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Influenza burden, prevention and treatment in asthma – a scoping review by the EAACI Influenza in Asthma Task ForceJürgen Schwarze1, MD, PhD, Peter Openshaw2, FMedSci, Akhilesh Jha2, MRCP (UK), Stefano R del Giacco3, MD, Davide Firinu3, MD, Olympia Tsilochristou4, MD, Graham Roberts5, DM, FRCPCH, Anna Selby5, BM BCh, Cezmi Akdis6, MD, PhD, Ioana Agache7, MD, PhD, Adnan Custovic8, MD, PhD, Enrico Heffler9, MD, PhD, Georgia Pinna10, MD, Musa Khaitov11 , PhD, Alexandra Nikonova11, Nikolaos Papadopoulos12, MD, PhD, Ather Akhlaq13, PhD, Ulugbek Nurmatov14, Harald Renz15, MD, Aziz Sheikh16, FRSE, FMedSci, Chrysanthi Skevaki15, MD, PhDAuthor affiliations:1 Centre for Inflammation Research, University of Edinburgh, The Queens Medical Research Institute, Edinburgh, UK2 Respiratory Sciences, National Heart and Lung Institute, Imperial College London, UK3 Department of Medical Sciences and Public Health “M. Aresu”, University of Cagliari, Cagliari, Italy4 Department of Pediatric Allergology, King’s College, London, UK5 Faculty of Medicine, University of Southampton, Southampton and David Hide Asthma and Allergy Centre, St Mary’s Hospital, Newport, Isle of Wight, UK6 Swiss Institute of Allergy and Asthma Research, University of Zurich, Davos, Switzerland7 Department of Allergy and Clinical Immunology, Faculty of Medicine, Transylvania University Brasov, Brasov, Romania8 Department of Paediatrics, Imperial College London, UK9 Personalized Medicine, Asthma and Allergy Clinic, Department of Biomedical Sciences, Humanitas University, Milan, Italy10 Department of Medical Microbiology, National Kapodistrian University of Athens, Athens, Greece11 National Research Center Institute of Immunology of Federal Medicobiological Agency, Moscow, Russia12 Division of Infection, Inflammation & Respiratory Medicine, The University of Manchester, Manchester, UK and Allergy Dpt, 2nd Paediatric Clinic, National Kapodistrian University of Athens, Greece13 Division of Population Medicine, School of Medicine, Cardiff University, Cardiff, UK14 Department of Health and Hospital Management, Institute of Business Management, Korangi Creek, Karachi - 75190, Pakistan15 Institute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, Philipps University Marburg, University Hospital Giessen & Marburg, Marburg, Germany16 Asthma UK Centre for Applied Research, Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Edinburgh, UK Author for correspondenceChrysanthi Skevaki, MD, PhDInstitute of Laboratory Medicine, Philipps University MarburgBaldingerstrasse, 35043 Marburg, GermanyPhone +49 6421 586 6235email: Chrysanthi.Skevaki@uk-gm.deKey words: <5 maximum>Viral infection, vaccination, antivirals, respiratory, heath care utilizationShort title: <50 characters>Influenza burden in asthma – a scoping reviewAbstract <Unstructured: 200 word limit>To address uncertainties in the prevention and management of influenza in people with asthma, we performed a scoping review of the published literature on influenza burden; current vaccine recommendations; vaccination coverage; immunogenicity, efficacy, effectiveness and safety of influenza vaccines; and the benefits of antiviral drugs in people with asthma. We found significant variation in the reported rates of influenza detection in individuals with acute asthma exacerbations making it unclear to what degree influenza causes exacerbations of underlying asthma. The strongest evidence of an association was seen in studies of children. Countries in the European Union currently recommend influenza vaccination of adults with asthma; however, coverage varied between regions. Coverage was lower among children with asthma. Coverage was lower among asthmatic children (redundant). Limited data suggest that good seroprotection and seroconversion can be achieved in both children and adults with asthma and that vaccination confers a degree of protection against influenza illness and asthma related morbidity to children with asthma. There were insufficient data to determine efficacy in adults. Overall, influenza vaccines appeared to be safe for people with asthma. We identify knowledge gaps and make recommendations on future research needs in relation to influenza in patients with asthma. IntroductionAsthma is a heterogeneous chronic inflammatory lung disease characterized by intermittent airflow obstruction and increased reactivity to bronchoconstrictive triggers. Presently, an estimated 300 million people worldwide suffer from asthma ADDIN EN.CITE <EndNote><Cite ExcludeAuth="1" ExcludeYear="1"><RecNum>230</RecNum><DisplayText>(1)</DisplayText><record><rec-number>230</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481280825">230</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors></contributors><titles><title>Global Atlas of Asthma. Published by the European Academy of Allergy and Clinical Immunology. Editors: Cezmi A. Akdis, Ioana Agache, 2013</title></titles><dates></dates><urls></urls></record></Cite></EndNote>(1). In Europe, more than 30 million people are affected, with six million suffering severe symptoms and 1.5 million life-threatening attacks ADDIN EN.CITE <EndNote><Cite ExcludeAuth="1" ExcludeYear="1"><RecNum>231</RecNum><DisplayText>(2)</DisplayText><record><rec-number>231</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481280864">231</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors></contributors><titles><title>ERS: The European Lung White Book 2003.</title></titles><dates></dates><urls></urls></record></Cite></EndNote>(2). Asthma onset and acute asthma exacerbations (ΑΑΕ) have been strongly associated with respiratory viral and (to a lesser extent) bacterial infections PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5EYXJ2ZWF1eDwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+

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ADDIN EN.CITE.DATA (3-7). Influenza viruses cause respiratory infections, typically during winter months. Most significant disease is caused by influenza A and B, which may escape immune pressure by undergoing antigenic drift and recombination; such genetic changes lead to new subtypes, which can cause epidemic or pandemic outbreaks PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TaW1vbnNlbjwvQXV0aG9yPjxZZWFyPjIwMTM8L1llYXI+

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ADDIN EN.CITE.DATA (12). To address uncertainties over the prevention and management of influenza in patients with asthma, we performed a scoping review and discuss the current knowledge of the burden imposed by influenza on patients with asthma, current vaccine recommendations and vaccination coverage in various regions, the evidence regarding immunogenicity, efficacy, effectiveness and safety of influenza vaccines, and the possible benefits of antiviral drugs in patients with asthma. We conclude by identifying knowledge gaps and future research needs in relation to influenza in asthma patients. Methods We systematically searched relevant published, unpublished and in-progress original research and systematic reviews that were pertinent to the subject matter of this EAACI Task Force. This involved searching databases of peer-reviewed published literature (Cochrane Library, EMBASE and CINAHL, MEDLINE and Google Scholar) and research in progress (i.e. and ) for the period 2000–2015. In addition, we wrote to a panel of international experts in an attempt to identify additional unpublished or in-progress work. There were no restrictions on language of publication. We were particularly interested in randomized controlled trials (RCTs) on questions relating to the immunogenicity, efficacy and/or effectiveness of influenza vaccine among asthmatics, and epidemiological studies relating to the influenza incidence/prevalence and public health burden and safety of influenza vaccine. Systematic reviews with or without meta-analysis were of interest if they focused on any of the questions of interest. The searches (see Appendix 1) were undertaken and allocated to relevant sub-group leads depending on the focus of the inquiry. Where possible, studies reported in languages other than English were translated. Within subgroups, two reviewers independently reviewed the titles and if necessary abstracts of potentially eligible studies to decide on eligibility; disagreements on study eligibility were resolved through discussion among the reviewers. Studies were then – in the specific context of asthma/allergy – categorized by topic area, namely: i) Global burden of influenza; ii) Influenza vaccination recommendations and coverage; iii) Immunogenicity of influenza vaccines; iv) Efficacy of influenza vaccines; v) Effectiveness of influenza vaccines; vi). Safety of influenza vaccines; and vii). Antiviral treatments against influenza. Reports were then scrutinized and interpreted by experts on the subject matter. Any disagreements on issues to do with interpretation were resolved through discussion.The searches were first conducted in 2014 and then updated in October 2015.The key characteristics and findings of all eligible studies were summarized in data tables, and the findings narratively synthesized. These are presented by topic in Table 1.Global burden of influenza in patients with asthma 2a. Influenza-attributable health care utilization in asthma patients Asthma is the most common underlying disease in patients with influenza admitted to healthcare facilities, both in adults cj48bGFuZ3VhZ2U+RW5nbGlzaDwvbGFuZ3VhZ2U+PC9yZWNvcmQ+PC9DaXRlPjxDaXRlPjxBdXRo

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ADDIN EN.CITE.DATA (18, 44-47). Asthma was also the most common comorbidity among pregnant women hospitalized with H1N1 infection, with a prevalence ranging from 8-33% PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NaWxsZXI8L0F1dGhvcj48WWVhcj4yMDEwPC9ZZWFyPjxS

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ADDIN EN.CITE.DATA (53, 54), and a relative risk (RR) of 4.47 (95% CI 1.49–13.39) in Israel PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TaGltb25pPC9BdXRob3I+PFllYXI+MjAwODwvWWVhcj48

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ADDIN EN.CITE.DATA (55). The same applied to children PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DcmlzaW5lbDwvQXV0aG9yPjxZZWFyPjIwMTI8L1llYXI+

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ADDIN EN.CITE.DATA (35), and Argentina ADDIN EN.CITE <EndNote><Cite><Author>Libster</Author><Year>2010</Year><RecNum>107</RecNum><DisplayText>(59)</DisplayText><record><rec-number>107</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481209720">107</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Libster, R.</author><author>Coviello, S.</author><author>Cavalieri, M. L.</author><author>Morosi, A.</author><author>Alabart, N.</author><author>Alvarez, L.</author><author>Ferrero, F.</author><author>Edwards, K. M.</author><author>Polack, F. P.</author></authors></contributors><titles><title>Pediatric hospitalizations due to influenza in 2010 in Argentina</title><secondary-title>N Engl J Med</secondary-title><alt-title>The New England journal of medicine</alt-title></titles><periodical><full-title>New England Journal of Medicine</full-title><abbr-1>N. Engl. J. Med.</abbr-1><abbr-2>N Engl J Med</abbr-2></periodical><pages>2472-3</pages><volume>363</volume><number>25</number><keywords><keyword>Argentina/epidemiology</keyword><keyword>Child</keyword><keyword>Cost of Illness</keyword><keyword>Hospitalization/*statistics &amp; numerical data</keyword><keyword>Humans</keyword><keyword>*Influenza A Virus, H1N1 Subtype</keyword><keyword>Influenza, Human/*epidemiology/virology</keyword><keyword>Pandemics/statistics &amp; numerical data</keyword></keywords><dates><year>2010</year><pub-dates><date>Dec 16</date></pub-dates></dates><isbn>1533-4406 (Electronic)&#xD;0028-4793 (Linking)</isbn><accession-num>21158677</accession-num><urls><related-urls><url>;(59)), with a 21-fold risk observed in South Korea PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MZWU8L0F1dGhvcj48WWVhcj4yMDEyPC9ZZWFyPjxSZWNO

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ADDIN EN.CITE.DATA (63) and a RR of 15.20 (95% CI 1.16-199.63) in China >15 years of age ADDIN EN.CITE <EndNote><Cite><Author>Jiang</Author><Year>2015</Year><RecNum>4</RecNum><DisplayText>(65)</DisplayText><record><rec-number>4</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481208311">4</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Jiang, H</author><author>Yu, D</author><author>Ruan, F</author><author>Xu, W</author><author>Huang, T</author><author>Li, L</author><author>Wang, K</author><author>Liu, S</author><author>Zhang, H</author><author>Jia, P</author></authors></contributors><titles><title>Clinical characteristics of adult influenza inpatients in ten provinces in China and analysis of severe risk factors</title><secondary-title>Zhonghua liuxingbingxue zazhi</secondary-title></titles><pages>216-221</pages><volume>36</volume><number>3</number><dates><year>2015</year></dates><isbn>0254-6450</isbn><urls></urls></record></Cite></EndNote>(65). Severe disease was especially common in those developing pneumonia PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NY0tlbm5hPC9BdXRob3I+PFllYXI+MjAxMzwvWWVhcj48

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ADDIN EN.CITE.DATA (45). In a multivariate analysis of H1N1 pediatric patients, asthma was associated with increased mortality in ICU-admitted children and adolescents (OR 1.34, p=0.05) PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Ub3JyZXM8L0F1dGhvcj48WWVhcj4yMDEyPC9ZZWFyPjxS

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ADDIN EN.CITE.DATA (22). Two other studies confirmed this finding PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5OZ3V5ZW4tVmFuLVRhbTwvQXV0aG9yPjxZZWFyPjIwMTA8

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ADDIN EN.CITE.DATA (22).2b. Influenza-induced acute asthma exacerbationsInfluenza, like other respiratory viral infections, can lead to AAE and was found to account for 32.0% ADDIN EN.CITE <EndNote><Cite><Author>Wark</Author><Year>2001</Year><RecNum>162</RecNum><DisplayText>(66)</DisplayText><record><rec-number>162</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481210247">162</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Wark, P. A. B.</author><author>Johnston, S. L.</author><author>Moric, I.</author><author>Simpson, J. L.</author><author>Hensley, M. J.</author><author>Gibson, P. G.</author></authors></contributors><titles><title>Neutrophil degranulation and cell lysis is associated with clinical severity in virus-induced asthma</title><secondary-title>European Respiratory Journal</secondary-title></titles><periodical><full-title>European Respiratory Journal</full-title><abbr-1>Eur. Respir. J.</abbr-1><abbr-2>Eur Respir J</abbr-2></periodical><pages>68-75</pages><volume>19</volume><number>1</number><dates><year>2001</year><pub-dates><date>2001/01/01</date></pub-dates></dates><publisher>European Respiratory Society (ERS)</publisher><isbn>0903-1936&#xD;1399-3003</isbn><urls><related-urls><url>;(66) and 9.8% ADDIN EN.CITE <EndNote><Cite><Author>Atmar</Author><Year>1998</Year><RecNum>165</RecNum><DisplayText>(67)</DisplayText><record><rec-number>165</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481210247">165</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Atmar, Robert L.</author><author>Guy, Elizabeth</author><author>Guntupalli, Kalpalatha K.</author><author>Zimmerman, Janice L.</author><author>Bandi, Venkata D.</author><author>Baxter, Barbara D.</author><author>Greenberg, Stephen B.</author></authors></contributors><titles><title>Respiratory Tract Viral Infections in Inner-City Asthmatic Adults</title><secondary-title>Archives of Internal Medicine</secondary-title></titles><periodical><full-title>Archives of Internal Medicine</full-title><abbr-1>Arch. Intern. Med.</abbr-1><abbr-2>Arch Intern Med</abbr-2></periodical><pages>2453</pages><volume>158</volume><number>22</number><dates><year>1998</year><pub-dates><date>1998/12/07</date></pub-dates></dates><publisher>American Medical Association (AMA)</publisher><isbn>0003-9926</isbn><urls><related-urls><url>;(67) of AAEs in two studies of adults with asthma outpatients. However, the method used to identify the presence of influenza in AAE episodes largely determines the outcome. A direct comparison of molecular (PCR), serological, and immunofluorescent (IFA) detection in the same cohort of adults with asthma found influenza rates of 24.0%, 18.3%, and 2.0% respectively in AAEs PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TaW1wc29uPC9BdXRob3I+PFllYXI+MjAwMzwvWWVhcj48

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ADDIN EN.CITE.DATA (68). Thus, the validity of studies that applied conventional influenza identification techniques such as cytopathic effect in cell culture followed by indirect immunofluoresence to confirm viral presence PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BemV2ZWRvPC9BdXRob3I+PFllYXI+MjAwMzwvWWVhcj48

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ADDIN EN.CITE.DATA (69, 73, 74), while several groups identified influenza infection as the cause of AAE, with most reporting rates of influenza-positive samples between 2.4% and 15.5% PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CdWV2aW5nPC9BdXRob3I+PFllYXI+MjAwNDwvWWVhcj48

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ADDIN EN.CITE.DATA (57, 75-78). A recent study showed an accentuated propensity for loss of asthma control when children were infected with pH1N1 (38%) compared with other common respiratory virus infections ADDIN EN.CITE <EndNote><Cite><Author>Kloepfer</Author><Year>2012</Year><RecNum>161</RecNum><DisplayText>(79)</DisplayText><record><rec-number>161</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481210247">161</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kloepfer, Kirsten M.</author><author>Olenec, Jaime P.</author><author>Lee, Wai Ming</author><author>Liu, Guiyan</author><author>Vrtis, Rose F.</author><author>Roberg, Kathy A.</author><author>Evans, Michael D.</author><author>Gangnon, Ronald E.</author><author>Lemanske, Robert F.</author><author>Gern, James E.</author></authors></contributors><titles><title>Increased H1N1 Infection Rate in Children with Asthma</title><secondary-title>American Journal of Respiratory and Critical Care Medicine</secondary-title></titles><periodical><full-title>American Journal of Respiratory and Critical Care Medicine</full-title><abbr-1>Am. J. Respir. Crit. Care Med.</abbr-1><abbr-2>Am J Respir Crit Care Med</abbr-2><abbr-3>American Journal of Respiratory &amp; Critical Care Medicine</abbr-3></periodical><pages>1275-1279</pages><volume>185</volume><number>12</number><dates><year>2012</year><pub-dates><date>2012/06/15</date></pub-dates></dates><publisher>American Thoracic Society</publisher><isbn>1073-449X&#xD;1535-4970</isbn><urls><related-urls><url>;(79). Among children with asthma hospitalized for severe AAE, three studies reported an influenza-associated burden of 2.6% PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NYW5kZWxjd2FqZzwvQXV0aG9yPjxZZWFyPjIwMTA8L1ll

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ADDIN EN.CITE.DATA (76), 3.4% ADDIN EN.CITE <EndNote><Cite><Author>Biscardi</Author><Year>2004</Year><RecNum>155</RecNum><DisplayText>(80)</DisplayText><record><rec-number>155</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481210247">155</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Biscardi, S.</author><author>Lorrot, M.</author><author>Marc, E.</author><author>Moulin, F.</author><author>Boutonnat-Faucher, B.</author><author>Heilbronner, C.</author><author>Iniguez, J. L.</author><author>Chaussain, M.</author><author>Nicand, E.</author><author>Raymond, J.</author><author>Gendrel, D.</author></authors></contributors><titles><title>Mycoplasma pneumoniae and Asthma in Children</title><secondary-title>Clinical Infectious Diseases</secondary-title></titles><periodical><full-title>Clinical Infectious Diseases</full-title><abbr-1>Clin. Infect. Dis.</abbr-1><abbr-2>Clin Infect Dis</abbr-2></periodical><pages>1341-1346</pages><volume>38</volume><number>10</number><dates><year>2004</year><pub-dates><date>2004/05/15</date></pub-dates></dates><publisher>Oxford University Press (OUP)</publisher><isbn>1058-4838&#xD;1537-6591</isbn><urls><related-urls><url>;(80) and 3.7% PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NaWxsZXI8L0F1dGhvcj48WWVhcj4yMDA4PC9ZZWFyPjxS

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ADDIN EN.CITE.DATA (81-83). Trivalent (TIV) and quadrivalent inactivated split-virus influenza vaccines are available, with TIV the most widely used throughout the EU. An intradermal vaccine is also available and more recently a quadrivalent live attenuated intranasal vaccine (LAIV) was approved for use in the UK in children aged 2–18 years ADDIN EN.CITE <EndNote><Cite ExcludeAuth="1" ExcludeYear="1"><RecNum>232</RecNum><DisplayText>(82, 84)</DisplayText><record><rec-number>232</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481282485">232</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors></contributors><titles><title>O’Flanagan, D, Cotter, S, Mereckiene, J. Seasonal influenza vaccination in EU / EEA, influenza season 2011-12, VENICE II Consortium. 1–67, 2013.</title></titles><dates></dates><urls></urls></record></Cite><Cite ExcludeAuth="1" ExcludeYear="1"><RecNum>234</RecNum><record><rec-number>234</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481282604">234</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors></contributors><titles><title>Public Health England. Influenza: the green book. Immun. against Infect. Dis. 185–218. Public Health England, 2014.</title></titles><dates></dates><urls></urls></record></Cite></EndNote>(82, 84). However, vaccine uptake for clinical risk groups varied from 31% in Portugal to 82% in Northern Ireland PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Fc3Bvc2l0bzwvQXV0aG9yPjxZZWFyPjIwMDY8L1llYXI+

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ADDIN EN.CITE.DATA (85). In comparison, in the USA vaccination coverage reached around 50% in adults and children ADDIN EN.CITE <EndNote><Cite ExcludeAuth="1" ExcludeYear="1"><RecNum>235</RecNum><DisplayText>(94)</DisplayText><record><rec-number>235</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481283151">235</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors></contributors><titles><title>Centre for Disease Control and Prevention. Vaccination Coverage Among Persons with Asthma — United States 2010–2011 Influenza Season.</title><secondary-title>MMWR</secondary-title></titles><pages>973–978</pages><volume>62</volume><dates><year>2013</year></dates><urls></urls></record></Cite></EndNote>(94). To address the question of such historically low vaccination rates amongst those with asthma, many studies employed cross-sectional surveys to analyse the socio-demographic variables that predict vaccine uptake. The strongest factors associated with higher vaccine coverage, were older age, recent contact with healthcare providers, non-smoking status, presence of co-morbidities, more severe asthma, and (surprisingly) lower household income PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5KaW3DqW5lei1HYXJjw61hPC9BdXRob3I+PFllYXI+MjAw

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ADDIN EN.CITE.DATA (86-89, 94-100), although regarding there are conflicting reports for the latter ADDIN EN.CITE <EndNote><Cite><Author>Vázquez-Fernández del Pozo</Author><Year>2007</Year><RecNum>123</RecNum><DisplayText>(92)</DisplayText><record><rec-number>123</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481209721">123</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Vázquez-Fernández del Pozo, S</author><author>Hernández-Barrera, V</author><author>Carrasco-Garrido, P</author><author>Alvarez-Martín, E</author><author>López-de Andrés, A</author><author>Gil de Miguel, A</author><author>Jiménez-García, R</author></authors></contributors><titles><title>Influenza vaccination coverage and related factors among Spanish children</title><secondary-title>Journal of Infection</secondary-title></titles><periodical><full-title>Journal of Infection</full-title><abbr-1>J. Infect.</abbr-1><abbr-2>J Infect</abbr-2></periodical><pages>483-489</pages><volume>54</volume><number>5</number><dates><year>2007</year></dates><isbn>0163-4453</isbn><urls></urls></record></Cite></EndNote>(92). Variables that were associated with lower vaccination uptake included younger age groups PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5LZWVuYW48L0F1dGhvcj48WWVhcj4yMDA3PC9ZZWFyPjxS

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ADDIN EN.CITE.DATA (85, 93, 94). A more detailed exploration assessing health attitudes suggested that the misbelief that the vaccination was not necessary or could actually cause influenza or side effects was predictive of non-adherence PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CdXl1a3Rpcnlha2k8L0F1dGhvcj48WWVhcj4yMDE0PC9Z

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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CdXl1a3Rpcnlha2k8L0F1dGhvcj48WWVhcj4yMDE0PC9Z

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ADDIN EN.CITE.DATA (103, 104, 106). A survey of 1225 US allergists suggested that 85% of these offered influenza vaccinations to adults and children. Younger allergists (<45 years) were more likely to offer vaccination, especially to children ADDIN EN.CITE <EndNote><Cite><Author>Clark</Author><Year>2012</Year><RecNum>177</RecNum><DisplayText>(109)</DisplayText><record><rec-number>177</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481210247">177</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Clark, Sarah J.</author><author>Cowan, Anne E.</author><author>Wortley, Pascale M.</author></authors></contributors><titles><title>Perspectives of Allergists/Immunologists on the 2009–2010 H1N1 Vaccination Effort</title><secondary-title>Journal of Asthma</secondary-title></titles><periodical><full-title>Journal of Asthma</full-title><abbr-1>J. Asthma</abbr-1><abbr-2>J Asthma</abbr-2></periodical><pages>184-189</pages><volume>49</volume><number>2</number><dates><year>2012</year><pub-dates><date>2012/02/02</date></pub-dates></dates><publisher>Informa Healthcare</publisher><isbn>0277-0903&#xD;1532-4303</isbn><urls><related-urls><url>;(109). Pediatricians were more likely than family physicians to routinely recommend influenza vaccination to children with asthma (adjusted OR 3.49, 95% CI 1.68-7.22), with decisions also being made depending on asthma phenotype (i.e. intermittent vs. persistent) ADDIN EN.CITE <EndNote><Cite><Author>Dombkowski</Author><Year>2008</Year><RecNum>178</RecNum><DisplayText>(110)</DisplayText><record><rec-number>178</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481210247">178</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Dombkowski, Kevin J.</author><author>Leung, Sonia W.</author><author>Clark, Sarah J.</author></authors></contributors><titles><title>Physician Perspectives Regarding Annual Influenza Vaccination Among Children With Asthma</title><secondary-title>Ambulatory Pediatrics</secondary-title></titles><periodical><full-title>Ambulatory Pediatrics</full-title><abbr-1>Ambul. Pediatr.</abbr-1><abbr-2>Ambul Pediatr</abbr-2></periodical><pages>294-299</pages><volume>8</volume><number>5</number><dates><year>2008</year><pub-dates><date>2008/09</date></pub-dates></dates><publisher>Elsevier BV</publisher><isbn>1530-1567</isbn><urls><related-urls><url>;(110).The success of vaccination programmes was affected by complex factors such as the nature of healthcare provision (e.g. free care or insurance based), education levels, and cultural acceptance of the vaccine. Therefore, national health surveys with information on vaccination status linked with medical and socio-demographic details, (such as that of Spain with data spanning more than two decades PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5KaW3DqW5lei1HYXJjw61hPC9BdXRob3I+PFllYXI+MjAw

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ADDIN EN.CITE.DATA (86-89, 111) can aid in assessing the impact of influenza vaccination, at population level.Simple interventions such as allowing for year-round scheduling of appointments for vaccination can be effective ADDIN EN.CITE <EndNote><Cite><Author>Paul</Author><Year>2006</Year><RecNum>197</RecNum><DisplayText>(112)</DisplayText><record><rec-number>197</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481210247">197</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Paul, Ian M.</author><author>Eleoff, Sara B.</author><author>Shaffer, Michele L.</author><author>Bucher, Ryan M.</author><author>Moyer, Kathleen M.</author><author>Gusic, Maryellen E.</author></authors></contributors><titles><title>Improving Influenza Vaccination Rates for Children Through Year-round Scheduling</title><secondary-title>Ambulatory Pediatrics</secondary-title></titles><periodical><full-title>Ambulatory Pediatrics</full-title><abbr-1>Ambul. Pediatr.</abbr-1><abbr-2>Ambul Pediatr</abbr-2></periodical><pages>230-234</pages><volume>6</volume><number>4</number><dates><year>2006</year><pub-dates><date>2006/07</date></pub-dates></dates><publisher>Elsevier BV</publisher><isbn>1530-1567</isbn><urls><related-urls><url>;(112). Nevertheless, it is likely that only major policy shifts will lead to significantly higher vaccination rates, due to more clear and consistent messaging about the importance and acceptability of influenza vaccination to patients and healthcare workers alike. This is illustrated by the increase in influenza vaccination uptake among children with asthma from 36% (2005–2006) to 50% (2010–2011) after the US Centre for Disease Control and prevention (CDC) advised vaccinating all children, regardless of risk ADDIN EN.CITE <EndNote><Cite ExcludeAuth="1" ExcludeYear="1"><RecNum>235</RecNum><DisplayText>(94)</DisplayText><record><rec-number>235</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481283151">235</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors></contributors><titles><title>Centre for Disease Control and Prevention. Vaccination Coverage Among Persons with Asthma — United States 2010–2011 Influenza Season.</title><secondary-title>MMWR</secondary-title></titles><pages>973–978</pages><volume>62</volume><dates><year>2013</year></dates><urls></urls></record></Cite></EndNote>(94). With its favourable safety and cost-benefit profile PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DYXRlczwvQXV0aG9yPjxZZWFyPjIwMTM8L1llYXI+PFJl

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ADDIN EN.CITE.DATA (12, 113, 114) there is a need for health campaigns to raise awareness amongst the public and clinicians of the benefits of influenza vaccination and to improve implementation of guidelines.4. Immunogenicity of influenza vaccines in asthma There is uncertainty about the level of protection that influenza vaccines afford in people with asthma. Influenza vaccine immunogenicity, a prerequisite for protection, is usually assessed by haemagglutinin inhibition assay (HI) measuring seroprotection rate (percentage of subjects with antibody titres ≥1:40), seroconversion rate (percentage of subjects with ≥4-fold increase in antibody titre), antibody geometric mean titre (GMT), and GMT ratio (GMT post vaccination/GMT pre-vaccination). We identified limited data on influenza vaccine immunogenicity in asthma. Only one study of TIV in children aged 0.5–3 years compared healthy controls to recurrent wheezers. It found good and similar seroconversion and seroprotection rates to all three vaccine strains (H1N1, H3N2, and B) in both groups (after 1 month), with higher pre-and post-vaccination GMTs in children with wheeze, but a higher GMT ratio in healthy controls PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYWU8L0F1dGhvcj48WWVhcj4yMDEzPC9ZZWFyPjxSZWNO

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ADDIN EN.CITE.DATA (115). In children with asthma, TIV and a virosomal inactivated subunit influenza vaccine induced good seroprotection and seroconversion at 1 month in both pre-school and school-age children, with some reduction in GMTs by 6 months PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5QZWRyb3phPC9BdXRob3I+PFllYXI+MjAwOTwvWWVhcj48

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ADDIN EN.CITE.DATA (118). In the latter group and in young children with recurrent wheeze, corticosteroid treatment or dose (I would add corticosteroid treatment and corticosteroid dose to make it clearer) did not influence influenza vaccine immunogenicity PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYWU8L0F1dGhvcj48WWVhcj4yMDEzPC9ZZWFyPjxSZWNO

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ADDIN EN.CITE.DATA (115, 118). 5. Efficacy of influenza vaccines in asthmaData on the efficacy of influenza vaccination in asthma are limited, with only two randomized studies addressing the efficacy of TIV in patients with stable asthma. One study, conducted in Turkey, included 128 adults with asthma who received either TIV or no vaccination PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BYmFkb2dsdTwvQXV0aG9yPjxZZWFyPjIwMDQ8L1llYXI+

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ADDIN EN.CITE.DATA (119). No significant difference in the frequency of upper respiratory tract infections (URTI) or AAE rate was found between vaccinated and non-vaccinated participants; however, this study had significant limitations (see Table 1). In a larger randomized, double-blind, placebo-controlled trial from the Netherlands PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CdWV2aW5nPC9BdXRob3I+PFllYXI+MjAwNDwvWWVhcj48

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ADDIN EN.CITE.DATA (120). In contrast, a conference abstract PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5GYXl5YXogSmFoYW5pPC9BdXRob3I+PFllYXI+MjAxMjwv

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ADDIN EN.CITE.DATA (121) reported significantly lower AAE rates in children <5 years with asthma following TIV (13%) compared with placebo (53%).For LAIV, we found no efficacy data in asthma compared to non-vaccination. A large European multi-center, randomized, open-label trial compared intranasal cold-adapted LAIV to intramuscular TIV in children and adolescents aged 6–17 years with asthma, and reported a 34.7% reduction in culture-con?rmed in?uenza illness after LAIV PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5GbGVtaW5nPC9BdXRob3I+PFllYXI+MjAwNjwvWWVhcj48

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ADDIN EN.CITE.DATA (122). A re-analysis of efficacy data from two randomized, multinational trials PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Bc2hrZW5hemk8L0F1dGhvcj48WWVhcj4yMDA2PC9ZZWFy

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ADDIN EN.CITE.DATA (123, 124) comparing LAIV to TIV, demonstrated that 2–5 year old children with mild-to-moderate asthma or prior wheezing, receiving LAIV had fewer cases of culture-confirmed influenza illness than TIV recipients PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BbWJyb3NlPC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48

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ADDIN EN.CITE.DATA (125).6. Effectiveness of influenza vaccination in asthma While efficacy studies reflect a treatment’s performance in tightly controlled clinical trials, effectiveness studies reflect how well a treatment works in practice and are more representative of real life. Influenza vaccination may be less effective than expected due to differences between the characteristics of patients vaccinated in the general population and those recruited into efficacy trials. Furthermore, the influenza vaccine may not contain the prevalent virus strain, and vaccine coverage may be suboptimal. There are limited data on the effectiveness of influenza vaccination in patients with asthma or high-risk populations that included asthma. Six studies assessed the effectiveness of seasonal influenza vaccines, while one other studied the H1N1 pandemic vaccine PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Lb3NoaW88L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFyPjxS

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ADDIN EN.CITE.DATA (129), while a nested case-control study suggested that influenza vaccination was associated with fewer acute general practice visits for respiratory problems in children with long-term conditions ADDIN EN.CITE <EndNote><Cite><Author>Hak</Author><Year>2005</Year><RecNum>208</RecNum><DisplayText>(130)</DisplayText><record><rec-number>208</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481210247">208</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hak, Eelko</author></authors></contributors><titles><title>Clinical Effectiveness of Influenza Vaccination in Persons Younger Than 65 Years With High-Risk Medical Conditions</title><secondary-title>Archives of Internal Medicine</secondary-title></titles><periodical><full-title>Archives of Internal Medicine</full-title><abbr-1>Arch. Intern. Med.</abbr-1><abbr-2>Arch Intern Med</abbr-2></periodical><pages>274</pages><volume>165</volume><number>3</number><dates><year>2005</year><pub-dates><date>2005/02/14</date></pub-dates></dates><publisher>American Medical Association (AMA)</publisher><isbn>0003-9926</isbn><urls><related-urls><url>;(130). However, another case-control study suggested that vaccination was associated with an increased risk of unscheduled attendance for asthma care ADDIN EN.CITE <EndNote><Cite><Author>Christy</Author><Year>2004</Year><RecNum>27</RecNum><DisplayText>(131)</DisplayText><record><rec-number>27</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481208311">27</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Christy, C</author><author>Aligne, CA</author><author>Auinger, P</author><author>Pulcino, T</author><author>Weitzman, M</author></authors></contributors><titles><title>Effectiveness of influenza vaccine for the prevention of asthma exacerbations</title><secondary-title>Archives of disease in childhood</secondary-title></titles><periodical><full-title>Archives of Disease in Childhood</full-title><abbr-1>Arch. Dis. Child.</abbr-1><abbr-2>Arch Dis Child</abbr-2></periodical><pages>734-735</pages><volume>89</volume><number>8</number><dates><year>2004</year></dates><isbn>1468-2044</isbn><urls></urls></record></Cite></EndNote>(131). In this study, the cases and controls were poorly balanced in terms of ethnicity and likelihood of vaccination in previous years. Although an adjusted analysis was undertaken, this may not have taken into account all the differences between the groups.Only one study focused on adults with asthma PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Lb3NoaW88L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFyPjxS

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ADDIN EN.CITE.DATA (126). In this study, the H1N1 influenza vaccine was found to be protective against influenza in those aged under 61 years, but not in older patients. Also, it did not protect against AAE. Two other studies enrolled adults with long-term ADDIN EN.CITE <EndNote><Cite><Author>Hak</Author><Year>2005</Year><RecNum>208</RecNum><DisplayText>(130)</DisplayText><record><rec-number>208</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481210247">208</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hak, Eelko</author></authors></contributors><titles><title>Clinical Effectiveness of Influenza Vaccination in Persons Younger Than 65 Years With High-Risk Medical Conditions</title><secondary-title>Archives of Internal Medicine</secondary-title></titles><periodical><full-title>Archives of Internal Medicine</full-title><abbr-1>Arch. Intern. Med.</abbr-1><abbr-2>Arch Intern Med</abbr-2></periodical><pages>274</pages><volume>165</volume><number>3</number><dates><year>2005</year><pub-dates><date>2005/02/14</date></pub-dates></dates><publisher>American Medical Association (AMA)</publisher><isbn>0003-9926</isbn><urls><related-urls><url>;(130) or high-risk conditions ADDIN EN.CITE <EndNote><Cite><Author>Herrera</Author><Year>2007</Year><RecNum>207</RecNum><DisplayText>(132)</DisplayText><record><rec-number>207</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481210247">207</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Herrera, Guillermo A.</author><author>Iwane, Marika K.</author><author>Cortese, Margaret</author><author>Brown, Cedric</author><author>Gershman, Ken</author><author>Shupe, Alyson</author><author>Averhoff, Francisco</author><author>Chaves, Sandra S.</author><author>Gargiullo, Paul</author><author>Bridges, Carolyn B.</author></authors></contributors><titles><title>Influenza vaccine effectiveness among 50–64-year-old persons during a season of poor antigenic match between vaccine and circulating influenza virus strains: Colorado, United States, 2003–2004</title><secondary-title>Vaccine</secondary-title></titles><periodical><full-title>Vaccine</full-title><abbr-1>Vaccine</abbr-1><abbr-2>Vaccine</abbr-2></periodical><pages>154-160</pages><volume>25</volume><number>1</number><dates><year>2007</year><pub-dates><date>2007/01</date></pub-dates></dates><publisher>Elsevier BV</publisher><isbn>0264-410X</isbn><urls><related-urls><url>;(132); the first demonstrated a reduction in general practice visits, hospitalization and deaths from respiratory problems, while the second demonstrated a protective effect against influenza and influenza related hospitalization. Asthma was not analysed separately in these studies and it is thus not clear if influenza vaccination was beneficial for people with asthma.A recent systematic review reports a 59-78% reduction in asthma attacks leading to emergency visits and/or hospitalizations after influenza vaccination and a vaccine effectiveness of 45% (95% CI 31 to 56) for laboratory-confirmed influenza in people with asthma based on a metanalysis of two test-negative design case-control studies ADDIN EN.CITE <EndNote><Cite ExcludeAuth="1" ExcludeYear="1"><RecNum>248</RecNum><DisplayText>(133)</DisplayText><record><rec-number>248</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1496656515">248</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors></contributors><titles><title><style face="normal" font="default" size="100%">Vasiliou E. et al Effectiveness of influenza vaccines in asthma: a systematic review and meta-analysis. Clin Infect Dis. </style><style face="italic" font="default" size="100%">In press</style></title></titles><dates></dates><urls></urls></record></Cite></EndNote>(133). 7. Safety of influenza vaccines in asthma Large retrospective and prospective studies have demonstrated the safety of influenza vaccines in children and adults with asthma, for both TIV and LAIV PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DYXN0cm88L0F1dGhvcj48WWVhcj4yMDAxPC9ZZWFyPjxS

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ADDIN EN.CITE.DATA (137).A common concern is the safety of egg-derived influenza vaccines in patients with egg-allergy, a frequent co-morbidity in children with asthma. The last case of anaphylaxis after influenza vaccination occurred more than 25 years ago at a time when the egg content of vaccines was much higher. The ovalbumin content of most current vaccines is less than 1.2 μg/mL, and an egg-free influenza vaccine is also available. Several studies demonstrated that influenza vaccines containing low levels of egg protein (≤1.2mμg/mL) were safe even in egg-allergic patients PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DaHVuZzwvQXV0aG9yPjxZZWFyPjIwMTA8L1llYXI+PFJl

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ADDIN EN.CITE.DATA (144, 145). For 6.6% of children with asthma/recurrent wheeze, the parents reported wheeze within 72 hours of LAIV, but most wheeze episodes only required routine treatment; there was no hospitalization and no increase in respiratory symptoms in the four weeks after LAIV. Based on the robust evidence that influenza vaccines are safe in asthma patients with and without egg allergy, British immunization guidelines ADDIN EN.CITE <EndNote><Cite ExcludeAuth="1" ExcludeYear="1"><RecNum>238</RecNum><DisplayText>(146)</DisplayText><record><rec-number>238</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481284864">238</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors></contributors><titles><title>The Green Book- Immunisation against infectious disease. Chapter 19 – Influenza, 2014. ;(146) now recommend administration of LAIV in the community to children from 2 years of age, including those with asthma, irrespective of egg allergy, unless they have severe or acutely exacerbated asthma (regardless of the egg-allergy status?). US and Canadian guidelines remain more conservative and still suggest that vaccines containing egg proteins (e.g. LAIV) should not be used in children with egg allergy and/or asthma PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Hcm9oc2tvcGY8L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFy

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ADDIN EN.CITE.DATA (147-149).8. Antiviral treatment against influenza in patients with asthmaFor asthma patients with suspected influenza infection, treatment with antiviral medication as early as possible, prior to laboratory confirmation of influenza, is currently recommended PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5OYXRoYW48L0F1dGhvcj48WWVhcj4yMDAxPC9ZZWFyPjxS

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ADDIN EN.CITE.DATA (150-154). Since amantadine and rimantadine are limited by drug resistance, they have been replaced by neuraminidase inhibitors (NI). The currently marketed NIs are zanamivir and oseltamivir. However, post-marketing surveillance has revealed bronchospasm and worsening of lung function in a few cases when asthma patients were treated with zanamivir inhalation PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NY05pY2hvbGw8L0F1dGhvcj48WWVhcj4yMDAxPC9ZZWFy

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ADDIN EN.CITE.DATA (151, 152). Oseltamivir was not associated with any significant respiratory adverse effects and is recommended for treatment and chemoprophylaxis of influenza in children and adults with high-risk chronic conditions, including asthma PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MaW48L0F1dGhvcj48WWVhcj4yMDA2PC9ZZWFyPjxSZWNO

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ADDIN EN.CITE.DATA (156-158). However, large-scale telephone surveys in the USA showed that having asthma, in contrast to diabetes, was not associated with increased rates of antiviral treatment of influenza cases PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CaWdnZXJzdGFmZjwvQXV0aG9yPjxZZWFyPjIwMTQ8L1ll

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ADDIN EN.CITE.DATA (159). Data on the efficacy of NI in asthma patients PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DYXNzPC9BdXRob3I+PFllYXI+MjAwMDwvWWVhcj48UmVj

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ADDIN EN.CITE.DATA (162). A meta-analysis, based on a single RCT, reported improved FEV1 after oral oseltamivir given to children with asthma and influenza infection, but no effects on peak flow or AAEs PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TaHVuLVNoaW48L0F1dGhvcj48WWVhcj4yMDA5PC9ZZWFy

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ADDIN EN.CITE.DATA (164, 165), a finding that is currently controversial. As high rates of resistance limit the effectiveness of the currently available antiviral drugs, new NI (laninamivir, peramivir) and an RNA-dependent RNA polymerase inhibitor (favipiravir) are currently undergoing clinical trials ADDIN EN.CITE <EndNote><Cite><Author>Kohno</Author><Year>2011</Year><RecNum>229</RecNum><DisplayText>(166)</DisplayText><record><rec-number>229</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481210247">229</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kohno, S.</author><author>Kida, H.</author><author>Mizuguchi, M.</author><author>Hirotsu, N.</author><author>Ishida, T.</author><author>Kadota, J.</author><author>Shimada, J.</author></authors></contributors><titles><title>Intravenous Peramivir for Treatment of Influenza A and B Virus Infection in High-Risk Patients</title><secondary-title>Antimicrobial Agents and Chemotherapy</secondary-title></titles><periodical><full-title>Antimicrobial Agents and Chemotherapy</full-title><abbr-1>Antimicrob. Agents Chemother.</abbr-1><abbr-2>Antimicrob Agents Chemother</abbr-2><abbr-3>Antimicrobial Agents &amp; Chemotherapy</abbr-3></periodical><pages>2803-2812</pages><volume>55</volume><number>6</number><dates><year>2011</year><pub-dates><date>2011/04/04</date></pub-dates></dates><publisher>American Society for Microbiology</publisher><isbn>0066-4804&#xD;1098-6596</isbn><urls><related-urls><url>;(166). Laninamivir showed similar efficacy and safety to oseltamivir in the treatment of influenza in asthma patients ADDIN EN.CITE <EndNote><Cite><Author>Watanabe</Author><Year>2013</Year><RecNum>16</RecNum><DisplayText>(167)</DisplayText><record><rec-number>16</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481208311">16</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Watanabe, A.</author></authors></contributors><titles><title>A randomized double-blind controlled study of laninamivir compared with oseltamivir for the treatment of influenza in patients with chronic respiratory diseases</title><secondary-title>Journal of Infection and Chemotherapy</secondary-title></titles><pages>89-97</pages><volume>19</volume><number>1</number><keywords><keyword>Antiviral Agents [adverse effects] [therapeutic use]</keyword><keyword>Asthma [complications]</keyword><keyword>Chronic Disease</keyword><keyword>Double-Blind Method</keyword><keyword>Enzyme Inhibitors [therapeutic use]</keyword><keyword>Influenza A Virus, H1N1 Subtype [drug effects]</keyword><keyword>Influenza, Human [drug therapy] [virology]</keyword><keyword>Neuraminidase [antagonists &amp; inhibitors]</keyword><keyword>Oseltamivir [adverse effects] [therapeutic use]</keyword><keyword>Treatment Outcome</keyword><keyword>Zanamivir [adverse effects] [analogs &amp; derivatives] [therapeutic use]</keyword><keyword>Adult[checkword]</keyword><keyword>Aged[checkword]</keyword><keyword>Female[checkword]</keyword><keyword>Humans[checkword]</keyword><keyword>Male[checkword]</keyword><keyword>Middle Aged[checkword]</keyword><keyword>Sr-airways</keyword></keywords><dates><year>2013</year></dates><accession-num>CN-00844191</accession-num><work-type>Randomized Controlled Trial; Research Support, Non-U.S. Gov&apos;t</work-type><urls><related-urls><url> 22907567</custom3><electronic-resource-num>10.1007/s10156-012-0460-1</electronic-resource-num></record></Cite></EndNote>(167).9. ConclusionsWe observed significant variation in the reported rates of influenza detection among AAE episodes in both children and adults, with higher rates observed in the latter age group. This may be attributed to major differences in inclusion criteria, disease definitions, virus detection methodology, small population sizes and the limited number of available studies. Therefore, it is presently unclear to what degree influenza causes exacerbation of underlying asthma. All European Union countries currently recommend influenza vaccination of people with asthma, with TIV being the most widely used vaccine. Nonetheless, vaccination coverage varies between regions, and is significantly lower among children with asthma. Several factors and misbeliefs have been shown to predict non-adherence to influenza vaccination, while healthcare worker endorsement highly promotes vaccination. Major policy shifts and health campaigns may help in raising awareness and improve guideline implementation.The limited immunogenicity data suggest that good seroprotection and seroconversion can be achieved in children and adults with asthma. However, higher vaccine doses may be required in elderly patients. Available studies suggest increased efficacy of LAIV in reducing influenza illness in children/adolescents with asthma compared to TIV, but do not provide evidence of efficacy of TIV in reducing influenza illness in asthmatics concurring with a recent systematic review PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DYXRlczwvQXV0aG9yPjxZZWFyPjIwMTM8L1llYXI+PFJl

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ADDIN EN.CITE.DATA (12). There are some limited data to suggest that influenza vaccination reduces asthma-related morbidity in children in real-life settings, as has been concluded in another recent systematic review ADDIN EN.CITE <EndNote><Cite ExcludeAuth="1" ExcludeYear="1"><RecNum>248</RecNum><DisplayText>(133)</DisplayText><record><rec-number>248</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1496656515">248</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors></contributors><titles><title><style face="normal" font="default" size="100%">Vasiliou E. et al Effectiveness of influenza vaccines in asthma: a systematic review and meta-analysis. Clin Infect Dis. </style><style face="italic" font="default" size="100%">In press</style></title></titles><dates></dates><urls></urls></record></Cite></EndNote>(133). The only data to suggest that vaccination may have a beneficial impact in adults with asthma are from studies of patients with long-term or high-risk conditions, not just asthma. The effectiveness outcomes of these studies are difficult to interpret due to lack of an agreed definition for asthma and/or influenza, and insufficient information on the type of vaccination used. Lack of randomization is also a limitation, as differences in the characteristics of those who do and do not receive the vaccine, such as disease severity and socioeconomic status, may independently impact on the likelihood of asthma morbidity, and analyses may not control for all these differences. Despite these limitations, population-based effectiveness studies are the only way to assess the impact of vaccination in real-life healthcare settings. Inactivated influenza vaccines appear to be safe for people with asthma, and, provided they have low egg protein content (≤1.2 μg/mL), also for those with egg allergy. LAIV is also safe in asthma and egg allergy with the exception of severe or acutely exacerbated asthma, where LAIV cannot be given. Oseltamivir is the NI that is currently used in asthma. Although it has moderately beneficial effects on influenza illness in healthy people, there are insufficient data to determine its efficacy and effectiveness in people with asthma. However, novel NIs are currently in development. 10. Recommendations and future needsPeople with asthma are at high risk of more severe forms of influenza, with increased hospitalization and admission at healthcare facilities, therefore:Education campaigns for both the general population and healthcare providers are needed to promote an increase in annual influenza vaccination, early case recognition and consideration of early empirical antiviral therapy, and to reduce influenza-attributable healthcare utilization among asthmatics.Large cohort and case control studies using standardized definitions (for AAE), sensitive influenza detection methods, such as PCR, and comprehensive assessment of respiratory pathogens are necessary in both children and adults with asthma. There is a need to develop more internationally co-ordinated registries, e.g. for Europe, that accurately collate vaccination status along with medical and socio-demographic details to assess the impact of public health interventions over time. Multiple sources of data must be used to record vaccination status (e.g. self-reported as well as medical notes, vaccination card or billing data). Targeted vaccination of children and at risk groups is needed.Further studies of influenza vaccine immunogenicity, comparing healthy and asthmatic populations, are required to determine if people with asthma have normal influenza vaccine responses or if they require influenza vaccines with enhanced immunogenicity. The discovery and development of improved immune correlates of protection against influenza will enable more meaningful testing of vaccine immunogenicity. In view of the uncertainty around the degree of protection that influenza vaccination affords in people of all ages with asthma, further efficacy data need to be collected in this population. Data should be stratified by age and asthma severity, using adequately powered, randomised, placebo-controlled trials that compare both TIV and LAIV to non-vaccinated controls. Further studies are needed to evaluate the effectiveness of influenza vaccination in patients with asthma, but must be designed to minimize any risk of bias. Safety data in asthma with and without egg allergy are required for new influenza vaccines, and, depending on egg protein content, for new LAIV batches.There is a need to collect more safety data on zanamivir in patients with chronic respiratory disease, and efficacy data on oseltamivir in children with asthma. Development and testing of new anti-influenza drugs among asthmatics is needed. References ADDIN EN.REFLIST 1.Global Atlas of Asthma. Published by the European Academy of Allergy and Clinical Immunology. Editors: Cezmi A. Akdis, Ioana Agache, 2013.2.ERS: The European Lung White Book 2003.3.Darveaux JI, Lemanske RF. Infection-Related Asthma. Journal of Allergy and Clinical Immunology: In Practice 2014;2(6):658-663.4.Edwards MR, Bartlett NW, Hussell T, Openshaw P, Johnston SL. The microbiology of asthma. 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Post-licensure surveillance of quadrivalent live attenuated influenza vaccine United States, Vaccine Adverse Event Reporting System (VAERS), July 2013-June 2014. Vaccine 2015;33(16):1987-1992.193.Biggerstaff M, Jhung M, Reed C, Garg S, Balluz L, Fry A, et al. Impact of medical and behavioural factors on influenza-like illness, healthcare-seeking, and antiviral treatment during the 2009 H1N1 pandemic: USA, 2009–2010. Epidemiol Infect 2014;142(01):114-125.AcknowledgementsWe thank Dr Ron Hogg (OmniScience SA, Geneva, Switzerland) for his excellent medical writing services and ADME Osterhaus (affiliation) for his endorsement of this review as the chair of the European Scientific Working group on Influenza (ESWI). The work was supported by the European Academy of Allergy and Clinical Immunology (EAACI).Author contributionsAll authors are members of the EAACI Influenza and Asthma Task Force. Skevaki and Schwarze conceived and designed the study. Aziz Sheikh developed the search protocol. Ather Akhlaq, Ulugbek Nurmatov performed the systematic literature search, reviewed and selected the relevant publications. All authors except the former three performed data extraction, compiled the summary tables, contributed to interpretation of results and contributed to writing the first draft of the manuscript, which was reviewed by Skevaki and Schwarze and then revised by all authors. All authors approved the final version of the manuscript.Table 1. Studies included in the systematic review, by sectionSection 2a. Influenza-attributable health care utilization in asthma patients Authors, YearCountryStudy PeriodType of studyInterventionOutcome measureKey findingPopulation characteristicsLimitations/ commentsChacon et al. 2015 ADDIN EN.CITE <EndNote><Cite><Author>Chacon</Author><Year>2015</Year><RecNum>1</RecNum><DisplayText>(168)</DisplayText><record><rec-number>1</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481208311">1</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Chacon, Rafael</author><author>Mirza, Sara</author><author>Rodriguez, David</author><author>Paredes, Antonio</author><author>Guzman, Giselle</author><author>Moreno, Lourdes</author><author>Then, Cecilia J</author><author>Jara, Jorge</author><author>Blanco, Natalia</author><author>Bonilla, Luis</author></authors></contributors><titles><title>Demographic and clinical characteristics of deaths associated with influenza A (H1N1) pdm09 in Central America and Dominican Republic 2009–2010</title><secondary-title>BMC public health</secondary-title></titles><periodical><full-title>BMC Public Health</full-title><abbr-1>BMC Public Health</abbr-1><abbr-2>BMC Public Health</abbr-2></periodical><pages>734</pages><volume>15</volume><number>1</number><dates><year>2015</year></dates><isbn>1471-2458</isbn><urls></urls></record></Cite></EndNote>(168)Guatemala May 2009 - June 2010Epidemiological retrospective studyNADemographic and clinical characteristics of deaths associated with influenza A (H1N1) pdm09.History of Asthma in 11% of the 112 dead patients with a pre-existing medical condition (7% children < 5 years, 11% people aged 5-59, 16% people aged 60+ and 18% of the 14 dead pregnant or postpartum women)183 children and adults aged 0-60+ years. 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ADDIN EN.CITE.DATA (43)USA2003-2009 (seasonal)2009-2010 (H1N1)Epidemiological retrospective, population-based studyNAFrequency and severity of influenza complications in hospitalized children.History of asthma in 31% of children hospitalized for seasonal influenza vs. 42% in children hospitalized for influenza A (H1N1).Asthma exacerbation as a complication in 27% of children with influenza A vs. 18% in children with seasonal influenza (overall, 22% of total).6769 children and adolescents aged <18 years hospitalized for both seasonal and H1N1 influenza.Hagerman et al. 2015 ADDIN EN.CITE <EndNote><Cite><Author>Hagerman</Author><Year>2015</Year><RecNum>3</RecNum><DisplayText>(169)</DisplayText><record><rec-number>3</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481208311">3</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hagerman, Andrés</author><author>Posfay Barbe, Klara Maria</author><author>Duppenthaler, Andrea</author><author>Heininger, Ulrich</author><author>Berger, Christoph</author><author>The, Pigs Influenza Study Group</author></authors></contributors><titles><title>Clinical characteristics and outcomes in children hospitalised with pandemic influenza A/H1N1/09 virus infection–a nationwide survey by the Pediatric Infectious Diseases Group of Switzerland</title><secondary-title>Swiss medical weekly</secondary-title></titles><periodical><full-title>Swiss Medical Weekly</full-title><abbr-1>Swiss Med. Wkly.</abbr-1><abbr-2>Swiss Med Wkly</abbr-2></periodical><pages>w14171</pages><volume>145</volume><dates><year>2015</year></dates><isbn>1424-7860</isbn><urls></urls></record></Cite></EndNote>(169)SwitzerlandJune 2009 - Jan 2010Prospective/ retrospective study performed in 11 hospitalsNAClinical characteristics of the influenza-hospitalized children.Asthma 12% among the comorbidities of the 126 influenza-hospitalized children.326 patients aged ≤18 years (189 <5 years; 126 with comorbidities hospitalized in eleven children’s hospitals in Switzerland with a positive influenza A/H1N1/09 RT-PCR from a nasopharyngeal specimen.Study performed in 11 hospitals in Switzerland.Jiang et al. 2015 ADDIN EN.CITE <EndNote><Cite><Author>Jiang</Author><Year>2015</Year><RecNum>4</RecNum><DisplayText>(65)</DisplayText><record><rec-number>4</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481208311">4</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Jiang, H</author><author>Yu, D</author><author>Ruan, F</author><author>Xu, W</author><author>Huang, T</author><author>Li, L</author><author>Wang, K</author><author>Liu, S</author><author>Zhang, H</author><author>Jia, P</author></authors></contributors><titles><title>Clinical characteristics of adult influenza inpatients in ten provinces in China and analysis of severe risk factors</title><secondary-title>Zhonghua liuxingbingxue zazhi</secondary-title></titles><pages>216-221</pages><volume>36</volume><number>3</number><dates><year>2015</year></dates><isbn>0254-6450</isbn><urls></urls></record></Cite></EndNote>(65)ChinaDec 2008 - June 2014Epidemiological retrospective studyNAClinical characteristics and severe case risk factors for adult inpatient cases of confirmed influenza. Out of the 240 (7.8%) cases of laboratory-confirmed influenza, (H1N, pdm2009 and H3N2), asthma was the most important risk factor for severe cases (RR = 15.200, 95% CI: 1.157-199.633).240 adults aged ≥15 years consistent with?SARI?case definition who were monitored by?SARI?sentinel hospitals in ten cities in China.Data extrapolated from abstract in English. Study performed in ten provinces of China.Kwon et al. 2014 ADDIN EN.CITE <EndNote><Cite><Author>Kwon</Author><Year>2014</Year><RecNum>5</RecNum><DisplayText>(170)</DisplayText><record><rec-number>5</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481208311">5</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kwon, Jang-Mi</author><author>Shim, Jae Won</author><author>Kim, Deok Soo</author><author>Jung, Hye Lim</author><author>Park, Moon Soo</author><author>Shim, Jung Yeon</author></authors></contributors><titles><title>Prevalence of respiratory viral infection in children hospitalized for acute lower respiratory tract diseases, and association of rhinovirus and influenza virus with asthma exacerbations</title><secondary-title>Korean journal of pediatrics</secondary-title></titles><periodical><full-title>Korean Journal of Pediatrics</full-title><abbr-1>Korean J. Pediatr.</abbr-1><abbr-2>Korean J Pediatr</abbr-2></periodical><pages>29-34</pages><volume>57</volume><number>1</number><dates><year>2014</year></dates><isbn>1738-1061</isbn><urls></urls></record></Cite></EndNote>(170)South KoreaMay 2010 -Apr 2011Retrospective studyNAPrevalence of year-round respiratory viral infection in children with LRTI and the relationship between respiratory viral infection and allergen sensitization in exacerbating asthma.Influenza virus was detected in 7 (25%) of the 28 asthma patients hospitalized for asthma exacerbation.18 asthmatics (64.3%) had atopic sensitization.Influenza virus responsible for asthma exacerbations with an OR 11.9 (1.5-90.4) for atopic asthma), 0.9 (0.1-12.3) for non-atopic asthma, 4.0 (1.2-13.8) for asthma in general.309 children (median age 26 months) who were hospitalized for acute LRTIs (pneumonia, bronchitis, bronchiolitis or asthma).Park et al. 2013 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5QYXJrPC9BdXRob3I+PFllYXI+MjAxMzwvWWVhcj48UmVj

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ADDIN EN.CITE.DATA (171)South KoreaJan - Dec 2009Multi-site case-control studyNAAssociation of asthma status and severity of H1N1 influenza in adults.Of the 91 cases, 12(13%) and 3 of 54 controls (5%) were asthmatics (p=NS); of those without other comorbidities except asthma, 8 of 56 cases (14%) and 2 of 49 (4%) controls had asthma (p=NS).91 cases (47.3±21.1 years) with a positive PCR for H1N1 influenza and were admitted to the ICU or general ward with a diagnosis of H1N1 influenza.56 controls (45.0±20.6 years) with a positive PCR for H1N1 influenza, but were not admitted to hospitals.Placzek et al. 2014 ADDIN EN.CITE <EndNote><Cite><Author>Placzek</Author><Year>2014</Year><RecNum>7</RecNum><DisplayText>(172)</DisplayText><record><rec-number>7</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481208311">7</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Placzek, Hilary ED</author><author>Madoff, Lawrence C</author></authors></contributors><titles><title>Association of age and comorbidity on 2009 influenza A pandemic H1N1-related intensive care unit stay in Massachusetts</title><secondary-title>American journal of public health</secondary-title></titles><periodical><full-title>American Journal of Public Health</full-title><abbr-1>Am. J. Public Health</abbr-1><abbr-2>Am J Public Health</abbr-2></periodical><pages>e118-e125</pages><volume>104</volume><number>11</number><dates><year>2014</year></dates><isbn>1541-0048</isbn><urls></urls></record></Cite></EndNote>(172)USAOct 2008 - Apr 2009 (seasonal influenza)Apr 2009 -Sept 2009 (H1N1)Epidemiological retrospective studyNAAssociation of age and comorbidity on 2008-2009 seasonal influenza and 2009 Influenza A (H1N1)-related ICU stay.Asthma was the most prevalent risk factor for hospitalization, occurring in 28% (n=148) of the pH1N1 population, and 24% (n=174) of those with seasonal influenza.1254 children and adults aged <5-64 years with seasonal and H1N1 influenza admitted to an ICU.Stripeli et al. 2015 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TdHJpcGVsaTwvQXV0aG9yPjxZZWFyPjIwMTU8L1llYXI+

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ADDIN EN.CITE.DATA (173)GreeceOct 2009 - Feb 2010 andJan 2011 - May 2011 (pH1N1)2002 -2003 and 2004 -2005 (Influenza A)Epidemiological retrospective studyNAEpidemiological and clinical characteristics of children hospitalized with pH1N1 compared with those of children hospitalized with seasonal influenza A in previous years.Asthma was the most common underlying illness in both cohorts, but it was considerably more prevalent in the seasonal influenza group (19% vs. 7%; P=0.048).146 children with pH1N1 aged 0-14 years and 138 children with seasonal influenza aged 6 months-14 years who were hospitalized for both pH1N1 and influenza A.Taha 2014 ADDIN EN.CITE <EndNote><Cite><Author>Taha</Author><Year>2014</Year><RecNum>9</RecNum><DisplayText>(51)</DisplayText><record><rec-number>9</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481208311">9</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Taha, Inass</author></authors></contributors><titles><title>Characteristics of pregnant Women admitted with 2009 H1N1 Influenza in a referral maternity hospital at Al-Madinah, Saudi Arabia</title><secondary-title>Egyptian Journal of Hospital Medicine (July 2013)</secondary-title></titles><pages>650-657</pages><volume>52</volume><dates><year>2014</year></dates><urls></urls></record></Cite></EndNote>(51)Saudi ArabiaJune 2009 - Feb 2010Retrospective cohort studyNACharacteristics of pregnant Women admitted with 2009 H1N1 Influenza in a referral maternity hospital.Bronchial asthma was present in 15 (45.5%) of pregnant women admitted with influenza.33 pregnant women; mean age 27.7±5.6 years.Tam et al. 2014 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5UYW08L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFyPjxSZWNO

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ADDIN EN.CITE.DATA (69)BrazilNDRetrospective NALaboratory confirmed IFV/ culture and IFA0.0% (0)36 children aged 2-14 yearsThumerelle et al. 2003 ADDIN EN.CITE <EndNote><Cite><Author>Thumerelle</Author><Year>2003</Year><RecNum>154</RecNum><DisplayText>(77)</DisplayText><record><rec-number>154</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481210247">154</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Thumerelle, C.</author><author>Deschildre, A.</author><author>Bouquillon, C.</author><author>Santos, C.</author><author>Sardet, A.</author><author>Scalbert, M.</author><author>Delbecque, L.</author><author>Debray, P.</author><author>Dewilde, A.</author><author>Turck, D.</author><author>Leclerc, F.</author></authors></contributors><titles><title>Role of viruses and atypical bacteria in exacerbations of asthma in hospitalized children: A prospective study in the Nord-Pas de Calais region (France)</title><secondary-title>Pediatric Pulmonology</secondary-title></titles><periodical><full-title>Pediatric Pulmonology</full-title><abbr-1>Pediatr. Pulmonol.</abbr-1><abbr-2>Pediatr Pulmonol</abbr-2></periodical><pages>75-82</pages><volume>35</volume><number>2</number><dates><year>2003</year><pub-dates><date>2003/01/13</date></pub-dates></dates><publisher>Wiley-Blackwell</publisher><isbn>8755-6863&#xD;1099-0496</isbn><urls><related-urls><url>;(77)France 1 Oct 1998 - 30 June 1999ProspectiveNALaboratory confirmed IFV/IFA, serology or both 3.6% (3) 82 inpatients aged 2-16 yearsBiscardi et al. 2004 ADDIN EN.CITE <EndNote><Cite><Author>Biscardi</Author><Year>2004</Year><RecNum>155</RecNum><DisplayText>(80)</DisplayText><record><rec-number>155</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481210247">155</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Biscardi, S.</author><author>Lorrot, M.</author><author>Marc, E.</author><author>Moulin, F.</author><author>Boutonnat-Faucher, B.</author><author>Heilbronner, C.</author><author>Iniguez, J. L.</author><author>Chaussain, M.</author><author>Nicand, E.</author><author>Raymond, J.</author><author>Gendrel, D.</author></authors></contributors><titles><title>Mycoplasma pneumoniae and Asthma in Children</title><secondary-title>Clinical Infectious Diseases</secondary-title></titles><periodical><full-title>Clinical Infectious Diseases</full-title><abbr-1>Clin. Infect. Dis.</abbr-1><abbr-2>Clin Infect Dis</abbr-2></periodical><pages>1341-1346</pages><volume>38</volume><number>10</number><dates><year>2004</year><pub-dates><date>2004/05/15</date></pub-dates></dates><publisher>Oxford University Press (OUP)</publisher><isbn>1058-4838&#xD;1537-6591</isbn><urls><related-urls><url>;(80)France1 Jan 1999 - 30 June 2001ProspectiveNALaboratory confirmed IFV/culture and IFA 3.4% (4)119 inpatients aged 2-15 years0.0% (0)51 first episode (initial asthma)Bueving et al. 2004 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CdWV2aW5nPC9BdXRob3I+PFllYXI+MjAwNDwvWWVhcj48

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ADDIN EN.CITE.DATA (75)Netherlands1999-2001Double-blind, randomized, placebo-controlled trialInactivated influenza vaccine vs placeboLaboratory confirmed IFV/ culture, IFA and RT-PCR 7.2% (17)235 children aged 6-18 yearsLow number of IFV positive samples in first season-compensated by recruitment of higher number of subjects in second seasonJohnston et al. 2005 ADDIN EN.CITE <EndNote><Cite><Author>Johnston</Author><Year>2005</Year><RecNum>157</RecNum><DisplayText>(73)</DisplayText><record><rec-number>157</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481210247">157</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Johnston, Neil W.</author><author>Johnston, Sebastian L.</author><author>Duncan, Joanne M.</author><author>Greene, Justina M.</author><author>Kebadze, Tatiana</author><author>Keith, Paul K.</author><author>Roy, Madan</author><author>Waserman, Susan</author><author>Sears, Malcolm R.</author></authors></contributors><titles><title>The September epidemic of asthma exacerbations in children: A search for etiology</title><secondary-title>Journal of Allergy and Clinical Immunology</secondary-title></titles><periodical><full-title>Journal of Allergy and Clinical Immunology</full-title><abbr-1>J. Allergy Clin. Immunol.</abbr-1><abbr-2>J Allergy Clin Immunol</abbr-2><abbr-3>Journal of Allergy &amp; Clinical Immunology</abbr-3></periodical><pages>132-138</pages><volume>115</volume><number>1</number><dates><year>2005</year><pub-dates><date>2005/01</date></pub-dates></dates><publisher>Elsevier BV</publisher><isbn>0091-6749</isbn><urls><related-urls><url>;(73)Canada10-30 Sept 2001ProspectiveNALaboratory confirmed IFV/PCR 0.0% (0) 52 children aged 5-15 yearsKetsuriani et al. 2007 ADDIN EN.CITE <EndNote><Cite><Author>Khetsuriani</Author><Year>2007</Year><RecNum>158</RecNum><DisplayText>(74)</DisplayText><record><rec-number>158</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481210247">158</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Khetsuriani, Nino</author><author>Kazerouni, N. Neely</author><author>Erdman, Dean D.</author><author>Lu, Xiaoyan</author><author>Redd, Stephen C.</author><author>Anderson, Larry J.</author><author>Teague, W. Gerald</author></authors></contributors><titles><title>Prevalence of viral respiratory tract infections in children with asthma</title><secondary-title>Journal of Allergy and Clinical Immunology</secondary-title></titles><periodical><full-title>Journal of Allergy and Clinical Immunology</full-title><abbr-1>J. Allergy Clin. Immunol.</abbr-1><abbr-2>J Allergy Clin Immunol</abbr-2><abbr-3>Journal of Allergy &amp; Clinical Immunology</abbr-3></periodical><pages>314-321</pages><volume>119</volume><number>2</number><dates><year>2007</year><pub-dates><date>2007/02</date></pub-dates></dates><publisher>Elsevier BV</publisher><isbn>0091-6749</isbn><urls><related-urls><url>;(74)USAMar 2003 - Feb 2004 ProspectiveNALaboratory confirmed IFV/PCR 0.0% (0) 65 children aged 2-17 yearsModest sample sizeMiller et al. 2008 ADDIN EN.CITE <EndNote><Cite><Author>Miller</Author><Year>2008</Year><RecNum>116</RecNum><DisplayText>(57)</DisplayText><record><rec-number>116</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481209720">116</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Miller, E Kathryn</author><author>Griffin, Marie R</author><author>Edwards, Kathryn M</author><author>Weinberg, Geoffrey A</author><author>Szilagyi, Peter G</author><author>Staat, Mary A</author><author>Iwane, Marika K</author><author>Zhu, Yuwei</author><author>Hall, Caroline B</author><author>Fairbrother, Gerry</author></authors></contributors><titles><title>Influenza burden for children with asthma</title><secondary-title>Pediatrics</secondary-title></titles><periodical><full-title>Pediatrics</full-title><abbr-1>Pediatrics</abbr-1><abbr-2>Pediatrics</abbr-2></periodical><pages>1-8</pages><volume>121</volume><number>1</number><dates><year>2008</year></dates><isbn>0031-4005</isbn><urls></urls></record></Cite></EndNote>(57)USA2002-2004Prospective NALaboratory confirmed IFV/PCR or culture15.5% (38) 245 outpatients3.7% (19) 513 inpatients aged 6-59 months Vallet et al. 2009 ADDIN EN.CITE <EndNote><Cite><Author>Vallet</Author><Year>2009</Year><RecNum>160</RecNum><DisplayText>(78)</DisplayText><record><rec-number>160</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481210247">160</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Vallet, Christelle</author><author>Pons-Catalano, Charlotte</author><author>Mandelcwajg, Alexis</author><author>Wang, Andrew</author><author>Raymond, Josette</author><author>Lebon, Pierre</author><author>Gendrel, Dominique</author></authors></contributors><titles><title>Human Bocavirus: A Cause of Severe Asthma Exacerbation in Children</title><secondary-title>Journal of Pediatrics</secondary-title></titles><periodical><full-title>Journal of Pediatrics</full-title><abbr-1>J. Pediatr.</abbr-1><abbr-2>J Pediatr</abbr-2></periodical><pages>286-288</pages><volume>155</volume><number>2</number><dates><year>2009</year><pub-dates><date>2009/08</date></pub-dates></dates><publisher>Elsevier BV</publisher><isbn>0022-3476</isbn><urls><related-urls><url>;(78)France1 Oct 2005 - 30 Nov 2007ProspectiveNALaboratory confirmed IFV/IFA 2.4% (4) 166 inpatients aged 2-15 yearsKwon et al. 2013 ADDIN EN.CITE <EndNote><Cite><Author>Kwon</Author><Year>2014</Year><RecNum>5</RecNum><DisplayText>(170)</DisplayText><record><rec-number>5</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481208311">5</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kwon, Jang-Mi</author><author>Shim, Jae Won</author><author>Kim, Deok Soo</author><author>Jung, Hye Lim</author><author>Park, Moon Soo</author><author>Shim, Jung Yeon</author></authors></contributors><titles><title>Prevalence of respiratory viral infection in children hospitalized for acute lower respiratory tract diseases, and association of rhinovirus and influenza virus with asthma exacerbations</title><secondary-title>Korean journal of pediatrics</secondary-title></titles><periodical><full-title>Korean Journal of Pediatrics</full-title><abbr-1>Korean J. Pediatr.</abbr-1><abbr-2>Korean J Pediatr</abbr-2></periodical><pages>29-34</pages><volume>57</volume><number>1</number><dates><year>2014</year></dates><isbn>1738-1061</isbn><urls></urls></record></Cite></EndNote>(170)KoreaApr 2010 -Apr 2011ProspectiveNALaboratory confirmed IFV/RT-PCR25.0% (7)28 inpatients aged 60±34 months (Mean±SD)Modest sample size, selection of the study population, short duration (1 year) of the study, single medical center, and subjects were limited to children with LRTIs severe enough to require hospitalization.Mandelcwajg et al. 2010 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NYW5kZWxjd2FqZzwvQXV0aG9yPjxZZWFyPjIwMTA8L1ll

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ADDIN EN.CITE.DATA (76)FranceNov 2005 -Mar 2009RetrospectiveNALaboratory confirmed IFV/ IFA14.0% (15) 107 outpatients2.6% (6) 232 inpatients aged 1.5-15 yearsADULTSWark et al. 2001 ADDIN EN.CITE <EndNote><Cite><Author>Wark</Author><Year>2001</Year><RecNum>162</RecNum><DisplayText>(66)</DisplayText><record><rec-number>162</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481210247">162</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Wark, P. A. B.</author><author>Johnston, S. L.</author><author>Moric, I.</author><author>Simpson, J. L.</author><author>Hensley, M. J.</author><author>Gibson, P. G.</author></authors></contributors><titles><title>Neutrophil degranulation and cell lysis is associated with clinical severity in virus-induced asthma</title><secondary-title>European Respiratory Journal</secondary-title></titles><periodical><full-title>European Respiratory Journal</full-title><abbr-1>Eur. Respir. J.</abbr-1><abbr-2>Eur Respir J</abbr-2></periodical><pages>68-75</pages><volume>19</volume><number>1</number><dates><year>2001</year><pub-dates><date>2001/01/01</date></pub-dates></dates><publisher>European Respiratory Society (ERS)</publisher><isbn>0903-1936&#xD;1399-3003</isbn><urls><related-urls><url>;(66) Australia/UK2 Feb - 1 Dec 1998ProspectiveNALaboratory confirmed IFV/RT-PCR, serology, culture and IFA24% (12)49 outpatients aged 16-74 years Simpson et al. 2003 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TaW1wc29uPC9BdXRob3I+PFllYXI+MjAwMzwvWWVhcj48

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ADDIN EN.CITE.DATA (68)Australia/UKNDProspectiveNALaboratory confirmed IFV/PCR or serology or IFA PCR screening: 24.0% (12) Serology screening: 18.4% (9) IFA screening: 2.0% (1) 49 inpatients aged 16-74 yearsTan et al. 2003 ADDIN EN.CITE <EndNote><Cite><Author>Tan</Author><Year>2003</Year><RecNum>115</RecNum><DisplayText>(72)</DisplayText><record><rec-number>115</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481209720">115</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Tan, Wan C</author><author>Xiang, Xueyu</author><author>Qiu, Diwen</author><author>Ng, Tze Pin</author><author>Lam, Sin F</author><author>Hegele, Richard G</author></authors></contributors><titles><title>Epidemiology of respiratory viruses in patients hospitalized with near-fatal asthma, acute exacerbations of asthma, or chronic obstructive pulmonary disease</title><secondary-title>The American Journal of Medicine</secondary-title></titles><pages>272-277</pages><volume>115</volume><number>4</number><dates><year>2003</year></dates><isbn>0002-9343</isbn><urls></urls></record></Cite></EndNote>(72)SingaporeNDProspectiveNALaboratory confirmed IFV/RT-PCR, dot blot and DIG-probe hybridization20.7% (6)29 inpatients aged 42±15 years (Mean±SD)Uneven sex distribution (prevalence of females in acute asthma group).Iikura et al. 2014 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5JaWt1cmE8L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFyPjxS

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ADDIN EN.CITE.DATA (70)JapanMay 2011-Dec 2012ProspectiveNALaboratory confirmed IFV/RT-PCR10.0% (5)50 inpatients aged 28-92 yearsAlthough 98% of patients had a common cold history receding their AAE, a pathogen was detected from nasopharyngeal swabs in only 70% of cases. Overall, 15 major viruses and 6 major bacteria were evaluated by multiplex PCR analysis. It is possible that other minor pathogens may be involved in AAE. Other potential reasons for the low yield include inappropriate timing of sampling, lower respiratory tract infections, misinterpretation of allergic rhinitis symptoms, and single testing upon admission.Teichtal et al. 1997 ADDIN EN.CITE <EndNote><Cite><Author>Teichtahl</Author><Year>1997</Year><RecNum>164</RecNum><DisplayText>(71)</DisplayText><record><rec-number>164</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481210247">164</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Teichtahl, Harry</author><author>Buckmaster, Nicholas</author><author>Pertnikovs, Eric</author></authors></contributors><titles><title>The Incidence of Respiratory Tract Infection in Adults Requiring Hospitalization for Asthma</title><secondary-title>Chest</secondary-title></titles><periodical><full-title>Chest</full-title><abbr-1>Chest</abbr-1><abbr-2>Chest</abbr-2></periodical><pages>591-596</pages><volume>112</volume><number>3</number><dates><year>1997</year><pub-dates><date>1997/09</date></pub-dates></dates><publisher>Elsevier BV</publisher><isbn>0012-3692</isbn><urls><related-urls><url>;(71)AustraliaAug 1993-July 1994ProspectiveNALaboratory confirmed IFV/Culture and serology 19.0% (15)79 inpatients aged 16-66 yearsAtmar et al. 1998 ADDIN EN.CITE <EndNote><Cite><Author>Atmar</Author><Year>1998</Year><RecNum>165</RecNum><DisplayText>(67)</DisplayText><record><rec-number>165</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481210247">165</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Atmar, Robert L.</author><author>Guy, Elizabeth</author><author>Guntupalli, Kalpalatha K.</author><author>Zimmerman, Janice L.</author><author>Bandi, Venkata D.</author><author>Baxter, Barbara D.</author><author>Greenberg, Stephen B.</author></authors></contributors><titles><title>Respiratory Tract Viral Infections in Inner-City Asthmatic Adults</title><secondary-title>Archives of Internal Medicine</secondary-title></titles><periodical><full-title>Archives of Internal Medicine</full-title><abbr-1>Arch. Intern. Med.</abbr-1><abbr-2>Arch Intern Med</abbr-2></periodical><pages>2453</pages><volume>158</volume><number>22</number><dates><year>1998</year><pub-dates><date>1998/12/07</date></pub-dates></dates><publisher>American Medical Association (AMA)</publisher><isbn>0003-9926</isbn><urls><related-urls><url>;(67)USA6 Dec 1991-3 May 1994Prospective NALaboratory confirmed IFV/Culture, serology and RT-PCR 37.9% (11)29 inpatients aged 19-50 years9 Dec 1992-31 May 1993Cross-sectional9.8% (12)122 outpatients aged 17-77 years*as reported in the original article3a. Current influenza vaccine recommendations for people with asthmaAuthors, yearCountryStudy PeriodType of studyInterventionOutcome measureKey findingsPopulation characteristicsLimitations/commentsGrohskopf et al. 2014 ADDIN EN.CITE <EndNote><Cite><Author>Grohskopf</Author><Year>2014</Year><RecNum>56</RecNum><DisplayText>(175)</DisplayText><record><rec-number>56</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481208311">56</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Grohskopf, Lisa A</author><author>Olsen, Sonja J</author><author>Sokolow, Leslie Z</author><author>Bresee, Joseph S</author><author>Cox, Nancy J</author><author>Broder, Karen R</author><author>Karron, Ruth A</author><author>Walter, Emmanuel B</author></authors></contributors><titles><title>Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP)—United States, 2014–15 influenza season</title><secondary-title>MMWR Morb Mortal Wkly Rep</secondary-title></titles><periodical><full-title>MMWR: Morbidity and Mortality Weekly Report</full-title><abbr-1>MMWR Morb. Mortal. Wkly. Rep.</abbr-1><abbr-2>MMWR Morb Mortal Wkly Rep</abbr-2><abbr-3>MMWR: Morbidity &amp; Mortality Weekly Report</abbr-3></periodical><pages>691-7</pages><volume>63</volume><number>32</number><dates><year>2014</year></dates><urls></urls></record></Cite></EndNote>(175)USA2013-2014National Recommendations after reviewing literature based on GRADE approachLAIV and IIV in asthmaEfficacy and safetyAdvise that children between 2-4 years who have asthma or wheezing in previous 12 months should not be given LAIV.Adults and children including those with asthma. Population size unavailable.Grohskopf et al. 2015 ADDIN EN.CITE <EndNote><Cite><Author>Grohskopf</Author><Year>2015</Year><RecNum>57</RecNum><DisplayText>(147)</DisplayText><record><rec-number>57</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481208311">57</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Grohskopf, Lisa A</author><author>Sokolow, Leslie Z</author><author>Olsen, Sonja J</author><author>Bresee, Joseph S</author><author>Broder, Karen R</author><author>Karron, Ruth A</author></authors></contributors><titles><title>Prevention and control of influenza with vaccines: Recommendations of the Advisory Committee on immunization practices, United States, 2015-16 influenza season</title><secondary-title>MMWR Morb Mortal Wkly Rep</secondary-title></titles><periodical><full-title>MMWR: Morbidity and Mortality Weekly Report</full-title><abbr-1>MMWR Morb. Mortal. Wkly. Rep.</abbr-1><abbr-2>MMWR Morb Mortal Wkly Rep</abbr-2><abbr-3>MMWR: Morbidity &amp; Mortality Weekly Report</abbr-3></periodical><pages>818-825</pages><volume>64</volume><number>30</number><dates><year>2015</year></dates><urls></urls></record></Cite></EndNote>(147)USA2014 - 2015National Recommendations after reviewing literature based on GRADE approachLAIV and IIV in asthmaEfficacy and safety-All adults and children including those with asthma. Population size unavailable.No change from 2014 -2015Byington et al. 2014 ADDIN EN.CITE <EndNote><Cite><Author>Byington</Author><Year>2014</Year><RecNum>58</RecNum><DisplayText>(176)</DisplayText><record><rec-number>58</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481208311">58</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Byington, Carrie L</author><author>Barnett, Elizabeth D</author><author>Davies, H Dele</author><author>Edwards, Kathryn M</author><author>Jackson, Mary Anne</author><author>Maldonado, Yvonne A</author><author>Murray, Dennis L</author><author>Rathore, Mobeen H</author><author>Sawyer, Mark H</author><author>Schutze, Gordon E</author></authors></contributors><titles><title>Recommendations for Prevention and Control of Influenza in Children, 2014–2015</title><secondary-title>Pediatrics</secondary-title></titles><periodical><full-title>Pediatrics</full-title><abbr-1>Pediatrics</abbr-1><abbr-2>Pediatrics</abbr-2></periodical><pages>e1503-e1519</pages><volume>134</volume><number>5</number><dates><year>2014</year></dates><isbn>0031-4005</isbn><urls></urls></record></Cite></EndNote>(176)USA2013 - 2014National Recommendations from American Academy of PaediatricsLAIV and IIV in asthmaEfficacy and safetyAnnual vaccination (trivalent or quadrivalent) recommended for everyone with special effort made towards asthmatics.Asthma present in 26% hospitalized children with confirmed influenza during the 2013-14 season.All children aged >6 months including those with asthma. 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ADDIN EN.CITE.DATA (126)JapanSept-Oct 2010Questionnaire-based cross-sectional survey NAReceipt of H1N1 vaccine and infection status as well as recording of ACT score.Incidence of H1N1 pdm09 infection 6.7% (95% CI 5.7–7.6).Vaccine receipt in 63.9% (95% CI 62.1-65.8%).Infected patients (n=170) had significantly lower rates of vaccination, were younger and had experienced more night symptoms and sleep disturbance in the preceding 2 weeks.2,555 asthma patients, aged ≥16 years.Good characterization of asthmatics but no objective definition of influenza infection.Pennant et al. 2015 ADDIN EN.CITE <EndNote><Cite><Author>Pennant</Author><Year>2015</Year><RecNum>43</RecNum><DisplayText>(177)</DisplayText><record><rec-number>43</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481208311">43</key></foreign-keys><ref-type name="Conference Proceedings">10</ref-type><contributors><authors><author>Pennant, Keyana N</author><author>Costa, John J</author><author>Fuhlbrigge, Anne L</author><author>Sax, Paul E</author><author>Szent-Gyorgyi, Lara E</author><author>Coblyn, Jonathan</author><author>Desai, Sonali P</author></authors></contributors><titles><title>Improving Influenza and Pneumococcal Vaccination Rates in Ambulatory Specialty Practices</title><secondary-title>Open forum infectious diseases</secondary-title></titles><pages>ofv119</pages><volume>2</volume><number>4</number><dates><year>2015</year></dates><publisher>Oxford University Press</publisher><isbn>2328-8957</isbn><urls></urls></record></Cite></EndNote>(177)USA2009-2015Prospective interventional quality improvement studyPhysician reminders, patient letters, nurse-drivenChange in vaccination uptake rate.Vaccine receipt improved from 59% to 64% between 2011 and 2014 influenza seasons.1142 asthma patients in an allergy clinic aged ≥13 years (85 declined vaccine). Gnatiuc et al. 2015 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HbmF0aXVjPC9BdXRob3I+PFllYXI+MjAxNTwvWWVhcj48

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ADDIN EN.CITE.DATA (178)Global (23 countries)2008 onwardInternational cross sectional survey comparing high income and low-middle income countriesParticipants with doctor diagnosed asthma underwent reversibility testing with salbutamolUse of respiratory medicines and uptake of influenza vaccine in preceding 12 months.Overall influenza vaccination uptake rates: 1.4% in LMIC vs. 28.4% in HIC (P = 0.0001).15,590 adults with asthma and COPD, aged ≥40 years (unclear what proportion are asthmatic).Rare example of research comparing multiple countries from across the income spectrumThe age criteria for the study likely excluded a large proportion of asthmatics Vernacchio et al. 2014 ADDIN EN.CITE <EndNote><Cite><Author>Vernacchio</Author><Year>2014</Year><RecNum>45</RecNum><DisplayText>(179)</DisplayText><record><rec-number>45</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481208311">45</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Vernacchio, Louis</author><author>Francis, Mary E</author><author>Epstein, Daniel M</author><author>Santangelo, Jean</author><author>Trudell, Emily K</author><author>Reynolds, Meghan E</author><author>Risko, Wanessa</author></authors></contributors><titles><title>Effectiveness of an asthma quality improvement program designed for maintenance of certification</title><secondary-title>Pediatrics</secondary-title></titles><periodical><full-title>Pediatrics</full-title><abbr-1>Pediatrics</abbr-1><abbr-2>Pediatrics</abbr-2></periodical><pages>e242-e248</pages><volume>134</volume><number>1</number><dates><year>2014</year></dates><isbn>0031-4005</isbn><urls></urls></record></Cite></EndNote>(179)USA2009-2012Learning collaborative modelRegular face to face meetings and electronic communication between healthcare teamsUptake of influenza seasonal vaccination. Uptake of asthma action plans.Inconsistent improvements in rates of vaccine uptake. Significant increase in implementation of asthma action plans.594 patients with persistent asthma, aged 5-17 years.Blackwell et al. 2015 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CbGFja3dlbGw8L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFy

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ADDIN EN.CITE.DATA (180)USA2009-2010Cross-sectional surveyTelephone surveyReceipt of vaccine in previous 12 months.Asthmatics receiving H1N1 vaccine: OR 1.13 (CI 0.97-1.33).667 children, aged 4 months to 17 years, including asthmatics.Aigbogun et al. 2015 ADDIN EN.CITE <EndNote><Cite><Author>Aigbogun</Author><Year>2015</Year><RecNum>47</RecNum><DisplayText>(181)</DisplayText><record><rec-number>47</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481208311">47</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Aigbogun, NW</author><author>Hawker, JI</author><author>Stewart, A</author></authors></contributors><titles><title>Interventions to increase influenza vaccination rates in children with high-risk conditions—A systematic review</title><secondary-title>Vaccine</secondary-title></titles><periodical><full-title>Vaccine</full-title><abbr-1>Vaccine</abbr-1><abbr-2>Vaccine</abbr-2></periodical><pages>759-770</pages><volume>33</volume><number>6</number><dates><year>2015</year></dates><isbn>0264-410X</isbn><urls></urls></record></Cite></EndNote>(181)Global2014Systematic reviewNAUptake of vaccination rates in high-risk children.Reminder letters useful in improving uptake but less evidence for telephone recall.9 studies in children with asthma, aged 6 months to 19 years.Mazurek et al. 2014 ADDIN EN.CITE <EndNote><Cite><Author>Mazurek</Author><Year>2014</Year><RecNum>48</RecNum><DisplayText>(182)</DisplayText><record><rec-number>48</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481208311">48</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mazurek, Jacek M</author><author>White, Gretchen E</author><author>Moorman, Jeanne E</author><author>Storey, Eileen</author></authors></contributors><titles><title>Influenza Vaccination Among Persons with Work-Related Asthma</title><secondary-title>American journal of preventive medicine</secondary-title></titles><periodical><full-title>American Journal of Preventive Medicine</full-title><abbr-1>Am. J. Prev. Med.</abbr-1><abbr-2>Am J Prev Med</abbr-2></periodical><pages>203-211</pages><volume>47</volume><number>2</number><dates><year>2014</year></dates><isbn>0749-3797</isbn><urls></urls></record></Cite></EndNote>(182)USA2006-2009Cross-sectional surveyTelephone surveyInfluenza vaccination uptake in the preceding 12 months.42.7% uptake rate. Higher rates in those aged 50-64 years, unemployment and in those requiring urgent treatment for worsening symptoms.28,809 adults aged 18-64 years with work-related asthma.O’Halloran, 2015 ADDIN EN.CITE <EndNote><Cite><Author>O’Halloran</Author><Year>2016</Year><RecNum>49</RecNum><DisplayText>(183)</DisplayText><record><rec-number>49</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481208311">49</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>O’Halloran, Alissa C</author><author>Lu, Peng-jun</author><author>Williams, Walter W</author><author>Bridges, Carolyn B</author><author>Singleton, James A</author></authors></contributors><titles><title>Influenza Vaccination Coverage Among People With High-Risk Conditions in the US</title><secondary-title>American journal of preventive medicine</secondary-title></titles><periodical><full-title>American Journal of Preventive Medicine</full-title><abbr-1>Am. J. Prev. Med.</abbr-1><abbr-2>Am J Prev Med</abbr-2></periodical><volume>50</volume><number>e15-e26</number><dates><year>2016</year></dates><isbn>0749-3797</isbn><urls></urls></record></Cite></EndNote>(183)USA2012-2013Cross-sectional surveyTelephone surveyInfluenza vaccination uptake in the preceding 12 months.Uptake rate of 29% (95% CI 26.5-31.7%).8,831 adults, aged 18-64 years with “pulmonary disease”.Lin et al. 2015 ADDIN EN.CITE <EndNote><Cite><Author>Lin</Author><Year>2016</Year><RecNum>50</RecNum><DisplayText>(184)</DisplayText><record><rec-number>50</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481208311">50</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lin, Chyongchiou Jeng</author><author>Nowalk, Mary Patricia</author><author>Zimmerman, Richard K</author><author>Moehling, Krissy K</author><author>Conti, Tracey</author><author>Allred, Norma J</author><author>Reis, Evelyn C</author></authors></contributors><titles><title>Reducing Racial Disparities in Influenza Vaccination Among Children With Asthma</title><secondary-title>Journal of Pediatric Health Care</secondary-title></titles><periodical><full-title>Journal of Pediatric Health Care</full-title><abbr-1>J. Pediatr. Health Care</abbr-1><abbr-2>J Pediatr Health Care</abbr-2></periodical><pages>208-215</pages><volume>30</volume><number>3</number><dates><year>2016</year></dates><isbn>0891-5245</isbn><urls></urls></record></Cite></EndNote>(184)USA2010-2013Prospective interventional quality improvement studyUtilized the “4 pillars immunization toolkit”Influenza vaccination rates pre and post intervention.Uptake rates increased between 2010-11 to 2012-2013 seasons in: Non-White children: 46% to 61%; White children: 58% to 65%.8,250 asthmatic children aged 6 months-18 years.This intervention reduced the racial disparity seen in vaccination uptake rates.Shoup et al. 2015 ADDIN EN.CITE <EndNote><Cite><Author>Shoup</Author><Year>2015</Year><RecNum>51</RecNum><DisplayText>(185)</DisplayText><record><rec-number>51</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481208311">51</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Shoup, J. A.</author><author>Madrid, C.</author><author>Koehler, C.</author><author>Lamb, C.</author><author>Ellis, J.</author><author>Ritzwoller, D. P.</author></authors></contributors><titles><title>Effectiveness and cost of influenza vaccine reminders for adults with asthma or chronic obstructive pulmonary disease</title><secondary-title>American Journal of Managed Care</secondary-title></titles><periodical><full-title>American Journal of Managed Care</full-title><abbr-1>Am. J. Manag. Care</abbr-1><abbr-2>Am J Manag Care</abbr-2></periodical><pages>e405-13</pages><volume>21</volume><number>7</number><keywords><keyword>Sr-airways</keyword></keywords><dates><year>2015</year></dates><accession-num>CN-01087206</accession-num><urls><related-urls><url> 26295268</custom3><electronic-resource-num>86255 [pii]</electronic-resource-num></record></Cite></EndNote>(185)USA2012-2013Pragmatic 3-arm randomized control trialThree arms:1. Postcard reminder2. Telephone reminder3. Postcard & telephone reminderChange in influenza vaccination rate.No difference in intervention groups.Telephone (interactive voice response) calls were most cost-effective.12,285 adults aged 19-64 years with asthma or COPD.Buyuktiryaki et al. 2014 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CdXl1a3Rpcnlha2k8L0F1dGhvcj48WWVhcj4yMDE0PC9Z

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ADDIN EN.CITE.DATA (103)Turkey2010Cross-sectional survey of parentsQuestionnaireH1N1 and seasonal influenza vaccination rates with analysis of demographic factors, asthma control parameters and parental attitudes towards vaccination.16.8 % received H1N1 vaccine; 45.7% received seasonal vaccine.Significant factors influencing uptake included low educational background of parents, previous vaccination with seasonal influenza and having a family member vaccinated against Influenza A/H1N1.Asthma control parameters had no influence on uptake of the vaccine and physician recommendation (84.8%) was important in the decision-making process for immunization.625 children and adolescents aged 6-18 years with asthma.Skupin et al. 2015 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Ta3VwaW48L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFyPjxS

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ADDIN EN.CITE.DATA (186)USA2013Cross-sectional surveyQuestionnaireInfluenza vaccination uptake in preceding year.Black patients had much lower vaccination rates (62.1%) than White (83.8%) or Asian (93.3%) patients.Belief in efficacy in vaccine and physicians recommendation important determinants in higher vaccination rates.472 adults attending internal medicine and allergy clinics.Hart et al. 2014 ADDIN EN.CITE <EndNote><Cite ExcludeAuth="1" ExcludeYear="1"><RecNum>247</RecNum><DisplayText>(187)</DisplayText><record><rec-number>247</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1496333345">247</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors></contributors><titles><title>Hart RJ, Stevenson MD, Levine AJ, Bryant KA, Sikes KL, Paul RI. Assessing Intent and Willingness to Immunize Children Against Influenza in the Pediatric Emergency Department. Presented at the Southern Regional Meeting, New Orleans, 2014.</title></titles><dates></dates><urls></urls></record></Cite></EndNote>(187)USA2013Cross-sectional surveyStructured interviewVaccination uptake in previous year and parental intent to vaccinate in upcoming flu season.64% (95% CI 59-70%) received vaccine in previous year.37% of those parents with intent to vaccinate did not actually do so.224 children, aged 6 months-17 years, attending paediatric emergency department.Unclear what proportion are asthmatic at baseline.Lo, 2014 ADDIN EN.CITE <EndNote><Cite><Author>Lo</Author><RecNum>54</RecNum><DisplayText>(188)</DisplayText><record><rec-number>54</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481208311">54</key></foreign-keys><ref-type name="Conference Proceedings">10</ref-type><contributors><authors><author>Lo, Huay-ying</author></authors></contributors><titles><title>Improving Influenza Vaccination Rates for Asthma Patients Admitted to Pediatric Hospital Medicine</title><secondary-title>2014 AAP National Conference and Exhibition</secondary-title></titles><dates></dates><publisher>American Academy of Pediatrics</publisher><urls></urls></record></Cite></EndNote>(188)USA2013-2014Prospective interventional quality improvement studyImplementation of influenza immunization bundleVaccination rate pre- and post-intervention.Vaccination rate improvement from 19% (6-26%) to 39% (9-55%).117 children attending hospital with asthma exacerbation.Regan, 2014 ADDIN EN.CITE <EndNote><Cite><Author>Regan</Author><Year>2014</Year><RecNum>55</RecNum><DisplayText>(189)</DisplayText><record><rec-number>55</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481208311">55</key></foreign-keys><ref-type name="Conference Proceedings">10</ref-type><contributors><authors><author>Regan, Annette</author></authors></contributors><titles><title>The use of electronic health record data extraction for estimating influenza vaccination coverage and effectiveness</title><secondary-title>The 20th IEA World Congress of Epidemiology (17-21 August 2014, Anchorage, AK)</secondary-title></titles><dates><year>2014</year></dates><publisher>WCE</publisher><urls></urls></record></Cite></EndNote>(189)Australia2013Cross-sectional survey of electronic outpatient recordsNAAssessment of proportion of people immunized and estimate of vaccine effectiveness.29.7% vaccination rate in asthmatics vs. 52.2% in those with coronary heart disease.In all patients, combined clinical and pathological data suggested vaccination had effectiveness of 56% in preventing infection: OR 0.44 (95% CI 0.24-0.79).2731 general practice patients with clinical and pathological data.ACT asthma control test; LMIC low-middle income countries; HIC high-income companies; COPD chronic obstructive pulmonary disease OR odds ration; CI confidence interval; NA not available; Section 4. Immunogenicity of influenza vaccines in asthma Authors, yearCountryStudy periodType of studyInterventionOutcome measureKey findingPopulation characteristicsLimitations/commentsBae et al. 2013 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYWU8L0F1dGhvcj48WWVhcj4yMDEzPC9ZZWFyPjxSZWNO

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ADDIN EN.CITE.DATA (115)Korea2011-2012 influenza seasonPhase 4, multi-center, open label studyTIV (H1N1, H3N2, B) (7.5 μg per strain) Two doses in vaccine na?ve children; one dose in previously vaccinated Interval between first and second dose not stated.Short-term seroconversion rates, seroprotection rates, GMT, and GMT ratio; HI assay Safety: local and systemic adverse events.Seroconversion and seroprotection rates in wheezers were similar to healthy children and significant for all 3 strains. The GMT was higher in the one dose-group vs. the two-dose group both in healthy children and in wheezers. The GMT ratio was significantly higher in healthy children than wheezers for the H1N1, H3N2 strains. No difference between steroid-treated and non-treated wheezers.68 healthy children and 62 recurrent wheezers aged 6 months to 3 years. Chronic and high dose ICS excluded. No adjustment for ICS dose. Age significantly lower in healthy controls (1-2 y) than in wheezers (2-3 y). Busse et al. 2011 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CdXNzZTwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+PFJl

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ADDIN EN.CITE.DATA (118)US2009 influenza autumn seasonRandomized, open-label studyMonovalent H1N1 tested at two doses (15 vs. 30 μg) twice at 21 days intervalShort term rates and GMT of seroconversion and seroprotection; HI assay and microneutralization.The 2 dosing groups did not differ in seroconversion rates. In mild-to-moderate asthma the two doses offered equal seroprotection. In severe asthma seroprotection was significantly higher with the 30 μg dose In severe asthmatics >60 years old the seroprotection was achieved only with the 30 μg dose The second dose provided no additional benefit. Atopy, BMI, systemic corticosteroid or ICS dose had no influence on HI GMTs or on seroprotection rates.Adolescents and adults (12-79) with asthma; special subgroup > 60 years with mild-to-moderate and severe asthma (including use of OCS).No healthy controls for comparison.Pedrosa et al. 2009 ADDIN EN.CITE <EndNote><Cite><Author>Pedroza</Author><Year>2009</Year><RecNum>198</RecNum><DisplayText>(116)</DisplayText><record><rec-number>198</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481210247">198</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Pedroza, Alvaro</author><author>Huerta, José G.</author><author>de la Luz Garcia, Maria</author><author>Rojas, Arsheli</author><author>López-Martínez, Irma</author><author>Penagos, Martín</author><author>Franco-Paredes, Carlos</author><author>Deroche, Christele</author><author>Mascare?as, Cesar</author></authors></contributors><titles><title>The safety and immunogenicity of influenza vaccine in children with asthma in Mexico</title><secondary-title>International Journal of Infectious Diseases</secondary-title></titles><periodical><full-title>International Journal of Infectious Diseases</full-title><abbr-1>Int. J. Infect. Dis.</abbr-1><abbr-2>Int J Infect Dis</abbr-2></periodical><pages>469-475</pages><volume>13</volume><number>4</number><dates><year>2009</year><pub-dates><date>2009/07</date></pub-dates></dates><publisher>Elsevier BV</publisher><isbn>1201-9712</isbn><urls><related-urls><url>;(116)Mexico2001-2002 influenza seasonDouble-blind, placebo controlled, randomized study Inactivated TIV (H1N1, H3N2,B); dose 15 μg per strain; twice at 28 days intervalSafety: local and systemic adverse events; lung function; short-term rate of seroconversion; HI assay.Significant rate of seroconversion after the first and second dose for all 3 strains.Children 5-9 years with mild intermittent and moderate asthma.No healthy controls for comparison. Study funded by industry.Asthma severity assessed only as LF; no data on exacerbations. Subjects with a history of allergy to egg protein excluded. Previous influenza vaccination status not reported.Zuccotti, et al. 2007 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5adWNjb3R0aTwvQXV0aG9yPjxZZWFyPjIwMDc8L1llYXI+

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ADDIN EN.CITE.DATA (117)Italy2005-2006 influenza seasonObservational prospective open label multi-centre studyVirosomal-adjuvanted TIV (H1N1, H3N2,B); dose 15 μg per strain; single dose Short (at one month) and long-term (at 6 months) seroconversion (≥1:40) and seroprotection (≥1:10); HI assay; both rate and fold-increase in GMT. Seroconversion and seroprotection in relation to pre-existing antibodies. Safety: local and systemic adverse events.Seroconversion: Both rates and GMT significantly high at both 1 and 6 months for all 3 strains Better GMT increase for the B strain in children 6-9 years compared to 3-5 years. Seroprotection: At one month satisfactory in both age groups, decreased seroprotection for H3N2 for children aged 6-9 years. At 6 months: >80% in children aged 6-9 years; significantly lower (<70%) in children aged 3-5 years. Both seroconversion and seroprotection to any specific strain significantly lower without pre-existing antibodies.Children with asthma aged 3-9 years (subgroups 3-5 years and 6-9 years). No data on asthma severity. No healthy controls. More than 50% of children had pre-existing antibodies at baseline. Baseline GMTs were relatively high for all 3 strains. Subjects with history of egg allergy and/or severe atopy were excluded. BMI body mass index; ICS inhaled corticosteroids; LF lung function; GMT geometric mean titer; HI hemagglutinin inhibition; OCS oral corticosteroids; SPT skin prick test; TIV trivalent influenza vaccines Section 5. Efficacy of influenza vaccines in asthmaAuthors, yearCountryStudy PeriodType of studyIntervention Outcome measureKey findingPopulation characteristicsLimitations/ commentsAbadoglu et al. 2004 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BYmFkb2dsdTwvQXV0aG9yPjxZZWFyPjIwMDQ8L1llYXI+

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ADDIN EN.CITE.DATA (119)TurkeyRecruitment: Sept -Nov 2001.Follow-up until Mar 2002Randomized, controlled trialTIV vs. no vaccineFrequency of URTI infections and asthma exacerbations during the winter following vaccination.URTI and asthma exacerbation rates similar between vaccinated and non-vaccinated groups = no protective effect.Asthmatic adults aged 22-84 years. In total: 128 Vaccination: 86 Nothing: 42.Lack of knowledge on rate of influenza epidemic in tested period or on the cause of URTI. Relatively low number of subjects enrolled.Bueving et al. 2004 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CdWV2aW5nPC9BdXRob3I+PFllYXI+MjAwNDwvWWVhcj48

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ADDIN EN.CITE.DATA (120)The Netherlands1999-2000 2000-2001Double-blind, placebo controlled, randomized study TIV vs. placeboSymptom scores (to detect infection); pharyngeal swab and spirometry; quality of life (QoL).In in?uenza-positive weeks of illness: - no effect was found for respiratory symptoms recorded in the diaries - moderately bene?cial effect on QoL throughout the seasons: No differences for respiratory symptoms and QoL.Asthmatic children aged 6-18 yrs.In total: 696 (296 in 1999 -2000 and 400 in 2000 -2001) 347: in?uenza vaccine and 349 placebo. Relatively few in?uenza- positive weeks of illness. Bueving et al. 2004 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CdWV2aW5nPC9BdXRob3I+PFllYXI+MjAwNDwvWWVhcj48

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ADDIN EN.CITE.DATA (75)The Netherlands1999-20002000-2001Double-blind, placebo controlled, randomized study TIV vs. placeboSymptom scores (to detect infection) Pharyngeal swab. Blood samples for in?uenza virus -speci?c antibodies (immunogenicity).Influenza vaccination did not result in a significant reduction of the number, severity, or duration of asthma exacerbations caused by influenza.696 asthmatic children aged 618 years.Fayyaz Jahani et al. 2012 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5GYXl5YXogSmFoYW5pPC9BdXRob3I+PFllYXI+MjAxMjwv

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ADDIN EN.CITE.DATA (121)IranNDRandomized, placebo-controlled studyTIVAsthma exacerbations.Lower asthma exacerbation rates following TIV (13%) than after placebo (53%).140 asthmatic children aged 6 to 60 months.Conference abstract, thus limited information.Fleming et al. 2006 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5GbGVtaW5nPC9BdXRob3I+PFllYXI+MjAwNjwvWWVhcj48

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ADDIN EN.CITE.DATA (122)Multicenter (UK & Europe)Oct 2002 - May 2003Reactive-CT to examine relative efficacy of CAIV-T vs. TIVCAIV-T vs. TIVSurveillance for in?uenza-like symptoms. Nasal swab viral culture culture-con?rmed in?uenza illness. Primary efficacy endpoint: incidence of culture-con?rmed in?uenza illness caused by a community-acquired subtype antigenically similar to that in the vaccine.CAIV-T had a signi?cantly greater relative ef?cacy of 35% compared with TIV. There was no evidence of a signi?cant increase in adverse pulmonary outcomes for CAIV-T compared with TIV. CAIV-T was well tolerated in children and adolescents with asthma. Asthmatic children aged 6 to 17 years.CAIV-T (n=1114) TIV (n=1115).No placebo group, therefore the absolute ef?cacy of each vaccine cannot be calculated.Ambrose et al. 2012 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BbWJyb3NlPC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48

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ADDIN EN.CITE.DATA (125)Meta-analysis of two randomized, multinational trialsCAIV-T vs. TIVCulture confirmed influenza illness during the influenza surveillance period. Rate of wheezing, hospitalization, adverse events.Children receiving LAIV had fewer cases of culture-confirmed influenza illness than TIV recipients.1940 children aged 2-5 years with asthma or prior wheezing.Post hoc definition of study cohorts, but this is in part addressed by the sub-population analysis. Identification of subjects asthma or history of wheezing relied on investigator judgment without validation. TIV trivalent influenza vaccines; URTI upper respiratory tract infection; QoL quality of life; CAIV-T trivalent, cold-adapted influenza vaccine; LAIV live attenuated influenza vaccineSection 6. Effectiveness of influenza vaccination in asthmaAuthors, yearCountryStudy PeriodType of studyInterventionOutcome measureKey findingPopulation characteristicsLimitations/ commentsChristy et al. 2004 ADDIN EN.CITE <EndNote><Cite><Author>Christy</Author><Year>2004</Year><RecNum>27</RecNum><DisplayText>(131)</DisplayText><record><rec-number>27</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481208311">27</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Christy, C</author><author>Aligne, CA</author><author>Auinger, P</author><author>Pulcino, T</author><author>Weitzman, M</author></authors></contributors><titles><title>Effectiveness of influenza vaccine for the prevention of asthma exacerbations</title><secondary-title>Archives of disease in childhood</secondary-title></titles><periodical><full-title>Archives of Disease in Childhood</full-title><abbr-1>Arch. Dis. Child.</abbr-1><abbr-2>Arch Dis Child</abbr-2></periodical><pages>734-735</pages><volume>89</volume><number>8</number><dates><year>2004</year></dates><isbn>1468-2044</isbn><urls></urls></record></Cite></EndNote>(131)USA1996-1997Retrospective nested case control studyInfluenza vaccineAsthma-related hospitalization, clinic and emergency department visits.Adjusted OR (95% CI) associated with vaccine for asthma related: Hospitalization 1.9 (0.9-3.9).Clinic visit 2.9 (2.0-4.1).Emergency department visits 2.0 (1.2-3.1).Primary care cohort. 400 randomly selected children with asthma who had been vaccinated, and 400 who had not. Age range 1-19 years. Two groups were not balanced in terms of ethnicity and likelihood of receiving vaccine in previous year, but this was taken into account in adjusted analysis.Study suggests that vaccine associated with worse outcomes. Patients with more severe asthma or those more likely to present may be more likely to have been vaccinated although controlling for these did not alter the results. Hak 2005 ADDIN EN.CITE <EndNote><Cite><Author>Hak</Author><Year>2005</Year><RecNum>208</RecNum><DisplayText>(130)</DisplayText><record><rec-number>208</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481210247">208</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hak, Eelko</author></authors></contributors><titles><title>Clinical Effectiveness of Influenza Vaccination in Persons Younger Than 65 Years With High-Risk Medical Conditions</title><secondary-title>Archives of Internal Medicine</secondary-title></titles><periodical><full-title>Archives of Internal Medicine</full-title><abbr-1>Arch. Intern. Med.</abbr-1><abbr-2>Arch Intern Med</abbr-2></periodical><pages>274</pages><volume>165</volume><number>3</number><dates><year>2005</year><pub-dates><date>2005/02/14</date></pub-dates></dates><publisher>American Medical Association (AMA)</publisher><isbn>0003-9926</isbn><urls><related-urls><url>;(130)Netherlands1999-2000Nested case control study Influenza vaccinationAll cause mortality, hospitalization, general practice visits for influenza, pneumonia and other acute respiratory problems.High-risk children <18 years, 43% (10%-64%) of visits were prevented by vaccination after adjustment. High-risk adults (18-64 years) 78% of deaths (39-92%), 87% of hospitalizations (39-97%), and 26% of GP visits (7-47%) were prevented. Elderly persons vaccine prevented 50% of deaths (95% CI, 23-68%) and 48% of hospitalization (7- 71%) were prevented. All age groups with long term medical conditions. >75,000 patients in primary care cohort.No separate analysis for asthma. Adjusted for previous medical utilisation and comorbidities. Herrera et al. 2007 ADDIN EN.CITE <EndNote><Cite><Author>Herrera</Author><Year>2007</Year><RecNum>207</RecNum><DisplayText>(132)</DisplayText><record><rec-number>207</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481210247">207</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Herrera, Guillermo A.</author><author>Iwane, Marika K.</author><author>Cortese, Margaret</author><author>Brown, Cedric</author><author>Gershman, Ken</author><author>Shupe, Alyson</author><author>Averhoff, Francisco</author><author>Chaves, Sandra S.</author><author>Gargiullo, Paul</author><author>Bridges, Carolyn B.</author></authors></contributors><titles><title>Influenza vaccine effectiveness among 50–64-year-old persons during a season of poor antigenic match between vaccine and circulating influenza virus strains: Colorado, United States, 2003–2004</title><secondary-title>Vaccine</secondary-title></titles><periodical><full-title>Vaccine</full-title><abbr-1>Vaccine</abbr-1><abbr-2>Vaccine</abbr-2></periodical><pages>154-160</pages><volume>25</volume><number>1</number><dates><year>2007</year><pub-dates><date>2007/01</date></pub-dates></dates><publisher>Elsevier BV</publisher><isbn>0264-410X</isbn><urls><related-urls><url>;(132)USA2003-2004Case-control studyInfluenza vaccineLaboratory confirmed influenza report.Influenza: vaccine “efficacy” was 60% (43 -72%) and 48% (21 -66%) among those without and with high-risk medical conditions.Influenza-related hospitalization: vaccine “efficacy” was 90% (68 -97%) and 36% (0 -63%) against for persons without and with high-risk conditions.330 cases, 1055 randomly recruited controls. Age range 50-64 years.No separate data for asthma. Apparent effectiveness may be inflated by potential tendency to not test vaccinated people and miss an influenza diagnosis on a vaccinated patient. Authors say “efficacy” but study set up as an effectiveness study. Vaccine strains did not closely match circulating influenza strains.Koshio et al. 2014 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Lb3NoaW88L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFyPjxS

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ADDIN EN.CITE.DATA (126)JapanSept-Oct 2010Survey Vaccination against “ new type of influenza”: H1N1 pdm09.Report of a “new type of influenza”: H1N1 pdm09.For influenza, OR (95% CI) for previous vaccination was 0.62 (0.42-0.90) for younger patients ≤61 years); among older patients OR was 1.38 (0.66-2.89) For infection-induced asthma exacerbation, OR (95% CI) for previous vaccination was 1.67 (0.60-4.66) for younger patients and 1.71 (0.50-5.83) for older ones.2555 adults with asthma.There may have been other differences between vaccinated and non-vaccinated patients that explained the difference in risk of influenza. Influenza cases were not laboratory proven. This study looked at pandemic rather than ordinary influenza. Kramarz et al. 2001 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5LcmFtYXJ6PC9BdXRob3I+PFllYXI+MjAwMTwvWWVhcj48

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ADDIN EN.CITE.DATA (127)USA1993-1996Population based, retrospective cohort study Influenza vaccineExacerbation of asthma.Adjusted incidence rate ratios of asthma exacerbations after vaccination were 0.78 (0.55-1.10), 0.59 (0.43-0.81), and 0.65 (0.52-0.80) compared with the period before vaccination during the 3 influenza seasons.Children aged 1-6 years with asthma in 4 large health maintenance organizations. (>70,000 patients).As a database-based analysis, the asthma diagnostic labelling and recording of asthma exacerbations may not be completely accurate.Differences in patients receiving vaccination may have explained the difference in exacerbations.Adjusted for asthma severity. Ong et al. 2009 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Pbmc8L0F1dGhvcj48WWVhcj4yMDA5PC9ZZWFyPjxSZWNO

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ADDIN EN.CITE.DATA (129)USASurveyInfluenza vaccineExacerbation of asthma defined by oral corticosteroid, hospital visit or emergency department visit.In the multivariate analyses, current influenza vaccination status was independently associated with significantly decreased OR of using oral steroids in the previous 12 months (0.29, 0.10-0.84). There was no association with hospitalization (1.39; 0.340 -5.67) nor emergency department visits.80 children with asthma in a paediatric clinic.Retrospective approach may have introduced recall bias. Factors influencing likelihood of vaccination may have influenced likelihood of exacerbation, confounding the results.Triggers other than influenza may have been responsibly for the exacerbation. Smits et al. 2002 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TbWl0czwvQXV0aG9yPjxZZWFyPjIwMDI8L1llYXI+PFJl

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ADDIN EN.CITE.DATA (128)Netherlands1995-1997Retrospective cohort study Inactive influenza vaccinationPhysician diagnosed acute respiratory illness.Vaccine effectiveness was 27% (-7 to 51%) after adjustments. For those <6 years, it was 55% (20 to 75%) compared with -5% (-81 to 39%) in older ones. Children with asthma aged 0-12 years in primary care. Over 300 patients in each season.Patients vaccinated may have been different to others and these factors may have impacted on likelihood of developing respiratory illness. Adjusted for previous healthy utilizationJaiwong et al. 2015 ADDIN EN.CITE <EndNote><Cite><Author>Jaiwong</Author><Year>2015</Year><RecNum>30</RecNum><DisplayText>(190)</DisplayText><record><rec-number>30</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481208311">30</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Jaiwong, C</author><author>Ngamphaiboon, J</author></authors></contributors><titles><title>Effects of inactivated influenza vaccine on respiratory illnesses and asthma-related events in children with mild persistent asthma in Asia</title><secondary-title>Asian Pacific Journal of Allergy and Immunology</secondary-title></titles><periodical><full-title>Asian Pacific Journal of Allergy and Immunology</full-title><abbr-1>Asian Pac. J. Allergy Immunol.</abbr-1><abbr-2>Asian Pac J Allergy Immunol</abbr-2><abbr-3>Asian Pacific Journal of Allergy &amp; Immunology</abbr-3></periodical><pages>3</pages><volume>33</volume><number>1</number><dates><year>2015</year></dates><isbn>0125-877X</isbn><urls></urls></record></Cite></EndNote>(190)ThailandJune 2012 - Aug 2013Cross-sectional non-randomized studyTIV vs. no vaccineRespiratory illnesses and asthma-related events.The immunized group had significantly reduced: acute respiratory tract illnesses; asthma exacerbations; ER visits; bronchodilator usage and systemic steroid administrations; number of hospitalizations (p<0.001) and their duration (p <0.034).93 mild persistent asthmatic children aged 1-14 years (48 patients: 2 doses of inactivated influenza).Non-randomized study. Small sample size. Lack of info related to other confounding factors in asthmatic exacerbations such as compliance and controller usage, other virus and bacterial infections, pollution, emotional conditions of the patient.Yokoushi et al. 2014 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Zb2tvdWNoaTwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+

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ADDIN EN.CITE.DATA (191)JapanMay 2009 -Feb 2010Retrospective, cross-sectional, questionnaire-based surveyInactivated, split-virus, non-adjuvanted monovalent vs. no vaccineVaccination rates. Vaccine effectiveness against physician-diagnosed influenza A infection, and consecutive. asthma parison of positive influenza diagnosis rates between vaccinated and unvaccinated children with and without asthma showed that: Unvaccinated children with asthma had an elevated odds ratio (13.235; 95% CI; 5.564-32.134).Treatment for asthma exacerbations was needed in a larger proportion of unvaccinated children.Vaccine effectiveness against physician diagnosed influenza was 87% (95% CI, 78-93%) overall, 92% (95% CI, 81-96%) in children with asthma and 81% (95% CI, 63-91%) in children without asthma, respectively.460 children with (n=144) and without asthma (n=316).Other environmental factors that may cause asthma exacerbation were not considered. No data on atopic comorbidities.Retrospective study. Physician diagnosed influenza infection with or without a positive rapid antigen test result for influenza A during the pandemic period.ER emergency room; OR odds ratio; GP general practitioner; TIV trivalent influenza vaccine; CI confidence intervalSection 7. Safety of influenza vaccines in asthma Authors, yearCountryStudy PeriodType of studyInterventionOutcome measureKey findingsPopulation characteristicsLimitations/ comments Greenhawt et al, 2012 ADDIN EN.CITE <EndNote><Cite><Author>Greenhawt</Author><Year>2012</Year><RecNum>210</RecNum><DisplayText>(140)</DisplayText><record><rec-number>210</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481210247">210</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Greenhawt, Matthew J.</author><author>Spergel, Jonathan M.</author><author>Rank, Matthew A.</author><author>Green, Todd D.</author><author>Masnoor, Darlene</author><author>Sharma, Hemant</author><author>Bird, J. Andrew</author><author>Chang, Jinny E.</author><author>Sinh, Divya</author><author>Teich, Esther</author><author>Kelso, John M.</author><author>Sanders, Georgiana M.</author></authors></contributors><titles><title>Safe administration of the seasonal trivalent influenza vaccine to children with severe egg allergy</title><secondary-title>Annals of Allergy, Asthma &amp; Immunology</secondary-title></titles><pages>426-430</pages><volume>109</volume><number>6</number><dates><year>2012</year><pub-dates><date>2012/12</date></pub-dates></dates><publisher>Elsevier BV</publisher><isbn>1081-1206</isbn><urls><related-urls><url>;(140)USAOct 2010 - Mar 2012Phase 1: randomized, controlled trial. Phase 2: retrospective, observational trialPhase 1: Group A: graded 2 dose TIV challenge Group B: sham (saline) 1st dose followed by full TIV dose Phase 2: participants who declined study and received TIV from their allergist or had already received TIV in primary care.Safety of TIV in egg-allergic children with severe allergy.No allergic reactions were recorded.Egg-allergic children with severe allergy (mean age 12 years). All patients had previous confirmed severe allergic reactions to egg.Howe et al. 2011 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Ib3dlPC9BdXRob3I+PFllYXI+MjAxMTwvWWVhcj48UmVj

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ADDIN EN.CITE.DATA (141)USAPhase 1: Oct 2004- Feb 2009 Phase 2: 2009-2010Phase 1: Retrospective, observational study. Phase 2: Prospective observational study.TIVSafety of TIV in egg-allergic and non-allergic patients.No severe allergic reactions have been recorded.ChildrenMiller et al. 2003 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NaWxsZXI8L0F1dGhvcj48WWVhcj4yMDAzPC9ZZWFyPjxS

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ADDIN EN.CITE.DATA (137)USADouble-blind, placebo controlled trial.Influenza vaccineT-cell immune response to vaccine components in patients with asthma who experience bronchospasm.Increased influenza (but not egg) antigen-induced mononuclear cell proliferation, unrelated to asthma exacerbations after vaccine. No differences in cytokine production in response to either influenza or egg antigen in association with asthma exacerbations. Bronchospasm after immunization is not related to vaccination.Adults, mean age 43 years.Chung et al. 2010 ADDIN EN.CITE <EndNote><Cite><Author>Chung</Author><Year>2010</Year><RecNum>34</RecNum><DisplayText>(138)</DisplayText><record><rec-number>34</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481208311">34</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Chung, Erica Y</author><author>Huang, Lin</author><author>Schneider, Lynda</author></authors></contributors><titles><title>Safety of influenza vaccine administration in egg-allergic patients</title><secondary-title>Pediatrics</secondary-title></titles><periodical><full-title>Pediatrics</full-title><abbr-1>Pediatrics</abbr-1><abbr-2>Pediatrics</abbr-2></periodical><pages>e1024-e1030</pages><volume>125</volume><number>5</number><dates><year>2010</year></dates><isbn>0031-4005</isbn><urls></urls></record></Cite></EndNote>(138)USA2002-2009Retrospective, observational studyInfluenza vaccineTolerability of the vaccine, defined as the lack of localized or systemic adverse reactions, in egg-allergic and non-allergic patients.95% of egg-allergic patients who received the vaccine skin test tolerated the influenza vaccine without any serious adverse reactions.Children, 6 months - 18 years.Gagnon et al. 2010 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HYWdub248L0F1dGhvcj48WWVhcj4yMDEwPC9ZZWFyPjxS

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ADDIN EN.CITE.DATA (139)CanadaOct-Dec 2009Prospective, observational studyAdjuvanted monovalent 2009 pandemic influenza A/H1N1 influenza vaccineRisk of anaphylaxis in children with egg allergy administered an adjuvanted monovalent 2009 pandemic influenza A/H1N1 influenza vaccine.No patient had an anaphylactic reaction.Children and adults.Greenhawt et al. 2010 ADDIN EN.CITE <EndNote><Cite><Author>Greenhawt</Author><Year>2010</Year><RecNum>213</RecNum><DisplayText>(143)</DisplayText><record><rec-number>213</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481210247">213</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Greenhawt, Matthew J.</author><author>Chernin, Anna S.</author><author>Howe, Laura</author><author>Li, James T.</author><author>Sanders, Georgiana</author></authors></contributors><titles><title>The safety of the H1N1 influenza A vaccine in egg allergic individuals</title><secondary-title>Annals of Allergy, Asthma &amp; Immunology</secondary-title></titles><pages>387-393</pages><volume>105</volume><number>5</number><dates><year>2010</year><pub-dates><date>2010/11</date></pub-dates></dates><publisher>Elsevier BV</publisher><isbn>1081-1206</isbn><urls><related-urls><url>;(143)USAOct 2009- Feb 2010Controlled, prospective trialH1N1 influenza vaccineSafety of administering H1N1 to egg-allergic patients compared with non-egg-allergic, paediatric, control patients.No significant allergic reactions were recorded.Children and adults aged 6 months to 24 years.Esposito et al. 2008 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Fc3Bvc2l0bzwvQXV0aG9yPjxZZWFyPjIwMDg8L1llYXI+

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ADDIN EN.CITE.DATA (142)ItalyNov-Dec 2007Prospective studyVirosomal adjuvanted influenza vaccineTo evaluate whether the virosomal adjuvanted influenza vaccine that has been shown to have the lowest egg protein content could be administered to children with even severe egg allergy without any risk of allergic reactions.Administration of the whole vaccine was safe and well tolerated by all of the children, with no differences between those with and without egg allergy, or between those with egg allergy of different severity.Children >3 years.Castro et al. 2001 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DYXN0cm88L0F1dGhvcj48WWVhcj4yMDAxPC9ZZWFyPjxS

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ADDIN EN.CITE.DATA (134)USASep-Nov 2000Multicenter, randomized, double blind, placebo-controlled, crossover trialTIV or placeboSafety of TIV in adults and children with asthma.The frequency of asthma exacerbations was similar in the two weeks after the TIV or placebo injection. The exacerbation rates were similar in subgroups defined according to age, severity of asthma, and other factors.Children and adults aged 3-64 years.Baxter et al. 2012 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYXh0ZXI8L0F1dGhvcj48WWVhcj4yMDEyPC9ZZWFyPjxS

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ADDIN EN.CITE.DATA (135)USAOct 2003 - March 2008Prospective observational post-marketing studyLAIV, TIV or placebo.Safety of LAIV, compared to TIV and placebo in children.Asthma/wheezing major adverse events were not statistically increased in LAIV recipients. No anaphylaxis events occurred.Children aged 5-17 years.Ambrose et al. 2012 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BbWJyb3NlPC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48

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ADDIN EN.CITE.DATA (125)Study 1: 2004-2005 Study 2: 2002-2003Post-hoc analysis of two randomized, multinational trials of LAIV and TIV in children aged 6 -71 monthsLAIV vs. TIVSafety of LAIV in asthmatic children younger than 6 years.Wheezing, lower respiratory illness, and hospitalization were not significantly increased in children receiving LAIV compared with TIV. Increased upper respiratory symptoms and irritability were observed in LAIV recipients.Children aged 2-5 years.Gaglani et al. 2008 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HYWdsYW5pPC9BdXRob3I+PFllYXI+MjAwODwvWWVhcj48

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ADDIN EN.CITE.DATA (136)USA1998-2002Open-label field trialTrivalent LAIVSafety of the intranasal LAIV3 in children with intermitted wheezing/asthma.No increased risk for medically-attended acute respiratory illnesses, including asthma exacerbation.Children aged 1.5-18 years.Haber et al. 2015 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IYWJlcjwvQXV0aG9yPjxZZWFyPjIwMTU8L1llYXI+PFJl

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ADDIN EN.CITE.DATA (192)USALAIV4 reports: 2013-2014 LAIV3 reports: 2010-2013Analysis of reports received at the “Vaccine Adverse Event Reporting System”LAIV4 vs. LAIV3Medical records were reviewed for non-manufacturer serious reports (i.e., death, hospitalization, prolonged hospitalization, life-threatening illness, permanent disability) and reports of selected conditions of interest.No new or unexpected safety concerns with LAIV4. The safety pro?le of LAIV4 was similar to LAIV3. Just over 94% of LAIV4 reports were non-serious and the most common adverse events were mild, self-limited conditions (e.g., fever, headache and cough).Children and adults aged 2-49 years. 12.7 million doses of LAIV4 were distributed.General limitations of passive surveillance. Turner et al. 2015 ADDIN EN.CITE <EndNote><Cite><Author>Turner</Author><Year>2015</Year><RecNum>41</RecNum><DisplayText>(145)</DisplayText><record><rec-number>41</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481208311">41</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Turner, Paul J</author><author>Southern, Jo</author><author>Andrews, Nick J</author><author>Miller, Elizabeth</author><author>Erlewyn-Lajeunesse, Michel</author><author>SNIFFLE Study Investigators</author></authors></contributors><titles><title>Safety of live attenuated influenza vaccine in atopic children with egg allergy</title><secondary-title>Journal of Allergy and Clinical Immunology</secondary-title></titles><periodical><full-title>Journal of Allergy and Clinical Immunology</full-title><abbr-1>J. Allergy Clin. Immunol.</abbr-1><abbr-2>J Allergy Clin Immunol</abbr-2><abbr-3>Journal of Allergy &amp; Clinical Immunology</abbr-3></periodical><pages>376-81</pages><volume>136</volume><number>2</number><dates><year>2015</year></dates><isbn>0091-6749</isbn><urls></urls></record></Cite></EndNote>(145)UK Sept 2013 - Jan 2014Prospective, multi-centre, open-label, phase IV intervention studyLAIVClinical symptoms after LAIV administration to estimate incidence of 1. Allergic reaction within 2 hours, 2. Delayed allergic symptoms within 72 hours, 3. Non-allergic adverse events; and change in nasal airway patency (acoustic rhinometry).LAIV appeared to be safe in children with egg allergy and additional asthma or recurrent wheeze. No systemic allergic reactions reported. Eight children had mild, self-limiting, potentially IgE-mediated allergic symptoms. 26 (9.4%; 95% CI for population, 6.2% to 13.4%) children experienced lower respiratory tract symptoms within 72 hours, including 13 with parent-reported wheeze. None of these episodes required medical intervention beyond routine treatment.282 children with egg allergy aged 2-17 years.The egg protein content of LAIV batches may vary, thus data from this study may not be applicable to future LAIV stocks in which egg content may be higher. TIV trivalent influenza vaccine; LAIV live attenuated influenza vaccine; CI confidence intervalSection 8. Antiviral treatment against influenza in patients with atshmaAuthors, yearCountryStudy PeriodType of studyInterventionOutcome measureKey findingPopulation characteristicsLimitations/ comments Johnston et al. 2005 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Kb2huc3RvbjwvQXV0aG9yPjxZZWFyPjIwMDU8L1llYXI+

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ADDIN EN.CITE.DATA (162)Randomized studyOseltamivir (2 mg/kg) or placebo twice daily, as a syrupEffects of oseltamivir among influenza-infected children with asthma. Oseltamivir is safe and well tolerated among asthmatic children, may reduce symptom duration and helps improve lung function and reduce asthma exacerbations during influenza infection.Asthmatic children aged 6-12 years. Analysis was performed for both the intent-to-treat infected (n=179) and per protocol (n=162) populations.Lin et al.2006 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MaW48L0F1dGhvcj48WWVhcj4yMDA2PC9ZZWFyPjxSZWNO

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ADDIN EN.CITE.DATA (156) China 2002-2003Randomized, open-label, controlled trialOseltamivir 7 5 mg twice daily for 5 days (oseltamivir group), or symptomatic treatment (control group) within 48 h after symptom onsetDuration and severity of illness in influenza-infected patients, incidence of complications, antibiotic use, hospitalization and total medical cost.Oseltamivir is effective and well tolerated in high-risk patients with chronic respiratory or cardiac diseases. It can reduce the duration and severity of influenza symptoms and decrease the incidence of secondary complications and antibiotic use, without increasing the total medical cost.118 Chinese patients (mean age 48.1 years) with chronic respiratory diseases (chronic bronchitis, obstructive emphysema, bronchial asthma or bronchiectasis) or chronic cardiac disease. Only 8 patients with bronchial asthma.Cass et al. 2000 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DYXNzPC9BdXRob3I+PFllYXI+MjAwMDwvWWVhcj48UmVj

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ADDIN EN.CITE.DATA (160)UK2000Double-blind, randomized, placebo controlled, two way cross-over study, 7 day wash out period.10 mg zanamivir as a dry powder (265 mg) or a placebo, twice daily on day 1 and then four times daily from day 2 to day 14.Safety of Zanamivir in asthmatics.Zanamivir inhaled as a dry powder does not significantly affect the pulmonary function and airway responsiveness of subjects with mild/moderate asthma and therefore its use in such patients/subjects is not precluded.13 subjects, aged 19-49 years, with asthma.Shun-Shin et al. 2009 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TaHVuLVNoaW48L0F1dGhvcj48WWVhcj4yMDA5PC9ZZWFy

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ADDIN EN.CITE.DATA (163)Systematic review and meta-analysis of randomized controlled trialsNAEffects of the neuraminidase inhibitors oseltamivir and zanamivir in treatment of children with seasonal influenza and prevention of transmission to children in households.Oseltamivir did not reduce asthma exacerbations or improve peak flow in children with asthma.Children aged ≤12 years in the community (not admitted to hospital) with confirmed or clinically suspected influenza.Based on only one trial.Jefferson et al. 2014 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5KZWZmZXJzb248L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFy

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ADDIN EN.CITE.DATA (164)Systematic review NAPotential benefit and harm of oseltamivir by reviewing all clinical study reports (or similar document when no clinical study report exists) of randomized placebo controlled trials and regulatory comments.Ozeltamivir had no effect in children with asthma, but there was an effect in otherwise healthy children.Children and adults who either were healthy before exposure to respiratory agents or had a chronic illness (such as asthma, diabetes, hypertension) but excluding people with immune suppression.Jefferson et al. 2014 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5KZWZmZXJzb248L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFy

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ADDIN EN.CITE.DATA (165)Cochrane reviewNAPotential benefit and harm of neuraminidase inhibitors for influenza in all age groups by reviewing all clinical study reports of published and unpublished randomized, placebo-controlled trials and regulatory comments.For the treatment of adults, oseltamivir reduced the time to first alleviation of symptoms by 16.8 hours (95% CI 8.4-25.1, p<0.0001). This represents a reduction in the time to first alleviation of symptoms from 7 to 6.3 days. There was no effect in asthmatic children, but in otherwise healthy children there was a reduction by 29 hours (95% CI 12-47 hours, p=0.001). All age groups. 53 trials in Stage 1 and 46 in Stage 2 (formal analysis), including 20 oseltamivir (9623 participants) and 26 zanamivir trials (14,628 participants).Watanabe, 2013 ADDIN EN.CITE <EndNote><Cite><Author>Watanabe</Author><Year>2013</Year><RecNum>16</RecNum><DisplayText>(167)</DisplayText><record><rec-number>16</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481208311">16</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Watanabe, A.</author></authors></contributors><titles><title>A randomized double-blind controlled study of laninamivir compared with oseltamivir for the treatment of influenza in patients with chronic respiratory diseases</title><secondary-title>Journal of Infection and Chemotherapy</secondary-title></titles><pages>89-97</pages><volume>19</volume><number>1</number><keywords><keyword>Antiviral Agents [adverse effects] [therapeutic use]</keyword><keyword>Asthma [complications]</keyword><keyword>Chronic Disease</keyword><keyword>Double-Blind Method</keyword><keyword>Enzyme Inhibitors [therapeutic use]</keyword><keyword>Influenza A Virus, H1N1 Subtype [drug effects]</keyword><keyword>Influenza, Human [drug therapy] [virology]</keyword><keyword>Neuraminidase [antagonists &amp; inhibitors]</keyword><keyword>Oseltamivir [adverse effects] [therapeutic use]</keyword><keyword>Treatment Outcome</keyword><keyword>Zanamivir [adverse effects] [analogs &amp; derivatives] [therapeutic use]</keyword><keyword>Adult[checkword]</keyword><keyword>Aged[checkword]</keyword><keyword>Female[checkword]</keyword><keyword>Humans[checkword]</keyword><keyword>Male[checkword]</keyword><keyword>Middle Aged[checkword]</keyword><keyword>Sr-airways</keyword></keywords><dates><year>2013</year></dates><accession-num>CN-00844191</accession-num><work-type>Randomized Controlled Trial; Research Support, Non-U.S. Gov&apos;t</work-type><urls><related-urls><url> 22907567</custom3><electronic-resource-num>10.1007/s10156-012-0460-1</electronic-resource-num></record></Cite></EndNote>(167)Japan2009Double-blind, randomized controlled trialLaninamivir group: singe inhalation of 40 mg laninamivir and placebo oseltamivir capsules twice daily for 5 days. Oseltamivir group: one capsule (75 mg) of oseltamivir orally twice daily for 5 days and laninamivir placebo powder once on day 1.Efficacy and safety of laninamivir octanoate, an inhaled neuraminidase inhibitor for the treatment of influenza patients with chronic respiratory diseases.Laninamivir octanoate showed similar efficacy and safety to oseltamivir in the treatment of influenza, including that caused by influenza A(H1N1)2009, in patients with chronic respiratory diseases.203 patients aged ≥20 years. Most patients had underlying bronchial asthma.Kohno 2011 ADDIN EN.CITE <EndNote><Cite><Author>Kohno</Author><Year>2011</Year><RecNum>229</RecNum><DisplayText>(166)</DisplayText><record><rec-number>229</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481210247">229</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kohno, S.</author><author>Kida, H.</author><author>Mizuguchi, M.</author><author>Hirotsu, N.</author><author>Ishida, T.</author><author>Kadota, J.</author><author>Shimada, J.</author></authors></contributors><titles><title>Intravenous Peramivir for Treatment of Influenza A and B Virus Infection in High-Risk Patients</title><secondary-title>Antimicrobial Agents and Chemotherapy</secondary-title></titles><periodical><full-title>Antimicrobial Agents and Chemotherapy</full-title><abbr-1>Antimicrob. Agents Chemother.</abbr-1><abbr-2>Antimicrob Agents Chemother</abbr-2><abbr-3>Antimicrobial Agents &amp; Chemotherapy</abbr-3></periodical><pages>2803-2812</pages><volume>55</volume><number>6</number><dates><year>2011</year><pub-dates><date>2011/04/04</date></pub-dates></dates><publisher>American Society for Microbiology</publisher><isbn>0066-4804&#xD;1098-6596</isbn><urls><related-urls><url>;(166)JapanJan-May 2009Multicenter, uncontrolled, randomized, double-blind studyPeramivir intravenously administered at 300 or 600 mg/day for 1 to 5 days, as neededEfficacy and safety of the novel anti-influenza virus drug peramivir in high-risk patients.In the 600 mg group about 50% shorter duration of illness. In 33% of patients adverse drug reactions, described as “not particularly problematic clinically” with quick recovery in all cases. 37 influenza patients, ≥20 years, with risk factors, including asthma.5 patients with asthma were also taking steroids.Biggerstaff et al. 2014 ADDIN EN.CITE <EndNote><Cite><Author>Biggerstaff</Author><Year>2014</Year><RecNum>241</RecNum><DisplayText>(193)</DisplayText><record><rec-number>241</rec-number><foreign-keys><key app="EN" db-id="5exdx2dfizdzfiewsv8p295z50z9d5zvv0zt" timestamp="1481300306">241</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Biggerstaff, M</author><author>Jhung, MA</author><author>Reed, C</author><author>Garg, S</author><author>Balluz, L</author><author>Fry, AM</author><author>Finelli, L</author></authors></contributors><titles><title>Impact of medical and behavioural factors on influenza-like illness, healthcare-seeking, and antiviral treatment during the 2009 H1N1 pandemic: USA, 2009–2010</title><secondary-title>Epidemiology and infection</secondary-title></titles><periodical><full-title>Epidemiology and Infection</full-title><abbr-1>Epidemiol. Infect.</abbr-1><abbr-2>Epidemiol Infect</abbr-2><abbr-3>Epidemiology &amp; Infection</abbr-3></periodical><pages>114-125</pages><volume>142</volume><number>01</number><dates><year>2014</year></dates><isbn>1469-4409</isbn><urls></urls></record></Cite></EndNote>(193)USA2009-2010USA state-based, random-digit-dialled telephone surveynoneIn?uenza antiviral treatment prescription in influenza like illness (ILI).26% of respondents with ILI received clinical influenza diagnosis. Of these 36% received antiviral treatment. Being younger and employed but not high-risk conditions, including asthma, were associated with antiviral treatment. 216,431 adults ≥18 years, non-institutionalizedData in this study are self-reported and subject to recall and social desirability bias.Diagnosis and treatment are not verified.Biggerstaff et al. 2014 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CaWdnZXJzdGFmZjwvQXV0aG9yPjxZZWFyPjIwMTQ8L1ll

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ADDIN EN.CITE.DATA (159)USA2010-2011USA state-based, random-digit-dialled telephone survey noneIn?uenza antiviral treatment prescription in influenza like illness (ILI).Among adults with a physician diagnosis of in?uenza, 34% received antiviral treatment. Having asthma was not associated with antiviral treatment.75,088 adults (18->65 years) and 15,649 children (0-17 years) were interviewed.Data in this study are self-reported and subject to recall and social desirability bias. Diagnosis and treatment arte not verified.COPD chronic obstructive pulmonary disease; NAI neuraminidase inhibitor; CI confidence interval.Figure 122225270065500Figure 1. Global seasonal influenza vaccination policies for people with asthma. Source data obtained from following references: Europe1,2; Americas3,4; Africa5,6; Asia2,7-9; Oceania7. The following countries have vaccination policies for chronic disease, which includes asthma in the majority of cases: Argentina, Bahamas, Belize, Bolivia, Brazil, Chile, Colombia, Costa Rica, Cuba, Dominican Republic, Ecuador, Egypt, El Salvador, Fiji, Grenada, Ivory Coast, Mauritius, Mexico, Morocco, Panama, Paraguay, Peru, Philippines, Saint Lucia, Thailand, Trinidad and Tobago, Uruguay and Venezuela. This graphic is licenced by a Creative Commons Attribution-ShareAlike 3.0 Unported License: . 1. O’Flanagan, D et al. Seasonal influenza vaccination in EU / EEA, influenza season 2011-12, VENICE II Consortium. 2013;1–67.2. WHO. Evaluation of seasonal influenza vaccination policies and coverage in the WHO European Region. Results from the 2008/2009 and 2009/2010 influenza seasons Based on a joint VENICE–ECDC–WHO survey. 2010;1–29.3. Ropero-alvarez, AM Influenza Vaccine Use In the Americas Network for Evaluation of Influenza Vaccine Effectiveness REVELAC-i. Pan American Health Organization. 2014. . Ropero-Alvarez, AM et al. Expansion of seasonal influenza vaccination in the Americas. BMC Public Health. 2009;9:361.5. Duque, J et al. Influenza vaccines and influenza antiviral drugs in Africa: are they available and do guidelines for their use exist? BMC Public Health. 2014;14:41.6. Green, RJ et al. Influenza Guideline for South Africa – Update 2008. S. Afr. Med. J. 2008;98:224–230.7. Dwyer, D et al. Seasonal influenza vaccine policies, recommendations and use in the World Health Organization’s Western Pacific Region. West. Pacific Surveill. response J. WPSAR. 2013;4:51–9.8. Gupta, V et al. Influenza vaccination guidelines and vaccine sales in Southeast Asia: 2008-2011. 2012;PLoS One 7:e52842.9. Kang, J. Effectiveness and safety of seasonal influenza vaccination in children with underlying respiratory diseases and allergy. Korean J. Pediatr. 2014;57:164–170.Appendix 1Search strategy: Medline formatRespiratory Hypersensitivity/ or Bronchial Hyperractivity or Asthma/ or Status Asthmaticus/(asthma or asthma exacerbation or asthma attack or acute asthma or acute asthmatic attack or asthmatic children or wheez*).mp.(bronchial disorder or airway reactivity or airway hyperresponsiveness or bronchial hyperreactivity or bronchial hyperresponsiveness or lung function or ventilatory function or FEV or FEF or FVC or PEF).mp.or/1-3Influenza, Human/ or Influenza vaccines/ or Influenza A virus or Influenza B virus or Influenzavirus C/ or Influenza A Virus, H5N1 Subtype/ or Influenza A Virus, H1N1 Subtype/ or Influenza A Virus, H3N2 Subtype/exp Epidemiologic Studies/ or exp Intervention Studies/ or exp Evaluation Studies/ or exp Comparative Studies/ or exp Follow-up Studies/ or exp Prospective Studies/ or exp Cohort Studies/ or exp Case-Control Studies/ or exp Cross-Sectional Studies/(prospectiv* or cohort or birth cohort or analytical stud* or cohort stud* or case-control stud*or cross-sectional stud*).mp.Review literature as Topic/ or systematic review.mp.Clinical trial/ or Controlled Clinical Trial/ or Randomized Controlled Trial/exp Placebos/ or exp Random Allocation/ or exp Double-Blind Method/ or exp Single-Blind Method/(trial or clinical trial or controlled clinical trial or random* or randomi?ed controlled trial or double-blind design or single blind design).mp.exp Survey/ or survey.mp.or/6-124 AND 5 AND 13limit 14 to yr=”2000-2014”limit 15 to human Search Strategy: free-field format(Asthma or acute asthmatic attack or status asthmaticus or wheez* or respiratory hypersensitivity or bronchial hyperreactivity or bronchial hyperresponsiveness or airway hyperreactivity or airway hyperresponsiveness)AND (Influenza, human or influenza vaccin* or influenza A virus or influenza B virus or influenzavirus C or influenza A virus subtype H1N1 or Influenza A virus subtype H3N2 or Influenza A virus subtype H5N1)AND(Analytical stud* or epidemiologic* or compar* or evaluat* or follow-up or observation* or cohort stud* or case-control stud* or cross-sectional stud* or systematic review or intervention* or trial* or RCT or double-blind or single-blind or control* or random* or prospective or retrospective) ................
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