Bronchial challenge testing in mild to moderate asthmatics

Jaising M Phadtare; Nagsen N Ramraje; Jenam P Mehta; Rohit Ratnakar Hegde

doi:10.4103/0972-6691.187560

ORIGINAL ARTICLE

Year : 2016 | Volume : 30 | Issue : 1 | Page : 12-16

Bronchial challenge testing in mild to moderate asthmatics

Jaising M Phadtare, Nagsen N Ramraje, Jenam P Mehta, Rohit Ratnakar Hegde
Department of Pulmonary Medicine, Grant Government Medical College, Mumbai, Maharashtra, India

Date of Web Publication

2-Aug-2016

Correspondence Address:
Rohit Ratnakar Hegde
Department of Pulmonary Medicine, Grant Government Medical College, Mumbai - 400 008, Maharashtra
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/0972-6691.187560

Abstract

Background: Bronchial challenge is almost confirmatory test for airway reactivity, a significant test for confirming asthma. Methodology: Already established methodology for the test was used by the direct method using graded concentrations of histamine and using FEV1 as parameter. Results: Fifty mild to moderate asthmatic patients were assessed for airway hyper-responsiveness The youngest was 18 years, the oldest 51 years, the mean age was 34 years. Forty-four percent were males and 56% were females. Bronchial challenge tests were positive in 90% of mild to moderate asthmatic patients. Conclusion: There was a significant linear correlation of PC20 levels with forced expiratory volume in the first second. There was no significant correlation of PC20 levels with serum IgE levels.

Keywords: Asthma, bronchial challenge test, PC ₂₀

How to cite this article:
Phadtare JM, Ramraje NN, Mehta JP, Hegde RR. Bronchial challenge testing in mild to moderate asthmatics. Indian J Allergy Asthma Immunol 2016;30:12-6

How to cite this URL:
Phadtare JM, Ramraje NN, Mehta JP, Hegde RR. Bronchial challenge testing in mild to moderate asthmatics. Indian J Allergy Asthma Immunol [serial online] 2016 [cited 2023 Apr 2];30:12-6. Available from: https://www.ijaai.in/text.asp?2016/30/1/12/187560

Introduction

Asthma, as defined by GINA 2011, is a chronic inflammatory disorder of airways in which many cells and cellular elements play a role. The chronic inflammation is associated with airway hyperresponsiveness that leads to recurrent episodes of wheezing, chest tightness, breathlessness, and coughing particularly at night or early in the morning. These episodes are usually associated with widespread, but variable airflow obstruction within the lung that is often reversible either spontaneously or with treatment. ^[1] Bronchial hyperresponsiveness (BHR) is a characteristic feature of asthma and is attributed to underlying inflammation in the airways. ^[2] Measuring BHR is helpful in the assessment and characterization of airway diseases. The severity of BHR at baseline may also predict the anticipated response to the treatment in asthmatics ^[3] and can be used as an objective measure in optimizing therapeutic regimen in the long-term management of asthma. BHR can be diagnosed with bronchoprovocative testing which involves the applications of a stimulus to the airways to elicit bronchoconstriction, and the resultant airflow limitation is measured. Airway hyperresponsiveness is termed nonspecific when triggered by chemical or physical stimuli and specific when provocated by allergens. Nonspecific airway hyperresponsiveness is a characteristic feature of asthma and has been included in the defining characteristic of the condition. ^[4]

In 1921, Alexander and Paddock showed that pilocarpine consistently induced asthmatic symptoms in asthmatic subjects but not in normals. ^[5] Although the phenomenon of BHR was originally discovered in 1910, aerosol provocation techniques were developed in 1940's. The first demonstration of increased bronchial response to provocation by nonspecific stimulation was done by Curry in 1946. ^[6] In later 1950's, Tiffeneau ^[7] described inhalation provocation tests and subsequent development by different investigators has resulted in a wide variety of methods and agents that can be used in the assessment of BHR. In 1974, Spector and Vandenplas standardized the criteria for bronchial provocation test. ^[8],[9] In 1999, Crapo et al. developed the statement of American Thoracic Society on guidelines for methacholine and exercise challenge testing.

Agents used for bronchoprovocation testing

Numerous agents are known to stimulate bronchoconstriction and have been studied as provocative stimulants.

Indications for bronchoprovocation testing

When a strong clinical suspicion for asthma exists and spirometry performed pre- and post-bronchodilator has not established a diagnosis
Diagnosis of occupational asthma
Used to assess the response to asthma therapy and tailor the therapeutic regimen accordingly ^[10]
In asthmatic patients to assess the degree of responsiveness and gradation of asthmatics.

Contraindications ^[11]

Severe airflow limitation (forced expiratory volume in the first second [FEV ₁ ] <50% predicted or <1.0 L)
Heart attack or stroke in last 3 months
Uncontrolled hypertension, systolic blood pressure (BP) >200, and diastolic BP > 100
Known aortic aneurysm.

Most common agents used are histamine ^[11] and methacholine.

Materials and methods

This prospective study was conducted at a pulmonary unit of a tertiary care public hospital. The participants of the study were adults subjects above the age of 18 years. Before proceeding with the study, the required proforma and plan of the study were submitted to the ethics committee for research on human subjects of the institute and were approved. In all, a total number of fifty subjects were selected for the study over 2 years. Patients with respiratory complaints such as breathlessness, wheezing, cough, and recurrent rhinitis were selected randomly from the outpatient department (OPD) at our center and were screened for the presence of bronchial asthma by symptomatology, history, clinical examination, chest X-ray, X-ray paranasal sinuses (PNS), and serum IgE levels. Patients whose pulmonary function test (PFT) showed mild to moderate obstruction were later subjected to bronchial challenge testing by histamine.

Inclusion criteria

Patients who have been diagnosed as bronchial asthma
Adults between 18 and 60 years
Either sex.

Exclusion criteria

Smokers
Lower respiratory tract infection in past 4 weeks
Bacillary pulmonary tuberculosis
Individuals with FEV ₁ <60% of predicted value
Patients having acute exacerbation of symptoms in past 4 weeks
Debilitated patients
Individuals with valvular heart disease.

All patients were instructed regarding the study, the procedure, and complications. Written and valid consent were taken from the patient for performing the tests.

Withholding medications before bronchial challenge

The PFTs were performed on the machine manufactured by MasterScreen Diffusion Jaeger and the bronchial challenge tests were performed on a machine manufactured by APS Jaeger. Histamine was delivered through a 5 breath dosimeter in our institution. PFTs were performed and reversibility was carried out in mild to moderate obstructive ventilatory defect by short acting B agonists. Such patients were subjected to bronchial challenge testing next day with graded dilutions of histamine.

Spirometry was performed 30 s and 90 s after each histamine dose and drop in FEV ₁ was observed. If the drop was >20%, then the test was stopped there, and the patient was given a short acting 400 μg of salbutamol and reversibility was performed. Patients were also explained about the possible side effects, i.e., chest tightness, nasal congestion, sudden onset breathlessness, and to report them to the doctor immediately. Loaded injections of epinephrine and atropine were kept ready on the table in case of an untoward reaction. PC ₂₀ was calculated on the basis of positivity of bronchial challenge test by the following formula:

where, C ₁ = Second to last methacholine/histamine concentration, C ₂ = Final methacholine/histamine concentration causing 20% fall in FEV ₁ , R ₁ = Percent fall in FEV ₁ after C ₁ , and R ₂ = Percent fall in FEV ₁ after C ₂

Results

Distribution

Age-wise distribution

In our study, the youngest subject was 18 years old, and the oldest subject was 51 years old. The mean age was 34.22 years old.

Gender-wise distribution

In this study, the population of male was 44.4% and female was 54.6%.

Study of bronchial challenge with histamine in mild to moderate asthma

In our study, 90% of mild to moderate asthma patients had positive bronchial challenge testing with histamine. Ten percent had a negative bronchial challenge test.

Correlation between PC ₂₀ and forced expiratory volume in the first second

Using the correlation coefficient test highly significant linear correlation was found between FEV ₁ % predicted and PC ₂₀ levels, i.e., as FEV ₁ increases PC ₂₀ increases.

Correlation between PC ₂₀ and serum IgE

Using correlation coefficient test, no correlation was found between serum IgE levels and PC ₂₀ levels.

Discussion

Around 300 million people in this world are suffering from bronchial asthma. Bronchial challenge tests are one of the important tools in diagnosing asthma, to assess the degree of responsiveness and gradation of asthmatics, to assess the response to asthma therapy, and tailor the therapeutic regimen accordingly. The purpose of this study was to assess the bronchial hyperreactivity in asthmatics and to see the effects of treatment. The study also shows a correlation between PC ₂₀ and other variables. In our study, patients attending (OPD) of a pulmonary unit of a tertiary care public hospital with respiratory complaints were screened by symptomatology, history, clinical examination, spirometry, serum IgE levels, CXR, X-ray PNS, and bronchial challenge tests were performed in fifty patients over a period of 2 years.

Patients having a positive bronchial challenge test, the minimum age was 18 years, and the maximum age was 51 years. The mean age was 34.22 years. The population of male patients was 46.4% and female patients was 54.6% thus showing a slightly higher prevalence of asthma in females. Of these fifty patients, 62% had maxillary sinusitis, 40% had turbinate hypertrophy, and 30% had frontal sinusitis. The results have been shown to be comparable with an earlier study conducted by Leynaert et al., in 2004 ^[12] in which they showed 75-80% of all asthmatics had rhinosinusitis.

In our study, of these fifty patients with bronchial asthma, 45 patients (90%) had a positive bronchial challenge test with increasing dilutions of histamine, while 5 patients (10%) had a negative test. Similar results have been obtained by James and Ryan in 1997 by testing airway hyperresponsiveness. ^[13] These results are also comparable to a study done in 1991 by Backer et al. in which they have mentioned the sensitivity and specificity of histamine challenge tests in asthma. ^[14]

In the present study, we have used the correlation coefficient test to study the correlation between PC ₂₀ and FEV ₁ . It was observed that there is a highly significant linear correlation between PC ₂₀ and FEV ₁ , i.e., as FEV ₁ decreases, PC ₂₀ also decreases (r = 0.567 and P < 0.01). Dirksen et al. ^[15] and Molema et al. in 1989 ^[16] have shown similar linear relations between FEV ₁ and PC ₂₀ . We also studied the correlation between serum IgE levels and PC ₂₀ levels and it was shown that there is no correlation between the two variables (r = −1.118 and P > 0.05). Similar results have been observed by Takeda et al. in 1993 ^[17] in volume of clinical and experimental allergy.

Conclusions

Bronchial challenge tests were positive in 90% of mild to moderate asthmatic patients
There was a significant linear correlation of PC ₂₀ levels with FEV ₁ and peak expiratory flow rate in patients with mild to moderate asthma
There was no significant correlation of PC ₂₀ levels with serum IgE levels.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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