Download Study design: Descriptive / Cross-sectional study

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
BANGALORE
Annexure II
PROFORMA FOR REGISTRATION OF SUBJECT FOR
DISSERTATION
1. NAME OF THE CANDIDATE
ADDRESS
: Dr. GLENN AUSTIN FERNANDES
: 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 outpatient 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 selflimited 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 <18 years)
•
Patients who refuse consent.
7.2 METHOD OF COLLECTION OF DATA:
Sample size: 50 patients
Study design: Descriptive / Cross-sectional study
After obtaining informed consent, patients satisfying inclusion and exclusion criteria
will undergo a detailed clinical evaluation. History will be collected according to the
proforma. A physical examination will be done with special emphasis looking for features of
a) airway hyper-reactivity b) upper airway cough syndrome(7) c) Gastro esophageal Reflux
Disease and d) mucus hyper-secretion. A chest x-ray will also be done as part of routine
evaluation.
Sputum microscopy for cytological evaluation will be done if the patient has active
expectoration. In patients with non-productive cough, sputum will be induced using
hypertonic saline nebulisation and will be subjected to cytological analysis.
After initial spirometric values are recorded, 3% saline solution will be administered
at room temperature for 5 min using a nebulizer. Subjects will be encouraged to cough out
sputum into a sterile container after rinsing their mouth and throat, and this process will be
repeated three times. Slides are prepared and stained for differential cell counts as per
standard technique (8). If squamous cells accounted for > 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 hyperreactivity, Pearson’s correlation will be used.
7.3
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: