for 12 weeks (w12), and a control group (n = 22) that received no steroid treatment. METHODS: Barcelona Smell Test 24 (BAST-24), nasal congestion, tissue eosinophilia, and nasal nitric oxide (nNO) were assessed. RESULTS: Before treatment, patients showed a significant impairment of smell detection (30.7 +/- 39.5%), identification (7.1 +/- 16.1%), and forced choice (13.8 +/- 23.3%) in BAST-24 compared to healthy population. At w2, the treatment group showed a significant improvement in detection, identification, and forced choice. Positive effect was also seen after 12 weeks of intranasal corticosteroids. A significant reduction of nasal congestion (1.17 +/- 1.0 vs. 2.73 +/- 0.5) and polyp tissue eosinophilia (10.9 +/- 4.2 vs. 41.2 +/- 12.2) with an increase of nNO (650 +/- 317 vs. 420 +/- 221 ppb) were observed at w2 compared to w0 and to the control group. These effects were also seen at w12. CONCLUSIONS: Combined oral and intranasal corticosteroids improve smell and nasal congestion and decrease nasal inflammation, as measured by reduced tissue eosinophilia and increased detection of nNO. Severity of smell loss correlates with degree of nasal congestion but not with inflammation, as measured by tissue eosinophilia or nasally exhaled nNO. Our findings suggest that improvement in smell may be related to improved conduction of odorants to the olfactory neuroepithelium.", "author" : [ { "dropping-particle" : "", "family" : "Alobid", "given" : "Isam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benitez", "given" : "Pedro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cardelus", "given" : "Sara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borja Callejas", "given" : "Francisco", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lehrer-Coriat", "given" : "Eduardo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pujols", "given" : "Laura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Picado", "given" : "Cesar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mullol", "given" : "Joaquim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Laryngoscope", "id" : "ITEM-5", "issue" : "1", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "50-56", "title" : "Oral plus nasal corticosteroids improve smell, nasal congestion, and inflammation in sino-nasal polyposis", "type" : "article-journal", "volume" : "124" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1002/alr.21373", "ISSN" : "20426976", "author" : [ { "dropping-particle" : "", "family" : "Banglawala", "given" : "Sarfaraz M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oyer", "given" : "Samuel L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lohia", "given" : "Shivangi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Psaltis", "given" : "Alkis J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soler", "given" : "Zachary M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schlosser", "given" : "Rodney J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Forum of Allergy & Rhinology", "id" : "ITEM-6", "issue" : "12", "issued" : { "date-parts" : [ [ "2014", "12" ] ] }, "page" : "986-994", "title" : "Olfactory outcomes in chronic rhinosinusitis with nasal polyposis after medical treatments: a systematic review and meta-analysis", "type" : "article-journal", "volume" : "4" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "220,258\u2013262", "plainTextFormattedCitation" : "220,258\u2013262", "previouslyFormattedCitation" : "219,257\u2013261" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }220,258–262). Indeed, extensive guidelines exist for the management of CRS, in which initial medical treatment with corticosteroids is recommended (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1013-0047", "PMID" : "22764607", "abstract" : "The European Position Paper on Rhinosinusitis and Nasal Polyps 2012 is the update of similar evidence based position papers published in 2005 and 2007.The document contains chapters on definitions and classification, we now also proposed definitions for difficult to treat rhinosinusitis, control of disease and better definitions for rhinosinusitis in children. More emphasis is placed on the diagnosis and treatment of acute rhinosinusitis. Throughout the document the terms chronic rhinosinusitis without nasal polyps and chronic rhinosinusitis with nasal polyps are used to further point out differences in pathophysiology and treatment of these two entities. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. Last but not least all available evidence for management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is analyzed and presented and management schemes based on the evidence are proposed.", "author" : [ { "dropping-particle" : "", "family" : "Fokkens", "given" : "Wytske J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lund", "given" : "Valerie J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mullol", "given" : "Joachim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bachert", "given" : "Claus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alobid", "given" : "Isam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baroody", "given" : "Fuad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cohen", "given" : "Noam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cervin", "given" : "Anders", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Douglas", "given" : "Richard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gevaert", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Georgalas", "given" : "Christos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goossens", "given" : "Herman", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harvey", "given" : "Richard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hellings", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hopkins", "given" : "Claire", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jones", "given" : "Nick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Joos", "given" : "Guy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kalogjera", "given" : "Livije", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kern", "given" : "Bob", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kowalski", "given" : "Marek", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Price", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Riechelmann", "given" : "Herbert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schlosser", "given" : "Rodney", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Senior", "given" : "Brent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thomas", "given" : "Mike", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Toskala", "given" : "Elina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voegels", "given" : "Richard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "De Yun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wormald", "given" : "Peter John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology. Supplement", "id" : "ITEM-1", "issue" : "23", "issued" : { "date-parts" : [ [ "2012", "3" ] ] }, "page" : "1-298", "title" : "European Position Paper on Rhinosinusitis and Nasal Polyps 2012.", "type" : "article-journal", "volume" : "50" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/alr.21695", "ISSN" : "2042-6984", "PMID" : "26889651", "abstract" : "BACKGROUND The body of knowledge regarding rhinosinusitis(RS) continues to expand, with rapid growth in number of publications, yet substantial variability in the quality of those presentations. In an effort to both consolidate and critically appraise this information, rhinologic experts from around the world have produced the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR:RS). METHODS Evidence-based reviews with recommendations(EBRRs) were developed for scores of topics, using previously reported methodology. Where existing evidence was insufficient for an EBRR, an evidence-based review (EBR)was produced. The sections were then synthesized and the entire manuscript was then reviewed by all authors for consensus. RESULTS The resulting ICAR:RS document addresses multiple topics in RS, including acute RS (ARS), chronic RS (CRS)with and without nasal polyps (CRSwNP and CRSsNP), recurrent acute RS (RARS), acute exacerbation of CRS (AECRS), and pediatric RS. CONCLUSION As a critical review of the RS literature, ICAR:RS provides a thorough review of pathophysiology and evidence-based recommendations for medical and surgical treatment. It also demonstrates the significant gaps in our understanding of the pathophysiology and optimal management of RS. Too often the foundation upon which these recommendations are based is comprised of lower level evidence. 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"parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Woodworth", "given" : "Bradford A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wormald", "given" : "Peter-John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wright", "given" : "Erin D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhou", "given" : "Bing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kennedy", "given" : "David W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International forum of allergy & rhinology", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2016", "2" ] ] }, "page" : "S22-209", "title" : "International Consensus Statement on Allergy and Rhinology: Rhinosinusitis.", "type" : "article-journal", "volume" : "6 Suppl 1" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1177/0194599815572097", "ISBN" : "0194-5998", "ISSN" : "1097-6817", "PMID" : "25832968", "abstract" : "OBJECTIVE: This update of a 2007 guideline from the American Academy of Otolaryngology-Head and Neck Surgery Foundation provides evidence-based recommendations to manage adult rhinosinusitis, defined as symptomatic inflammation of the paranasal sinuses and nasal cavity. Changes from the prior guideline include a consumer added to the update group, evidence from 42 new systematic reviews, enhanced information on patient education and counseling, a new algorithm to clarify action statement relationships, expanded opportunities for watchful waiting (without antibiotic therapy) as initial therapy of acute bacterial rhinosinusitis (ABRS), and 3 new recommendations for managing chronic rhinosinusitis (CRS). PURPOSE: The purpose of this multidisciplinary guideline is to identify quality improvement opportunities in managing adult rhinosinusitis and to create explicit and actionable recommendations to implement these opportunities in clinical practice. Specifically, the goals are to improve diagnostic accuracy for adult rhinosinusitis, promote appropriate use of ancillary tests to confirm diagnosis and guide management, and promote judicious use of systemic and topical therapy, which includes radiography, nasal endoscopy, computed tomography, and testing for allergy and immune function. Emphasis was also placed on identifying multiple chronic conditions that would modify management of rhinosinusitis, including asthma, cystic fibrosis, immunocompromised state, and ciliary dyskinesia. ACTION STATEMENTS: The update group made strong recommendations that clinicians (1) should distinguish presumed ABRS from acute rhinosinusitis (ARS) caused by viral upper respiratory infections and noninfectious conditions and (2) should confirm a clinical diagnosis of CRS with objective documentation of sinonasal inflammation, which may be accomplished using anterior rhinoscopy, nasal endoscopy, or computed tomography. The update group made recommendations that clinicians (1) should either offer watchful waiting (without antibiotics) or prescribe initial antibiotic therapy for adults with uncomplicated ABRS; (2) should prescribe amoxicillin with or without clavulanate as \ufb01rst-line therapy for 5 to 10 days (if a decision is made to treat ABRS with an antibiotic); (3) should reassess the patient to confirm ABRS, exclude other causes of illness, and detect complications if the patient worsens or fails to improve with the initial management option by 7 days after diagnosis or worsens d\u2026", "author" : [ { "dropping-particle" : "", "family" : "Rosenfeld", "given" : "Richard M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Piccirillo", "given" : "Jay F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chandrasekhar", "given" : "Sujana S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brook", "given" : "Itzhak", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ashok Kumar", "given" : "Kaparaboyna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kramper", "given" : "Maggie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Orlandi", "given" : "Richard R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "James N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Patel", "given" : "Zara M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peters", "given" : "Anju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walsh", "given" : "Sandra a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Corrigan", "given" : "Maureen D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Otolaryngology\u2013 Head and Neck Surgery", "id" : "ITEM-3", "issue" : "2 suppl", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "S1-S39", "title" : "Clinical Practice Guideline (Update): Adult Sinusitis.", "type" : "article-journal", "volume" : "152" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.4193/Rhino15.199", "ISSN" : "03000729", "PMID" : "26569006", "abstract" : "INTRODUCTION: Promoting the assessment of health interventions using outcomes that matter to patients and practitioners is a key principle of Cochrane. Cochrane UK therefore commissioned the OMIPP project: Outcomes that are Most Important for Patients, Public and Practitioners to identify the outcomes they felt most important and should be evaluated in Cochrane reviews of health interventions for Chronic Rhinosinusitis (CRS). METHODOLOGY: Using direct emailing, social media and printed cards, an online survey was distributed to a wide range of people involved in the care of patients with CRS. Patients and practitioners were asked to list the 3 outcomes from treatments most important to them. Responses were analysed through development of a thematic framework based on the data. RESULTS: Two hundred and thirty-five people completed the survey; 155 practitioners and 80 patients. Respondents provided 653 suggestions of important outcomes. 73% concerned symptoms of CRS, (nasal discharge or drip, facial pain, nasal blockage, headache, impaired sense of smell, congestion and breathing difficulties); 9% concerned quality of life, 4% reducing the need for further treatment and 4% side effects of treatment. Objective measurements of disease formed only 3% of responses. There was high level of agreement between patients and practitioners. Of 10 current Cochrane reviews on CRS, 9 include symptomatic outcomes identified by our survey as most important to patients and healthcare practitioners. CONCLUSIONS: We have identified outcomes that both patients and their doctors consider should be included in reviews evaluating treatments of rhinosinusitis. We recommend that primary outcomes in future reviews focus on symptom-based outcomes. The ability to extract these data from relevant trials is dependent upon their inclusion in trials, and so it is important that building on this work a core outcome set for rhinosinusitis research is developed.", "author" : [ { "dropping-particle" : "", "family" : "Hopkins", "given" : "Claire", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Philpott", "given" : "Carl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crowe", "given" : "Sally", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Regan", "given" : "Sandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Degun", "given" : "Aneeka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papachristou", "given" : "Iliatha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schilder", "given" : "Anne G M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-4", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "20-26", "title" : "Identifying the most important outcomes for systematic reviews of interventions for rhinosinusitis in adults: Working with Patients, Public and Practitioners", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1002/14651858.CD011996.pub2", "ISSN" : "13616137", "PMID" : "27115217", "abstract" : "BACKGROUND: This review is one of six looking at the primary medical management options for patients with chronic rhinosinusitis.Chronic rhinosinusitis is common and is characterised by inflammation of the lining of the nose and paranasal sinuses leading to nasal blockage, rhinorrhoea, facial pressure/pain and loss of sense of smell. The condition can occur with or without nasal polyps. The use of topical (intranasal) corticosteroids has been widely advocated for the treatment of chronic rhinosinusitis given the belief that inflammation is a major component of this condition.\\n\\nOBJECTIVES: To assess the effects of intranasal corticosteroids in people with chronic rhinosinusitis.\\n\\nSEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 8); MEDLINE; EMBASE; ; ICTRP and additional sources for published and unpublished trials. The date of the search was 11 August 2015.\\n\\nSELECTION CRITERIA: Randomised controlled trials (RCTs) with a follow-up period of at least three months comparing intranasal corticosteroids (e.g. beclomethasone dipropionate, triamcinolone acetonide, flunisolide, budesonide) against placebo or no treatment in patients with chronic rhinosinusitis.\\n\\nDATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Our primary outcomes were disease-specific health-related quality of life (HRQL), patient-reported disease severity and the commonest adverse event - epistaxis. Secondary outcomes included general HRQL, endoscopic nasal polyp score, computerised tomography (CT) scan score and the adverse events of local irritation or other systemic adverse events. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics.\\n\\nMAIN RESULTS: We included 18 RCTs with a total of 2738 participants. Fourteen studies had participants with nasal polyps and four studies had participants without nasal polyps. Only one study was conducted in children. Intranasal corticosteroids versus placebo or no interventionOnly one study (20 adult participants without polyps) measured our primary outcome disease-specific HRQL using the Rhinosinusitis Outcome Measures-31 (RSOM-31). They reported no significant difference (numerical data not available) (very low quality evidence).Our second primary outcome, disease severity , was measured using the Chronic Sinusitis Survey in a\u2026", "author" : [ { "dropping-particle" : "", "family" : "Chong", "given" : "Lee Yee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Head", "given" : "Karen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hopkins", "given" : "Claire", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Philpott", "given" : "Carl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schilder", "given" : "Anne G M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burton", "given" : "Martin J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cochrane Database of Systematic Reviews", "id" : "ITEM-5", "issue" : "4", "issued" : { "date-parts" : [ [ "2016" ] ] }, "title" : "Intranasal steroids versus placebo or no intervention for chronic rhinosinusitis", "type" : "article-journal", "volume" : "2016" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1002/14651858.CD011993.pub2", "ISSN" : "13616137", "PMID" : "27115215", "abstract" : "BACKGROUND: This review is one of six looking at the primary medical management options for patients with chronic rhinosinusitis.Chronic rhinosinusitis is common and is characterised by inflammation of the lining of the nose and paranasal sinuses leading to nasal blockage, nasal discharge, facial pressure/pain and loss of sense of smell. The condition can occur with or without nasal polyps. Topical (intranasal) corticosteroids are used with the aim of reducing inflammation in the sinonasal mucosa in order to improve patient symptoms. OBJECTIVES: To assess the effects of different types of intranasal steroids in people with chronic rhinosinusitis. SEARCH METHODS: The Cochrane ENT Information Specialist searched the ENT Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 7); MEDLINE; EMBASE; ; ICTRP and additional sources for published and unpublished trials. The date of the search was 11 August 2015. SELECTION CRITERIA: Randomised controlled trials (RCTs) with a follow-up period of at least three months comparing first-generation intranasal corticosteroids (e.g. beclomethasone dipropionate, triamcinolone acetonide, flunisolide, budesonide) with second-generation intranasal corticosteroids (e.g. ciclesonide, fluticasone furoate, fluticasone propionate, mometasone furoate, betamethasone sodium phosphate), or sprays versus drops, or low-dose versus high-dose intranasal corticosteroids. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Our primary outcomes were disease-specific health-related quality of life (HRQL), patient-reported disease severity and the commonest adverse event - epistaxis (nosebleed). Secondary outcomes included general HRQL, endoscopic nasal polyp score, computerised tomography (CT) scan score and the adverse event of local irritation. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics. MAIN RESULTS: We included nine RCTs (911 participants), including four different comparisons. None of the studies evaluated our first primary outcome measure, disease-specific HRQL. Fluticasone propionate versus beclomethasone dipropionateWe identified two small studies (56 participants with polyps) that evaluated disease severity and looked at the primary adverse effect: epistaxis , but no other outcomes. We cannot report any numerical data but the study authors reported no difference between the two steroids. The ev\u2026", "author" : [ { "dropping-particle" : "", "family" : "Chong", "given" : "Lee Yee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Head", "given" : "Karen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hopkins", "given" : "Claire", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Philpott", "given" : "Carl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burton", "given" : "Martin J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schilder", "given" : "Anne G M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cochrane Database of Systematic Reviews", "id" : "ITEM-6", "issue" : "4", "issued" : { "date-parts" : [ [ "2016" ] ] }, "title" : "Different types of intranasal steroids for chronic rhinosinusitis", "type" : "article-journal", "volume" : "2016" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "DOI" : "10.1002/14651858.CD011992.pub2", "ISSN" : "13616137", "PMID" : "27115214", "abstract" : "BACKGROUND: This review is one of a suite of six Cochrane reviews looking at the primary medical management options for patients with chronic rhinosinusitis.Chronic rhinosinusitis is a common condition involving inflammation of the lining of the nose and paranasal sinuses. It is characterised by nasal blockage and nasal discharge, facial pressure/pain and loss of sense of smell. The condition can occur with or without nasal polyps. Oral corticosteroids are used to control the inflammatory response and improve symptoms. OBJECTIVES: To assess the effects of a short course of oral corticosteroids as an adjunct ('add-on') therapy in people with chronic rhinosinusitis who are already on standard treatments. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 7); MEDLINE; EMBASE; ; ICTRP and additional sources for published and unpublished trials. The date of the search was 11 August 2015. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing a short course (up to 21 days) of oral corticosteroids to placebo or no treatment, where all patients were also receiving pharmacological treatment for chronic rhinosinusitis. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Our primary outcomes were disease-specific health-related quality of life (HRQL), patient-reported disease severity, and the adverse event of mood or behavioural disturbances. Secondary outcomes included general HRQL, endoscopic nasal polyp score, computerised tomography (CT) scan score, and the adverse events of insomnia, gastrointestinal disturbances and osteoporosis. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics. MAIN RESULTS: Two trials with a total of 78 participants met the inclusion criteria. Both the populations and the 'standard' treatments differed in the two studies. Oral steroids as an adjunct to intranasal corticosteroids One trial in adults with nasal polyps included 30 participants. All participants used intranasal corticosteroids and were randomised to either short-course oral steroids (oral methylprednisolone, 1 mg/kg and reduced progressively over a 21-day treatment course) or no additional treatment. None of the primary outcome measures of interest in this review were reported by the study. There may have been an important reduction in the size o\u2026", "author" : [ { "dropping-particle" : "", "family" : "Head", "given" : "Karen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chong", "given" : "Lee Yee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hopkins", "given" : "Claire", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Philpott", "given" : "Carl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schilder", "given" : "Anne G M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burton", "given" : "Martin J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cochrane Database of Systematic Reviews", "id" : "ITEM-7", "issue" : "4", "issued" : { "date-parts" : [ [ "2016" ] ] }, "title" : "Short-course oral steroids as an adjunct therapy for chronic rhinosinusitis", "type" : "article-journal", "volume" : "2016" }, "uris" : [ "" ] }, { "id" : "ITEM-8", "itemData" : { "DOI" : "10.1002/14651858.CD011991.pub2", "ISSN" : "13616137", "PMID" : "27113367", "abstract" : "BACKGROUND: This review is one of a suite of six Cochrane reviews looking at the primary medical management options for patients with chronic rhinosinusitis.Chronic rhinosinusitis is a common condition involving inflammation of the lining of the nose and paranasal sinuses. It is characterised by nasal blockage and nasal discharge, facial pressure/pain and loss of sense of smell. The condition can occur with or without nasal polyps. Oral corticosteroids are used to control the inflammatory response and improve symptoms., OBJECTIVES: To assess the effects of oral corticosteroids compared with placebo/no intervention or other pharmacological interventions (intranasal corticosteroids, antibiotics, antifungals) for chronic rhinosinusitis., SEARCH METHODS: The Cochrane ENT Information Specialist searched the ENT Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 7); MEDLINE; EMBASE; ; ICTRP and additional sources for published and unpublished trials. The date of the search was 11 August 2015., SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing a short course (up to 21 days) of oral corticosteroids with placebo or no treatment or compared with other pharmacological interventions., DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Our primary outcomes were disease-specific health-related quality of life (HRQL), patient-reported disease severity, and the adverse event of mood or behavioural disturbances. Secondary outcomes included general HRQL, endoscopic nasal polyp score, computerised tomography (CT) scan score and the adverse events of insomnia, gastrointestinal disturbances and osteoporosis. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics., MAIN RESULTS: We included eight RCTs (474 randomised participants), which compared oral corticosteroids with placebo or no intervention. All trials only recruited adults with chronic rhinosinusitis with nasal polyps. All trials reported outcomes at two to three weeks, at the end of the short-course oral steroid treatment period. Three trials additionally reported outcomes at three to six months. Two of these studies prescribed intranasal steroids to patients in both arms of the trial at the end of the oral steroid treatment period. Oral steroids versus placebo or no intervention Disease-specific health-related quality of life was reported by one study. This study re\u2026", "author" : [ { "dropping-particle" : "", "family" : "Head", "given" : "Karen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chong", "given" : "Lee Yee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hopkins", "given" : "Claire", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Philpott", "given" : "Carl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burton", "given" : "Martin J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schilder", "given" : "Anne G M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cochrane Database of Systematic Reviews", "id" : "ITEM-8", "issue" : "4", "issued" : { "date-parts" : [ [ "2016" ] ] }, "title" : "Short-course oral steroids alone for chronic rhinosinusitis", "type" : "article-journal", "volume" : "2016" }, "uris" : [ "" ] }, { "id" : "ITEM-9", "itemData" : { "DOI" : "10.1002/14651858.CD006991.pub2", "abstract" : "Background: Nasal polyps cause nasal obstruction, discharge and reduction in or loss of sense of smell, but their aetiology is unknown. The management of chronic rhinosinusitis with nasal polyps, aimed at improving these symptoms, includes both surgical and medical treatments, but there is no universally accepted management protocol.Objectives: To assess the effectiveness of endonasal/endoscopic surgery versus medical treatment in chronic rhinosinusitis with nasal polyps.Search methods: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the search was 20 February 2014.Selection criteria: Randomised controlled trials of any surgical intervention (e.g. polypectomy, endoscopic sinus surgery) versus any medical treatment (e.g. intranasal and/or systemic steroids), including placebo, in adult patients with chronic rhinosinusitis with nasal polyps.Data collection and analysis: We used the standard methodological procedures expected by The Cochrane Collaboration. Meta-analysis was not possible due to the heterogeneity of the studies and the selective (incomplete) outcome reporting by the studies.Main results: Four studies (231 participants randomised) are included in the review. No studies were at low risk of bias. The studies compared different types of surgery versus various types and doses of systemic and topical steroids and antibiotics. There were three comparison pairs: (1) endoscopic sinus surgery (ESS) versus systemic steroids (one study, n = 109), (2) polypectomy versus systemic steroids (two studies, n = 87); (3) ESS plus topical steroid versus antibiotics plus high-dose topical steroid (one study, n = 35). All participants also received topical steroids but doses and types were the same between the treatment arms of each study, except for the study using antibiotics. In that study, the medical treatment arm had higher doses than the surgical arm. In two of the studies, the authors failed to report the outcomes of interest. Although there were important differences in the types of treatments and comparisons used in these studies, the results were similar. Primary outcomes: symptom scores and quality of life scoresThere were no important differences between groups in either the patient-reported disease-specific sym\u2026", "author" : [ { "dropping-particle" : "", "family" : "Joanne", "given" : "Rimmer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wytske", "given" : "Fokkens", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yee", "given" : "Chong Lee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Claire", "given" : "Hopkins", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cochrane Database of Systematic Reviews", "id" : "ITEM-9", "issue" : "12", "issued" : { "date-parts" : [ [ "2014" ] ] }, "title" : "Surgical versus medical interventions for chronic rhinosinusitis with nasal polyps", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "86,87,263\u2013269", "plainTextFormattedCitation" : "86,87,263\u2013269", "previouslyFormattedCitation" : "86,87,262\u2013268" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }86,87,263–269). We would refer you to these guidelines for management of such patients. With regards to non-CRS-related causes of olfactory dysfunction, the literature base is less robust, and it is difficult to draw firm conclusions regarding the utility of steroids in such patients. In 2012, Schriever et al. published results from a retrospective analysis of psychophysical olfactory scores before and after treatment with 14 days of systemic methylprednisolone. Patients with olfactory dysfunction of any cause were included, though the majority (52%) had olfactory loss secondary to sinonasal disease. Overall, 26.6% of patients improved by more than 6 points on TDI testing (the minimal clinically important difference). However, a control group was not included in this study and the validity of findings should be confirmed using a prospective, controlled study (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.4193/Rhino.11.207", "ISSN" : "03000729", "PMID" : "22888485", "abstract" : "BACKGROUND AND AIM: Olfactory dysfunction is a common complaint in a large number of people. As the aetiologies of olfactory dysfunction vary greatly so do the treatment approaches. The aim of this retrospective study was to evaluate treatment with systemic corticosteroids, particularly focusing on its effectiveness on the different olfactory dysfunction aetiologies. Although a prospective randomized control trail is preferred for such an investigation, using the current approach, we were able to test a very large patient population. MATERIAL AND METHODS: A total of 425 patients with olfactory dysfunction were treated with systemic corticosteroids for 14 days. Olfactory performance was measured using the `Sniffin` Sticks` battery before and after the treatment. RESULTS: The treatment with systemic corticosteroids significantly increased the performance on the TDI score and on each of the three subtests; threshold, discrimination and identification. In 26.6% of the patients improvement of more than six points of the TDI score was observed. The treatment proved to be more effective in patients with sinunasal olfactory dysfunction, where this percentage increased to 36.7, compared to other aetiologies. In addition, the increase in olfactory function was negatively correlated with the TDI score before the treatment. CONCLUSION: This study confirms the effectiveness of systemic corticosteroids on olfactory dysfunction in a large patient population. Specifically, the results show that treatment is: (a) more effective in patients with sinunasal than in patients with idiopathic olfactory dysfunction, (b) most effective in patients with sinunasal disease with nasal polyps, and (c), at best, effective in half of the patients. The current study may provide help in counselling patients.", "author" : [ { "dropping-particle" : "", "family" : "Schriever", "given" : "V. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Merkonidis", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gupta", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "284-289", "title" : "Treatment of smell loss with systemic methylprednisolone.", "type" : "article-journal", "volume" : "50" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "270", "plainTextFormattedCitation" : "270", "previouslyFormattedCitation" : "269" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }270). Jiang et al. assessed threshold scores following administration of high dose systemic prednisolone, in patients with posttraumatic olfactory loss (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00405-010-1240-0", "ISSN" : "1434-4726", "PMID" : "20379733", "abstract" : "The objective of this study was to treat posttraumatic anosmia with oral steroid and evaluate its effect. One-hundred sixteen posttraumatic patients whose olfactory thresholds were -1.0 by the phenyl ethyl alcohol threshold test assembled in our department. They were treated with a course of high-dose steroid, and followed up for at least 3 months. During the latter period of this study, magnetic resonance imaging was performed to measure the volumes of olfactory bulbs and to detect subfrontal lobe damage. Among them, 19 (16.4%) patients' olfactory thresholds improved after steroid treatment, but the other 97 patients' thresholds did not change. The incidences of loss of consciousness and intracranial hemorrhage after head injury, the ratios of admission and craniotomy, the intervals between head injury and steroid treatment, the volumes of olfactory bulbs, and the incidences of subfrontal lobe damage were not significantly different between patients whose thresholds improved and those whose thresholds did not improve. However, patients with olfactory improvement were significantly younger than those who remained unchanged. Our study showed that oral steroid treatment might improve olfactory acuity in some patients with posttraumatic anosmia, but the possibility of spontaneous recovery cannot be ruled out.", "author" : [ { "dropping-particle" : "", "family" : "Jiang", "given" : "Rong-San", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Shang-Heng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liang", "given" : "Kai-Li", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shiao", "given" : "Jiun-Yih", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hsin", "given" : "Chung-Han", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Su", "given" : "Mao-Chang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "1563-7", "title" : "Steroid treatment of posttraumatic anosmia.", "type" : "article-journal", "volume" : "267" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "271", "plainTextFormattedCitation" : "271", "previouslyFormattedCitation" : "270" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }271). Improved olfaction was seen in 16.4% of the study population. However, this modest improvement is difficult to interpret given that the study did not include a control group.Systemic steroids have also been combined with other agents, namely Zinc, vitamin B and Ginkgo biloba (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1177/0194599815571272", "ISBN" : "0194-5998", "ISSN" : "0194-5998", "PMID" : "25715353", "abstract" : "OBJECTIVES: To study the effects of zinc and steroid in the treatment of traumatic anosmia. STUDY DESIGN: A prospective, randomized study. SETTING: Academic medical center. SUBJECTS AND METHODS: Patients with a clear history of loss of smell after head injury and whose thresholds were -1 measured by the phenyl ethyl alcohol threshold test were included in this study from January 2010 to May 2013. They were randomly divided into 4 groups. Patients in group 1 were treated with zinc gluconate for a month and high-dose prednisolone with tapering for 2 weeks. Those in group 2 took only zinc gluconate, and those in group 3 took only prednisolone. Patients in group 4 did not take any medicine. All patients were followed up by phenyl ethyl alcohol threshold testing, and magnetic resonance imaging was performed to measure the volume of olfactory bulbs. RESULTS: Thirty-nine patients in group 1, 35 in group 2, 34 in group 3, and 37 in group 4 completed the study. The recovery of olfactory function was observed in 11 patients (28.2%) in group 1, in 9 (25.7%) in group 2, in 4 (11.8%) in group 3, and in 1 (2.7%) in group 4. The recovery rates of olfactory function of groups 1 and 2 were significantly higher than the recovery rate of group 4. The volume of olfactory bulbs was not significantly different between those with and without improved olfactory function. CONCLUSION: Our results show that zinc gluconate has a promising effect in treating traumatic anosmia.", "author" : [ { "dropping-particle" : "", "family" : "Jiang", "given" : "R S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Twu", "given" : "C W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liang", "given" : "K L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Otolaryngol Head Neck Surg", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "954-958", "title" : "Medical treatment of traumatic anosmia", "type" : "article-journal", "volume" : "152" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Seo", "given" : "Beom Seol", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Hyun Jong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mo", "given" : "Ji-Hun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Chul Hee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rhee", "given" : "Chae-Seo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Jeon-Whun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arch Otolaryngol Head Neck Surg", "id" : "ITEM-2", "issue" : "10", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "1000-1004", "title" : "Treatment of Postviral Olfactory Loss With Glucocorticoids,", "type" : "article-journal", "volume" : "135" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1055/s-2004-825676", "ISSN" : "0935-8943", "PMID" : "15538662", "abstract" : "BACKGROUND: Aim of the present, unblinded, multicentric, open trial was to compare effects of 3 treatments in patients with olfactory dysfunction. METHODS: Treatments included administration of systemic corticosteroids (oral prednisolone), local corticosteroids (mometasone nasal spray), and systemic vitamin B, respectively. A total of 192 patients participated (95 women, 97 men; mean age 56 years). Duration of the smell loss ranged from 1 to 288 months (average 45 months). Olfactory dysfunction was due to infections of the upper respiratory tract (n = 72), sinunasal disease (n = 19), and posttraumatic olfactory loss (n = 10); the largest portion was classified as idiopathic (n = 85); other causes were rare (n = 6). RESULTS: Following systemic administration of corticosteroids improvement of olfactory function was observed (p < 0.001). Similarly, improvement of the sense of smell was found 2 (p = 0.03) and 6 months (p = 0.001) after local administration of mometasone, respectively. In contrast, after administration of vitamin B no significant change of olfactory function was seen after 2 months, while improvement was present after 6 months (p = 0.001). Duration of olfactory dysfunction had no effect on changes of smell function. CONCLUSIONS: These results indicate that improvement of olfactory function is found in olfactory dysfunction of different causes. Adequately controlled, blinded studies are needed to further explore potential effects of the various treatments.", "author" : [ { "dropping-particle" : "", "family" : "Heilmann", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Just", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "G\u00f6ktas", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hauswald", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "H\u00fcttenbrink", "given" : "K-B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Laryngo- rhino- otologie", "id" : "ITEM-3", "issue" : "11", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "729-34", "title" : "Effects of systemic or topical administration of corticosteroids and vitamin B in patients with olfactory loss", "type" : "article-journal", "volume" : "83" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "272\u2013274", "plainTextFormattedCitation" : "272\u2013274", "previouslyFormattedCitation" : "271\u2013273" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }272–274). These studies suggest a possible additive benefit for the former two, though the additional benefit from Ginkgo biloba did not reach statistical significance. In addition to anti-inflammatory effects, animal studies suggest that corticosteroids may lead to the modification of olfactory gene expression (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/alr.21586", "ISSN" : "20426984", "PMID" : "26140380", "abstract" : "BACKGROUND: Olfaction is one of the important senses for humans. Systemic glucocorticoids are the most commonly used medications for olfactory loss because of their strong anti-inflammatory effects. However, their effect on olfactory function is still controversial and the precise mechanism is not clear. To gain a global view of the effect of systematic glucocorticoid treatment on gene expression in the olfactory mucosa (OM), we profiled these changes in a murine model of olfaction in order to identify underlying molecular mechanisms.\\n\\nMETHODS: C57BL/6 mice were injected daily for 2 weeks (WK2) with dexamethasone (DEX, intraperitoneally, 1 mg/kg body weight) vs 1 day of DEX (D1) vs controls, which received saline (Ctrl) (n = 9/group). Total RNA from the OM was used to analyze global gene expression. Genes showing changes in expression were compared using the Database for Annotation, Visualization and Integrated Discovery (DAVID, v6.7) and the General Olfactory Sensitivity Database (GOSdb; ).\\n\\nRESULTS: Between the WK2 and Ctrl groups, 3351 genes were differentially expressed, of which 236 genes were related to olfactory function. Genes involved in axon guidance, cell projection, and inflammation were enriched and overlapped significantly with those in the GOSdb.\\n\\nCONCLUSION: Systemic glucocorticoids exert effects on transcription of a notable number of genes in the OM and appear to orchestrate changes related to axon guidance, cell projection, and inflammation. Further examination may allow targeted therapies that lack the side effects of this category of medication.", "author" : [ { "dropping-particle" : "", "family" : "Tian", "given" : "Jun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinto", "given" : "Jayant M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xin", "given" : "Yi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Henghui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Li", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sun", "given" : "Zhifu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wei", "given" : "Yongxiang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Forum of Allergy and Rhinology", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "907-918", "title" : "Dexamethasone affects mouse olfactory mucosa gene expression and attenuates genes related to neurite outgrowth", "type" : "article-journal", "volume" : "5" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "275", "plainTextFormattedCitation" : "275", "previouslyFormattedCitation" : "274" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }275).When considering use of systemic corticosteroids, the risk of side effects must be taken into account (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1302/0301-620X.96B2.31935", "ISSN" : "2049-4408", "PMID" : "24493194", "abstract" : "Corticosteroid use has been implicated in the development of osteonecrosis of the femoral head (ONFH). The exact mechanism and predisposing factors such as age, gender, dosage, type and combination of steroid treatment remain controversial. Between March and July 2003, a total of 539 patients with severe acute respiratory syndrome (SARS) were treated with five different types of steroid. There were 129 men (24%) and 410 women (76%) with a mean age of 33.7 years (21 to 59). Routine screening was undertaken with radiographs, MRI and/or CT to determine the incidence of ONFH. Of the 129 male patients with SARS, 51 (39.5%) were diagnosed as suffering from ONFH, compared with only 79 of 410 female patients (19.3%). The incidence of ONFH in the patients aged between 20 and 49 years was much higher than that of the group aged between 50 and 59 years (25.9% (127 of 491) versus 6.3% (3 of 48); p = 0.018). The incidence of ONFH in patients receiving one type of steroid was 12.5% (21 of 168), which was much lower than patients receiving two different types (28.6%; 96 of 336) or three different types of steroid (37.1%; 13 of 35).", "author" : [ { "dropping-particle" : "", "family" : "Guo", "given" : "K J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "F C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guo", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "F L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhu", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zheng", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The bone & joint journal", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "259-62", "title" : "The influence of age, gender and treatment with steroids on the incidence of osteonecrosis of the femoral head during the management of severe acute respiratory syndrome: a retrospective study.", "type" : "article-journal", "volume" : "96-B" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.steroids.2013.01.004", "ISBN" : "1878-5867 (Electronic)\\r0039-128X (Linking)", "ISSN" : "0039128X", "PMID" : "23357434", "abstract" : "Glucocorticoid-induced osteonecrosis is a common and severe adverse event. We conducted a meta-analysis to investigate whether polymorphisms in target genes were associated with the risk of corticosteroid-induced osteonecrosis. Published literature from PubMed and EMBASE were searched for eligible publications. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a fixed- or random-effects model. There were 23 articles with 35 genes described the relationship between polymorphisms and glucocorticoid-induced osteonecrosis. Meta-analyses were carried out for those SNPs with three or more eligible studies, which included four SNPs located in three genes (PAI-1, MTHFR, ABCB1). The meta-analysis revealed that the PAI-1 4G allele was associated with an increased risk of osteonecrosis compared with the 5G allele (combined studies: OR = 1.932, 95% CI = 1.145-3.261). The OR for the 4G/4G vs. 5G/5G genotype of PAI-1 was 3.217 (95% CI 1.667-6.209 with combined studies), The relative risk of osteonecrosis was increased in the 4G allele vs. 5G/5G and 4G/4G genotype vs. 5G allele, with odds ratios of 2.304 (95% CI = 1.235-4.299) and 2.307 (95% CI = 1.527-3.485) in combined studies, respectively. The ABCB1 C3435T genotype distributions available confirmed that the C allele increased osteonecrosis risk compared with the T allele (OR 1.668, 95% CI = 1.214-2.293) and TT genotype (OR 2.946, 95% CI = 1.422-6.101). There was no evidence for significant association between MTHFR C677T and ABCB1 G2677T/A polymorphisms and risk of osteonecrosis. Results of this meta-analysis indicate that the PAI-1 4G/5G and ABCB1 C3435T polymorphisms may be risk factors for osteonecrosis. \u00a9 2013 Elsevier Inc. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Gong", "given" : "Li Li", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fang", "given" : "Lian Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "He Yao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peng", "given" : "Jian Hao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Si", "given" : "Kun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhu", "given" : "Jin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Han", "given" : "Fei Fei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Yue Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Du", "given" : "Guan Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pei", "given" : "Li Xia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Li Hong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Steroids", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "401-408", "title" : "Genetic risk factors for glucocorticoid-induced osteonecrosis: A meta-analysis", "type" : "article-journal", "volume" : "78" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.3928/01477447-20140626-54", "ISSN" : "1938-2367", "PMID" : "24992058", "abstract" : "Although the association between chronic, high-dose corticosteroid use and osteonecrosis is well known, the incidence of osteonecrosis following short-term, low-dose steroid taper packs has never been reported across a large population. The goal of this study was to report the incidence and risk of osteonecrosis after methylprednisolone taper pack (MTP) prescriptions in a multicenter electronic medical records database. A commercially available software platform was used to evaluate the records of 24,533,880 patients to determine the incidence of osteonecrosis in patients who had received single or multiple MTP over a 12-year period. This was compared with the incidence of osteonecrosis in patients who had never been prescribed an MTP. Patients with a history of osteonecrosis or prior corticosteroid use were excluded from the study. A total of 98,390 patients were identified who had received a single MTP. One hundred thirty (0.132%; 95% confidence interval [CI], 0.176%-0.283%) of these patients were subsequently diagnosed with osteonecrosis. The incidence of osteonecrosis in patients who had been prescribed 2 or more MTPs was 0.230% (95% CI, 0.176%-0.283%). Compared with the 0.083% incidence of osteonecrosis in the control group that had never been prescribed an MTP, the relative risk of osteonecrosis after the prescription of a single MTP or multiple MTPs was 1.591 and 2.763, respectively, with a statistically significant difference between cohorts (P<.001). Short-term, low-dose oral corticosteroid administration may be associated with a low but statistically significant increased incidence of osteonecrosis when compared with patients who have never been prescribed a steroid product.", "author" : [ { "dropping-particle" : "", "family" : "Dilisio", "given" : "Matthew F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Orthopedics", "id" : "ITEM-3", "issue" : "7", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "e631-6", "title" : "Osteonecrosis Following Short-term, Low-dose Oral Corticosteroids: A Population-based Study of 24 Million Patients.", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "276\u2013278", "plainTextFormattedCitation" : "276\u2013278", "previouslyFormattedCitation" : "275\u2013277" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }276–278). At present, evidence-based guidelines regarding the acceptable frequency of systemic corticosteroid use do not exist. It therefore falls to the individual clinician to exercise the appropriate prudence, particularly in cases of non-CRS related olfactory loss, where the evidence supporting steroid use is poor. Recommendations:Systemic and/or topical steroids should be prescribed in patients with olfactory dysfunction secondary to CRS and other inflammatory conditions according to existing guidelines.There is limited evidence to support use of steroids for other causes of olfactory dysfunction.The risk of potential side effects should be taken into account when prescribing systemic corticosteroids. Phosphodiesterase inhibitorsPhosphodiesterase inhibitors are theorised to improve olfactory function through preventing degradation of intracellular cAMP (see anatomy and physiology section). Two studies in 2009 demonstrated improved olfactory function following phosphodiesterase inhibitor administration. The first of these was a prospective study which assessed “Sniffin’ Sticks” scores before and after administration of pentoxifylline (which was in this case being given for otological conditions) (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/00006534-198006000-00008", "ISBN" : "0032-1052", "ISSN" : "0032-1052", "PMID" : "7384277", "abstract" : "Objective: To investigate the effect of pentoxifylline, an unspecific phosphodiesterase inhibitor, on olfactory function. Design: Longitudinal study. Patients: Nineteen patients who received pentoxifyl- line to treat inner-ear conditions. MainOutcomeMeasures: Evaluation of olfactory func- tion (ie, odor threshold, odor discrimination, and odor identification) before and after administration of pen- toxifylline and assessment of nasal airflow. Results: Administration of pentoxifylline had no sig- nificant effect on nasal airflow (P=.84). After adminis- tration of pentoxifylline, patients demonstrated a de- crease in odor threshold toward lower odor concentrations (P=.01). The odor threshold shift after administration of pentoxifylline was more pronounced in younger pa- tients than in older patients (correlation between age and change in odor threshold: r=\u2212.72; P=.001). No such changes were observed for suprathreshold olfactory tasks (odor discrimination and odor identification). Six of the 19 patients were found to have hyposmia. Two patients demonstrated a clinically significant decrease in odor threshold after drug administration. Conclusions: The present findings may indicate a role for pentoxifylline in the treatment of olfactory loss. Double-blind, placebo-controlled studies are needed to verify whether pentoxifylline can improve olfactory sen- sitivity in patients with olfactory disorders", "author" : [ { "dropping-particle" : "", "family" : "Gudziol", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arch Otolaryngol Head Neck Surg", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "291-5", "title" : "Effects of Pentoxifylline on Olfactory Sensitivity", "type" : "article-journal", "volume" : "135" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "279", "plainTextFormattedCitation" : "279", "previouslyFormattedCitation" : "278" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }279). The authors demonstrated a significant improvement in odour threshold levels, in keeping with a theorised improvement in peripheral olfactory function. However, a mixture of normosmic and impaired patients were included in this study and there was heterogeneity in the route of pentoxifylline administration. The second study by Henkin and colleagues utilised an unblinded controlled trial design to assess the effect of oral theophylline on olfactory function in hyposmic patients with reduced nasal/saliva cAMP/cGMP levels (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/MAJ.0b013e3181914a97", "ISSN" : "0002-9629", "PMID" : "19359985", "abstract" : "BACKGROUND: To test the hypothesis that theophylline is effective in correcting smell loss in patients with hyposmia.\\n\\nMETHODS: Three hundred twelve patients with smell loss (hyposmia) were evaluated to determine characteristics of their loss by psychophysical measurements of detection and recognition thresholds, magnitude estimation and hedonic values for 4 odors (pyridine, nitrobenzene, thiophene, and amyl acetate) by use of a forced-choice 3-stimuli staircase design previously documented in a double-blind study. Patients were then treated in a fixed design open-label clinical trial with oral theophylline. Drug was given in equal divided doses from 200 to 800 mg daily for 2- to 8-month periods and subjective and psychophysical measurements of smell function and blood theophylline levels were measured; results were compared with those obtained before treatment.\\n\\nRESULTS: Subjective smell loss improved in 157 (50.3%) patients; smell function was considered normal by 34 (21.7%). Overall, 10.9% of patients in the study considered smell function returned to normal. However, measurements of mean detection and recognition thresholds improved significantly at each drug level; measurements of mean magnitude estimation and hedonic also improved. Improvement was greater at drug doses of 600 and 800 mg than at 200 or 400 mg. Once improvement occurred, as long as treatment was maintained, it persisted for as long as follow-up was measured.\\n\\nCONCLUSION: Theophylline was effective in improving smell function in patients with smell loss. Improvement persisted as long as treatment was continued, which extended from 6 to 72 months.", "author" : [ { "dropping-particle" : "", "family" : "Henkin", "given" : "Robert I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Velicu", "given" : "Irina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schmidt", "given" : "Loren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American journal of the medical sciences", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "396-406", "title" : "An open-label controlled trial of theophylline for treatment of patients with hyposmia.", "type" : "article-journal", "volume" : "337" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "280", "plainTextFormattedCitation" : "280", "previouslyFormattedCitation" : "279" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }280). Whilst this study also demonstrated improved olfactory function with treatment, the patient population (i.e. those with low cAMP/cGMP levels) and study design (an increasing dose of theophylline was given where response was deemed suboptimal – a design which may have neglected spontaneous recovery) limits the generalisability of the results. Disappointing results have been demonstrated following double-blind administration of sildenafil (a cGMP type 5 phosphodiesterase inhibitor) and caffeine (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00405-015-3879-z", "ISSN" : "0937-4477", "author" : [ { "dropping-particle" : "", "family" : "Meusel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Albinus", "given" : "Janine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Welge-Luessen", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "H\u00e4hner", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Archives of Oto-Rhino-Laryngology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "title" : "Short-term effect of caffeine on olfactory function in hyposmic patients", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.juro.2006.08.060", "ISBN" : "0022-5347 (Print)", "ISSN" : "00225347", "PMID" : "17162058", "abstract" : "Purpose: Sildenafil is the first member of a new class of oral drugs effective for erectile dysfunction. However, approximately 20% of patients complain about nasal congestion after sildenafil administration. Materials and Methods: Because nasal airflow and olfaction are closely linked, the sense of smell was evaluated in 20 young, healthy volunteers after the administration of 50 and 100 mg sildenafil, and placebo in a double-blinded, crossover study. Olfactory function was evaluated using a standardized and validated test (Sniffin' Sticks??). To investigate a possible impact of G-protein ??3 subunit C825T polymorphism on the effect of sildenafil on olfaction the genotype of all subjects was determined. Results: The effect of sildenafil on olfaction was only present at a dose of 100 mg but not at a dose of 50 mg sildenafil. The genotypes TT, CC and TC of the G-protein ??3 C825T polymorphism had no impact on the change in olfactory function. Conclusions: Higher sildenafil doses may produce decreased olfactory sensitivity. ?? 2007 American Urological Association.", "author" : [ { "dropping-particle" : "", "family" : "Gudziol", "given" : "V.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muck-Weymann", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seizinger", "given" : "O.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rauh", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siffert", "given" : "W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Urology", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "258-261", "title" : "Sildenafil Affects Olfactory Function", "type" : "article-journal", "volume" : "177" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "282,283", "plainTextFormattedCitation" : "282,283", "previouslyFormattedCitation" : "281,282" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }282,283). Finally, application of topical theophylline to supravital mouse olfactory epithelium, did not lead to enhancement of associated EOG recordings (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00405-009-1076-7", "ISSN" : "09374477", "PMID" : "19727789", "abstract" : "Options for the treatment of hyposmia are limited;available therapies do not provide a long-lasting effect.A recent study suggests that an unspecific phosphodiesterase inhibitor (PDE-I) increases olfactory sensitivity due to interaction with the signal transduction in the olfactory epithelium. The aim of the present study was to investigate whether theophylline, an unspecific PDE-I, evokes changes in the electro-olfactogram (EOG) which would support the hypothesis of a drug-related impact on signal transduction.In addition, the uptake of topically administered theophylline in the olfactory epithelium should be investigated. EOG was obtained in 29 samples of supravital mouse olfactory epithelia. Olfactory stimulation (phenylethyl alcohol, PEA and hydrogen sulfide, H2S) was performed using an air dilution olfactometer. Theophylline concentration in the olfactory epithelium of five samples was measured by means of high pressure liquid chromatography. Administration of theophylline resulted in a tendency towards smaller EOG amplitudes (p = 0.055), being reduced by 13 and 25% in response to stimulation with PEA or H2S,respectively. In comparison to the application of Ringer's solution, theophylline resulted in a significant (p = 0.031)decrease of the EOG amplitude. Latency was not significantly(p = 0.10) influenced by drug administration. The theophylline concentration in the olfactory epithelium ranged from 0.21 to 1.53 microg/mg. Theophylline seems to be taken up into the olfactory epithelium of supravital mice and to interact with the olfactory signal transduction.", "author" : [ { "dropping-particle" : "", "family" : "Gudziol", "given" : "Volker", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pietsch", "given" : "J\u00f6rg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Witt", "given" : "Martin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Archives of Oto-Rhino-Laryngology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "239-243", "title" : "Theophylline induces changes in the electro-olfactogram of the mouse", "type" : "article-journal", "volume" : "267" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "284", "plainTextFormattedCitation" : "284", "previouslyFormattedCitation" : "283" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }284).Recommendations:Currently there is insufficient evidence to support use of phosphodiesterase inhibitors in the treatment of olfactory dysfunction.Intranasal calcium buffersFree calcium within the nasal mucus layer plays a role in negative feedback inhibition of the intracellular olfactory signalling cascade (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/0006-8993(90)90605-B", "ISBN" : "0006-8993 (Print) 0006-8993 (Linking)", "ISSN" : "00068993", "PMID" : "2113412", "abstract" : "The time-dependent decay of the olfactory receptor potential was analyzed with a solitary cell preparation by using the whole-cell patch clamp technique. During prolonged stimulation by 10 mM N-amylacetate under standard conditions, 17 out of 63 isolated olfactory cells responded with slow depolarization. Of these 17 cells, response amplitudes in 14 cells ('phasic/tonic' response) gradually decayed within 9 s, with a half-decay time of 1.71 ?? 1.10 s (mean ?? S.D.). The relative amplitude (ratio of tonic component to peak amplitude, Vtonic/Vmax) was 0.29 ?? 0.10. The response decay was attributed to the inactivation of the odorant-activated conductance. The recovery after inactivation, which was determined with double pulse experiments, was dependent on the resting interval. The inactivation of the odorant-activated conductance was found to be observed only when the external medium contained Ca2+. In addition, it was found that the odorant-activated conductance was capable of permeating Ca2+ (PCa/PNa = 6.5), and a rise in the internal EGTA concentration (to 50 mM) inhibited the inactivation. These observations suggest that the decay of the olfactory response to prolonged stimulation is mediated by Ca2+ influx. ?? 1990.", "author" : [ { "dropping-particle" : "", "family" : "Kurahashi", "given" : "Takashi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shibuya", "given" : "Tatsuaki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Brain Research", "id" : "ITEM-1", "issue" : "1-2", "issued" : { "date-parts" : [ [ "1990" ] ] }, "page" : "261-268", "title" : "Ca2+-dependent adaptive properties in the solitary olfactory receptor cell of the newt", "type" : "article-journal", "volume" : "515" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "285", "plainTextFormattedCitation" : "285", "previouslyFormattedCitation" : "284" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }285,ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "abstract" : "When olfactory receptor neurons are exposed to sustained application of odours, the elicited ionic current is transient. This adaptation-like effect appears to require the influx of Ca2+ through the odour-sensitive conductance; in the absence of extracellular Ca2+ the current remains sustained. Odour transduction proceeds through a G-protein-based second messenger system, resulting finally in the direct activation of an ion channel by cyclic AMP. This channel is one possible site for a negative feedback loop using Ca2+ as a messenger. In recordings of single cyclic AMP gated channels from olfactory receptor neurons, the open probability of the channel in saturating cAMP concentrations was dependent on the concentration of intracellular Ca2+. It could be reduced from 0.6 in 100 nM Ca2+ to 0.09 in 3-mu-M Ca2+. However, as neither the single channel conductance nor the mean open time were affected by Ca2+ concentration, this does not appear to be a mechanism of simple channel block. Rather, these results suggest that intracellular Ca2+ acts allosterically to stabilize a closed state of the channel.", "author" : [ { "dropping-particle" : "", "family" : "Zufall", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shepherd", "given" : "G M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Firestein", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Proc R Soc Lond B Biol Sci", "id" : "ITEM-1", "issue" : "1317", "issued" : { "date-parts" : [ [ "1991" ] ] }, "page" : "225-230", "title" : "Inhibition of the Olfactory Cyclic-Nucleotide Gated Ion Channel by Intracellular Calcium", "type" : "article-journal", "volume" : "246" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "286", "plainTextFormattedCitation" : "286", "previouslyFormattedCitation" : "285" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }286). It is therefore theorised that sequestration of such free calcium, using buffer solutions such as sodium citrate, may lead to amplification of the olfactory signal and consequent improvement in olfactory function. In 2005 Panagiotopoulos and colleagues reported improved odour identification scores in hyposmic patients treated with intranasal sodium citrate (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "03000729", "PMID" : "16008069", "abstract" : "It is well documented that cytoplasmic Ca++ regulates sensitivity to cyclic adenosine monophosphate (cAMP). There is also evidence that Ca++ in the mucus may also modulate sensitivity to cAMP in vivo. Assuming that mucosal Ca++ could significantly change the excitability of the receptor neurons, we examined the alterations in the olfactory sensitivity by creating small changes in mucosal Ca++. Thirty one patients complaining of olfactory loss were examined and their olfactory acuity was measured before and after the administration of a sodium citrate buffer solution in the nasal cleft. Thirty patients (96.8%) improved their scores in less than an hour period of time. Furthermore, 23 of them (74.2%) realized an improvement in their own sense of smell.", "author" : [ { "dropping-particle" : "", "family" : "Panagiotopoulos", "given" : "Georgios", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Naxakis", "given" : "Stefanos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papavasiliou", "given" : "Antonios", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Filipakis", "given" : "Konstantinos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papatheodorou", "given" : "Georgios", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goumas", "given" : "Panagiotis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "130-134", "title" : "Decreasing nasal mucus Ca++ improves hyposmia", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "287", "plainTextFormattedCitation" : "287", "previouslyFormattedCitation" : "286" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }287). Whilst subgroup analysis according to aetiology was not undertaken in this study, it is worth noting that the majority of these patients had post-infectious hyposmia. Using a single-blind, placebo-controlled study design, Whitcroft et al. also demonstrated an improvement in the odour identification scores of patients with post-infectious hyposmia, following administration of intranasal sodium citrate (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.4193/Rhino16.054", "author" : [ { "dropping-particle" : "", "family" : "Whitcroft", "given" : "Katherine L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Merkonidis", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cuevas", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haehner", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Philpott", "given" : "Carl M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "1-6", "title" : "Intranasal sodium citrate improves olfaction in post-viral hyposmia", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "288", "plainTextFormattedCitation" : "288", "previouslyFormattedCitation" : "287" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }288). A further, prospective and internally controlled study in post-infectious patients showed significantly improved composite threshold and identification scores after sodium citrate treatment (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/COA.12789", "ISSN" : "1749-4486", "author" : [ { "dropping-particle" : "", "family" : "Whitcroft", "given" : "K L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ezzat", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cuevas", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andrews", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Otolaryngology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "1-7", "title" : "The effect of intranasal sodium citrate on olfaction in post\u2010infectious loss: results from a prospective, placebo\u2010controlled trial in 49 patients", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "289", "plainTextFormattedCitation" : "289", "previouslyFormattedCitation" : "288" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }289). Additional basic and clinical research into the utility of intranasal calcium sequestration in post-infectious olfactory loss should be undertaken.[Table 5]Olfactory trainingOlfactory training involves repeated daily exposure of a subject to a range of odourants. In 2009, Hummel and colleagues prospectively investigated the utility of such training in a group of patients with olfactory loss due to post-infectious, posttraumatic or idiopathic aetiologies (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/lary.20101", "ISBN" : "1531-4995 (Electronic)", "ISSN" : "0023852X", "PMID" : "19235739", "abstract" : "Objectives: Olfactory function is known to be modulated by repeated exposure to odors. The aim of this investigation was whether patients with olfactory loss would benefit from ''Training'' with odors in terms of an improvement of their general olfactory function. It was hypothesized that olfactory Training should produce both an improved sensitivity towards the odors used in the Training process and an overall increase of olfactory function. Study Design: The prospective study was per-formed in patients with olfactory dysfunction. Methods: One group of patients performed the Training (n \u00bc 40), whereas another part did not (n \u00bc 16). Exclusion criteria for patients were sinunasal disease. Olfactory training was performed over a pe-riod of 12 weeks. Patients exposed themselves twice daily to four intense odors (phenyl ethyl alcohol: rose, eucalyptol: eucalyptus, citronellal: lemon, and euge-nol: cloves). Olfactory testing was performed before and after training using the ''Sniffin' Sticks'' (thresh-olds for phenyl ethyl alcohol, tests for odor discrimi-nation and odor identification) in addition to thresh-old tests for the odors used in the training process. Results: Compared to baseline, training patients experienced an increase in their olfactory function, which was observed for the Sniffin' Sticks test score and for thresholds for the odors used in the training process. In contrast, olfactory function was unchanged in patients who did not perform olfactory training. The present results indicate that the struc-tured, short-term exposure to selected odors may increase olfactory sensitivity.", "author" : [ { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reden", "given" : "Karo Rissom Jens", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "H\u00e4hner", "given" : "Aantje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weidenbecher", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "H\u00fcttenbrink", "given" : "Karl Bernd", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Laryngoscope", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "496-499", "title" : "Effects of olfactory Training in patients with olfactory loss", "type" : "article-journal", "volume" : "119" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "300", "plainTextFormattedCitation" : "300", "previouslyFormattedCitation" : "299" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }300). Forty of these patients underwent twice-daily smell training using 4 odourants: phenylethylalcohol (rose), eucalyptol (eucalyptus), citronellal (lemon), and eugenol (cloves). Compared with baseline psychophysical olfactory test scores (using “Sniffin’ Sticks”), the training group significantly improved at 12 weeks, whereas the non-training group did not. This study was replicated by Haehner et al. in 70 patients with Parkinson’s disease (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0061680", "ISBN" : "10.1371/journal.pone.0061680", "ISSN" : "19326203", "PMID" : "23613901", "abstract" : "OBJECTIVE: Decrease of olfactory function in Parkinson's disease (PD) is a well-investigated fact. Studies indicate that pharmacological treatment of PD fails to restore olfactory function in PD patients. The aim of this investigation was whether patients with PD would benefit from \"training\" with odors in terms of an improvement of their general olfactory function. It has been hypothesized that olfactory training should produce both an improved sensitivity towards the odors used in the training process and an overall increase of olfactory function.\\n\\nMETHODS: We recruited 70 subjects with PD and olfactory loss into this single-center, prospective, controlled non-blinded study. Thirty-five patients were assigned to the olfactory training group and 35 subjects to the control group (no training). Olfactory training was performed over a period of 12 weeks while patients exposed themselves twice daily to four odors (phenyl ethyl alcohol: rose, eucalyptol: eucalyptus, citronellal: lemon, and eugenol: cloves). Olfactory testing was performed before and after training using the \"Sniffin' Sticks\" (thresholds for phenyl ethyl alcohol, tests for odor discrimination, and odor identification) in addition to threshold tests for the odors used in the training process.\\n\\nRESULTS: Compared to baseline, trained PD patients experienced a significant increase in their olfactory function, which was observed for the Sniffin' Sticks test score and for thresholds for the odors used in the training process. Olfactory function was unchanged in PD patients who did not perform olfactory training.\\n\\nCONCLUSION: The present results indicate that olfactory training may increase olfactory sensitivity in PD patients.", "author" : [ { "dropping-particle" : "", "family" : "Haehner", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tosch", "given" : "Clara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wolz", "given" : "Martin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klingelhoefer", "given" : "Lisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fauser", "given" : "Mareike", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Storch", "given" : "Alexander", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reichmann", "given" : "Heinz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1-7", "title" : "Olfactory Training in Patients with Parkinson's Disease", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "301", "plainTextFormattedCitation" : "301", "previouslyFormattedCitation" : "300" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }301). Again, psychophysical test scores significantly improved only in the training group (n=35). A more recent study from Gei?ler et al.(ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00405-013-2747-y", "ISBN" : "0937-4477", "ISSN" : "14344726", "PMID" : "24096819", "abstract" : "Olfactory training consisting of daily suprathreshold odor exposure over 12 weeks seems to improve olfactory function. It is unknown if a longer period of training might be more effective. A prospective non-randomized clinical study was performed including 39 patients with olfactory loss after an upper respiratory tract infection (URTI) of less than 24 months duration. Patients exposed themselves with suprathreshold concentrations of four odors (rose, eucalyptus, lemon, cloves) applied in ''Sniffin' Sticks'' felt-tip pens over 32 weeks. Olfactory function was performed before (T1), after 16 weeks (T2), and 32 weeks of training (T3) using the 'the Sniffin' Sticks test kit calculating the TDI score (Threshold, Discrimination, Identification). The mean TDI score showed a non-significant trend of improvement at T2, and was significantly increased at T3 (p = 0.021). Overall, 31 patients (79%) showed an increased TDI score at T3. The increase of TDI from T1 to T3 was 4.6 \u00b1 5.1. Age, gender, duration and initial severity of olfactory loss had no influence on the improvement (all p > 0.05). Only patients with a D score lower than the median value of 8 showed a significantly higher increase of the D score at T3 (p = 0.004). The present study confirmed that olfactory training improves olfactory function in patients with olfactory loss after URTI. A longer duration of training over 32 weeks seems to increase the effectiveness in comparison to a 12-week period. This was tested in a completed German multicenter trial to be published soon containing a control group to include the effect of a spontaneous recovery after URTI.", "author" : [ { "dropping-particle" : "", "family" : "Geissler", "given" : "K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reimann", "given" : "H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gudziol", "given" : "H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bitter", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guntinas-Lichius", "given" : "O.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Archives of Oto-Rhino-Laryngology", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "1557-1562", "title" : "Olfactory training for patients with olfactory loss after upper respiratory tract infections", "type" : "article-journal", "volume" : "271" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "302", "plainTextFormattedCitation" : "302", "previouslyFormattedCitation" : "301" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }302) demonstrated improved psychophysical test scores following prolonged training (32 weeks), however, these results are limited by lack of a comparative control group. A randomised, controlled, multicentre study led by Damm et al. in 144 patients also recently showed that olfactory training with high odour concentrations resulted in greater improvement than very low odour concentrations (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/lary.24340", "ISBN" : "1531-4995", "ISSN" : "15314995", "PMID" : "23929687", "abstract" : "OBJECTIVES/HYPOTHESIS: The aim of this study was to evaluate the effects of olfactory training (OT) on olfactory function in patients with persistent postinfectious olfactory dysfunction (PIOD).\\n\\nSTUDY DESIGN: Randomized, single-blind, controlled, multicenter crossover study.\\n\\nMETHODS: Twelve tertiary university medical centers participated. Investigations were performed at three visits (baseline, after 18 weeks, and after 36 weeks), including only subjects with PIOD of <24-months duration. At each visit, participants received detailed assessment of olfactory function. Seventy subjects trained with high concentrations of four odors for 18 weeks; the other half (n = 74) trained with low concentrations of odors. For the following 18 weeks this regimen was switched.\\n\\nRESULTS: After 18 weeks, olfactory function improved in the high-training group in 18 of 70 participants (26%), whereas only 11/74 improved in the low-training group (15%). In subjects with a duration of olfactory dysfunction of <12 months, olfactory function improved in 15/24 participants (63%) of the high-training group and in 6/31 participants (19%) of the low-training group (P = .03).\\n\\nCONCLUSIONS: OT improves PIOD, and the use of odors at higher concentrations is beneficial to improvement. OT is a safe procedure and appears to be particularly useful in patients who start OT within 12 months after the onset of the disorder. OT is the first successful therapy regime in patients with PIOD.\\n\\nLEVEL OF EVIDENCE: 1b.", "author" : [ { "dropping-particle" : "", "family" : "Damm", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pikart", "given" : "Louisa K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reimann", "given" : "Heike", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burkert", "given" : "Silke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "G\u00f6ktas", "given" : "\u00d6nder", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haxel", "given" : "Boris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frey", "given" : "Sabine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Charalampakis", "given" : "Ioannis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beule", "given" : "Achim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Renner", "given" : "Berthold", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "H\u00fcttenbrink", "given" : "Karl Bernd", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Laryngoscope", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "826-831", "title" : "Olfactory training is helpful in postinfectious olfactory loss: A randomized, controlled, multicenter study", "type" : "article-journal", "volume" : "124" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "303", "plainTextFormattedCitation" : "303", "previouslyFormattedCitation" : "302" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }303) indicating that olfactory training in fact is not related to sniffing but to olfactory stimulation; this study was also the first “quasi placebo” controlled study demonstrating the efficacy of olfactory training. Altundag and colleagues also showed improved olfactory function following training for 9 months (using 4 different odours every 3 months), with greater benefit being seen following longer training duration (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/lary.25245", "ISBN" : "0023-852x", "ISSN" : "15314995", "PMID" : "26031472", "abstract" : "OBJECTIVES/HYPOTHESIS: Patients with olfactory dysfunction benefit from repeated exposure to odors, so-called olfactory training (OT). This does not mean occasional smelling but the structured sniffing of a defined set of odors, twice daily, for a period of 4 months or longer. In this prospective study, we investigated whether the effect of OT might increase through the use of more odors and extension of the training period.\\n\\nSTUDY DESIGN AND METHODS: This study shows OT results when performed with four or 12 odors for 36 weeks in patients with postinfectious olfactory dysfunction. A total of 85 subjects participated (mean age 45.6\u2009\u00b1\u200910.5 years, range 24-68 years). Three groups were formed: 1) In the modified olfactory training (MOT) group, patients used three sets of four different odors sequentially. 2) Participants in the classical odor training (COT) group used four odors. 3) Participants in the control group did not perform OT. All groups were matched for age and sex distribution of participants.\\n\\nRESULTS: Both participants in the COT and MOT groups reached better scores than controls in terms of odor discrimination and odor identification. Continuing OT with four different odors after the 12th and 24th weeks produced better results in terms of odor discrimination and odor identification scores as compared to using the same four odors throughout the entire study.\\n\\nCONCLUSION: This study confirmed the effectiveness of OT. Increasing the duration of OT and changing the odors enhances the success rate of this therapy.\\n\\nLEVEL OF EVIDENCE: 2b. Laryngoscope, 125:1763-1766, 2015.", "author" : [ { "dropping-particle" : "", "family" : "Altundag", "given" : "Aytug", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cayonu", "given" : "Melih", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kayabasoglu", "given" : "Gurkan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salihoglu", "given" : "Murat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tekeli", "given" : "Hakan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saglam", "given" : "Omer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Laryngoscope", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1763-1766", "title" : "Modified olfactory training in patients with postinfectious olfactory loss", "type" : "article-journal", "volume" : "125" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "304", "plainTextFormattedCitation" : "304", "previouslyFormattedCitation" : "303" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }304). Whilst each of the latter three studies addressed patients with post-infectious olfactory loss, Konstantinidis and colleagues have shown good results following training in patients with posttraumatic dysfunction (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/lary.24390", "ISSN" : "0023852X", "PMID" : "24114690", "abstract" : "OBJECTIVES/HYPOTHESIS: There is evidence that the olfactory system can be modulated by repeated exposure to odors, a procedure called olfactory training. The aim of this study was to assess the effectiveness of olfactory training in patients with postinfectious and post-traumatic olfactory dysfunction.\\n\\nSTUDY DESIGN: Prospective study of 119 patients with postinfectious and post-traumatic olfactory dysfunction.\\n\\nMETHODS: Two groups of patients (postinfectious and post-traumatic) performed the olfactory training (n = 49 and n = 23, respectively) over a period of 16 weeks and were compared with two control groups of the same etiology (n = 32 and n = 15). Patients with sinunasal, neurologic, or idiopathic disease were excluded. Training was performed twice daily with the use of four odors (phenyl ethyl alcohol [rose], eucalyptol [eucalyptus], citronellal [lemon], and eugenol [cloves]). Olfactory testing was performed by means of the Sniffin' Sticks test battery (threshold, discrimination, identification) at the time of diagnosis, and 8 and 16 weeks later. All patients evaluated their olfactory function by means of a visual analogue scale (0-100).\\n\\nRESULTS: Compared to controls, training patients in both groups presented significantly higher scores of olfactory function as measured by the Sniffin' Sticks test. This increase was measured in 67.8% of postinfectious and 33.2% of post-traumatic patients. Subjective ratings were in accordance with the olfactory test results. Subset analysis showed that olfactory function mainly increased olfactory identification followed by discrimination in both training groups.\\n\\nCONCLUSIONS: The present study suggests that a 16-week short-term exposure to specific odors may increase olfactory sensitivity in patients with postinfectious and post-traumatic olfactory dysfunction.", "author" : [ { "dropping-particle" : "", "family" : "Konstantinidis", "given" : "Iordanis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsakiropoulou", "given" : "Evangelia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bekiaridou", "given" : "Paschalia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kazantzidou", "given" : "Chrysa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Constantinidis", "given" : "Jannis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Laryngoscope", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "85-90", "title" : "Use of olfactory training in post-traumatic and postinfectious olfactory dysfunction", "type" : "article-journal", "volume" : "123" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "305", "plainTextFormattedCitation" : "305", "previouslyFormattedCitation" : "304" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }305). Few studies, however, have addressed the effect of training in patients with sinonasal disease (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Fleiner", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lau", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goktas", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Ear Nose And Throat Journal", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "198-203", "title" : "Active olfactory training for the treatment of smell disorders", "type" : "article-journal", "volume" : "91" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "306", "plainTextFormattedCitation" : "306", "previouslyFormattedCitation" : "305" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }306) (for a list of studies see Table 6; for a meta-analysis on studies on olfactory training see (281)).The exact underlying pathophysiological mechanism for improvement following smell training is unknown. However, it is postulated to involve increased regenerative capacity of olfactory neurons as a result of repeated odourant exposure (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1113/jphysiol.2003.054726", "ISSN" : "0022-3751", "PMID" : "14678505", "abstract" : "Of those people who are anosmic to androstenone, a proportion can acquire sensitivity to it by repeated exposure and even those who are able to smell it can lower their threshold with this treatment. Using olfactory threshold testing, intranasal electrophysiology and EEG we show for the first time that: (1) the subjects' detection threshold is proportional to the amplitude of the olfactory evoked potential (EOG) recorded inside the nose; (2) the EOG amplitude is correlated with the amplitude of the olfactory event-related potential (OERP) recorded on the scalp; and (3) with repetitive exposure, human subjects acquire a reduced threshold for androstenone and, as they do so, their EOG and OERP increase. These observations support the existence of odourant-specific plasticity in the peripheral olfactory system.", "author" : [ { "dropping-particle" : "", "family" : "Wang", "given" : "Liwei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Lixin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jacob", "given" : "Tim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of physiology", "id" : "ITEM-1", "issue" : "Pt 1", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "236-244", "title" : "Evidence for peripheral plasticity in human odour response.", "type" : "article-journal", "volume" : "554" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "307", "plainTextFormattedCitation" : "307", "previouslyFormattedCitation" : "306" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }307). [Table 6]Given the low associated cost and high safety of olfactory training, it is an attractive treatment modality, which can be employed with relative impunity. Recommendations:Smell training can be recommended in patients with olfactory loss of several aetiologies (this treatment requires further evaluation in patients with sinonasal disease).SurgerySurgical intervention is largely reserved for treatment of patients with CRS ± polyps. Again, as for treatment with steroids, extensive guidelines exist for the use of surgery in such patients. Furthermore, two recent Cochrane reviews have been published regarding the utility of surgery in these patients, though olfaction is not extensively discussed as an outcome (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/14651858.CD006991.pub2", "abstract" : "BACKGROUND: Nasal polyps cause nasal obstruction, discharge and reduction in or loss of sense of smell, but their aetiology is unknown. The management of chronic rhinosinusitis with nasal polyps, aimed at improving these symptoms, includes both surgical and medical treatments, but there is no universally accepted management protocol.\\nOBJECTIVES: To assess the effectiveness of endonasal/endoscopic surgery versus medical treatment in chronic rhinosinusitis with nasal polyps.\\nSEARCH METHODS: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the search was 20 February 2014.\\nSELECTION CRITERIA: Randomised controlled trials of any surgical intervention (e.g. polypectomy, endoscopic sinus surgery) versus any medical treatment (e.g. intranasal and/or systemic steroids), including placebo, in adult patients with chronic rhinosinusitis with nasal polyps.\\nDATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by The Cochrane Collaboration. Meta-analysis was not possible due to the heterogeneity of the studies and the selective (incomplete) outcome reporting by the studies.\\nMAIN RESULTS: Four studies (231 participants randomised) are included in the review. No studies were at low risk of bias. The studies compared different types of surgery versus various types and doses of systemic and topical steroids and antibiotics. There were three comparison pairs: (1) endoscopic sinus surgery (ESS) versus systemic steroids (one study, n = 109), (2) polypectomy versus systemic steroids (two studies, n = 87); (3) ESS plus topical steroid versus antibiotics plus high-dose topical steroid (one study, n = 35). All participants also received topical steroids but doses and types were the same between the treatment arms of each study, except for the study using antibiotics. In that study, the medical treatment arm had higher doses than the surgical arm. In two of the studies, the authors failed to report the outcomes of interest. Although there were important differences in the types of treatments and comparisons used in these studies, the results were similar.\\nPRIMARY OUTCOMES: symptom scores and quality of life scores There were no important differences between groups in either the patient-reported disease-\u2026", "author" : [ { "dropping-particle" : "", "family" : "Sharma", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakhani", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rimmer", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hopkins", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cochrane Database of Systematic Reviews", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2014", "12", "1" ] ] }, "page" : "CD006990", "publisher-place" : "Chichester, UK", "title" : "Surgical interventions for chronic rhinosinusitis with nasal polyps", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/14651858.CD006991.pub2.", "abstract" : "BACKGROUND: Nasal polyps cause nasal obstruction, discharge and reduction in or loss of sense of smell, but their aetiology is unknown. The management of chronic rhinosinusitis with nasal polyps, aimed at improving these symptoms, includes both surgical and medical treatments, but there is no universally accepted management protocol. OBJECTIVES: To assess the effectiveness of endonasal/endoscopic surgery versus medical treatment in chronic rhinosinusitis with nasal polyps. SEARCH METHODS: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the search was 20 February 2014. SELECTION CRITERIA: Randomised controlled trials of any surgical intervention (e.g. polypectomy, endoscopic sinus surgery) versus any medical treatment (e.g. intranasal and/or systemic steroids), including placebo, in adult patients with chronic rhinosinusitis with nasal polyps. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by The Cochrane Collaboration. Meta-analysis was not possible due to the heterogeneity of the studies and the selective (incomplete) outcome reporting by the studies. MAIN RESULTS: Four studies (231 participants randomised) are included in the review. No studies were at low risk of bias. The studies compared different types of surgery versus various types and doses of systemic and topical steroids and antibiotics. There were three comparison pairs: (1) endoscopic sinus surgery (ESS) versus systemic steroids (one study, n = 109), (2) polypectomy versus systemic steroids (two studies, n = 87); (3) ESS plus topical steroid versus antibiotics plus high-dose topical steroid (one study, n = 35). All participants also received topical steroids but doses and types were the same between the treatment arms of each study, except for the study using antibiotics. In that study, the medical treatment arm had higher doses than the surgical arm. In two of the studies, the authors failed to report the outcomes of interest. Although there were important differences in the types of treatments and comparisons used in these studies, the results were similar. PRIMARY OUTCOMES: symptom scores and quality of life scores There were no important differences between groups in either the patient-reported disease-\u2026", "author" : [ { "dropping-particle" : "", "family" : "Rimmer", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fokkens", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chong", "given" : "L Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hopkins", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cochrane Database of Systematic Reviews ", "id" : "ITEM-2", "issue" : "12", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "CD006991", "title" : "Surgical versus medical interventions for chronic rhinosinusitis with nasal polyps ", "type" : "article-journal", "volume" : "12 " }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "313,314", "plainTextFormattedCitation" : "313,314", "previouslyFormattedCitation" : "312,313" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }313,314). A review of 20 studies published since 1991 shows that olfaction generally improves following functional endoscopic sinus surgery (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0022-2151 (Print)\\r0022-2151 (Linking)", "ISSN" : "0022-2151 (Print)", "PMID" : "1753193", "abstract" : "Considerable clinical success has been claimed for functional endoscopic sinus surgery but objective assessment of prospective series is lacking in the literature. Twenty-four patients with chronic rhino-sinusitis underwent assessment of symptoms by visual analogue scoring, nasomucociliary function by ciliary beat frequency, olfaction by qualitative olfactometry and nasal airway resistance by anterior rhinomanometry pre- and post-operatively. This demonstrated a significant improvement in all symptoms examined and in ciliary beat frequency. Quantitative olfaction and anterior rhinomanometry were not improved despite diminished symptoms. These results offer quantitative evidence of clinical improvement following functional endoscopic sinus surgery which supports the pathophysiological concepts on which the technique is based.", "author" : [ { "dropping-particle" : "", "family" : "Lund", "given" : "V J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holmstrom", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scadding", "given" : "G K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of laryngology and otology", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "1991" ] ] }, "page" : "832-835", "title" : "Functional endoscopic sinus surgery in the management of chronic rhinosinusitis. An objective assessment.", "type" : "article-journal", "volume" : "105" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0141-0768", "PMID" : "8196032", "author" : [ { "dropping-particle" : "", "family" : "Lund", "given" : "V J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "MacKay", "given" : "I S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of the Royal Society of Medicine", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "1994" ] ] }, "page" : "70-2", "title" : "Outcome assessment of endoscopic sinus surgery.", "type" : "article-journal", "volume" : "87" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISSN" : "0300-0729", "PMID" : "9569436", "abstract" : "One hundred and fifteen patients suffering from chronic sinusitis were observed to analyse the prevalence of olfactory dysfunction and the influence of FESS. Pre-operative questionnaires were supplemented by examination of olfactory thresholds and discrimination. Pre-operatively, 58% of the collective were aware or complained of any olfactory deficit. However, the olfactory tests demonstrated that of the collective 52% were hyposmic and 31% anosmic. Eight per cent of the hyposmic patients presented with an isolated reduction of their ability to discriminate odours. Post-operative improvements were found in 70%. Normosmia was post-operatively achieved in 25% of the hyposmic patients, but only in 5% of the anosmic patients. Olfaction changed to the worse in 8% after FESS. Therefore, the prevalence of olfactory dysfunction in chronic sinusitis is pre-operatively higher, and the rate of improvement is lower than generally assumed. The extent of sinus disease as measured by the degree of intranasal polyposis correlates with olfactory dysfunction. Resections of the middle turbinate may have a negative effect on olfaction, due to damage to the olfactory fila or alteration of the normal aerodynamic pattern within the olfactory cleft. However, this hypothesis is based on a few observations and needs to be verified by further investigations.", "author" : [ { "dropping-particle" : "", "family" : "Delank", "given" : "K W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stoll", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "1998" ] ] }, "page" : "15-19", "title" : "Olfactory function after functional endoscopic sinus surgery for chronic sinusitis.", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1067/mai.2001.112124", "ISSN" : "0091-6749", "PMID" : "11174186", "abstract" : "BACKGROUND: Controlled prospective studies are needed to determine whether surgical treatment in fact has an effect additive to that of medical treatment of nasal polyposis. OBJECTIVE: We sought to compare the effect of medical treatment versus combined surgical and medical treatment on olfaction, polyp score, and symptoms in nasal polyposis. METHODS: Thirty-two patients with nasal polyposis and symmetrical nasal airways were randomized to unilateral endoscopic sinus surgery after pretreatment with oral prednisolone for 10 days and local nasal budesonide bilaterally for 1 month. Postoperatively, patients were given local nasal steroids (budesonide). Patients were evaluated with nasal endoscopy, symptom scores, and olfactory thresholds. They were followed for 12 months. RESULTS: The sense of smell was improved by the combination of local and oral steroids. Surgery had no additional effect. Symptom scores improved significantly with medical treatment alone, but surgery had additional beneficial effects on nasal obstruction and secretion. After surgery, the polyp score decreased significantly on the operated side but remained the same on the unoperated side. Twenty-five percent of the patients were willing to undergo an operation also on the unoperated side at the end of the study. CONCLUSIONS: Medical treatment seems to be sufficient to treat most symptoms of nasal polyposis. When hyposmia is the primary symptom, no additional benefit seems to be gained from surgical treatment. If nasal obstruction is the main problem after steroid treatment, surgical treatment is indicated. Selection of those who will benefit from surgery should be based on the patient's symptoms and not on the examiner's polyp score.", "author" : [ { "dropping-particle" : "", "family" : "Blomqvist", "given" : "E H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lundblad", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Angg\u00e5rd", "given" : "a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haraldsson", "given" : "P O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stj\u00e4rne", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of allergy and clinical immunology", "id" : "ITEM-4", "issue" : "2", "issued" : { "date-parts" : [ [ "2001" ] ] }, "page" : "224-228", "title" : "A randomized controlled study evaluating medical treatment versus surgical treatment in addition to medical treatment of nasal polyposis.", "type" : "article-journal", "volume" : "107" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1053/S0196-0709(03)00067-X", "author" : [ { "dropping-particle" : "", "family" : "Perry", "given" : "Brian F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kountakis", "given" : "Stilianos E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Otolaryngol", "id" : "ITEM-5", "issue" : "6", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "366-369", "title" : "Subjective Improvement of Olfactory Function After Endoscopic Sinus Surgery for Chronic Rhinosinusitis", "type" : "article-journal", "volume" : "24" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "ISBN" : "0300-0729 (Print)\\r0300-0729", "ISSN" : "03000729", "PMID" : "14750349", "abstract" : "AIM: In this prospective study the effect of medical and surgical treatment on subjective olfaction was studied in patients with nasal polyposis (NPS). The effects on nasal obstruction, anterior and posterior rhinorrhea, sneezing and itching are reported in another article in this issue. PATIENTS AND METHODS: Protocol 1. Twenty-four patients with NPS who complained about anosmia were treated with a 7-days course of systemic steroids. Their subjective overall sense of smell was determined with a visual analog scale (VAS) before treatment, immediately after treatment, and two months later. Subsequently all patients underwent surgery bilaterally according to the nasalization principles. The sense of smell was re-evaluated at 1, 3, 6, 9, and 12 months postoperatively. Protocol 2. Thirty-two patients with NPS not responding to medical therapy who, for different reasons, did not receive oral steroid treatment, received surgery only and were followed up during one year after nasalization. Of these patients, 25 were anosmic and 7 normosmic. RESULTS: Protocol 1. Following the 7-day treatment with systemic steroids the olfactory score increased significantly. During the waiting time for surgery (64 +/- 39 days) this score deteriorated again in a significant way. One month after nasalization which included a depot injection of triamcinolone 80 mg the day after surgery, the olfactory score ameliorated again and remained stable at 3, 6, 9, and 12 months. None of the patients reported any intake of systemic steroids during the one-year of follow-up. Statistically, there was a trend suggesting that the 12 month post-nasalization score was better than the immediate post-oral steroid score. A good correlation between the improvement of the sense of smell after 7 days of systemic steroids and one year after nasalization was found. Protocol 2 One month after the nasalization protocol, olfaction in patients of the hypo-anosmic group had improved considerably. Scores at 3, 6, 9, and 12 remained very stable. The sense of smell in the normosmic group did not change after surgery and remained stable during the year of follow-up. In total, 49 patients with a severe loss of smell showed a significant improvement at 12 months after surgery. CONCLUSION: The present study shows that 1) long-lasting correction of olfactory dysfunction produced by nasal polyposis can be achieved through the combination of nasalization and low dose of nasal steroids, 2) middle turbinate resection does\u2026", "author" : [ { "dropping-particle" : "", "family" : "Jankowski", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bodino", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-6", "issue" : "4", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "220-230", "title" : "Olfaction in patients with nasal polyposis: Effects of systemic steroids and radical ethmoidectomy with middle turbinate resection (nasalisation)", "type" : "article-journal", "volume" : "41" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "DOI" : "10.1097/00005537-200405000-00027", "ISBN" : "1531-4995", "ISSN" : "0023-852X", "PMID" : "15126758", "abstract" : "OBJECTIVES: To conduct the first prospective, randomized, controlled trial evaluating and comparing the medical and surgical treatment of polypoid and nonpolypoid chronic rhinosinusitis (CRS). MATERIALS AND METHODS: Ninety patients with CRS were equally randomized either to medical or surgical therapy. All patients underwent pre- and posttreatment assessments of visual analogue score (VAS), the Sinonasal Outcome Test-20 (SNOT-20), the Short Form 36 Health Survey (SF-36), nitric oxide (NO), acoustic rhinometry, saccharine clearance time (SCT), and nasal endoscopy. Each patient had three assessments: before starting the treatment, after 6 months, and, finally, after 1 year. RESULTS: Both the medical and surgical treatment of CRS significantly improved almost all the subjective and objective parameters of CRS (P <.01), with no significant difference being found between the medical and surgical groups (P >.05), except for the total nasal volume in CRS (P <.01) and CRS without polyposis (P <.01) groups, in which the surgical treatment demonstrated greater changes. CONCLUSION: CRS should be initially targeted with maximal medical therapy (e.g., a 3 month course of a macrolide antibiotic, douche, and topical steroid), with surgical treatment being reserved for cases refractory to medical therapy. The presence of nasal polyps is not a poor prognostic factor for the efficacy of CRS therapy, either surgical or medical.", "author" : [ { "dropping-particle" : "", "family" : "Ragab", "given" : "Sameh M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lund", "given" : "Valerie J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scadding", "given" : "Glenis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Laryngoscope", "id" : "ITEM-7", "issue" : "5", "issued" : { "date-parts" : [ [ "2004" ] ] }, "note" : "SNOT-20 only - doesn't specify re olfaction", "page" : "923-930", "title" : "Evaluation of the medical and surgical treatment of chronic rhinosinusitis: a prospective, randomised, controlled trial.", "type" : "article-journal", "volume" : "114" }, "uris" : [ "" ] }, { "id" : "ITEM-8", "itemData" : { "ISSN" : "03000729", "PMID" : "15844495", "abstract" : "One hundred nine patients with chronic rhinosinusitis underwent functional endoscopic sinus surgery. Seventy seven patients had polyposis. The population was studied prospectively for 5 years postoperatively. Seventy two patients attended the 5 year follow-up visit. At 1, 2, 3, 4 and 5 years of follow-up all outcome measures except olfactory detection thresholds (visual analogue scores, endoscopic findings, nasal mucociliary clearance times, total nasal volumes) were significantly improved compared to preoperative baseline values. Olfactory detection thresholds were significantly improved at 1 and 2 years postoperation. Patient symptom scores were improved in a greater percentage of patients than more objective outcome measures. Thirty eight patients required a total of 88 postoperative rescue medication courses with prednisolone and antibiotic. Twelve patients failed the study as they required at least 1 rescue medication course a month for 2 consecutive months. We demonstrated an 89% 5 year \"survival\" rate with regards to the risk of failure. The patients were also entered into a randomised, stratified, prospective, double-blind, placebo controlled study of fluticasone propionate aqueous nasal spray 200 mcg twice daily, commencing 6 weeks after FESS, with a 5 year follow-up. The change in overall visual analogue score was significantly better in the FPANS group at 5 years. The changes in endoscopic oedema and polyp scores and in total nasal volumes were significantly better in the FPANS group at 4 years but not 5 years. Last value carried forward analysis demonstrated that changes in endoscopic polyp score and in total nasal volume was significantly better in the FPANS group at 5 years. Significantly more prednisolone rescue medication courses were prescribed in the placebo group. Of the 12 patients who failed the study, 10 were in the placebo group. This difference nearly achieved significance.", "author" : [ { "dropping-particle" : "", "family" : "Rowe-Jones", "given" : "Julian M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Medcalf", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Durham", "given" : "Stephen R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richards", "given" : "David H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mackay", "given" : "Ian S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-8", "issue" : "1", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "2-10", "title" : "Functional endoscopic sinus surgery: 5 year follow up and results of a prospective, randomised, stratified, double-blind, placebo controlled study of postoperative fluticasone propionate aqueous nasal spray", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] }, { "id" : "ITEM-9", "itemData" : { "DOI" : "10.1080/00016480600895078", "ISSN" : "0001-6489", "PMID" : "17453467", "abstract" : "This prospective study is the first in the literature to present long-term results of a combined medical and surgical treatment in patients with nasal polyposis (NP) including strict inclusion criteria, analysis of the results in terms of clinical amelioration, polyp size reduction, and steroid consumption. The results of the present study show that combined surgery and corticosteroid therapy is effective in the treatment of NP.", "author" : [ { "dropping-particle" : "", "family" : "Bonfils", "given" : "Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Acta oto-laryngologica", "id" : "ITEM-9", "issue" : "4", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "436-46", "title" : "Evaluation of the combined medical and surgical treatment in nasal polyposis. I: functional results.", "type" : "article-journal", "volume" : "127" }, "uris" : [ "" ] }, { "id" : "ITEM-10", "itemData" : { "DOI" : "10.1007/s00405-007-0409-7", "ISBN" : "0937-4477 (Print)", "ISSN" : "09374477", "PMID" : "17676329", "abstract" : "Nasal surgery is frequently performed. Predictors of surgical outcome in terms of chemosensory function are not clear. A total of 64 patients were included in this prospective study (41 men, 23 women; age range 22-67 years). Prior to surgery, patients received a detailed otorhinolaryngological examination including nasal endoscopy, and CT scans used to establish the Lund-Mackay score. Olfactory function was analyzed using a custom-built odor identification test which allowed separation of chemosensory function into \"olfactory\" and \"trigeminal\" portions. Retest was performed 6 months after surgery. In terms of the sense of smell, nasal surgery produced the highest success rates in women, high degree of polyposis, and aspirin-intolerance. Neither age, presence of asthma, nor the number of preoperative surgical interventions had a significant impact on the outcome of surgery in terms of chemosensory function. Although \"trigeminal scores\" changed to a lesser degree than \"olfactory scores\", the present results indicated that nasal surgery may also improve trigeminal function, although this needs further corroboration. Improvement of olfactory function following nasal surgery appears to last, on average, for at least 6 months. While the present results may be seen as an encouraging step towards the description of more detailed prognostic factors related to nasal surgery, results from the present investigation also point towards the idea that nasal polyposis is due to a multifactorial process that, so far, is not adequately addressed by current research. Future work is needed to identify further predictors of postoperative outcome in terms of olfactory function.", "author" : [ { "dropping-particle" : "", "family" : "Minovi", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ural", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Draf", "given" : "W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bockmuhl", "given" : "U.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Archives of Oto-Rhino-Laryngology", "id" : "ITEM-10", "issue" : "1", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "57-61", "title" : "Predictors of the outcome of nasal surgery in terms of olfactory function", "type" : "article-journal", "volume" : "265" }, "uris" : [ "" ] }, { "id" : "ITEM-11", "itemData" : { "DOI" : "10.1097/MLG.0b013e318170b5cb", "ISBN" : "1531-4995 (Electronic)", "ISSN" : "1531-4995", "PMID" : "18438263", "abstract" : "OBJECTIVE/HYPOTHESIS: This prospective study aimed to investigate predictors of nasal surgery in terms of olfactory function. STUDY DESIGN: Prospective study. METHODS: A total of 775 patients were included in this prospective study (482 men, 293 women; age range 10-81 years, mean age 41 years, standard deviation = 15.3 y). Prior to surgery, patients received a detailed otorhinolaryngologic examination including nasal endoscopy. Olfactory function was assessed with a standardized odor identification test (\"Sniffin' Sticks\"). In 356 patients, olfactory function was retested 4 months after surgery (63-339 days after surgery; mean 128 days, standard deviation = 29 days); 206 of these patients received sinus surgery, while 150 received surgery involving the septum. RESULTS: Using a conservative definition of change of olfactory function, following sinus surgery, improvement of the sense of smell was found in 23%, no change was seen in 68%, and decreased function was seen in 9% of the patients; in patients with septum surgery, improvement was seen in 13%, no change in 81%, and decreased function in 7%. Patients exhibiting a postoperative decrease of olfactory function had significantly higher preoperative olfactory scores than patients who experienced improvement. In terms of the sense of smell, nasal surgery produced the highest success rates in patients with eosinophilia and a high degree of polyposis. Neither age nor sex had a major impact on the outcome of surgery in terms of olfactory function. CONCLUSIONS: These results in a large group of patients confirm previous work. Apart from apparent success in 13 to 23% of patients, there is also a small but significant group of patients (7 to 9%) in whom olfactory function decreases after surgery. Because this decrease was mostly found in patients with relatively good preoperative olfactory function, this group should receive specific attention when counseling patients about the potential risks of nasal surgery.", "author" : [ { "dropping-particle" : "", "family" : "Pade", "given" : "J\u00fcrgen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Laryngoscope", "id" : "ITEM-11", "issue" : "7", "issued" : { "date-parts" : [ [ "2008" ] ] }, "note" : "Only septoplasty/SMR +/- turbinates and FESS. NO SRP", "page" : "1260-1264", "title" : "Olfactory function following nasal surgery.", "type" : "article-journal", "volume" : "118" }, "uris" : [ "" ] }, { "id" : "ITEM-12", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Federspil P, Wilhelm-Schwenk R", "given" : "Constantinidis J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-12", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "184-187", "title" : "Kinetics of olfactory function following endonasal sinus surgery for nasal polyposis", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] }, { "id" : "ITEM-13", "itemData" : { "DOI" : "10.1111/j.1398-9995.2008.01870.x", "ISSN" : "01054538", "PMID" : "19191775", "abstract" : "BACKGROUND: Nasal polyposis is a disease known to be associated with asthma. The management is anti-inflammatory, with topical and oral corticosteroids as the first-line treatment. The effect of surgical treatment on lower airway inflammation has not been sufficiently studied.\\n\\nAIM: The aim of this study is to investigate the effects of functional endoscopic sinus surgery (FESS) as well as fluticasone proprionate nasal drops (FPND) 400 microg b.i.d. on nasal and lower airway parameters in asthmatics with nasal polyposis.\\n\\nMETHODS: This was a prospective 21-week study of 68 patients with asthma and nasal polyposis, on the benefits of FESS on nasal '(butanol test, subjective olfaction, peak nasal inspiratory flow, congestion, rhinorrhoea, and polyp score)', and on the lower airway parameters (dyspnea, cough, mean daily peak expiratory flow rate (PEFR), and lung function tests). It also included a randomized, double-blind, placebo-controlled 14 weeks phase on FPND.\\n\\nRESULTS: Functional endoscopic sinus surgery significantly improved mean asthma symptom scores and daily PEFR and all nasal parameters including subjective and objective olfaction tests. This is the first study that shows the benefits of FESS on butanol tests in patients with nasal polyposis. We found no significant difference between topical treatment with FPND or placebo in the nasal or lower airway variables.\\n\\nCONCLUSION: Functional endoscopic sinus surgery improved nasal and asthma symptoms in patients with nasal polyposis. Functional endoscopic sinus surgery could be considered early in the natural course of nasal polyposis with concomitant asthma, as well as a second-line treatment in nasal polyposis patients with a reduced sense of smell. The potential benefits of FPND 400 microg b.i.d. were probably overshadowed by FESS.", "author" : [ { "dropping-particle" : "", "family" : "Ehnhage", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olsson", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kolbeck", "given" : "K. G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Skedinger", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dahl??n", "given" : "B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "??lenius", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stj??rne", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Allergy: European Journal of Allergy and Clinical Immunology", "id" : "ITEM-13", "issue" : "5", "issued" : { "date-parts" : [ [ "2009" ] ] }, "note" : "Ref for steroids and olfaction", "page" : "762-769", "title" : "Functional endoscopic sinus surgery improved asthma symptoms as well as PEFR and olfaction in patients with nasal polyposis", "type" : "article-journal", "volume" : "64" }, "uris" : [ "" ] }, { "id" : "ITEM-14", "itemData" : { "abstract" : "Aim: This prospective study aimed to assess treatment outcome on olfaction in patients undergoing Endoscopic Sinus Surgery (ESS) for nasal polyposis, and to evaluate the role of previous sinus surgery and the duration of olfactory deficit as prognostic factors for olfaction improvement. Methods: In total, 116 patients with nasal polyposis who underwent ESS were studied. Olfactory testing was performed using the Sniffin' Sticks test, preoperatively and 1-, 3- and 6-month postoperatively. Results: The values of the composite threshold discrimination identification score were significantly lower in patients with long duration of olfactory deficit and history of previous sinus surgery in all testing sessions. Adjustment for preoperative olfactory measures and all potential confounders revealed that both parameters remained strong independent predictors of normal olfactory function; a successful outcome was more frequent in patients with short duration of olfactory deficit and in patients who had not undergone previous sinus surgeries. However all patients achieved a significant stepwise increment of all indices of olfactory function over time, after ESS. Conclusions: Duration of olfactory deficit and previous sinus surgery presented highly significant predictive value for the short-term outcome of the olfactory function after ESS. However all patients suffering from nasal polyposis will probably improve olfaction significantly in a period up to six months after surgery.", "author" : [ { "dropping-particle" : "", "family" : "Danielides", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katotomichelakis", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balatsouras", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Riga", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Simopoulou", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kantas", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nikolettos", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-14", "issue" : "2", "issued" : { "date-parts" : [ [ "2009" ] ] }, "note" : "Improvement after FESS dependent on duration of olf dysfunction -- > smaller OB? would this return with training in these patients\n\nLook at ref:\n2,3,8,19,21-23, 24", "page" : "172-180", "title" : "Evaluation of prognostic factors for olfaction in nasal polyposis treated by Endoscopic Sinus Surgery", "type" : "article-journal", "volume" : "47" }, "uris" : [ "" ] }, { "id" : "ITEM-15", "itemData" : { "DOI" : "10.1016/j.otohns.2008.12.006", "ISSN" : "01945998", "PMID" : "19248934", "abstract" : "Objective: To examine the impact of endoscopic sinus surgery (ESS) on olfactory impairment in patients with chronic rhinosinusitis (CRS) over intermediate and long-term follow-up. We hypothesized that patients with mild olfactory dysfunction (hyposmia) would benefit from ESS, whereas patients with severe olfactory dysfunction (anosmia) would not. Study Design: Prospective, multi-institutional cohort study. Subjects and Methods: A total of 111 patients presenting for ESS for treatment of CRS were examined preoperatively, and at 6 and 12 months postoperatively. Demographic, comorbidity, and Smell Identification Test (SIT) data were collected at each time point. Univariate and multivariate analyses were performed. Results: The prevalence of gender-adjusted olfactory dysfunction prior to surgery was 67.5 percent. Surprisingly, hyposmic patients did not significantly improve after surgery. In contrast, patients with anosmia significantly improved after ESS (baseline, 6-month SIT scores: 9.7 ?? 2.0, 21.3 ?? 11.2; P = 0.001). Improvement was sustained at 12-month follow-up (21.7 ?? 10.7; P = 0.001). Multivariate linear regression analysis showed that baseline olfactory category and nasal polyposis were significantly associated with improvement in postoperative olfactory function (P = 0.035, P = 0.002). Conclusion: Contrary to our hypotheses, patients with severe olfactory dysfunction significantly improved after ESS and sustained improvement over time, whereas patients with mild olfactory dysfunction did not. ?? 2009 American Academy of Otolaryngology-Head and Neck Surgery Foundation.", "author" : [ { "dropping-particle" : "", "family" : "Litvack", "given" : "Jamie R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mace", "given" : "Jess", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Timothy L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Otolaryngology - Head and Neck Surgery", "id" : "ITEM-15", "issue" : "3", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "312-319", "title" : "Does olfactory function improve after endoscopic sinus surgery?", "type" : "article-journal", "volume" : "140" }, "uris" : [ "" ] }, { "id" : "ITEM-16", "itemData" : { "DOI" : "10.4193/Rhin09.097", "ISBN" : "0300-0729 (Print)\\r0300-0729 (Linking)", "ISSN" : "03000729", "PMID" : "20502751", "abstract" : "BACKGROUND: A positive effect of Endoscopic Sinus Surgery (ESS) as sole treatment on olfactory thresholds and sense of smell in patients with nasal polyposis has been questioned. The aim of this study was to test the hypothesis that ESS has a positive effect on sense of smell and olfactory threshold in nasal polyposis. METHODS: Uncontrolled post-hoc analysis of a prospective study of 160 patients, > or = 18 years, with bilateral nasal polyps that underwent ESS to treat bilateral nasal polyposis. The effect of ESS was assessed with an olfactory threshold test, a diary score and a smell and taste score, pre-, and post-ESS. RESULTS: All three effect measures were improved from pre-ESS to post-ESS. Olfactory threshold increased from 0.0 pre-ESS to 3.0 (p < 0.001), two weeks after surgery, and the smell diary score decreased from 3.0 to 1.7 during the same period (p < 0.001), i.e. improvement. The smell and taste score increased from 1.0 pre-ESS to 2.0 post-ESS (p = 0.002). Overall, the results were similar for patients with and without previous surgery, as well as for men and women. CONCLUSION: ESS without concomitant medical therapy seems to improve both sense of smell and olfactory thresholds in patients with nasal polyposis in the short term.", "author" : [ { "dropping-particle" : "", "family" : "Olsson", "given" : "Petter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stj\u00e4rne", "given" : "P\u00e4r", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-16", "issue" : "2", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "150-155", "title" : "Endoscopic Sinus Surgery improves olfaction in nasal polyposis, a multi-center study", "type" : "article-journal", "volume" : "48" }, "uris" : [ "" ] }, { "id" : "ITEM-17", "itemData" : { "DOI" : "10.1177/0194599811435638", "ISSN" : "0194-5998", "author" : [ { "dropping-particle" : "", "family" : "Ehnhage", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olsson", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kolbeck", "given" : "K.-G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Skedinger", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stjarne", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Otolaryngology -- Head and Neck Surgery", "id" : "ITEM-17", "issue" : "5", "issued" : { "date-parts" : [ [ "2012" ] ] }, "note" : "7, 20, 23, 24, 25", "page" : "834-841", "title" : "One Year after Endoscopic Sinus Surgery in Polyposis: Asthma, Olfaction, and Quality-of-Life Outcomes", "type" : "article-journal", "volume" : "146" }, "uris" : [ "" ] }, { "id" : "ITEM-18", "itemData" : { "DOI" : "10.1007/s00405-012-1972-0", "ISBN" : "1434-4726 (Electronic)\\r0937-4477 (Linking)", "ISSN" : "09374477", "PMID" : "22382399", "abstract" : "Olfactory dysfunction is a frequent symptom of nasal and sinunasal disease. Many of these patients undergo nasal sinus or nasal septum surgery. In this study, we evaluated the benefit of nasal surgery on olfactory function over a period of 12 months. Patients included in this study underwent either nasal sinus or nasal septum surgery. All patients were tested for olfactory function using the \"Sniffin' sticks\" 16 item odor identification test. In addition, patients were asked to rate their nasal patency as well as their olfactory function at each visit. 157 patients were tested 3.5 months after surgery and 52 patients were tested again 12 months after surgery. Olfactory function improved significantly 3.5 months after surgery in patients, who received nasal sinus surgery; no significant increase was found in patients treated with nasal septum surgery. At the 12-month follow-up, the increase in olfactory function over all patients just missed statistical significance. Individually, however, 19% of the patients exhibited improvement after 3.5 months and 17% after 12 months. These numbers increased in patients with rhinosinusitis with nasal polyps, who exhibited improvement of 30% after 3.5 months, and 32% after 12 months. Nasal sinus surgery produced an increase in measured olfactory function, but not nasal septum surgery. This increase appeared to be stable over the examined period of 12 months.", "author" : [ { "dropping-particle" : "", "family" : "Schriever", "given" : "V. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gupta", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pade", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Szewczynska", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Archives of Oto-Rhino-Laryngology", "id" : "ITEM-18", "issue" : "1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "note" : "Olfactory function was increased significantly 3.5 months after surgery, when compared to pre-surgical olfactory function. This positive effect was only seen in patients, who underwent sinus surgery and not in patients treated with septum surgery.", "page" : "107-111", "title" : "Olfactory function following nasal surgery: A 1-year follow-up", "type" : "article-journal", "volume" : "270" }, "uris" : [ "" ] }, { "id" : "ITEM-19", "itemData" : { "DOI" : "10.1007/s00405-013-2553-6", "ISSN" : "09374477", "PMID" : "23700266", "author" : [ { "dropping-particle" : "", "family" : "Baradaranfar", "given" : "Mohammad Hossein", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ahmadi", "given" : "Zeynab Sadat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dadgarnia", "given" : "Mohammad Hossein", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bemanian", "given" : "Mohammad Hossein", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atighechi", "given" : "Saeid", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karimi", "given" : "Ghasem", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Halvani", "given" : "Abolhasan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Behniafard", "given" : "Nasim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baradaranfar", "given" : "Amin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meybodi", "given" : "Tohid Emami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Archives of Oto-Rhino-Laryngology", "id" : "ITEM-19", "issue" : "2", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "311-6", "title" : "Comparison of the effect of endoscopic sinus surgery versus medical therapy on olfaction in nasal polyposis", "type" : "article-journal", "volume" : "271" }, "uris" : [ "" ] }, { "id" : "ITEM-20", "itemData" : { "DOI" : "10.1007/s12070-011-0439-8", "ISBN" : "1207001104", "ISSN" : "22313796", "PMID" : "24427662", "abstract" : "The aim of this research was to verify the effect of functional endoscopic sinus surgery (FESS) on olfactory dysfunction in patients who suffer from chronic rhinosinusitis. We enrolled prospective consecutive patients at a tertiary institution who were undergoing FESS; for these patients prolonged medical therapy for chronic rhinosinusitis had failed. Patients were asked to grade their olfactory dysfunction from 1 to 5 with 1 representing lack of any smell function and 5 representing a completely normal sense of smell. Moreover, the pre- and postoperative smell identification test of the University of Pennsylvania was performed for all participating patients. In addition, data including computed tomography scores, nasal endoscopy, and the presence or absence of asthma as well as smoking habits were recorded and analyzed. Patients were followed at least 1 year after surgery. Data were collected on 89 patients who had undergone sinus surgery. Postoperative olfactory function was 77% improved for all subjects as a group. Higher involvement of sinus in computed tomography correlated with poorer results in olfactory UPSIT40 score. Patients' olfaction was significantly related to polyp pathology, duration of disease, age, smoking habits and history of asthma. A variety of patients' characteristics have impact on olfactory outcome of sinusitis patients after FESS.", "author" : [ { "dropping-particle" : "", "family" : "Saedi", "given" : "Babak", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sadeghi", "given" : "Mohammad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yazdani", "given" : "Nasrin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Afshari", "given" : "Akram", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Indian Journal of Otolaryngology and Head and Neck Surgery", "id" : "ITEM-20", "issue" : "SUPPL2", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "283-287", "title" : "Effectiveness of FESS in Smell Improvement of Sinusitis Patients", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "73,188,210,219,220,258,260,315\u2013327", "plainTextFormattedCitation" : "73,188,210,219,220,258,260,315\u2013327", "previouslyFormattedCitation" : "73,188,209,218,219,257,259,314\u2013326" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }73,188,210,219,220,258,260,315–327). A recent study examining olfactory outcomes after surgery for CRS utilised the QOD-NS questionnaire and 40-item SIT, demonstrating the greatest improvement was seen in patients with the most preoperative disease on CT scans (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/alr.21679", "ISSN" : "20426976", "author" : [ { "dropping-particle" : "", "family" : "Soler", "given" : "Zachary M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Timothy L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alt", "given" : "Jeremiah A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramakrishnan", "given" : "Vijay R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mace", "given" : "Jess C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schlosser", "given" : "Rodney J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Forum of Allergy & Rhinology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2016", "4" ] ] }, "page" : "407-413", "title" : "Olfactory-specific quality of life outcomes after endoscopic sinus surgery", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "186", "plainTextFormattedCitation" : "186", "previouslyFormattedCitation" : "186" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }186). There is some difficulty, however, in comparing these studies, as marked heterogeneity exists in the methodology used. For example, 5 studies utilised only subjective measures of olfactory function, 4 utilised only odour identification and 7 only odour threshold testing (Table 8). The utility of surgery in addressing olfactory dysfunction due to causes other than CRS is less well established. In a follow up study, Schriever and colleagues demonstrated that nasal septoplasty had no beneficial effects on olfaction as measured at one year (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00405-012-1972-0", "ISBN" : "1434-4726 (Electronic)\\r0937-4477 (Linking)", "ISSN" : "09374477", "PMID" : "22382399", "abstract" : "Olfactory dysfunction is a frequent symptom of nasal and sinunasal disease. Many of these patients undergo nasal sinus or nasal septum surgery. In this study, we evaluated the benefit of nasal surgery on olfactory function over a period of 12 months. Patients included in this study underwent either nasal sinus or nasal septum surgery. All patients were tested for olfactory function using the \"Sniffin' sticks\" 16 item odor identification test. In addition, patients were asked to rate their nasal patency as well as their olfactory function at each visit. 157 patients were tested 3.5 months after surgery and 52 patients were tested again 12 months after surgery. Olfactory function improved significantly 3.5 months after surgery in patients, who received nasal sinus surgery; no significant increase was found in patients treated with nasal septum surgery. At the 12-month follow-up, the increase in olfactory function over all patients just missed statistical significance. Individually, however, 19% of the patients exhibited improvement after 3.5 months and 17% after 12 months. These numbers increased in patients with rhinosinusitis with nasal polyps, who exhibited improvement of 30% after 3.5 months, and 32% after 12 months. Nasal sinus surgery produced an increase in measured olfactory function, but not nasal septum surgery. This increase appeared to be stable over the examined period of 12 months.", "author" : [ { "dropping-particle" : "", "family" : "Schriever", "given" : "V. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gupta", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pade", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Szewczynska", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Archives of Oto-Rhino-Laryngology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "note" : "Olfactory function was increased significantly 3.5 months after surgery, when compared to pre-surgical olfactory function. This positive effect was only seen in patients, who underwent sinus surgery and not in patients treated with septum surgery.", "page" : "107-111", "title" : "Olfactory function following nasal surgery: A 1-year follow-up", "type" : "article-journal", "volume" : "270" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "326", "plainTextFormattedCitation" : "326", "previouslyFormattedCitation" : "325" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }326), though other studies have demonstrated benefit (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0300-0729 (Print)\\r0300-0729 (Linking)", "ISSN" : "03000729", "PMID" : "18444490", "abstract" : "BACKGROUND: Despite the common occurrence of rhinological pathology presenting to the ENT clinic, routine testing of olfactory ability is rarely performed. OBJECTIVES: The aim of this study was to determine the role of routine olfactory testing. METHODS: This was a prospective study conducted in the outpatient clinic of a district general hospital. Patients presenting with rhinological complaints had their olfactory status assessed using the combined olfactory test (COT) before and after rhinological surgery. RESULTS: Eighty patients (56 men, 24 women) had tests completed over a 12-month period. Patients assessed mostly had nasal polyposis, chronic rhinosinusitis or septal deformity. 83% of patients had either a complaint of olfactory disturbance or a COT score of 6 or less, or had both; but correlation between symptoms and scores was poor. Post-operative COT scores showed significant improvement (p = 0.02) with post-septoplasty patients showing the most significant improvement as a group (p = 0.001). CONCLUSIONS: Olfactory disturbance is very common in rhinological pathology and the patient's history alone cannot be relied upon. Simple olfactory assessment, such as with the combined olfactory test, is easy to perform and cheap to use and should be a commonly used resource in the ENT clinic. Formal testing can help to document any pre-existing olfactory loss and any post-operative changes as well as detecting unreported hyposmia.", "author" : [ { "dropping-particle" : "", "family" : "Philpott", "given" : "Carl M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rimal", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tassone", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prinsley", "given" : "P. R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Premachandra", "given" : "D. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "34-39", "title" : "A study of olfactory testing in patients with rhinological pathology in the ENT clinic", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "187", "plainTextFormattedCitation" : "187", "previouslyFormattedCitation" : "187" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }187). The effect of septorhinoplasty on olfaction has not yet been sufficiently demonstrated, though some reports suggest that it may lead to improved function (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/lary.23615", "ISSN" : "0023852X", "PMID" : "22991249", "abstract" : "OBJECTIVES/HYPOTHESIS: It is becoming increasingly important for clinicians to demonstrate the impact of their interventions. The Sino-Nasal Outcome Test-22 (SNOT-22) questionnaire is a disease-specific questionnaire involving 22 symptoms combining rhinologic issues with general health issues. We evaluated the SNOT-22 score as a quality-of-life outcome measure in septorhinoplasty surgery.\\n\\nSTUDY DESIGN: Outcome research.\\n\\nMETHODS: We carried out a prospective case series in 76 patients undergoing septorhinoplasty. Their SNOT-22 scores were compared pre- and postoperatively. We also recorded individual symptom scores to study the impact of surgery. To check its reliability, the SNOT-22 score was correlated to patient-reported symptoms on a visual analogue scale. Patients were screened for comorbid conditions. Interactions with the surgical technique and/or with the initial sinonasal disease were sought.\\n\\nRESULTS: The SNOT-22 is a reliable and responsive outcome measure in septorhinoplasty surgery. Septorhinoplasty was especially effective at addressing nasal obstruction, discharge, olfaction, related sleep disturbance, and emotional symptoms such as embarrassment or frustration. Comparison to the visual analogue scale instrument confirmed the outcome measured by the SNOT-22.\\n\\nCONCLUSIONS: The SNOT-22 could be used in routine clinical practice to highlight the impact of nasal disease in each patient and to measure the outcome and the effectiveness of the surgical intervention.", "author" : [ { "dropping-particle" : "", "family" : "Poirrier", "given" : "Anne Lise", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ahluwalia", "given" : "Suki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goodson", "given" : "Alexander", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ellis", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bentley", "given" : "Melissa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andrews", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Laryngoscope", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "76-81", "title" : "Is the Sino-Nasal Outcome Test-22 a suitable evaluation for septorhinoplasty?", "type" : "article-journal", "volume" : "123" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1111/coa.12463", "ISSN" : "17494486", "author" : [ { "dropping-particle" : "", "family" : "Randhawa", "given" : "P. S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watson", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lechner", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ritchie", "given" : "L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Choudhury", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andrews", "given" : "P. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Otolaryngology", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "15-20", "title" : "The outcome of septorhinoplasty surgery on olfactory function", "type" : "article-journal", "volume" : "41" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "328,329", "plainTextFormattedCitation" : "328,329", "previouslyFormattedCitation" : "327,328" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }328,329). In addition, surgery other than nasal surgery, e.g. gastric bypass does not seem to improve olfactory function (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s11695-011-0487-x", "ISSN" : "0960-8923", "author" : [ { "dropping-particle" : "", "family" : "Richardson", "given" : "Brynn E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vanderwoude", "given" : "Eric A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sudan", "given" : "Ranjan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leopold", "given" : "Donald A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thompson", "given" : "Jon S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity Surgery", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2012", "2", "7" ] ] }, "page" : "283-286", "publisher" : "Springer-Verlag", "title" : "Gastric Bypass Does Not Influence Olfactory Function in Obese Patients", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "330", "plainTextFormattedCitation" : "330", "previouslyFormattedCitation" : "329" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }330), though there is controversy in the literature (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1177/0003489416629162", "ISSN" : "0003-4894 (Print)", "PMID" : "26848035", "abstract" : "Introduction: The reduction in the preferences for sweet and fat containing tastes in obese patients who underwent bariatric surgery was relatively well shown; however, there are only limited data on the changes in the sensitivity of other tastes like sour, salty, and bitter.Methods: We investigated the changes in gustatory sensitivity of 52 morbidly obese patients (M/F, 22/30; age range, 19-60 years; BMI range, 32.5-63.0 kg/m2) after laparoscopic sleeve gastrectomy. The surgery was performed by the same surgeon using 5 ports technique. Gustatory sensitivity was tested preoperatively and 1 and 3 months after the surgery using standardized Taste Strips test.Results: There was a statistically significant improvement in the taste acuity to sweet, sour, salty, and bitter tastants in morbidly obese patients after the laparoscopic sleeve gastrectomy during the follow-up period of 3 months. Median whole test scores of the patients were increased from 11.5 preoperatively to 14 in the first and third months.Conclusion: In this study, we were able to show the significant improvement in gustatory sensitivity of morbidly obese patients after laparoscopic sleeve gastrectomy for the first time in literature. ", "author" : [ { "dropping-particle" : "", "family" : "Altun", "given" : "Huseyin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hanci", "given" : "Deniz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altun", "given" : "Hasan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Batman", "given" : "Burcin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Serin", "given" : "Rahmi Kursat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karip", "given" : "Aziz Bora", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akyuz", "given" : "Umit", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of Otology, Rhinology & Laryngology ", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "558-562", "title" : "Improved Gustatory Sensitivity in Morbidly Obese Patients After Laparoscopic Sleeve Gastrectomy", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "331", "plainTextFormattedCitation" : "331", "previouslyFormattedCitation" : "330" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }331).As mentioned above, without an obvious odour present, patients with phantosmia report experiencing a very unpleasant smell, often described as ‘rotten meat’, ‘chemical’ or ‘burnt’ (in some cases preceding a seizure or migraine; in others the smell is present persistently throughout the day). For patients with neurological conditions, the condition often dissipates with treatment. However for those without an obvious co-existing condition there is no universally accepted treatment. Surgical removal of the olfactory epithelium has been tried in a few patients (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1001/archotol.1991.01870240094016", "ISSN" : "0886-4470", "author" : [ { "dropping-particle" : "", "family" : "Leopold", "given" : "D. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwob", "given" : "J. E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Youngentob", "given" : "S. L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hornung", "given" : "D. 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The distortions are usually much more upsetting to a person's quality of life than a simple loss. An ipsilatersal loss of olfactory sensitivity is often identified in the nostril with any type of olfactory distortion. The pathophysiology of a stimulated distortion (troposmia) is likely a decreased number of functioning olfactory primary neurons so that an incomplete characterization of the odorant is made. In phantosmia, two possible causations include an abnormal signal or inhibition from the primary olfactory neurons or peripheral olfactory or trigeminal signals that \"trigger\" a central process. The clinician's goal is to carefully define the problem (e.g. taste versus smell, real versus perceived, one versus two nostrils), to perform the appropriate examination and testing and to provide therapy if possible. Treatment includes assurance with no active therapy (because many of these will naturally resolve), topical medications, systemic medications, anesthesia to parts of the nose and, rarely, referral for surgical excision of olfactory neurons. Endoscopic transnasal operations have the advantage of treating phantosmia and sometimes allowing a return of olfactory ability after the operation.", "author" : [ { "dropping-particle" : "", "family" : "Leopold", "given" : "Donald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemical Senses", "id" : "ITEM-2", "issue" : "7", "issued" : { "date-parts" : [ [ "2002" ] ] }, "page" : "611-615", "title" : "Distortion of Olfactory Perception: Diagnosis and Treatment", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "14,332", "plainTextFormattedCitation" : "14,332", "previouslyFormattedCitation" : "14,331" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }14,332). This procedure has not been validated and is high risk and should therefore be attempted only as a very last resort and only at an experienced, major medical centre. Topical application of cocaine hydrochloride can offer temporary relief (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/chemse/bjt047", "ISSN" : "1464-3553", "PMID" : "24122320", "abstract" : "Phantosmia, the perception of an odor when there are no odorants in the environment, can be a very debilitating symptom. In the 1960s, Zilstorff reported olfactory distortions could be treated by the topical application of a cocaine solution to the olfactory epithelium. In evaluating this treatment, we observed no long-term benefit using cocaine on 6 patients with phantosmia. Based on our observations, the patient's olfactory ability was not a determining factor in the initiation or quality of their phantosmia. Following topical cocainization, we observed a remarkable delay of hours to days in the return of olfactory ability, and when cocaine was applied to only 1 nostril, there was a decreased olfactory ability on the noncocainized side. These results may suggest the possibility that phantosmia is related to a central processing problem.", "author" : [ { "dropping-particle" : "", "family" : "Leopold", "given" : "Donald A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hornung", "given" : "David E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemical senses", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2013", "11" ] ] }, "page" : "803-6", "publisher" : "Oxford University Press", "title" : "Olfactory cocainization is not an effective long-term treatment for phantosmia.", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "333", "plainTextFormattedCitation" : "333", "previouslyFormattedCitation" : "332" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }333). In some patients phantosmia will spontaneously decline over time. [Table 7]Recommendations:Functional endoscopic surgery for olfactory loss caused by the CRS disease spectrum should be undertaken in line with existing guidelines (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1013-0047", "PMID" : "22764607", "abstract" : "The European Position Paper on Rhinosinusitis and Nasal Polyps 2012 is the update of similar evidence based position papers published in 2005 and 2007.The document contains chapters on definitions and classification, we now also proposed definitions for difficult to treat rhinosinusitis, control of disease and better definitions for rhinosinusitis in children. More emphasis is placed on the diagnosis and treatment of acute rhinosinusitis. Throughout the document the terms chronic rhinosinusitis without nasal polyps and chronic rhinosinusitis with nasal polyps are used to further point out differences in pathophysiology and treatment of these two entities. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. Last but not least all available evidence for management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is analyzed and presented and management schemes based on the evidence are proposed.", "author" : [ { "dropping-particle" : "", "family" : "Fokkens", "given" : "Wytske J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lund", "given" : "Valerie J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mullol", "given" : "Joachim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bachert", "given" : "Claus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alobid", "given" : "Isam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baroody", "given" : "Fuad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cohen", "given" : "Noam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cervin", "given" : "Anders", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Douglas", "given" : "Richard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gevaert", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Georgalas", "given" : "Christos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goossens", "given" : "Herman", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harvey", "given" : "Richard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hellings", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hopkins", "given" : "Claire", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jones", "given" : "Nick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Joos", "given" : "Guy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kalogjera", "given" : "Livije", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kern", "given" : "Bob", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kowalski", "given" : "Marek", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Price", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Riechelmann", "given" : "Herbert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schlosser", "given" : "Rodney", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Senior", "given" : "Brent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thomas", "given" : "Mike", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Toskala", "given" : "Elina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voegels", "given" : "Richard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "De Yun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wormald", "given" : "Peter John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology. Supplement", "id" : "ITEM-1", "issue" : "23", "issued" : { "date-parts" : [ [ "2012", "3" ] ] }, "page" : "1-298", "title" : "European Position Paper on Rhinosinusitis and Nasal Polyps 2012.", "type" : "article-journal", "volume" : "50" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "86", "plainTextFormattedCitation" : "86", "previouslyFormattedCitation" : "86" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }86).There is presently insufficient evidence to support other surgery types for olfactory dysfunction, though further characterisation of the effects of functional septorhinoplasty is required. ConclusionsIn the preceding sections we have provided an overview of current evidence and recommendations for the definition, investigation and management of olfactory dysfunction. We hope that these guidelines will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency and generalisability of work in this field. ACKNOWLEDGEMENTS:None.AUTHORSHIP CONTRIBUTION:Hummel TConceptual design. Supervision of project. Administrative support. Whitcroft KLConceptual design. Writing of manuscript. Integration of co-author comments.Andrews PReview of content and agreement with final recommendations.Altundag AReview of content and agreement with final recommendations.Cinghi CReview of content and agreement with final recommendations.Costanzo RMReview of content and agreement with final recommendations.Damm MReview of content and agreement with final recommendations.Frasnelli JReview of content and agreement with final recommendations.Gudziol HReview of content and agreement with final recommendations.Gupta NReview of content and agreement with final recommendations.Haehner AReview of content and agreement with final recommendations.Holbrook EReview of content and agreement with final recommendations.Hong SCReview of content and agreement with final recommendations.Hornung DReview of content and agreement with final recommendations.Hüttenbrink KBReview of content and agreement with final recommendations.Kamel RReview of content and agreement with final recommendations.Kobayashi MReview of content and agreement with final recommendations.Konstantinidis IReview of content and agreement with final recommendations.Landis BNReview of content and agreement with final recommendations.Leopold DAReview of content and agreement with final recommendations.Macchi AReview of content and agreement with final recommendations.Miwa TReview of content and agreement with final recommendations.Moesges RReview of content and agreement with final recommendations.Mullol JReview of content and agreement with final recommendations.Mueller CAReview of content and agreement with final recommendations.Ottaviano GReview of content and agreement with final recommendations.Passali GCReview of content and agreement with final recommendations.Philpott CReview of content and agreement with final recommendations.Pinto JMReview of content and agreement with final recommendations.Ramakrishnan VJReview of content and agreement with final recommendations.Rombaux PReview of content and agreement with final recommendations.Roth YReview of content and agreement with final recommendations.Schlosser RAReview of content and agreement with final recommendations.Shu BReview of content and agreement with final recommendations.Soler GReview of content and agreement with final recommendations.Stj?rne PReview of content and agreement with final recommendations.Stuck BAReview of content and agreement with final recommendations.Vodicka JReview of content and agreement with final recommendations.Welge-Luessen AReview of content and agreement with final recommendations.CONFLICT OF INTEREST:None.REFERENCES:ADDIN Mendeley Bibliography CSL_BIBLIOGRAPHY 1. 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Reden J, Herting B, Lill K, Kern R, Hummel T. Treatment of postinfectious olfactory disorders with minocycline: A double-blind, placebo-controlled study. Laryngoscope. 2011;121(3):679-682. doi:10.1002/lary.21401.298. Quint C, Temmel AF, Hummel T, Ehrenberger K. The quinoxaline derivative caroverine in the treatment of sensorineural smell disorders: a proof-of-concept study. Acta Otolaryngol. 2002;122(8):877-881. doi:10.1080/003655402/000028054.299. Hummel T, Heilmann S, Hüttenbriuk K-B. Lipoic acid in the treatment of smell dysfunction following viral infection of the upper respiratory tract. Laryngoscope. 2002;112(11):2076-2080. doi:10.1097/00005537-200211000-00031.300. Hummel T, Reden KRJ, H?hner A, Weidenbecher M, Hüttenbrink KB. Effects of olfactory Training in patients with olfactory loss. Laryngoscope. 2009;119(3):496-499. doi:10.1002/lary.20101.301. Haehner A, Tosch C, Wolz M, et al. Olfactory Training in Patients with Parkinson’s Disease. PLoS One. 2013;8(4):1-7. doi:10.1371/journal.pone.0061680.302. Geissler K, Reimann H, Gudziol H, Bitter T, Guntinas-Lichius O. Olfactory training for patients with olfactory loss after upper respiratory tract infections. Eur Arch Oto-Rhino-Laryngology. 2014;271(6):1557-1562. doi:10.1007/s00405-013-2747-y.303. Damm M, Pikart LK, Reimann H, et al. Olfactory training is helpful in postinfectious olfactory loss: A randomized, controlled, multicenter study. Laryngoscope. 2014;124(4):826-831. doi:10.1002/lary.24340.304. Altundag A, Cayonu M, Kayabasoglu G, et al. Modified olfactory training in patients with postinfectious olfactory loss. Laryngoscope. 2015;125(8):1763-1766. doi:10.1002/lary.25245.305. Konstantinidis I, Tsakiropoulou E, Bekiaridou P, Kazantzidou C, Constantinidis J. Use of olfactory training in post-traumatic and postinfectious olfactory dysfunction. Laryngoscope. 2013;123(12):85-90. doi:10.1002/lary.24390.306. Fleiner F, Lau L, Goktas O. Active olfactory training for the treatment of smell disorders. Ear Nose Throat J. 2012;91(5):198-203.307. Wang L, Chen L, Jacob T. Evidence for peripheral plasticity in human odour response. J Physiol. 2004;554(Pt 1):236-244. doi:10.1113/jphysiol.2003.054726.308. Konstantinidis I, Tsakiropoulou E, Constantinidis J. Long term effects of olfactory training in patients with post-infectious olfactory loss. Rhinology. 2016;54(2):170-175. doi:10.4193/Rhino15.264.309. Negoias S, Pietsch K, Hummel T. Changes in olfactory bulb volume following lateralized olfactory training. Brain Imaging Behav. 2016:1-8. doi:10.1007/s11682-016-9567-9.310. Poletti SC, Michel E, Hummel T. Olfactory Training Using Heavy and Light Weight Molecule Odors. Perception. 2016. doi:10.1177/0301006616672881.311. Kollndorfer K, Fischmeister FPS, Kowalczyk K, et al. Olfactory training induces changes in regional functional connectivity in patients with long-term smell loss. NeuroImage Clin. 2015;9:401-410. doi:10.1016/j.nicl.2015.09.004.312. Mori E, Petters W, Schriever VA, Valder C, Hummel T. Exposure to odours improves olfactory function in healthy children. Rhinology. 2015;53(3):221-226. doi:10.4193/Rhin14.192.313. Sharma R, Lakhani R, Rimmer J, Hopkins C. Surgical interventions for chronic rhinosinusitis with nasal polyps. Cochrane Database Syst Rev. 2014;(11):CD006990. doi:10.1002/14651858.CD006991.pub2.314. Rimmer J, Fokkens W, Chong LY, Hopkins C. Surgical versus medical interventions for chronic rhinosinusitis with nasal polyps . Cochrane Database Syst Rev . 2014;12(12):CD006991. doi:10.1002/14651858.CD006991.pub2..315. Lund VJ, Holmstrom M, Scadding GK. Functional endoscopic sinus surgery in the management of chronic rhinosinusitis. An objective assessment. J Laryngol Otol. 1991;105(10):832-835.316. Lund VJ, MacKay IS. Outcome assessment of endoscopic sinus surgery. J R Soc Med. 1994;87(2):70-72. . Blomqvist EH, Lundblad L, Angg?rd a, Haraldsson PO, Stj?rne P. A randomized controlled study evaluating medical treatment versus surgical treatment in addition to medical treatment of nasal polyposis. J Allergy Clin Immunol. 2001;107(2):224-228. doi:10.1067/mai.2001.112124.318. Perry BF, Kountakis SE. Subjective Improvement of Olfactory Function After Endoscopic Sinus Surgery for Chronic Rhinosinusitis. Am J Otolaryngol. 2003;24(6):366-369. doi:10.1053/S0196-0709(03)00067-X.319. Ragab SM, Lund VJ, Scadding G. Evaluation of the medical and surgical treatment of chronic rhinosinusitis: a prospective, randomised, controlled trial. Laryngoscope. 2004;114(5):923-930. doi:10.1097/00005537-200405000-00027.320. Rowe-Jones JM, Medcalf M, Durham SR, Richards DH, Mackay IS. Functional endoscopic sinus surgery: 5 year follow up and results of a prospective, randomised, stratified, double-blind, placebo controlled study of postoperative fluticasone propionate aqueous nasal spray. Rhinology. 2005;43(1):2-10.321. Bonfils P. Evaluation of the combined medical and surgical treatment in nasal polyposis. I: functional results. Acta Otolaryngol. 2007;127(4):436-446. doi:10.1080/00016480600895078.322. Minovi A, Hummel T, Ural A, Draf W, Bockmuhl U. Predictors of the outcome of nasal surgery in terms of olfactory function. Eur Arch Oto-Rhino-Laryngology. 2008;265(1):57-61. doi:10.1007/s00405-007-0409-7.323. Litvack JR, Mace J, Smith TL. Does olfactory function improve after endoscopic sinus surgery? Otolaryngol - Head Neck Surg. 2009;140(3):312-319. doi:10.1016/j.otohns.2008.12.006.324. Olsson P, Stj?rne P. Endoscopic Sinus Surgery improves olfaction in nasal polyposis, a multi-center study. Rhinology. 2010;48(2):150-155. doi:10.4193/Rhin09.097.325. Ehnhage A, Olsson P, Kolbeck K-G, Skedinger M, Stjarne P. One Year after Endoscopic Sinus Surgery in Polyposis: Asthma, Olfaction, and Quality-of-Life Outcomes. Otolaryngol -- Head Neck Surg. 2012;146(5):834-841. doi:10.1177/0194599811435638.326. Schriever VA, Gupta N, Pade J, Szewczynska M, Hummel T. Olfactory function following nasal surgery: A 1-year follow-up. Eur Arch Oto-Rhino-Laryngology. 2013;270(1):107-111. doi:10.1007/s00405-012-1972-0.327. Baradaranfar MH, Ahmadi ZS, Dadgarnia MH, et al. Comparison of the effect of endoscopic sinus surgery versus medical therapy on olfaction in nasal polyposis. Eur Arch Oto-Rhino-Laryngology. 2013;271(2):311-316. doi:10.1007/s00405-013-2553-6.328. Poirrier AL, Ahluwalia S, Goodson A, Ellis M, Bentley M, Andrews P. Is the Sino-Nasal Outcome Test-22 a suitable evaluation for septorhinoplasty? Laryngoscope. 2013;123(1):76-81. doi:10.1002/lary.23615.329. Randhawa PS, Watson N, Lechner M, Ritchie L, Choudhury N, Andrews PJ. The outcome of septorhinoplasty surgery on olfactory function. Clin Otolaryngol. 2016;41(1):15-20. doi:10.1111/coa.12463.330. Richardson BE, Vanderwoude EA, Sudan R, Leopold DA, Thompson JS. Gastric Bypass Does Not Influence Olfactory Function in Obese Patients. Obes Surg. 2012;22(2):283-286. doi:10.1007/s11695-011-0487-x.331. Altun H, Hanci D, Altun H, et al. Improved Gustatory Sensitivity in Morbidly Obese Patients After Laparoscopic Sleeve Gastrectomy. Ann Otol Rhinol Laryngol . 2016:558-562. doi:10.1177/0003489416629162.332. Leopold DA, Schwob JE, Youngentob SL, et al. Successful Treatment of Phantosmia With Preservation of Olfaction. Arch Otolaryngol - Head Neck Surg. 1991;117(12):1402-1406. doi:10.1001/archotol.1991.01870240094016.333. Leopold DA, Hornung DE. Olfactory cocainization is not an effective long-term treatment for phantosmia. Chem Senses. 2013;38(9):803-806. doi:10.1093/chemse/bjt047.334. Morrissey DK, Pratap U, Brown C, Wormald P-J. The role of surgery in the management of phantosmia. Laryngoscope. 2016;126(3):575-578. doi:10.1002/lary.25647.335. Altun H, Hanci D. Olfaction improvement after nasal septal perforation repair with the “cross-stealing” technique. Am J Rhinol Allergy. 2015;29(5):e142-e145. doi:10.2500/ajra.2015.29.4208.336. Leopold D. Distortion of Olfactory Perception: Diagnosis and Treatment. Chem Senses. 2002;27(7):611-615. doi:10.1093/chemse/27.7.611.337. Stevens CN, Stevens MH. Quantitative effects of nasal surgery on olfaction. Am J Otolaryngol. 1985;6(4):264-267. . CORRESPONDING AUTHOR:Thomas Hummel, M.D.; Smell and Taste Clinic, Department of Otorhinolaryngology, TU Dresden, Fetscherstrasse 74, 01307 Dresden, Germany; phone +49-351-458-4189; thummel@mail.zih.tu-dresden.de TABLES:Table 1:NormosmiaNormal olfactory function.Hyposmia(or ‘microsmia’)Quantitatively reduced olfactory function.Functional AnosmiaQuantitatively reduced olfaction to the extent that the subject has no function that is useful in daily life.AnosmiaAbsence of all olfactory function.Specific Anosmia(or ‘partial anosmia’)Quantitatively reduced ability to smell a specific odour despite preserved ability to smell most other odours. Thought to be a normal physiological trait with little clinical significance (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.cortex.2015.08.018", "ISSN" : "19738102", "PMID" : "26457822", "abstract" : "Selective processing of environmental stimuli improves processing capacity and allows adaptive modulation of behavior. The thalamus provides an effective filter of central sensory information processing. As olfactory projections, however, largely bypass the thalamus, other filter mechanisms must consequently have evolved for the sense of smell. We investigated whether specific anosmia - the inability to perceive a specific odor whereas detection of other substances is unaffected - represents an effective peripheral filter of olfactory information processing. In contrast to previous studies, we showed in a sample of 1600 normosmic subjects, that specific anosmia is by no means a rare phenomenon. Instead, while the affected odor is highly individual, the general probability of occurrence of specific anosmia is close to 1. In addition, 25 subjects performed daily olfactory training sessions with enhanced exposure to their particular \"missing\" smells for the duration of three months. This resulted in a significant improvement of sensitivity towards the respective specific odors. We propose specific anosmia to occur as a rule, rather than an exception, in the sense of smell. The lack of perception of certain odors may constitute a flexible peripheral filter mechanism, which can be altered by exposure.", "author" : [ { "dropping-particle" : "", "family" : "Croy", "given" : "Ilona", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olgun", "given" : "Selda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mueller", "given" : "Laura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schmidt", "given" : "Anna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muench", "given" : "Marcus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Cornelia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gisselmann", "given" : "Guenter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hatt", "given" : "Hanns", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cortex", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "180-187", "publisher" : "Elsevier Ltd", "title" : "Peripheral adaptive filtering in human olfaction? Three studies on prevalence and effects of olfactory training in specific anosmia in more than 1600 participants", "type" : "article-journal", "volume" : "73" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "12", "plainTextFormattedCitation" : "12", "previouslyFormattedCitation" : "12" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }12).Hyperosmia(or ‘superosmia’)Quantitatively increased ability to smell odours to abnormal level. This form of olfactory dysfunction is extremely rare, but has been described, for example, in association with migraine (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/BF00313864", "ISBN" : "0340-5354 (Print)\\r0340-5354 (Linking)", "ISSN" : "0340-5354", "PMID" : "4056833", "abstract" : "Osmophobia or hyperosmia featured in 25 of 50 migraineurs during the headache phase of their attacks. Pleasant or unpleasant odours could precipitate migraines in 11 patients in this series. Other sensory disturbances and precipitants were also studied. Neurological precipitation of attacks provides further support for a primary neural rather than a vascular pathogenesis of migraine.", "author" : [ { "dropping-particle" : "", "family" : "Blau", "given" : "J N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Solomon", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Neurology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1985" ] ] }, "page" : "275-6", "title" : "Smell and other sensory disturbances in migraine.", "type" : "article-journal", "volume" : "232" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "13", "plainTextFormattedCitation" : "13", "previouslyFormattedCitation" : "13" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }13).Parosmia (or ‘dysosmia’, ‘cacosmia’, ‘euosmia’ or ‘troposmia’)*Qualitative dysfunction in the presence of an odorant (i.e. distorted perception of an odour stimulus).PhantosmiaQualitative dysfunction in the absence of an odourant (i.e. an odourant is perceived without concurrent stimulus, an ‘olfactory hallucination’).Orthonasal olfactionThe perception of odourants anteriorly due to airflow from the nostrils to the olfactory clefts, e.g. during sniffing.Retronasal olfactionThe perception of odourants located within the oropharynx, caused by airflow to the olfactory clefts via the nasopharynx during swallowing or nasal exhalation. Retronasal olfaction forms the basis of flavour perception.Table 2:Conductive dysfunction Resulting from blockage of odourant transmission to the olfactory neuroepithelium.Sensorineural dysfunction Resulting from damage/loss of the olfactory neuroepithelium or nerve.Central dysfunction Resulting from damage/loss of the olfactory processing pathways of the central nervous system.Table 3:AgentsMedicationsAcidsBenzeneCadmiumChlorineEthyl acetateFormaldehydeHydrazineHydrogen sulphideLeadMercuryNitrous gasesPaint solventsSilicon dioxideTrichloroethyleneZinc gluconateAnaesthetics (local)cocaine hydrochlorideprocaine hydrochloridetetracaine hydrochlorideAntimicrobials aminoglycosidesmacrolidespenicillinstetracyclinesterbinafineAntithyroid medications propylthiouracilthiouracilChemotherapyAlpha-Receptor Antagonists Table 4:Psychophysical testOlfactory components assessed“Sniffin’ Sticks” (original version) Threshold, discrimination, identificationConnecticut Chemosensory Clinical Research Center TestThreshold, identificationT & T OlfactometerThreshold, identificationUniversity of Pennsylvania Smell Identification Test IdentificationSmell Diskettes TestIdentificationCross-Cultural Smell Identification TestIdentificationPocket Smell TestIdentificationSan Diego Odor Identification TestIdentificationScandinavian Odour Identification TestIdentificationSmell Threshold TestThresholdOlfactory Perception Threshold TestThresholdBarcelona Smell Test (BAST-24)Odourized Marker Test Snap & Sniff Olfactory Test SystemOpen EssenceOdour detection, identification, memory IdentificationThresholdIdentificationTable 5:AuthorYearStudy TypeTreatment MethodStudy Population; NResultsMedicationWhitcroft et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/COA.12789", "ISSN" : "1749-4486", "author" : [ { "dropping-particle" : "", "family" : "Whitcroft", "given" : "K L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ezzat", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cuevas", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andrews", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Otolaryngology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "1-7", "title" : "The effect of intranasal sodium citrate on olfaction in post\u2010infectious loss: results from a prospective, placebo\u2010controlled trial in 49 patients", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "289", "plainTextFormattedCitation" : "289", "previouslyFormattedCitation" : "288" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }289)2016Prospective, controlledIntranasal sodium citratePatients with post-infectious olfactory lossn=49Significant improvement in composite threshold and identification scores after treatment compared to placeboWhitcroft et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.4193/Rhino16.054", "author" : [ { "dropping-particle" : "", "family" : "Whitcroft", "given" : "Katherine L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Merkonidis", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cuevas", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haehner", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Philpott", "given" : "Carl M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "1-6", "title" : "Intranasal sodium citrate improves olfaction in post-viral hyposmia", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "288", "plainTextFormattedCitation" : "288", "previouslyFormattedCitation" : "287" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }288)2016Prospective, controlledIntranasal sodium citratePatients with olfactory loss of mixed causen=57Significantly improved identification scores in patients with post-infectious loss compared to placeboJiang et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1177/0194599815571272", "ISBN" : "0194-5998", "ISSN" : "0194-5998", "PMID" : "25715353", "abstract" : "OBJECTIVES: To study the effects of zinc and steroid in the treatment of traumatic anosmia. STUDY DESIGN: A prospective, randomized study. SETTING: Academic medical center. SUBJECTS AND METHODS: Patients with a clear history of loss of smell after head injury and whose thresholds were -1 measured by the phenyl ethyl alcohol threshold test were included in this study from January 2010 to May 2013. They were randomly divided into 4 groups. Patients in group 1 were treated with zinc gluconate for a month and high-dose prednisolone with tapering for 2 weeks. Those in group 2 took only zinc gluconate, and those in group 3 took only prednisolone. Patients in group 4 did not take any medicine. All patients were followed up by phenyl ethyl alcohol threshold testing, and magnetic resonance imaging was performed to measure the volume of olfactory bulbs. RESULTS: Thirty-nine patients in group 1, 35 in group 2, 34 in group 3, and 37 in group 4 completed the study. The recovery of olfactory function was observed in 11 patients (28.2%) in group 1, in 9 (25.7%) in group 2, in 4 (11.8%) in group 3, and in 1 (2.7%) in group 4. The recovery rates of olfactory function of groups 1 and 2 were significantly higher than the recovery rate of group 4. The volume of olfactory bulbs was not significantly different between those with and without improved olfactory function. CONCLUSION: Our results show that zinc gluconate has a promising effect in treating traumatic anosmia.", "author" : [ { "dropping-particle" : "", "family" : "Jiang", "given" : "R S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Twu", "given" : "C W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liang", "given" : "K L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Otolaryngol Head Neck Surg", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "954-958", "title" : "Medical treatment of traumatic anosmia", "type" : "article-journal", "volume" : "152" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "272", "plainTextFormattedCitation" : "272", "previouslyFormattedCitation" : "271" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }272)2015Prospective, controlledZinc and steroidTraumatic anosmian=145Zinc and steroid application showed significant improvement compared to “no treatment”; no difference in effectiveness between zinc and steroidTian et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/alr.21586", "ISSN" : "20426984", "PMID" : "26140380", "abstract" : "BACKGROUND: Olfaction is one of the important senses for humans. Systemic glucocorticoids are the most commonly used medications for olfactory loss because of their strong anti-inflammatory effects. However, their effect on olfactory function is still controversial and the precise mechanism is not clear. To gain a global view of the effect of systematic glucocorticoid treatment on gene expression in the olfactory mucosa (OM), we profiled these changes in a murine model of olfaction in order to identify underlying molecular mechanisms.\\n\\nMETHODS: C57BL/6 mice were injected daily for 2 weeks (WK2) with dexamethasone (DEX, intraperitoneally, 1 mg/kg body weight) vs 1 day of DEX (D1) vs controls, which received saline (Ctrl) (n = 9/group). Total RNA from the OM was used to analyze global gene expression. Genes showing changes in expression were compared using the Database for Annotation, Visualization and Integrated Discovery (DAVID, v6.7) and the General Olfactory Sensitivity Database (GOSdb; ).\\n\\nRESULTS: Between the WK2 and Ctrl groups, 3351 genes were differentially expressed, of which 236 genes were related to olfactory function. Genes involved in axon guidance, cell projection, and inflammation were enriched and overlapped significantly with those in the GOSdb.\\n\\nCONCLUSION: Systemic glucocorticoids exert effects on transcription of a notable number of genes in the OM and appear to orchestrate changes related to axon guidance, cell projection, and inflammation. Further examination may allow targeted therapies that lack the side effects of this category of medication.", "author" : [ { "dropping-particle" : "", "family" : "Tian", "given" : "Jun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinto", "given" : "Jayant M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xin", "given" : "Yi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Henghui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Li", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sun", "given" : "Zhifu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wei", "given" : "Yongxiang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Forum of Allergy and Rhinology", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "907-918", "title" : "Dexamethasone affects mouse olfactory mucosa gene expression and attenuates genes related to neurite outgrowth", "type" : "article-journal", "volume" : "5" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "275", "plainTextFormattedCitation" : "275", "previouslyFormattedCitation" : "274" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }275)2015ExperimentalDexamethasone injectionLaboratory miceExpression of genes in olfactory mucosa positively affected by glucocorticoidsHaehner et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00702-015-1433-1", "ISSN" : "14351463", "PMID" : "26224038", "abstract" : "The effects of rasagiline on olfaction in animal studies are convincing. However, apart from various anecdotal patient reports, they could not be reproduced in prospective studies in humans. Cross-sectional data of large patient groups are still missing. The aim of this study was therefore to determine the olfactory function in a broad heterogeneous Parkinson's disease (PD) population with and without rasagiline intake. In this single-center, cross-sectional study 224 PD patients with and without rasagiline (1 mg/day) participated. Seventy-four of them received rasagiline as mono, or adjunct therapy. One-hundred fifty patients were untreated or received PD medication other than rasagiline. Comprehensive olfactory testing was performed for phenyl-ethyl alcohol odor thresholds, odor discrimination, and odor identification. Olfactory function did not differ between the two treatment groups with disease duration up to 29 years. Rasagiline-treated patients with disease duration of less than 8 years, however, presented with significant better odor discrimination abilities compared to PD patients without rasagiline treatment. This effect was no longer evident in patients with longer disease duration and proofed to be independent of age, sex, and medication. Our results may suggest that rasagiline treatment has a positive effect on the processing of olfactory information in early PD.", "author" : [ { "dropping-particle" : "", "family" : "Haehner", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Habersack", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wienecke", "given" : "Miriam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Storch", "given" : "Alexander", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reichmann", "given" : "Heinz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Neural Transmission", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1541-1546", "publisher" : "Springer Vienna", "title" : "Early Parkinson's disease patients on rasagiline present with better odor discrimination", "type" : "article-journal", "volume" : "122" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "291", "plainTextFormattedCitation" : "291", "previouslyFormattedCitation" : "290" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }291)2015Cross-sectional, controlledRasagiline therapyPatients with Parkinson’s diseasen=224Rasagiline treated patients presented with significantly better odour discrimination when Parkinson’s disease duration was less than 8 yearsSch?pf et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.4193/Rhino15.065", "ISSN" : "03000729", "author" : [ { "dropping-particle" : "", "family" : "Schopf", "given" : "V.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kollndorfer", "given" : "K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pollak", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mueller", "given" : "C. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freiherr", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "371-378", "title" : "Intranasal insulin influences the olfactory performance of patients with smell loss, dependent on the body mass index: A pilot study", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "292", "plainTextFormattedCitation" : "292", "previouslyFormattedCitation" : "291" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }292)2015Prospective, controlledIntranasal insulinPatients with post-infectious olfactory lossn=10Immediate (short term) improvement of olfaction in 2 of 10;Haehner et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/mds.25661", "ISBN" : "08853185", "ISSN" : "08853185", "author" : [ { "dropping-particle" : "", "family" : "Haehner", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wolz", "given" : "Martin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klingelh\u00f6fer", "given" : "Lisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fauser", "given" : "Mareike", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Storch", "given" : "Alexander", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reichmann", "given" : "Heinz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Movement Disorders", "id" : "ITEM-1", "issue" : "14", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "2023-2027", "title" : "Effects of rasagiline on olfactory function in patients with Parkinson's disease", "type" : "article-journal", "volume" : "28" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "293", "plainTextFormattedCitation" : "293", "previouslyFormattedCitation" : "292" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }293)2013Prospective, controlledRasagiline treatmentPatients with Parkinson’s diseasen=34No significant improvement; however study end point not yet reachedSchriever et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.4193/Rhino.11.207", "ISSN" : "03000729", "PMID" : "22888485", "abstract" : "BACKGROUND AND AIM: Olfactory dysfunction is a common complaint in a large number of people. As the aetiologies of olfactory dysfunction vary greatly so do the treatment approaches. The aim of this retrospective study was to evaluate treatment with systemic corticosteroids, particularly focusing on its effectiveness on the different olfactory dysfunction aetiologies. Although a prospective randomized control trail is preferred for such an investigation, using the current approach, we were able to test a very large patient population. MATERIAL AND METHODS: A total of 425 patients with olfactory dysfunction were treated with systemic corticosteroids for 14 days. Olfactory performance was measured using the `Sniffin` Sticks` battery before and after the treatment. RESULTS: The treatment with systemic corticosteroids significantly increased the performance on the TDI score and on each of the three subtests; threshold, discrimination and identification. In 26.6% of the patients improvement of more than six points of the TDI score was observed. The treatment proved to be more effective in patients with sinunasal olfactory dysfunction, where this percentage increased to 36.7, compared to other aetiologies. In addition, the increase in olfactory function was negatively correlated with the TDI score before the treatment. CONCLUSION: This study confirms the effectiveness of systemic corticosteroids on olfactory dysfunction in a large patient population. Specifically, the results show that treatment is: (a) more effective in patients with sinunasal than in patients with idiopathic olfactory dysfunction, (b) most effective in patients with sinunasal disease with nasal polyps, and (c), at best, effective in half of the patients. The current study may provide help in counselling patients.", "author" : [ { "dropping-particle" : "", "family" : "Schriever", "given" : "V. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Merkonidis", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gupta", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "284-289", "title" : "Treatment of smell loss with systemic methylprednisolone.", "type" : "article-journal", "volume" : "50" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "270", "plainTextFormattedCitation" : "270", "previouslyFormattedCitation" : "269" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }270)2012RetrospectiveSystemic methyl-prednisoloneAll aetiologies of patients with smell lossn=425Best improvement in patients with sinonasal disease, but also in other aetiologies Lyckholm et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1536-0288", "abstract" : "Abnormalities in taste and smell are commonly reported in patients receiving chemotherapy and may hinder appetite, dietary intake, nutritional well-being, and quality of life. Oral zinc has been used to treat taste and smell abnormalities in several altered physiologic states, including renal failure, liver disease, head trauma, and pregnancy, with varying results. The authors conducted a double-blinded, placebo-controlled randomized clinic trial over 3 months. Eligible patients were those taking chemotherapy that had alterations in taste and/or smell. The measurement of the primary end point, improvement in altered taste and smell, was made using a 0-100 scale (100 describing no loss or distortion in taste and smell, and 0 describing the worst distortion or loss of taste and smell). Twenty-nine subjects were enrolled in each treatment group, of whom 31 were white, 26 African American, and 1 Native American. Forty-one patients were female. A wide range of cancer types was represented, with breast the most common (21 patients). The zinc dose was 220 mg orally twice daily (equivalent of 50 mg elemental zinc twice daily). There was no statistically significant improvement in loss or distortion of taste or smell with the addition of zinc. There was a trend toward improvement over time in all groups, except in the zinc group where there was a nonsignificant worsening in loss of smell over time. Zinc at standard doses did not provide significant benefit to taste or smell in patients receiving chemotherapy\\n", "author" : [ { "dropping-particle" : "", "family" : "Lyckholm", "given" : "Laurel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heddinger", "given" : "Steven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parker", "given" : "Gwendolyn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Coyne", "given" : "Patrick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramakrishnan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henkin I", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Pain & Palliative Care Pharmacotherapy", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "111-114", "title" : "A Randomized, Placebo Controlled Trial of Oral Zinc for Chemotherapy-Related Taste and Smell Disorders", "type" : "article-journal", "volume" : "26" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "294", "plainTextFormattedCitation" : "294", "previouslyFormattedCitation" : "293" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }294)2012Prospective, controlledOral zincChemotherapy-related smell disordersn=58No improvement in smell lossReden et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/lary.23405", "ISBN" : "1531-4995 (Electronic)\\r0023-852X (Linking)", "ISSN" : "0023-852X", "PMID" : "22752966", "abstract" : "Objectives/Hypothesis: In this study we investigated the effectiveness of vitamin A in postinfectious and posttraumatic smell disorders. A possible effect of vitamin A is likely due to the stimulation of regeneration and repair of the peripheral olfactory system. Study Design: Double-blind, randomized, placebo-controlled clinical trial. Methods: A total of 52 patients (age range, 20-70 years; mean age, 52 years) participated, 26 of whom received placebo (7 male, 19 female) and another 26 verum (8 male, 18 female). A standardized history was obtained in each patient. Olfactory function was measured by means of the Sniffin' Sticks test kit, a validated technique to investigate odor thresholds, odor discrimination, and odor identification. Vitamin A was prescribed at a dose of 10,000 IU per day for 3 months. Follow-up testing was performed on average 5 months after the first investigation. Results: Forty-four percent of all patients reported recovery of their sense of smell; 29% of the participants exhibited significant improvement in measured olfactory function. However, there was no significant difference between the outcome of patients receiving verum or placebo. Conclusions: The systemic application of vitamin A at a dose of 10,000 IU per day for 3 months does not appear to be useful in the treatment of postinfectious or posttraumatic olfactory loss. Copyright (copyright) 2012 The American Laryngological, Rhinological, and Otological Society, Inc.", "author" : [ { "dropping-particle" : "", "family" : "Reden", "given" : "Jens", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lill", "given" : "Katja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zahnert", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haehner", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Laryngoscope", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "1906-1909", "title" : "Olfactory function in patients with postinfectious and posttraumatic smell disorders before and after treatment with vitamin A: A double-blind, placebo-controlled, randomized clinical trial", "type" : "article-journal", "volume" : "122" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "295", "plainTextFormattedCitation" : "295", "previouslyFormattedCitation" : "294" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }295)2012Prospective, controlledVitamin A treatmentPatients with post-infectious and posttraumatic smell lossn=52No significant effectHenkin et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "1392510 [pii]\\r10.1001/2013.jamaoto.342", "ISBN" : "1538-361X (Electronic)\\r0886-4470 (Linking)", "ISSN" : "08864470", "PMID" : "23165381", "abstract" : "OBJECTIVE To determine whether intranasal theophylline methylpropyl paraben can correct hyposmia and hypogeusia. DESIGN We performed an open-label pilot study in patients with hyposmia and hypogeusia under the following 3 conditions: (1) before treatment, (2) after oral theophylline anhydrous treatment, and (3) after intranasal theophylline treatment. Under each condition, we performed subjective evaluations of taste and smell functions, quantitative measurements of taste (gustometry) and smell (olfactometry), and measurements of serum theophylline level and body weight. SETTING The Taste and Smell Clinic in Washington, DC. PATIENTS Ten patients with hyposmia and hypogeusia clinically related to the effects of viral illness, allergic rhinitis, traumatic brain injury, congenital hyposmia, and other chronic disease processes were selected. INTERVENTIONS Oral theophylline anhydrous, 200 to 800 mg/d for 2 to 12 months, was administered to each patient. This treatment was discontinued for 3 weeks to 4 months when intranasal theophylline methylpropyl paraben, 20 mug/d in each naris, was administered for 4 weeks. MAIN OUTCOME MEASURES At termination of each condition, taste and smell function was determined subjectively, by means of gustometry and olfactometry, with measurement of serum theophylline levels and body weight. RESULTS Oral theophylline treatment improved taste and smell acuity in 6 patients after 2 to 12 months of treatment. Intranasal theophylline treatment improved taste and smell acuity in 8 patients after 4 weeks, with improvement greater than after oral administration. No adverse effects accompanied intranasal drug use. Body weight increased with each treatment but was greater after intranasal than after oral administration. CONCLUSIONS Intranasal theophylline treatment is safer and more effective in improving hyposmia and hypogeusia than oral theophylline anhydrous treatment.", "author" : [ { "dropping-particle" : "", "family" : "Henkin", "given" : "R I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schultz", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Minnick-Poppe", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arch Otolaryngol Head Neck Surg", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "1064-1070", "title" : "Intranasal theophylline treatment of hyposmia and hypogeusia: a pilot study", "type" : "article-journal", "volume" : "138" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "296", "plainTextFormattedCitation" : "296", "previouslyFormattedCitation" : "295" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }296)2012ProspectiveTopical and systemic administration of theophylline Patients with viral illness, allergic rhinitis, head trauma, congenital hyposmia, other chronic disease processesn=10Oral theophylline treatment improved taste and smell acuity in 6/10 after 2-12 months. Intranasal theophylline treatment improved taste and smell acuity in 8/10 after 4 weeksReden et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/lary.21401", "ISSN" : "0023852X", "PMID" : "21287560", "abstract" : "Infection of the upper respiratory tract is one of the most common causes of olfactory loss. One of the possible underlying pathologic pathways is an increase of apoptosis of olfactory receptor neurons. Therefore, treatment with the antibiotic minocycline, which has been shown to act as an antiapoptotic agent, is thought to accelerate improvement of olfactory function. To investigate this idea, 55 patients with postinfectious olfactory dysfunction were tested for their olfactory ability.", "author" : [ { "dropping-particle" : "", "family" : "Reden", "given" : "Jens", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herting", "given" : "Birgit", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lill", "given" : "Katja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kern", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Laryngoscope", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "679-682", "title" : "Treatment of postinfectious olfactory disorders with minocycline: A double-blind, placebo-controlled study", "type" : "article-journal", "volume" : "121" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "297", "plainTextFormattedCitation" : "297", "previouslyFormattedCitation" : "296" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }297)2011Prospective, controlledMinocycline treatmentPatients with post-infectious smell lossn=55No significant effectPanagiotopoulos et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "03000729", "PMID" : "16008069", "abstract" : "It is well documented that cytoplasmic Ca++ regulates sensitivity to cyclic adenosine monophosphate (cAMP). There is also evidence that Ca++ in the mucus may also modulate sensitivity to cAMP in vivo. Assuming that mucosal Ca++ could significantly change the excitability of the receptor neurons, we examined the alterations in the olfactory sensitivity by creating small changes in mucosal Ca++. Thirty one patients complaining of olfactory loss were examined and their olfactory acuity was measured before and after the administration of a sodium citrate buffer solution in the nasal cleft. Thirty patients (96.8%) improved their scores in less than an hour period of time. Furthermore, 23 of them (74.2%) realized an improvement in their own sense of smell.", "author" : [ { "dropping-particle" : "", "family" : "Panagiotopoulos", "given" : "Georgios", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Naxakis", "given" : "Stefanos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papavasiliou", "given" : "Antonios", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Filipakis", "given" : "Konstantinos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papatheodorou", "given" : "Georgios", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goumas", "given" : "Panagiotis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "130-134", "title" : "Decreasing nasal mucus Ca++ improves hyposmia", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "287", "plainTextFormattedCitation" : "287", "previouslyFormattedCitation" : "286" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }287)2011ProspectiveSodium citrate buffer solution to the nasal cleftPatients with unspecified olfactory loss (5), head trauma (1), nasal surgery (7) and post-infectious (18), n=31 Measured improvement in 97% of patients with one hour; 74% noticed improvementJiang et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00405-010-1240-0", "ISSN" : "1434-4726", "PMID" : "20379733", "abstract" : "The objective of this study was to treat posttraumatic anosmia with oral steroid and evaluate its effect. One-hundred sixteen posttraumatic patients whose olfactory thresholds were -1.0 by the phenyl ethyl alcohol threshold test assembled in our department. They were treated with a course of high-dose steroid, and followed up for at least 3 months. During the latter period of this study, magnetic resonance imaging was performed to measure the volumes of olfactory bulbs and to detect subfrontal lobe damage. Among them, 19 (16.4%) patients' olfactory thresholds improved after steroid treatment, but the other 97 patients' thresholds did not change. The incidences of loss of consciousness and intracranial hemorrhage after head injury, the ratios of admission and craniotomy, the intervals between head injury and steroid treatment, the volumes of olfactory bulbs, and the incidences of subfrontal lobe damage were not significantly different between patients whose thresholds improved and those whose thresholds did not improve. However, patients with olfactory improvement were significantly younger than those who remained unchanged. Our study showed that oral steroid treatment might improve olfactory acuity in some patients with posttraumatic anosmia, but the possibility of spontaneous recovery cannot be ruled out.", "author" : [ { "dropping-particle" : "", "family" : "Jiang", "given" : "Rong-San", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Shang-Heng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liang", "given" : "Kai-Li", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shiao", "given" : "Jiun-Yih", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hsin", "given" : "Chung-Han", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Su", "given" : "Mao-Chang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "1563-7", "title" : "Steroid treatment of posttraumatic anosmia.", "type" : "article-journal", "volume" : "267" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "271", "plainTextFormattedCitation" : "271", "previouslyFormattedCitation" : "270" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }271)2010ProspectiveOral high-dose steroidsPosttraumatic anosmian=116Improvement in some patients; possibly spontaneous recoveryHenkin et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/MAJ.0b013e3181914a97", "ISSN" : "0002-9629", "PMID" : "19359985", "abstract" : "BACKGROUND: To test the hypothesis that theophylline is effective in correcting smell loss in patients with hyposmia.\\n\\nMETHODS: Three hundred twelve patients with smell loss (hyposmia) were evaluated to determine characteristics of their loss by psychophysical measurements of detection and recognition thresholds, magnitude estimation and hedonic values for 4 odors (pyridine, nitrobenzene, thiophene, and amyl acetate) by use of a forced-choice 3-stimuli staircase design previously documented in a double-blind study. Patients were then treated in a fixed design open-label clinical trial with oral theophylline. Drug was given in equal divided doses from 200 to 800 mg daily for 2- to 8-month periods and subjective and psychophysical measurements of smell function and blood theophylline levels were measured; results were compared with those obtained before treatment.\\n\\nRESULTS: Subjective smell loss improved in 157 (50.3%) patients; smell function was considered normal by 34 (21.7%). Overall, 10.9% of patients in the study considered smell function returned to normal. However, measurements of mean detection and recognition thresholds improved significantly at each drug level; measurements of mean magnitude estimation and hedonic also improved. Improvement was greater at drug doses of 600 and 800 mg than at 200 or 400 mg. Once improvement occurred, as long as treatment was maintained, it persisted for as long as follow-up was measured.\\n\\nCONCLUSION: Theophylline was effective in improving smell function in patients with smell loss. Improvement persisted as long as treatment was continued, which extended from 6 to 72 months.", "author" : [ { "dropping-particle" : "", "family" : "Henkin", "given" : "Robert I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Velicu", "given" : "Irina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schmidt", "given" : "Loren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American journal of the medical sciences", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "396-406", "title" : "An open-label controlled trial of theophylline for treatment of patients with hyposmia.", "type" : "article-journal", "volume" : "337" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "280", "plainTextFormattedCitation" : "280", "previouslyFormattedCitation" : "279" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }280)2009ProspectiveSystemic administration of theophylline in increasing doses over 2-8 monthsPatients with smell lossn=312Subjective smell loss improved in 157 patients (50.3%)Gudziol & Hummel (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/00006534-198006000-00008", "ISBN" : "0032-1052", "ISSN" : "0032-1052", "PMID" : "7384277", "abstract" : "Objective: To investigate the effect of pentoxifylline, an unspecific phosphodiesterase inhibitor, on olfactory function. Design: Longitudinal study. Patients: Nineteen patients who received pentoxifyl- line to treat inner-ear conditions. MainOutcomeMeasures: Evaluation of olfactory func- tion (ie, odor threshold, odor discrimination, and odor identification) before and after administration of pen- toxifylline and assessment of nasal airflow. Results: Administration of pentoxifylline had no sig- nificant effect on nasal airflow (P=.84). After adminis- tration of pentoxifylline, patients demonstrated a de- crease in odor threshold toward lower odor concentrations (P=.01). The odor threshold shift after administration of pentoxifylline was more pronounced in younger pa- tients than in older patients (correlation between age and change in odor threshold: r=\u2212.72; P=.001). No such changes were observed for suprathreshold olfactory tasks (odor discrimination and odor identification). Six of the 19 patients were found to have hyposmia. Two patients demonstrated a clinically significant decrease in odor threshold after drug administration. Conclusions: The present findings may indicate a role for pentoxifylline in the treatment of olfactory loss. Double-blind, placebo-controlled studies are needed to verify whether pentoxifylline can improve olfactory sen- sitivity in patients with olfactory disorders", "author" : [ { "dropping-particle" : "", "family" : "Gudziol", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arch Otolaryngol Head Neck Surg", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "291-5", "title" : "Effects of Pentoxifylline on Olfactory Sensitivity", "type" : "article-journal", "volume" : "135" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "279", "plainTextFormattedCitation" : "279", "previouslyFormattedCitation" : "278" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }279) 2009ProspectivePentoxifylline, either i.v. or orallyPatients being treated for otological conditions n=19 Improvement in odour thresholdsSeo et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Seo", "given" : "Beom Seol", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Hyun Jong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mo", "given" : "Ji-Hun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Chul Hee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rhee", "given" : "Chae-Seo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Jeon-Whun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arch Otolaryngol Head Neck Surg", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "1000-1004", "title" : "Treatment of Postviral Olfactory Loss With Glucocorticoids,", "type" : "article-journal", "volume" : "135" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "273", "plainTextFormattedCitation" : "273", "previouslyFormattedCitation" : "272" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }273)2009Prospective, controlledCorticosteroids combined with Ginkgo bilobaPatients with post-infectious smell lossn=71Similar improvement both in treatment with corticosteroids combined with Ginkgo biloba and in treatment only with corticosteroidsHeilmann et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1055/s-2004-825676", "ISSN" : "0935-8943", "PMID" : "15538662", "abstract" : "BACKGROUND: Aim of the present, unblinded, multicentric, open trial was to compare effects of 3 treatments in patients with olfactory dysfunction. METHODS: Treatments included administration of systemic corticosteroids (oral prednisolone), local corticosteroids (mometasone nasal spray), and systemic vitamin B, respectively. A total of 192 patients participated (95 women, 97 men; mean age 56 years). Duration of the smell loss ranged from 1 to 288 months (average 45 months). Olfactory dysfunction was due to infections of the upper respiratory tract (n = 72), sinunasal disease (n = 19), and posttraumatic olfactory loss (n = 10); the largest portion was classified as idiopathic (n = 85); other causes were rare (n = 6). RESULTS: Following systemic administration of corticosteroids improvement of olfactory function was observed (p < 0.001). Similarly, improvement of the sense of smell was found 2 (p = 0.03) and 6 months (p = 0.001) after local administration of mometasone, respectively. In contrast, after administration of vitamin B no significant change of olfactory function was seen after 2 months, while improvement was present after 6 months (p = 0.001). Duration of olfactory dysfunction had no effect on changes of smell function. CONCLUSIONS: These results indicate that improvement of olfactory function is found in olfactory dysfunction of different causes. Adequately controlled, blinded studies are needed to further explore potential effects of the various treatments.", "author" : [ { "dropping-particle" : "", "family" : "Heilmann", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Just", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "G\u00f6ktas", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hauswald", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "H\u00fcttenbrink", "given" : "K-B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Laryngo- rhino- otologie", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "729-34", "title" : "Effects of systemic or topical administration of corticosteroids and vitamin B in patients with olfactory loss", "type" : "article-journal", "volume" : "83" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "274", "plainTextFormattedCitation" : "274", "previouslyFormattedCitation" : "273" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }274)2004ProspectiveOral prednisolone; local corticosteroids; systemic Vitamin BPatients with olfactory dysfunction (differing aetiologies)n=192Improvement following systemic and local corticosteroids; also improvement with systemic Vitamin B after 6 monthsQuint et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/003655402/000028054", "ISBN" : "0001-6489", "ISSN" : "0001-6489", "PMID" : "12542209", "abstract" : "The treatment of non-conductive olfactory disorders is to a large extent an unsolved problem. This proof-of-concept study focused on possible effects of the N-methyl-D-aspartate (NMDA) antagonist caroverine. Potential mechanisms for the hypothesized effect included reduced feedback inhibition in the olfactory bulb as a consequence of NMDA antagonistic actions and antagonism of an excitotoxic action of glutamate. A total of 77 consecutive patients with non-conductive olfactory disorders were included in the study. Fifty-one patients received caroverine for 4 weeks (120 mg/day); 26 controls matched for age, gender and duration of olfactory loss were treated with zinc sulfate for the same length of time (400 mg/day). Olfactory sensitivity was evaluated before and after treatment. Testing included assessment of n-butanol odor threshold and odor identification. When compared to baseline, treatment with caroverine improved both odor thresholds (p = 0.005) and odor identification (p = 0.042) in anosmic patients. In hyposmic patients it significantly improved odor identification ability (p = 0.041). In contrast, zinc sulfate had no significant effect on olfactory function. These results indicate that caroverine appears to be effective for the treatment of non-conductive smell disorders.", "author" : [ { "dropping-particle" : "", "family" : "Quint", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Temmel", "given" : "A F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ehrenberger", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Acta Otolaryngol", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2002" ] ] }, "page" : "877-881", "title" : "The quinoxaline derivative caroverine in the treatment of sensorineural smell disorders: a proof-of-concept study", "type" : "article-journal", "volume" : "122" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "298", "plainTextFormattedCitation" : "298", "previouslyFormattedCitation" : "297" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }298)2002Prospective, controlledCaroverine applicationNon-conductive olfactory disordersn=77Significant improvement of odour identificationHummel et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/00005537-200211000-00031", "ISSN" : "0023-852X", "PMID" : "12439184", "abstract" : "OBJECTIVES/HYPOTHESIS: The study aimed to investigate the potential therapeutic effects of alpha-lipoic acid in olfactory loss following infections of the upper respiratory tract. Possible mechanisms of actions include the release of nerve growth factor and antioxidative effects, both of which may be helpful in the regeneration of olfactory receptor neurons. STUDY DESIGN: Unblinded, prospective clinical trial. METHODS: A total of 23 patients participated (13 women, 10 men; mean age 57 y, age range 22-79 y; mean duration of olfactory loss, 14 mo; range, 4 to 33 mo); 19 of them were hyposmic and 4 had functional anosmia. Alpha-lipoic acid was used orally at a dose of 600 mg/day; it was prescribed for an average period of 4.5 months. Olfactory function was assessed using olfactory tests for phenyl ethyl alcohol odor threshold, odor discrimination, and odor identification. RESULTS: Seven patients (30%) showed no change in olfactory function. Two patients (9%) exhibited a moderate decrease in olfactory function; in contrast, six patients (26%) showed moderate and eight patients (35%) remarkable increase in olfactory function. Two of the 4 patients with functional anosmia reached hyposmia; 5 of 19 hyposmic patients became normosmic. Overall, this resulted in a significant improvement in olfactory function following treatment (P =.002). At the end of treatment parosmias were less frequent (22%) than at the beginning of therapy (48%). Interestingly, recovery of olfactory function appeared to be more pronounced in younger patients than in patients above the age of 60 years (P =.018). CONCLUSIONS: The results indicate that alpha-lipoic acid may be helpful in patients with olfactory loss after upper respiratory tract infection. However, to judge the true potential of this treatment, the outcome of double-blind, placebo-controlled studies in large groups of patients must be awaited, especially when considering the relatively high rate of spontaneous recovery in olfactory loss after upper respiratory tract infection.", "author" : [ { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heilmann", "given" : "Stefan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "H\u00fcttenbriuk", "given" : "Karl-Bernd", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Laryngoscope", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2002" ] ] }, "page" : "2076-2080", "title" : "Lipoic acid in the treatment of smell dysfunction following viral infection of the upper respiratory tract.", "type" : "article-journal", "volume" : "112" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "299", "plainTextFormattedCitation" : "299", "previouslyFormattedCitation" : "298" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }299)2002ProspectiveOral application of alpha-lipoic acidOlfactory loss following respiratory infectionsn=23Significant improvement of olfaction; more pronounced in patients <60 years of ageTable 6:AuthorYearStudy TypeStudy Population; NResultsOlfactory trainingKonstantinidis et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.4193/Rhino15.264", "ISSN" : "03000729", "PMID" : "27017331", "abstract" : "BACKGROUND There is evidence of the effectiveness of repeated exposure to odours on short-term olfactory function. The aim of this study was to assess the long-term effects of olfactory training. METHODS We conducted a prospective study of 111 patients with post-infectious olfactory dysfunction. Two groups of patients performed olfactory training for 16 and 56 weeks, respectively, and were compared with a control group. The training was performed twice daily using four odours (phenyl ethyl alcohol, eucalyptol, citronellal, eugenol). Olfactory testing was performed by means of the Sniffin Sticks test as a baseline assessment and then every 8 weeks for 56 weeks. Subjective ratings were performed using a visual analogue scale (0-100). RESULTS Both training groups presented significantly higher scores than the controls. The long-term group had better results than the short-term group. Short-term training patients sustained their improvement within the follow-up period. Subsets analysis showed that training patients mainly increased identification and discrimination. Subjective ratings were in accordance with the olfactory test results. CONCLUSION Long-term olfactory training seems to be associated with better results in patients with post-infectious olfactory loss than a short-term scheme. Short-term training provides sustainable results at 56 weeks follow-up assessment.", "author" : [ { "dropping-particle" : "", "family" : "Konstantinidis", "given" : "I.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsakiropoulou", "given" : "E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Constantinidis", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "170-175", "title" : "Long term effects of olfactory training in patients with post-infectious olfactory loss", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "308", "plainTextFormattedCitation" : "308", "previouslyFormattedCitation" : "307" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }308)2016Prospective, controlledPost-infectious olfactory lossn=111Both short (16 weeks) and long term (56 weeks) training produced significantly improved olfactory function compared with control - with long term significantly better than shortNegoias et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s11682-016-9567-9", "ISSN" : "19317565", "abstract" : "Olfactory training plays a significant role in the treatment of hyposmia. It is known that repeated exposure to odors modifies olfactory function. In addition, numerous studies show that the olfactory bulb (OB) volume changes under various conditions, e.g. in patients suffering from olfactory dysfunction smaller OBs were found than in healthy subjects. The aim of this study was to investigate whether the OB volume changes in relation to lateralized olfactory training. Over a period of 4 months 97 healthy participants (34 men, 63 women) performed olfactory training. For the whole period, they were exposing the same nostril twice a day to 4 odors (lemon, rose, eucalyptus and cloves) while closing the other one. Before starting and after finishing the olfactory training, MRI scans were performed to measure the OB volume. Furthermore, participants underwent lateralized threshold and identification testing using the \u201cSniffin Sticks\u201d test battery. Although there was no significant change in olfactory function comparing results before and after training, it was found that the OB volume increased significantly by 11.3% in the trained nostril and 13.1% in the untrained nostril. No significant effect was found comparing the influence of gender, the exact duration and frequency of the training as well as the age of the subjects and the method of closing the untrained nostril. These data indicate that olfactory training induces a top-down process which ultimately leads to a bilateral increase in OB volume.", "author" : [ { "dropping-particle" : "", "family" : "Negoias", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pietsch", "given" : "K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Brain Imaging and Behavior", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "1-8", "publisher" : "Brain Imaging and Behavior", "title" : "Changes in olfactory bulb volume following lateralized olfactory training", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "309", "plainTextFormattedCitation" : "309", "previouslyFormattedCitation" : "308" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }309)2016Prospective, controlledHealthy participantsUnilateral olfactory training produced significant increase in bilateral OB volumePoletti et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1177/0301006616672881", "ISSN" : "1468-4233", "PMID" : "27703061", "abstract" : "BACKGROUND Repeated short-term exposure to odors is known to improve olfaction in patients with acquired olfactory dysfunction. The aim was to find out whether differences in molecular weight of odors used for olfactory training influences olfaction. We hypothesized a greater improvement following training with light weight molecule (LWM) odors. METHODS A prospective study was performed in patients with posttraumatic (PTOL) and postviral olfactory loss (PVOL). Olfactory training was performed over a period of 5 months. One group (n\u2009=\u200948) used four odors containing heavy weight molecules (HWM; >150\u2009g/mol) and another (n\u2009=\u200948) containing LWM (<150\u2009g/mol). Olfaction was tested before and after the training using the Sniffin' Sticks test. RESULTS Olfactory training was associated with olfactory improvement, with the improvement in PVOL patients being three times greater than that seen in the PTOL group. Compared with LWM training, HWM training was associated with a significantly greater improvement in Phenyl Ethyl Alcohol (PEA) threshold scores in PVOL patients; however, no such improvement could be shown for other subtests or in PTOL patients. CONCLUSION Overall, training was associated with olfactory improvement. With the exception of threshold scores in PVOL, there were no significant differences between LWM and HWM groups.", "author" : [ { "dropping-particle" : "", "family" : "Poletti", "given" : "Sophia C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Michel", "given" : "Elisabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Perception", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "title" : "Olfactory Training Using Heavy and Light Weight Molecule Odors.", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "310", "plainTextFormattedCitation" : "310", "previouslyFormattedCitation" : "309" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }310)2016ProspectivePost-infectious and posttraumatic olfactory lossn=96Training with light molecular weight molecules produced significantly improved PEA threshold compared to heavy weight moleculesKollndorfer et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.nicl.2015.09.004", "ISSN" : "22131582", "PMID" : "26594622", "abstract" : "Recently, olfactory training has been introduced as a promising treatment for patients with olfactory dysfunction. However, less is known about the neuronal basis and the influence on functional networks of this training. Thus, we aimed to investigate the neuroplasticity of chemosensory perception through an olfactory training program in patients with smell loss. The experimental setup included functional MRI (fMRI) experiments with three different types of chemosensory stimuli. Ten anosmic patients (7f, 3m) and 14 healthy controls (7f, 7m) underwent the same testing sessions. After a 12-week olfactory training period, seven patients (4f, 3m) were invited for follow-up testing using the same fMRI protocol. Functional networks were identified using independent component analysis and were further examined in detail using functional connectivity analysis. We found that anosmic patients and healthy controls initially use the same three networks to process chemosensory input: the olfactory; the somatosensory; and the integrative network. Those networks did not differ between the two groups in their spatial extent, but in their functional connectivity. After the olfactory training, the sensitivity to detect odors significantly increased in the anosmic group, which was also manifested in modifications of functional connections in all three investigated networks. The results of this study indicate that an olfactory training program can reorganize functional networks, although, initially, no differences in the spatial distribution of neural activation were observed.", "author" : [ { "dropping-particle" : "", "family" : "Kollndorfer", "given" : "K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fischmeister", "given" : "F. Ph S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kowalczyk", "given" : "K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoche", "given" : "E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mueller", "given" : "C. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trattnig", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sch\u00f6pf", "given" : "V.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "NeuroImage: Clinical", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "401-410", "publisher" : "The Authors", "title" : "Olfactory training induces changes in regional functional connectivity in patients with long-term smell loss", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "311", "plainTextFormattedCitation" : "311", "previouslyFormattedCitation" : "310" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }311)2014Prospective, controlledPost-infectious anosmian=7Olfactory training induced changes in functional connectivity evidenced with fMRI Altundag et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/lary.25245", "ISBN" : "0023-852x", "ISSN" : "15314995", "PMID" : "26031472", "abstract" : "OBJECTIVES/HYPOTHESIS: Patients with olfactory dysfunction benefit from repeated exposure to odors, so-called olfactory training (OT). This does not mean occasional smelling but the structured sniffing of a defined set of odors, twice daily, for a period of 4 months or longer. In this prospective study, we investigated whether the effect of OT might increase through the use of more odors and extension of the training period.\\n\\nSTUDY DESIGN AND METHODS: This study shows OT results when performed with four or 12 odors for 36 weeks in patients with postinfectious olfactory dysfunction. A total of 85 subjects participated (mean age 45.6\u2009\u00b1\u200910.5 years, range 24-68 years). Three groups were formed: 1) In the modified olfactory training (MOT) group, patients used three sets of four different odors sequentially. 2) Participants in the classical odor training (COT) group used four odors. 3) Participants in the control group did not perform OT. All groups were matched for age and sex distribution of participants.\\n\\nRESULTS: Both participants in the COT and MOT groups reached better scores than controls in terms of odor discrimination and odor identification. Continuing OT with four different odors after the 12th and 24th weeks produced better results in terms of odor discrimination and odor identification scores as compared to using the same four odors throughout the entire study.\\n\\nCONCLUSION: This study confirmed the effectiveness of OT. Increasing the duration of OT and changing the odors enhances the success rate of this therapy.\\n\\nLEVEL OF EVIDENCE: 2b. Laryngoscope, 125:1763-1766, 2015.", "author" : [ { "dropping-particle" : "", "family" : "Altundag", "given" : "Aytug", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cayonu", "given" : "Melih", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kayabasoglu", "given" : "Gurkan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salihoglu", "given" : "Murat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tekeli", "given" : "Hakan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saglam", "given" : "Omer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Laryngoscope", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1763-1766", "title" : "Modified olfactory training in patients with postinfectious olfactory loss", "type" : "article-journal", "volume" : "125" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "304", "plainTextFormattedCitation" : "304", "previouslyFormattedCitation" : "303" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }304)2015Prospective, controlledPost-infectious olfactory lossn=85Longer olfactory training with change of odour was effective for odour discrimination and identificationMori et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.4193/Rhin14.192", "ISBN" : "0300-0729 (Print)\\r0300-0729", "ISSN" : "03000729", "PMID" : "26363163", "abstract" : "BACKGROUND Short-term exposure to odours, also called \"olfactory training\" has been shown to improve olfactory function in healthy people but also in people with olfactory loss. Aim of this single center, prospective, controlled study was to investigate the change of olfactory function following twice-daily, short-term exposure to 4 odours over a period of approximately 12 weeks. MATERIAL AND METHODS We compared odour identification abilities and odour thresholds between an olfactory training group (TR group) and a group that did not perform such training (noTR group). Participants exposed themselves twice daily to 4 odours (\"rose\", \"eucalyptus\", \"lemon\", \"clove\"). Olfactory testing was performed before and after the training period using the \"Sniffin' Sticks\" test kit (odour identification plus odour thresholds). RESULTS At baseline the two groups were not significantly different in terms of age and measures of olfactory sensitivity. The TR group performed significantly better for odour thresholds for all 4 odours compared to the noTR group after 12 weeks of olfactory training. Also, with regard to odour identification the TR group outperformed the noTR group. No significant differences were found for diary-based intensity ratings. CONCLUSION Repeated exposure to odours seems to improve general olfactory sensitivity in children.", "author" : [ { "dropping-particle" : "", "family" : "Mori", "given" : "E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Petters", "given" : "W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schriever", "given" : "V. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valder", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "221-226", "title" : "Exposure to odours improves olfactory function in healthy children", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "312", "plainTextFormattedCitation" : "312", "previouslyFormattedCitation" : "311" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }312)2015Prospective, controlledHealthy children (age 9-15)n=72Improved threshold and identification in training group compared with non-trainingDamm et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/lary.24340", "ISBN" : "1531-4995", "ISSN" : "15314995", "PMID" : "23929687", "abstract" : "OBJECTIVES/HYPOTHESIS: The aim of this study was to evaluate the effects of olfactory training (OT) on olfactory function in patients with persistent postinfectious olfactory dysfunction (PIOD).\\n\\nSTUDY DESIGN: Randomized, single-blind, controlled, multicenter crossover study.\\n\\nMETHODS: Twelve tertiary university medical centers participated. Investigations were performed at three visits (baseline, after 18 weeks, and after 36 weeks), including only subjects with PIOD of <24-months duration. At each visit, participants received detailed assessment of olfactory function. Seventy subjects trained with high concentrations of four odors for 18 weeks; the other half (n = 74) trained with low concentrations of odors. For the following 18 weeks this regimen was switched.\\n\\nRESULTS: After 18 weeks, olfactory function improved in the high-training group in 18 of 70 participants (26%), whereas only 11/74 improved in the low-training group (15%). In subjects with a duration of olfactory dysfunction of <12 months, olfactory function improved in 15/24 participants (63%) of the high-training group and in 6/31 participants (19%) of the low-training group (P = .03).\\n\\nCONCLUSIONS: OT improves PIOD, and the use of odors at higher concentrations is beneficial to improvement. OT is a safe procedure and appears to be particularly useful in patients who start OT within 12 months after the onset of the disorder. OT is the first successful therapy regime in patients with PIOD.\\n\\nLEVEL OF EVIDENCE: 1b.", "author" : [ { "dropping-particle" : "", "family" : "Damm", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pikart", "given" : "Louisa K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reimann", "given" : "Heike", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burkert", "given" : "Silke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "G\u00f6ktas", "given" : "\u00d6nder", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haxel", "given" : "Boris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frey", "given" : "Sabine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Charalampakis", "given" : "Ioannis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beule", "given" : "Achim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Renner", "given" : "Berthold", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "H\u00fcttenbrink", "given" : "Karl Bernd", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Laryngoscope", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "826-831", "title" : "Olfactory training is helpful in postinfectious olfactory loss: A randomized, controlled, multicenter study", "type" : "article-journal", "volume" : "124" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "303", "plainTextFormattedCitation" : "303", "previouslyFormattedCitation" : "302" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }303)2014Prospective, controlledPost-infectious olfactory lossn=144Olfactory training was significantly more effective with high concentration of odours and dysfunction <12 monthsGei?ler et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00405-013-2747-y", "ISBN" : "0937-4477", "ISSN" : "14344726", "PMID" : "24096819", "abstract" : "Olfactory training consisting of daily suprathreshold odor exposure over 12 weeks seems to improve olfactory function. It is unknown if a longer period of training might be more effective. A prospective non-randomized clinical study was performed including 39 patients with olfactory loss after an upper respiratory tract infection (URTI) of less than 24 months duration. Patients exposed themselves with suprathreshold concentrations of four odors (rose, eucalyptus, lemon, cloves) applied in ''Sniffin' Sticks'' felt-tip pens over 32 weeks. Olfactory function was performed before (T1), after 16 weeks (T2), and 32 weeks of training (T3) using the 'the Sniffin' Sticks test kit calculating the TDI score (Threshold, Discrimination, Identification). The mean TDI score showed a non-significant trend of improvement at T2, and was significantly increased at T3 (p = 0.021). Overall, 31 patients (79%) showed an increased TDI score at T3. The increase of TDI from T1 to T3 was 4.6 \u00b1 5.1. Age, gender, duration and initial severity of olfactory loss had no influence on the improvement (all p > 0.05). Only patients with a D score lower than the median value of 8 showed a significantly higher increase of the D score at T3 (p = 0.004). The present study confirmed that olfactory training improves olfactory function in patients with olfactory loss after URTI. A longer duration of training over 32 weeks seems to increase the effectiveness in comparison to a 12-week period. This was tested in a completed German multicenter trial to be published soon containing a control group to include the effect of a spontaneous recovery after URTI.", "author" : [ { "dropping-particle" : "", "family" : "Geissler", "given" : "K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reimann", "given" : "H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gudziol", "given" : "H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bitter", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guntinas-Lichius", "given" : "O.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Archives of Oto-Rhino-Laryngology", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "1557-1562", "title" : "Olfactory training for patients with olfactory loss after upper respiratory tract infections", "type" : "article-journal", "volume" : "271" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "302", "plainTextFormattedCitation" : "302", "previouslyFormattedCitation" : "301" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }302)2014ProspectivePost-infectious olfactory lossn=39Longer duration of (≥32 weeks) increased effectiveness of trainingKonstantinidis et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/lary.24390", "ISSN" : "0023852X", "PMID" : "24114690", "abstract" : "OBJECTIVES/HYPOTHESIS: There is evidence that the olfactory system can be modulated by repeated exposure to odors, a procedure called olfactory training. The aim of this study was to assess the effectiveness of olfactory training in patients with postinfectious and post-traumatic olfactory dysfunction.\\n\\nSTUDY DESIGN: Prospective study of 119 patients with postinfectious and post-traumatic olfactory dysfunction.\\n\\nMETHODS: Two groups of patients (postinfectious and post-traumatic) performed the olfactory training (n = 49 and n = 23, respectively) over a period of 16 weeks and were compared with two control groups of the same etiology (n = 32 and n = 15). Patients with sinunasal, neurologic, or idiopathic disease were excluded. Training was performed twice daily with the use of four odors (phenyl ethyl alcohol [rose], eucalyptol [eucalyptus], citronellal [lemon], and eugenol [cloves]). Olfactory testing was performed by means of the Sniffin' Sticks test battery (threshold, discrimination, identification) at the time of diagnosis, and 8 and 16 weeks later. All patients evaluated their olfactory function by means of a visual analogue scale (0-100).\\n\\nRESULTS: Compared to controls, training patients in both groups presented significantly higher scores of olfactory function as measured by the Sniffin' Sticks test. This increase was measured in 67.8% of postinfectious and 33.2% of post-traumatic patients. Subjective ratings were in accordance with the olfactory test results. Subset analysis showed that olfactory function mainly increased olfactory identification followed by discrimination in both training groups.\\n\\nCONCLUSIONS: The present study suggests that a 16-week short-term exposure to specific odors may increase olfactory sensitivity in patients with postinfectious and post-traumatic olfactory dysfunction.", "author" : [ { "dropping-particle" : "", "family" : "Konstantinidis", "given" : "Iordanis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsakiropoulou", "given" : "Evangelia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bekiaridou", "given" : "Paschalia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kazantzidou", "given" : "Chrysa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Constantinidis", "given" : "Jannis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Laryngoscope", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "85-90", "title" : "Use of olfactory training in post-traumatic and postinfectious olfactory dysfunction", "type" : "article-journal", "volume" : "123" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "305", "plainTextFormattedCitation" : "305", "previouslyFormattedCitation" : "304" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }305)2013Prospective, controlled Post-traumatic and post-infectious olfactory lossn=119Significant improvement in both groupsHaehner et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0061680", "ISBN" : "10.1371/journal.pone.0061680", "ISSN" : "19326203", "PMID" : "23613901", "abstract" : "OBJECTIVE: Decrease of olfactory function in Parkinson's disease (PD) is a well-investigated fact. Studies indicate that pharmacological treatment of PD fails to restore olfactory function in PD patients. The aim of this investigation was whether patients with PD would benefit from \"training\" with odors in terms of an improvement of their general olfactory function. It has been hypothesized that olfactory training should produce both an improved sensitivity towards the odors used in the training process and an overall increase of olfactory function.\\n\\nMETHODS: We recruited 70 subjects with PD and olfactory loss into this single-center, prospective, controlled non-blinded study. Thirty-five patients were assigned to the olfactory training group and 35 subjects to the control group (no training). Olfactory training was performed over a period of 12 weeks while patients exposed themselves twice daily to four odors (phenyl ethyl alcohol: rose, eucalyptol: eucalyptus, citronellal: lemon, and eugenol: cloves). Olfactory testing was performed before and after training using the \"Sniffin' Sticks\" (thresholds for phenyl ethyl alcohol, tests for odor discrimination, and odor identification) in addition to threshold tests for the odors used in the training process.\\n\\nRESULTS: Compared to baseline, trained PD patients experienced a significant increase in their olfactory function, which was observed for the Sniffin' Sticks test score and for thresholds for the odors used in the training process. Olfactory function was unchanged in PD patients who did not perform olfactory training.\\n\\nCONCLUSION: The present results indicate that olfactory training may increase olfactory sensitivity in PD patients.", "author" : [ { "dropping-particle" : "", "family" : "Haehner", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tosch", "given" : "Clara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wolz", "given" : "Martin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klingelhoefer", "given" : "Lisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fauser", "given" : "Mareike", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Storch", "given" : "Alexander", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reichmann", "given" : "Heinz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1-7", "title" : "Olfactory Training in Patients with Parkinson's Disease", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "301", "plainTextFormattedCitation" : "301", "previouslyFormattedCitation" : "300" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }301)2013Prospective, controlled Patients with Parkinson’s diseasen=70Significant increase in olfactory functionFleiner et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Fleiner", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lau", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goktas", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Ear Nose And Throat Journal", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "198-203", "title" : "Active olfactory training for the treatment of smell disorders", "type" : "article-journal", "volume" : "91" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "306", "plainTextFormattedCitation" : "306", "previouslyFormattedCitation" : "305" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }306)2012Retrospective Olfactory loss of differing aetiologiesn=46Improvement of olfactionHummel et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/lary.20101", "ISBN" : "1531-4995 (Electronic)", "ISSN" : "0023852X", "PMID" : "19235739", "abstract" : "Objectives: Olfactory function is known to be modulated by repeated exposure to odors. The aim of this investigation was whether patients with olfactory loss would benefit from ''Training'' with odors in terms of an improvement of their general olfactory function. It was hypothesized that olfactory Training should produce both an improved sensitivity towards the odors used in the Training process and an overall increase of olfactory function. Study Design: The prospective study was per-formed in patients with olfactory dysfunction. Methods: One group of patients performed the Training (n \u00bc 40), whereas another part did not (n \u00bc 16). Exclusion criteria for patients were sinunasal disease. Olfactory training was performed over a pe-riod of 12 weeks. Patients exposed themselves twice daily to four intense odors (phenyl ethyl alcohol: rose, eucalyptol: eucalyptus, citronellal: lemon, and euge-nol: cloves). Olfactory testing was performed before and after training using the ''Sniffin' Sticks'' (thresh-olds for phenyl ethyl alcohol, tests for odor discrimi-nation and odor identification) in addition to thresh-old tests for the odors used in the training process. Results: Compared to baseline, training patients experienced an increase in their olfactory function, which was observed for the Sniffin' Sticks test score and for thresholds for the odors used in the training process. In contrast, olfactory function was unchanged in patients who did not perform olfactory training. The present results indicate that the struc-tured, short-term exposure to selected odors may increase olfactory sensitivity.", "author" : [ { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reden", "given" : "Karo Rissom Jens", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "H\u00e4hner", "given" : "Aantje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weidenbecher", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "H\u00fcttenbrink", "given" : "Karl Bernd", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Laryngoscope", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "496-499", "title" : "Effects of olfactory Training in patients with olfactory loss", "type" : "article-journal", "volume" : "119" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "300", "plainTextFormattedCitation" : "300", "previouslyFormattedCitation" : "299" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }300)2009Prospective, controlled Patients with olfactory dysfunction excluding sinonasal diseasen=56Improvement of olfactory sensitivityWang et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1113/jphysiol.2003.054726", "ISSN" : "0022-3751", "PMID" : "14678505", "abstract" : "Of those people who are anosmic to androstenone, a proportion can acquire sensitivity to it by repeated exposure and even those who are able to smell it can lower their threshold with this treatment. Using olfactory threshold testing, intranasal electrophysiology and EEG we show for the first time that: (1) the subjects' detection threshold is proportional to the amplitude of the olfactory evoked potential (EOG) recorded inside the nose; (2) the EOG amplitude is correlated with the amplitude of the olfactory event-related potential (OERP) recorded on the scalp; and (3) with repetitive exposure, human subjects acquire a reduced threshold for androstenone and, as they do so, their EOG and OERP increase. These observations support the existence of odourant-specific plasticity in the peripheral olfactory system.", "author" : [ { "dropping-particle" : "", "family" : "Wang", "given" : "Liwei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Lixin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jacob", "given" : "Tim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of physiology", "id" : "ITEM-1", "issue" : "Pt 1", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "236-244", "title" : "Evidence for peripheral plasticity in human odour response.", "type" : "article-journal", "volume" : "554" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "307", "plainTextFormattedCitation" : "307", "previouslyFormattedCitation" : "306" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }307)2004Prospective, controlled Patients anosmic to androstenonen=33Increased sensitivity following repeated exposureTable 7:AuthorYearStudy TypeTreatment MethodStudy Population; NResultsSurgeryMorrissey et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/lary.25647", "ISSN" : "0023852X", "abstract" : "The main challenge of surgery in the treatment of low back pain lies with the poor knowledge of the aetio-pathogenesis of this symptom. Surgical treatment requires the precise diagnosis of a surgically curable lesion. In low back disorders this research of a precise source of nociception remains elusive even in the presence of radiological abnormalities. Indeed, surgery may not be performed to treat a symptom (low back pain), but an objective condition or disease. Surgical treatment for low back pain is the subject of many controversies, but a certain number of attitudes can be (generally) agreed upon in a variety of low back disorders: (i) intervertebral disc herniation; (ii) degenerative spinal disease; (iii) spinal stenosis; (iv) lytic spondylolisthesis. However, there is a wide choice of attitudes, techniques and procedures for each of those indications and numerous conflicting result reports have been published. This chapter will try to preset the best available consensus regarding the indications and results of different surgical procedures in spinal disorders. Most of all, physicians should bear in mind that, in spine surgery perhaps more than in other fields, unreasonable patient (and surgeon) expectations will most likely lead to poor outcomes.", "author" : [ { "dropping-particle" : "", "family" : "Morrissey", "given" : "David K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pratap", "given" : "Upasna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brown", "given" : "Christopher", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wormald", "given" : "Peter-John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Laryngoscope", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2016", "3" ] ] }, "page" : "575-578", "title" : "The role of surgery in the management of phantosmia", "type" : "article-journal", "volume" : "126" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "334", "plainTextFormattedCitation" : "334", "previouslyFormattedCitation" : "333" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }334)2016RetrospectiveSurgical resection of olfactory neuroepitheliumPatients with peripheral phantosmian=3Resolution of phantosmia Hanci et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1177/0003489416629162", "ISSN" : "0003-4894 (Print)", "PMID" : "26848035", "abstract" : "Introduction: The reduction in the preferences for sweet and fat containing tastes in obese patients who underwent bariatric surgery was relatively well shown; however, there are only limited data on the changes in the sensitivity of other tastes like sour, salty, and bitter.Methods: We investigated the changes in gustatory sensitivity of 52 morbidly obese patients (M/F, 22/30; age range, 19-60 years; BMI range, 32.5-63.0 kg/m2) after laparoscopic sleeve gastrectomy. The surgery was performed by the same surgeon using 5 ports technique. Gustatory sensitivity was tested preoperatively and 1 and 3 months after the surgery using standardized Taste Strips test.Results: There was a statistically significant improvement in the taste acuity to sweet, sour, salty, and bitter tastants in morbidly obese patients after the laparoscopic sleeve gastrectomy during the follow-up period of 3 months. Median whole test scores of the patients were increased from 11.5 preoperatively to 14 in the first and third months.Conclusion: In this study, we were able to show the significant improvement in gustatory sensitivity of morbidly obese patients after laparoscopic sleeve gastrectomy for the first time in literature. ", "author" : [ { "dropping-particle" : "", "family" : "Altun", "given" : "Huseyin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hanci", "given" : "Deniz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altun", "given" : "Hasan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Batman", "given" : "Burcin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Serin", "given" : "Rahmi Kursat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karip", "given" : "Aziz Bora", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akyuz", "given" : "Umit", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of Otology, Rhinology & Laryngology ", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "558-562", "title" : "Improved Gustatory Sensitivity in Morbidly Obese Patients After Laparoscopic Sleeve Gastrectomy", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "331", "plainTextFormattedCitation" : "331", "previouslyFormattedCitation" : "330" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }331)2016 ProspectiveLaparoscopic Sleeve GastrectomyMorbidly obese patients with smell disordern=54Improvement of olfaction following surgery Randhawa et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/coa.12463", "ISSN" : "17494486", "author" : [ { "dropping-particle" : "", "family" : "Randhawa", "given" : "P. S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watson", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lechner", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ritchie", "given" : "L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Choudhury", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andrews", "given" : "P. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Otolaryngology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "15-20", "title" : "The outcome of septorhinoplasty surgery on olfactory function", "type" : "article-journal", "volume" : "41" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "329", "plainTextFormattedCitation" : "329", "previouslyFormattedCitation" : "328" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }329)2016ProspectiveFunctional septorhinoplastyAll patients listed for functional septorhinoplastyn=43Statistically significant improvement in screening odour identification scores, but no proven clinical benefitAltun et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2500/ajra.2015.29.4208", "ISSN" : "19458932", "PMID" : "2015441511", "abstract" : "Background: The surgical treatment of nasal septal perforation is known to improve nasal respiratory airflow and, thereby, should be beneficial to the patient's olfactory abilities. However, there are only limited data on the effect of nasal septal perforation repair (NSPR) on olfaction, and most studies reported contradictory results. Objective: The aim of this prospective study was to investigate the change in the olfactory abilities of 42 patients with a primary concern of nasal septal perforation. Methods: NSPR was performed with the \"cross-stealing\" technique. The inferior-based mucoperichondrial flap in one side and the superior-based mucoperichondrial flap from the other side of the nasal septum were passed to the opposite sides through the perforation. Surgery was completed by placing an interpositional graft between the flaps before suturing. The interpositional grafts were residual cartilage. The olfactory performance of the patients before and at 1, 3, and 6 months after the closure of the nasal septal perforation was measured by using an olfaction test kit. Results: The success rate with complete closure of nasal septal perforation with the \"cross-stealing\" technique was 92.8%. Analysis of the data indicated statistically significant improvement in olfactory function scored as odor threshold (T), odor discrimination (D), odor identification (I) and TDI at 1, 3, and 6 months after NSPR (p < 0.001 for all). The mean TDI score evaluated 6 months after NSPR was improved by 64%. Analyses of variance indicated statistically significant improvement in olfactory scores within time factors were calculated a reoperative v us 1, 3, and 6 months; 1 versus 3 and 6 months; and 3 versus 6 months (p < 0.001 for all). Analysis of the present data indicates a beneficial effect of NSPR on olfactory abilities of patients with perforation. Conclusion: Our data on the short- and long-term olfactory abilities of 42 patients with nasal septal perforation after NSPR when using an olfaction test kit indicated statistically significant improvement in olfactory function.", "author" : [ { "dropping-particle" : "", "family" : "Altun", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hanci", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Rhinology and Allergy", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "e142-e145", "title" : "Olfaction improvement after nasal septal perforation repair with the \"cross-stealing\" technique", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "335", "plainTextFormattedCitation" : "335", "previouslyFormattedCitation" : "334" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }335)2015 ProspectiveNasal septal perforation repairPatients with septal perforation and smell disordern=42Improvement in olfaction with successful closure of defect; closure success in 92.8%Razmpa et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Razmpa", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saedi", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Safavi", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohammadi", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "B-ENT", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "269-275", "title" : "Olfactory function after nasal plastic surgery", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "212", "plainTextFormattedCitation" : "212", "previouslyFormattedCitation" : "211" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }212)2013ProspectiveAesthetic septorhinoplastyPatients with normal olfaction and no nasal functional abnormalitiesn=102No significant change in odour identification scores post-operativelySchriever et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00405-012-1972-0", "ISBN" : "1434-4726 (Electronic)\\r0937-4477 (Linking)", "ISSN" : "09374477", "PMID" : "22382399", "abstract" : "Olfactory dysfunction is a frequent symptom of nasal and sinunasal disease. Many of these patients undergo nasal sinus or nasal septum surgery. In this study, we evaluated the benefit of nasal surgery on olfactory function over a period of 12 months. Patients included in this study underwent either nasal sinus or nasal septum surgery. All patients were tested for olfactory function using the \"Sniffin' sticks\" 16 item odor identification test. In addition, patients were asked to rate their nasal patency as well as their olfactory function at each visit. 157 patients were tested 3.5 months after surgery and 52 patients were tested again 12 months after surgery. Olfactory function improved significantly 3.5 months after surgery in patients, who received nasal sinus surgery; no significant increase was found in patients treated with nasal septum surgery. At the 12-month follow-up, the increase in olfactory function over all patients just missed statistical significance. Individually, however, 19% of the patients exhibited improvement after 3.5 months and 17% after 12 months. These numbers increased in patients with rhinosinusitis with nasal polyps, who exhibited improvement of 30% after 3.5 months, and 32% after 12 months. Nasal sinus surgery produced an increase in measured olfactory function, but not nasal septum surgery. This increase appeared to be stable over the examined period of 12 months.", "author" : [ { "dropping-particle" : "", "family" : "Schriever", "given" : "V. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gupta", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pade", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Szewczynska", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Archives of Oto-Rhino-Laryngology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "note" : "Olfactory function was increased significantly 3.5 months after surgery, when compared to pre-surgical olfactory function. This positive effect was only seen in patients, who underwent sinus surgery and not in patients treated with septum surgery.", "page" : "107-111", "title" : "Olfactory function following nasal surgery: A 1-year follow-up", "type" : "article-journal", "volume" : "270" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "326", "plainTextFormattedCitation" : "326", "previouslyFormattedCitation" : "325" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }326)2013Prospective Septoplasty ± reduction of turbinatesAll patients listed for nasal septal/turbinate surgeryn=44 No significant improvement in olfactory function at 3.5 monthsRichardson et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s11695-011-0487-x", "ISSN" : "0960-8923", "author" : [ { "dropping-particle" : "", "family" : "Richardson", "given" : "Brynn E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vanderwoude", "given" : "Eric A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sudan", "given" : "Ranjan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leopold", "given" : "Donald A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thompson", "given" : "Jon S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity Surgery", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2012", "2", "7" ] ] }, "page" : "283-286", "publisher" : "Springer-Verlag", "title" : "Gastric Bypass Does Not Influence Olfactory Function in Obese Patients", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "330", "plainTextFormattedCitation" : "330", "previouslyFormattedCitation" : "329" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }330) 2012ProspectiveGastric bypass surgery Morbidly obese patientsn=55Gastric bypass patients were more likely to have olfactory dysfunction pre-operatively than controls, but function was not affected by surgeryPade et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/MLG.0b013e318170b5cb", "ISBN" : "1531-4995 (Electronic)", "ISSN" : "1531-4995", "PMID" : "18438263", "abstract" : "OBJECTIVE/HYPOTHESIS: This prospective study aimed to investigate predictors of nasal surgery in terms of olfactory function. STUDY DESIGN: Prospective study. METHODS: A total of 775 patients were included in this prospective study (482 men, 293 women; age range 10-81 years, mean age 41 years, standard deviation = 15.3 y). Prior to surgery, patients received a detailed otorhinolaryngologic examination including nasal endoscopy. Olfactory function was assessed with a standardized odor identification test (\"Sniffin' Sticks\"). In 356 patients, olfactory function was retested 4 months after surgery (63-339 days after surgery; mean 128 days, standard deviation = 29 days); 206 of these patients received sinus surgery, while 150 received surgery involving the septum. RESULTS: Using a conservative definition of change of olfactory function, following sinus surgery, improvement of the sense of smell was found in 23%, no change was seen in 68%, and decreased function was seen in 9% of the patients; in patients with septum surgery, improvement was seen in 13%, no change in 81%, and decreased function in 7%. Patients exhibiting a postoperative decrease of olfactory function had significantly higher preoperative olfactory scores than patients who experienced improvement. In terms of the sense of smell, nasal surgery produced the highest success rates in patients with eosinophilia and a high degree of polyposis. Neither age nor sex had a major impact on the outcome of surgery in terms of olfactory function. CONCLUSIONS: These results in a large group of patients confirm previous work. Apart from apparent success in 13 to 23% of patients, there is also a small but significant group of patients (7 to 9%) in whom olfactory function decreases after surgery. Because this decrease was mostly found in patients with relatively good preoperative olfactory function, this group should receive specific attention when counseling patients about the potential risks of nasal surgery.", "author" : [ { "dropping-particle" : "", "family" : "Pade", "given" : "J\u00fcrgen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Laryngoscope", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2008" ] ] }, "note" : "Only septoplasty/SMR +/- turbinates and FESS. NO SRP", "page" : "1260-1264", "title" : "Olfactory function following nasal surgery.", "type" : "article-journal", "volume" : "118" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "73", "plainTextFormattedCitation" : "73", "previouslyFormattedCitation" : "73" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }73)2008ProspectiveSeptoplasty ± reduction of turbinatesAll patients listed for nasal septal/turbinate surgeryn=150At mean 4 months post op: 13% improved function, 81% stable function, 7% deterioration in functionPhilpott et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0300-0729 (Print)\\r0300-0729 (Linking)", "ISSN" : "03000729", "PMID" : "18444490", "abstract" : "BACKGROUND: Despite the common occurrence of rhinological pathology presenting to the ENT clinic, routine testing of olfactory ability is rarely performed. OBJECTIVES: The aim of this study was to determine the role of routine olfactory testing. METHODS: This was a prospective study conducted in the outpatient clinic of a district general hospital. Patients presenting with rhinological complaints had their olfactory status assessed using the combined olfactory test (COT) before and after rhinological surgery. RESULTS: Eighty patients (56 men, 24 women) had tests completed over a 12-month period. Patients assessed mostly had nasal polyposis, chronic rhinosinusitis or septal deformity. 83% of patients had either a complaint of olfactory disturbance or a COT score of 6 or less, or had both; but correlation between symptoms and scores was poor. Post-operative COT scores showed significant improvement (p = 0.02) with post-septoplasty patients showing the most significant improvement as a group (p = 0.001). CONCLUSIONS: Olfactory disturbance is very common in rhinological pathology and the patient's history alone cannot be relied upon. Simple olfactory assessment, such as with the combined olfactory test, is easy to perform and cheap to use and should be a commonly used resource in the ENT clinic. Formal testing can help to document any pre-existing olfactory loss and any post-operative changes as well as detecting unreported hyposmia.", "author" : [ { "dropping-particle" : "", "family" : "Philpott", "given" : "Carl M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rimal", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tassone", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prinsley", "given" : "P. R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Premachandra", "given" : "D. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rhinology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "34-39", "title" : "A study of olfactory testing in patients with rhinological pathology in the ENT clinic", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "187", "plainTextFormattedCitation" : "187", "previouslyFormattedCitation" : "187" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }187)2008ProspectiveNasal surgeryPatients undergoing nasal surgery (differing aetiologies)n=80Most marked improvement in septoplasty groupLeopold (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/chemse/27.7.611", "ISSN" : "14643553", "author" : [ { "dropping-particle" : "", "family" : "Leopold", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Chemical Senses", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2002", "9", "1" ] ] }, "page" : "611-615", "publisher" : "Oxford University Press", "title" : "Distortion of Olfactory Perception: Diagnosis and Treatment", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "336", "plainTextFormattedCitation" : "336", "previouslyFormattedCitation" : "335" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }336)2002Review article Intranasal removal of olfactory epitheliumPatients with phantosmian=18Resolution of phantosmia in all but one patientLeopold et al. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1001/archotol.1991.01870240094016", "ISSN" : "0886-4470", "author" : [ { "dropping-particle" : "", "family" : "Leopold", "given" : "D. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwob", "given" : "J. E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Youngentob", "given" : "S. L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hornung", "given" : "D. E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wright", "given" : "H. N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mozell", "given" : "M. 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(ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "01960709", "PMID" : "4037228", "abstract" : "A prospective study of 100 patients undergoing nasal surgery was done to quantitate the effects of nasal surgery on olfaction. Patients were evaluated pre- and postoperatively with regard to their subjective olfaction, and pre- and postoperative olfactograms were obtained using a simple office olfactometer. Thirty-two patients had normal olfaction during the course of study. Forty-nine improved following surgery. Eight patients had a decrease in olfaction after surgery. Two of these were related to allergic rhinitis. One patient had a total loss of olfaction following a septorhinoplasty. The authors conclude that most patients undergoing nasal surgery will have either an improvement or no change in olfaction after surgery.", "author" : [ { "dropping-particle" : "", "family" : "Stevens", "given" : "C N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stevens", "given" : "M H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Otolaryngol", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "1985" ] ] }, "page" : "264-267", "title" : "Quantitative effects of nasal surgery on olfaction", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "337", "plainTextFormattedCitation" : "337", "previouslyFormattedCitation" : "336" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }337)1985ProspectiveNasal surgeryPatients undergoing nasal surgery (differing aetiologies)n=100Similar numbers of improved olfaction and no change in olfactionLEGENDS FOR TABLES:Table 1: Definitions of terminology used in olfactory research/practice.Table 2: Definition of olfactory dysfunction according to anatomical location of lesion.Table 3: Abbreviated list of agents and medications that affect olfaction (adapted from ref (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0-8247-0719-2", "author" : [ { "dropping-particle" : "", "family" : "Murphy", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doty", "given" : "Richard L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duncan", "given" : "H J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "chapter-number" : "22", "container-title" : "Handbook of Olfaction and Gustation", "edition" : "3rd", "editor" : [ { "dropping-particle" : "", "family" : "Doty", "given" : "Richard L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "461-478", "publisher" : "Marcel Dekker", "publisher-place" : "New York", "title" : "Clinical disorders of olfaction", "type" : "chapter" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1007/s00228-015-1814-2", "ISSN" : "14321041", "author" : [ { "dropping-particle" : "", "family" : "L\u00f6tsch", "given" : "J\u00f6rn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daiker", "given" : "Helena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "H\u00e4hner", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ultsch", "given" : "Alfred", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hummel", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Journal of Clinical Pharmacology", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "461-471", "title" : "Drug-target based cross-sectional analysis of olfactory drug effects", "type" : "article-journal", "volume" : "71" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1371/journal.pone.0007647", "ISBN" : "1932-6203 (Electronic)\\r1932-6203 (Linking)", "ISSN" : "19326203", "PMID" : "19876403", "abstract" : "Intranasal medications are used to treat various nasal disorders. However, their effects on olfaction remain unknown. Zicam (zinc gluconate; Matrixx Initiatives, Inc), a homeopathic substance marketed to alleviate cold symptoms, has been implicated in olfactory dysfunction. Here, we investigated Zicam and several common intranasal agents for their effects on olfactory function. Zicam was the only substance that showed significant cytotoxicity in both mouse and human nasal tissue. Specifically, Zicam-treated mice had disrupted sensitivity of olfactory sensory neurons to odorant stimulation and were unable to detect novel odorants in behavioral testing. These findings were long-term as no recovery of function was observed after two months. Finally, human nasal explants treated with Zicam displayed significantly elevated extracellular lactate dehydrogenase levels compared to saline-treated controls, suggesting severe necrosis that was confirmed on histology. Our results demonstrate that Zicam use could irreversibly damage mouse and human nasal tissue and may lead to significant smell dysfunction.", "author" : [ { "dropping-particle" : "", "family" : "Lim", "given" : "Jae H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davis", "given" : "Greg E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Zhenshan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Vicky", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Yuping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rue", "given" : "Tessa C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Storm", "given" : "Daniel R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "id" : "ITEM-3", "issue" : "10", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "1-10", "title" : "Zicam-induced damage to mouse and human nasal tissue", "type" : "article-journal", "volume" : "4" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Nakamura", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nonomura", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fujiwara", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakano", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Eur Arch Otorhinolaryngol", "id" : "ITEM-4", "issued" : { "date-parts" : [ [ "1995" ] ] }, "page" : "48-52", "title" : "Olfactory disturbances caused by the anti-cancer drug tegafur", "type" : "article-journal", "volume" : "252" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Upadhyay", "given" : "UD", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holbrook", "given" : "EH", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Otolaryngologic Clinics of North America", "id" : "ITEM-5", "issue" : "6", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "1185-207", "title" : "Olfactory loss as a result of toxic exposure", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1002/j.1875-9114.1997.tb03058.x", "ISBN" : "0277-0008 (Print)\\n0277-0008 (Linking)", "ISSN" : "02770008", "PMID" : "9165552", "abstract" : "We reviewed the current literature (1980-1990, 1991-1996) concerning drugs associated with anosmia, hyposmia, dysgeusia, parageusia, and ageusia, and the impact of these adverse effects. Case reports of patients with sudden and delayed onset of one of these disorders with evidence for implication of a drug were included. Disturbances of taste and smell among the elderly and chronically ill, including those with thermal injury, decreases interest in eating and secondarily impairs healing of wounds. Mechanisms involved with these sensory disturbances include deposition of silver sulfate in nerves after use of topical agents containing silver, altered influx of calcium and other ions, chelation or depletion of tissue-bound zinc, disturbed bradykinin catabolism and second messenger synthesis, catabolism, and altered prostaglandin systems. Other mechanisms, particularly prolonged chemosensory disorders after early drug discontinuation, remain unknown.", "author" : [ { "dropping-particle" : "", "family" : "Ackerman", "given" : "B H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kasbekar", "given" : "Nishaminy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pharmacotherapy", "id" : "ITEM-6", "issue" : "3", "issued" : { "date-parts" : [ [ "1996" ] ] }, "page" : "482-496", "title" : "Disturbances of taste and smell induced by drugs.", "type" : "article-journal", "volume" : "17" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Henkin", "given" : "R I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pharmacology in medicine: principles and practice", "editor" : [ { "dropping-particle" : "", "family" : "Pradhan", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maickel", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-7", "issued" : { "date-parts" : [ [ "1986" ] ] }, "page" : "748-753", "publisher" : "SP Press Int", "publisher-place" : "Bethesda", "title" : "Drug effects on smell and taste", "type" : "chapter" }, "uris" : [ "" ] }, { "id" : "ITEM-8", "itemData" : { "DOI" : "10.1016/j.otc.2004.05.002", "ISBN" : "0030-6665 (Print)\\n0030-6665 (Linking)", "ISSN" : "00306665", "PMID" : "15563912", "abstract" : "The fact that so many varied medications reportedly affect taste and smell is a testament to the complexity of the gustatory and olfactory systems. The reception, transduction, propagation, and perception of a chemical tastant or odorant requires the effective operation of numerous mechanisms - all of which may be susceptible in one way or another to a prescribed medication. Just as a diuretic may block the apical ion channels on a taste bud, or an antifungal can inhibit cytochrome p450-dependent enzymes at the level of the receptors, a chemotherapeutic agent can destroy mitosis in a replicating receptor cell and a steroid can lead to candidal overgrowth on the tongue surface. Medications not only have a perceivable taste themselves at times, but they can alter the mechanisms responsible for the ultimate perception of tastes and smells - either by direct or secondary means. It should be emphasized, as noted earlier in this article, that while many medications are to blame for the impairment or distortion of the gustatory or olfactory systems, it is not uncommon that the underlying medical problem for which they are prescribed is actually the culprit. Examples include epilepsy, migraines, hypothyroidism, schizpophrenia, infections, and cancer. In fact, simple partial seizures emanating from regions of the brain such as the amygdala, hippocampus, parietal operculum, and rolandic operculum can lead to the chemosensory sensations that are most commonly considered unpleasant, such as \"rotten apples,\" \"cigarette,\" \"peculiar,\" or \"vomitus\" [72]. While removing or changing an offending medication can reverse the effects on smell or taste perception, it is important to remember that lasting impairment may occur. This is vital for a physician to recognize prior to prescribing a medication. It is also necessary to report this to patients who may be devastated by chemosensory alterations after starting a new medication (eg, pastry chef, perfumist, wine specialist, plumber). 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Evidence regarding surgery for CRS has not been included as this has been extensively described elsewhere (e.g. (ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1013-0047", "PMID" : "22764607", "abstract" : "The European Position Paper on Rhinosinusitis and Nasal Polyps 2012 is the update of similar evidence based position papers published in 2005 and 2007.The document contains chapters on definitions and classification, we now also proposed definitions for difficult to treat rhinosinusitis, control of disease and better definitions for rhinosinusitis in children. More emphasis is placed on the diagnosis and treatment of acute rhinosinusitis. Throughout the document the terms chronic rhinosinusitis without nasal polyps and chronic rhinosinusitis with nasal polyps are used to further point out differences in pathophysiology and treatment of these two entities. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. 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