RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,



RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

BANGALORE

Annexure II

PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION

1. NAME OF THE CANDIDATE : Dr. GLENN AUSTIN FERNANDES

ADDRESS : Post Graduate Student,

Department of Medicine

St. John’s Medical College Hospital,

Bangalore- 560034.

2. NAME OF THE INSTITUTION : St. John’s Medical College Hospital,

Bangalore- 560034.

3. COURSE OF STUDY AND SUBJECT: MD General Medicine

4. DATE OF ADMISSION TO THE COURSE: 18th March 2008

5. TITLE: Assessment of sputum cytology and airway hyper-reactivity in patients with Postinfectious Cough.

6. BRIEF RESUME OF THE INTENDED WORK:

6.1 NEED FOR THE STUDY:

Respiratory ailments are among the commoner ilnesses that bring patients to out-patient and in patient departments of a hospital. Of the wide spectrum of respiratory illnesses, post infectious cough is a frequent cause for outpatient department visits in respiratory medicine practice. Though a common problem, its systematic etiology in a cohort of patients is unknown. Also the reports of sputum analyses are from simple studies only. The management of this entity is unclear with no definitive proven treatment for this condition.

Hence it was a felt need to asssess the characteristics of post infectious cough in patients, with respect to the clinical characteristics, sputum examination findings, spirometry, bronchodilator response and histamine challenge test which would help in understanding the etiopathogenesis of this condition.

6.2 REVIEW OF LITERATURE:

Cough is an important defense mechanism to accelerate mucus clearance and clear excessive secretions and foreign material from the airway. It is one of the most common symptoms for which patients seek medical assistance. Cough is mediated by irritation of vagal nerve fibres, which innervate the airways from the larynx down to the alveoli. An important tussigenic zone met on inspiration is the larynx, but it is only the first in a chain of defensive cough reflexes. The bronchial, tracheal and laryngeal reflexes are transmitted to the brainstem, where the “cough center” is assumed to be located. This is regarded as a functional rather than an anatomical entity. Coughing may be produced by a number of different disorders in distinct anatomic sites. Dependent on the duration two categories of cough are distinguished: acute (lasting less than 3 weeks) and chronic (lasting 3-8 weeks or longer). Postinfectious persistent cough may last for several weeks or even months. The diagnosis of postinfectious cough excludes other underlying diseases. Postinfectious cough is associated with a significant deterioration in the patient’s quality of life (1).

Patients may complain of a persistent cough following symptoms of an upper respiratory tract infection; when the cough lasts for >3 weeks, it is no longer considered to be an acute cough. Instead, it is considered to be in the category of subacute cough which. In the definition of postinfectious cough are the following elements:

1) Symptoms follow an upper respiratory tract infection

2) Duration ≥ 3 weeks

3) The cough lasts ≤ 8 weeks

4) No infiltrates on chest radiography (2).

The pathogenesis of the postinfectious cough is not known; it has been thought to be due to the extensive disruption of epithelial integrity and widespread airway inflammation of the upper and/or lower airways with or without transient airway hyperresponsiveness. The percentage of lymphocytes and neutrophils in BAL fluid is high, and bronchial biopsy material shows a lymphocytic bronchitis (2). Although bronchial hyperresponsiveness is present in some patients with postinfectious cough, eosinophilic inflammation, which is typical of asthma, is absent (3).

Transient inflammation of the lower airways is likely to be important in the pathogenesis of some patients with postinfectious cough. This speculation is based on the fact that cough may be induced by the heightened responsiveness of the cough receptors, by bronchial hyperresponsiveness as is seen in cough-variant asthma, or by impaired mucociliary clearance from the disruption of the epithelial lining of the airways. Because airway inflammation causes mucus hypersecretion, retained secretions resulting from excessive mucus production and decreased clearance may be another important mechanism of cough. Additionally, persistent inflammation of the upper airway, particularly the nose and paranasal sinuses, can be the cause of or can contribute to postinfectious cough. When secretions drain into the hypopharynx and larynx or when there is inflammation of the upper airway, cough receptors can be stimulated, and this may persist for weeks or longer following an upper respiratory infection. Another mechanism to consider in postinfectious cough is gastroesophageal reflux. Although viral infection itself does not cause gastroesophageal reflux disease, the vigorous coughing that follows may induce or aggravate preexisting reflux disease because of the high abdominal pressures that are generated. Patients with the subacute postinfectious cough are therefore similar to those with chronic cough. The pathogenesis is frequently multifactorial (2).

In adults, postinfectious cough has been reported with a variable frequency. In retrospective studies of unselected patients with a history of upper respiratory tract infection, the frequency has ranged from 11 to 25%. During outbreaks of obvious infection with M pneumoniae and Bordetella pertussis, the frequency of postinfectious cough increases to 25 to 50% in selected series (2). In a study from Korea by Nam-hee Kwon et al. 34.8 %(n=184) of the patients were found to have subacute cough. 48.4 %(n=89) of patients with subacute cough had postinfectious cough. This study confirmed that postinfectious cough was the most common cause of cough during the subacute period (4).

The sputum induction method has been validated and standardized (5), providing a safe and relatively noninvasive way to collect material (sputum) from the lower airways. Examination of sputum cellularity makes it possible to exclude or identify inflammation (bronchitis), which is characterized as eosinophilic, neutrophilic, or a combination of the two. The importance of its use in the management of moderate-to-severe persistent asthma has grown as recent studies have demonstrated that the number of severe exacerbations and the number of hospital admissions are lower when induced sputum findings are used in order to design the anti-inflammatory treatment than when the treatment is based on the current guidelines. Induced sputum analysis has also allowed the recognition of nonasthmatic eosinophilic bronchitis as a treatable cause of chronic cough (6).

Current evidence demonstrates that determination of induced sputum cellularity provides, in a minimally invasive way, valid and specific information about the different types of inflammation present in airway diseases. Systematic application of inflammometry using induced sputum cell counts can be beneficial for patients with airway diseases, particularly those with asthma or chronic cough (6).

In a study done in the western population, sputum from patients with post infectious cough was found to have significantly lower percentage of eosinophils compared to patients with asthma. This study concluded that post infectious cough probably has different pathophysiological features when compared to allergic asthma (3).

The diagnosis of postinfectious cough is clinical and one of exclusion. A careful medical history, including knowledge of the medical history of contacts, and sometimes the physical examination may provide clues to the diagnosis. The postinfectious cough is self-limited and will usually resolve in time (2).

6.3 OBJECTIVE OF THE STUDY:

• To describe the epidemiological characteristics of patients presenting with the postinfectious cough.

• To analyse sputum produced or induced sputum of these patients for cytological characteristics and correlate it with airway function using

(i) Bronchodilator response

(ii) Histamine challenge test

7. MATERIALS AND METHODS:

7.1 SOURCE OF DATA:

Location: Out patients and In patients under Department of Medicine and

Chest medicine of St.John’s Medical College Hospital, Bangalore, India.

Study period: One year (December2009 - November 2010).

Inclusion Criteria:

• Patients with productive/nonproductive cough following a respiratory tract infection

• Cough Of duration greater than three weeks but lesser than eight weeks

• With normal chest x-ray

• Age ≥18 years

• Not on oral/parenteral/inhaled corticosteroids

• Patients who consent for the study.

Exclusion Criteria:

• Patients previously diagnosed to have respiratory ailments like bronchial asthma, chronic obstructive pulmonary disease, tuberculosis, bronchiectasis, cystic fibrosis, interstital lung disease, pleural inflammatory disease, pulmonary and pleural neoplasms

• Cardiac failure, current or past dyspnea

• Use of an angiotensin-converting-enzyme inhibitors and beta blockers within the past 2 months

• Pregnancy

• Children and adolescents (age 30% of cells samples are disregarded for assessment. Differential counts of eosinophils, neutrophils, macrophages, lymphocytes, and epithelial cells will be counted. Eosinophilic inflammation was defined as an eosinophil percentage of ≥ 3% of the total count, a marker for hyper-reactive airway.

Patients will also undergo spirometry using Powercube spirometer (Gangshorn Medizin electronics, Germany), as per standard technique at the laboratory of the department of chest diseases, St John’s Medical College Hospital Bangalore. Baseline spirometry with bronchodilator reversibility will be done and the values of the post-bronchodilator forced vital capacity (FVC) and forced expiratory volume (FEV1) will be noted. 400 mcg of inhaled salbutamol will be given and bronchodilator response assessed 15 minutes later. Airway reactivity will be defined by the presence of 12% and 200 ml change in FEV1 or FVC after administer of bronchodilators. If spirometry is normal histamine challenge test will be done according to American/Canadian Thoracic Society guidelines. Histamine diluted with physiologic saline solution will be administered using a nebulizer as a five-breath dosimeter protocol. The provocative concentration of histamine causing a 20% fall in FEV1 (PC20) will be adopted as the marker for bronchial hyper-reactivity.

Statistical analysis:

Data will be analyzed using Microsoft excel and SPSS version 11. Descriptive statistics i.e. Mean±SD, median will be to assess the baseline characteristics.

To identify the relationship between the sputum cytology and bronchial hyper-reactivity, Pearson’s correlation will be used.

3. Does the study require any investigations or interventions to be conducted on patients or other animals? If so, please describe briefly.

• Sputum induction using 3% saline

• Spiromety with bronchodilator response

• Histamine challenge test if spirometry normal.

7.4 Has ethical clearance been obtained from your institution?

Yes

8.0 LIST OF REFERENCES:

1. Gillisen,.Richter, Oster. Clinical efficacy of short term treatment with extra- fine HFA beclomethasone dipropionate in patients with post –infectious persistent cough. Journal of physiology and pharmacology,2007;58(5):223-232.

2. Sidney S. Braman, Postinfectious Cough, Chest 2006;129;138S-146S

3. Zimmerman B, Silverman FS, Tarlo SM, et al. Induced sputum: comparison of postinfectious cough with allergic asthma in children. J Allergy Clin Immunol 2000; 105:495–499.

4. Nam-Hee Kwon et al ,Causes and Clinical Features of Subacute Cough, CHEST May 2006 129 ( 5) 1142-1147.

5. Pizzichini E, Pizzichini MM, Leigh R, Djukanović R, Sterk PJ. Safety of sputum induction. Eur Respir J Suppl. 2002;37:S9-S18.

6.Pablo Moritz et al Determination of the inflammatory component of airway diseases by induced sputum cell counts: use in clinical practice, J Bras Pneumol. 2008;34(11):913-921.

7. Irwin et al, Diagnosis and Management of Cough, Executive Summary, Chest

2006; 129;1S-23S.

8. Todd, Sanford, Davinson. Clinical diagnosis and management by laboratory methods.17th edition. Saunders company, Philadelphia.

9. SIGNATURE OF CANDIDATE:

10. REMARKS OF THE GUIDE:

11. NAME AND DESIGNATION OF:

11.1 GUIDE: Dr. George D’Souza, M.D. DNB

Prof and Head

Dept. of Chest Medicine,

St. John’s Medical College Hospital,

Bangalore – 560 034.

11.2 SIGNATURE:

11.3 CO-GUIDE: Dr. Srinivas, M.D.D.M

Assistant Professor,

Dept. of Chest Medicine,

St. John’s Medical College Hospital,

Bangalore – 560 034.

11.4 SIGNATURE:

11.5 HEAD OF DEPARTMENT: Prof. S.D. Tarey, M.D.

Head of the Department,

Dept. of Medicine,

St. John’s Medical College Hospital,

Bangalore – 560 034.

11.6 SIGNATURE:

12. REMARKS OF THE PRINCIPAL:

12.1 SIGNATURE:

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