|Year : 2016 | Volume
| 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|
Rohit Ratnakar Hegde
Department of Pulmonary Medicine, Grant Government Medical College, Mumbai - 400 008, Maharashtra
Source of Support: None, Conflict of Interest: None
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 2019 Oct 13];30:12-6. Available from: http://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.  Bronchial hyperresponsiveness (BHR) is a characteristic feature of asthma and is attributed to underlying inflammation in the airways.  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  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. 
In 1921, Alexander and Paddock showed that pilocarpine consistently induced asthmatic symptoms in asthmatic subjects but not in normals.  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.  In later 1950's, Tiffeneau  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. , 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 
- In asthmatic patients to assess the degree of responsiveness and gradation of asthmatics.
Most common agents used are histamine  and methacholine.
- 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.
| 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.
- Patients who have been diagnosed as bronchial asthma
- Adults between 18 and 60 years
- Either sex.
All patients were instructed regarding the study, the procedure, and complications. Written and valid consent were taken from the patient for performing the tests.
- 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.
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|| |
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.
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  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.  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. 
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.  and Molema et al. in 1989  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  in volume of clinical and experimental allergy.
| Conclusions|| |
Financial support and sponsorship
- 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.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Global Initiative for Asthma (GINA); 2011.
WHO/NHLBI. Workshops Report: Global Strategy for Asthma Management and Prevention. Bethesda, MD: National Institutes of Health, National Heart, Lung and Blood Institute; 1995.
Juniper EF, Frith PA, Hargreave FE. Airway responsiveness to histamine and methacholine: Relationship to minimum treatment to control symptoms of asthma. Thorax 1981;36:575-9.
Cockcroft DW. Airway responsiveness. In: Barnes PJ, Grustein MM, Leff AR, Woolcock AJ, editors. Asthma. New York: Lippincott-Raven Publishers; 1997.
Alexander HL, Paddock R. Bronchial asthma, response to pilocarpine and epinephrine. Arch Int Med 1921;27:184.
Curry JJ. The action of histamine on the respiratory tract in normal and asthmatic subjects. J Clin Invest 1946;25:785-91.
Tiffeneau R. Hypersensibilité cholinergo-histaminique pulmonaire de l'asthmatique; relation avec l'hypersensibilité allergénique pulmonaire. Acta Allergol Suppl (Copenh) 1958;5:187-221.
Spector SL, Farr RS. Bronchial inhalation procedures in asthmatics. Med Clin North Am 1974;58:71-84.
Vandenplas O, Malo JL. Inhalation challenges with agents causing occupational asthma. Eur Respir J 1997;10:2612-29.
Sont JK, Willems LN, Bel EH, van Krieken JH, Vandenbroucke JP, Sterk PJ. Clinical control and histopathologic outcome of asthma when using airway hyperresponsiveness as an additional guide to long-term treatment. The AMPUL Study Group. Am J Respir Crit Care Med 1999;159(4 Pt 1):1043-51.
Crapo RO, Casaburi R, Coates AL, Enright PL, Hankinson JL, Irvin CG, et al.
Guidelines for methacholine and exercise challenge testing-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. Am J Respir Crit Care Med 2000;161:309-29.
Leynaert B, Neukirch C, Kony S, Guénégou A, Bousquet J, Aubier M, et al.
Association between asthma and rhinitis according to atopic sensitization in a population-based study. J Allergy Clin Immunol 2004;113:86-93.
James A, Ryan G. Testing airway responsiveness using inhaled methacholine or histamine. Respirology 1997;2:97-105.
Backer V, Groth S, Dirksen A, Bach-Mortensen N, Hansen KK, Laursen EM, et al.
Sensitivity and specificity of the histamine challenge test for the diagnosis of asthma in an unselected sample of children and adolescents. Eur Respir J 1991;4:1093-100.
Dirksen A, Madsen F, Engel T, Frølund L, Heinig JH, Mosbech H. Airway calibre as a confounder in interpreting bronchial responsiveness in asthma. Thorax 1992;47:702-6.
Molema J, van Herwaarden CL, Folgering HT. Effects of inhaled budesonide on the relationships between symptoms, lung function indices and airway hyperresponsiveness in patients with allergic asthma. Pulm Pharmacol 1989;1:179-85.
Takeda K, Shibasaki M, Takita H. Relation between bronchial responsiveness to methacholine and levels of IgE antibody against Dermatophagoides farinae
and serum IgE in asthmatic children. Clin Exp Allergy 1993;23:450-4.