Asthma bronchial challenge test

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Lakshmi Gopalakrishnan, M.B.B.S. [2]

Overview

Asthmatics may remain asymptomatic for a long period unless provoked by a stimuli such as a chemical irritant, an environmental allergen, cold or dry air, or rigorous exercise that may precipitate an acute attack. The bronchial challenge test is a procedure performed to provoke airway obstruction using a stimuli that is known to trigger bronchospasm, sudden contraction of the bronchioles. This test helps to identify the specific environmental stimuli that triggers an acute attack and also helps to determine the extent of the reaction.

On the other hand, asthma is overdiagnosed[1][2].

Bronchial Challenge Test

Bronchoprovocation Test

The rationale for bronchoprovocation testing is to assess the degree of underlying bronchial hyper-responsiveness that occurs because of recurrent bronchial inflammation. Bronchial hyper-responsiveness is defined as a state of hyperactive airways that may be easily triggered by an external stimulus to precipitate an episode of bronchospasm.[3]

Mechanisms of Benefit

  • Absence of bronchial hyper-responsiveness on bronchoprovocation test does rule-out the diagnosis of asthma.[4]
  • Asymptomatic airway hyper-responsiveness has shown to be associated with airway inflammation and remodeling and the appearance of asthmatic symptoms is because of an increase in the airway inflammation.[5]
  • The severity of disease has shown to be proportional to the degree of airway responsiveness.[6][7][8]
  • The degree of bronchial hyper-responsiveness has shown to be beneficial in discriminating the risk of near-fatal attacks and hence predict outcomes in symptomatic patients.[9]

Test Specificity

Bronchoprovocation test is not specific for the diagnosis of asthma; however, a negative test indicated by the absence bronchial hyper-responsiveness following allergen inhalation excludes asthma.

Indication

Procedure

  • The patient's medical history is taken to evaluate for possible triggers and a baseline spirometry is conducted to assess initial lung function. Following which, under controlled circumstances, the patient is exposed to specific triggers to assess the extent of bronchial hyper-responsiveness. Spirometry tests are repeated again after inhalation of the allergen and compared with the baseline results.
  • Pharmaceutical agents such as methacholine or histamine may be used as a provocative stimuli to confirm the diagnosis.[13][14][15]
  • Reversibility test or a post bronchodilator test helps to assess the reversibility of airway disease and differentiate between asthma and COPD; wherein, a bronchodilator is administered before performing another round of test for comparison.

Methacholine Challenge Test

Indication

In cases of inconclusive baseline spirometry results, the methacholine challenge test may be used to diagnosis asthma.

Dose

Lower doses of inhaled methacholine have shown to be sufficient to provoke bronchial hyperresponsiveness in asthmatics.

Sensitivity and Specificity

The sensitivity of a positive bronchial hyperactivity with methacholine challenge test is approximately 86%.[16] Patients with allergic rhinitis, COPD, bronchitis may test falsely positive.[4] However, irrespective of the false negatives, and false positive results associated with the test, a negative test demonstrating no airway reactivity, generally excludes the diagnosis of asthma.

Procedure

Based on the American Thoracic Society guidelines,[4] individuals must be specifically trained to perform this test. In addition, tests must be conducted in an appropriate facility. After a baseline spirometry, the patient breathes in incremental doses of nebulized methacholine that provokes narrowing of the airways resulting in bronchoconstriction and subsequently the FEV1 is measured a minute after the inhalation. The procedure is repeated until a 20% FEV1 reduction is observed.[14]

Interpretation

A reduction in FEV1 greater than 20% after provocation with methacholine is indicative of bronchial hyper-responsiveness.

Limitations

  • The test is physically demanding and the results may be affected if the patient is exhausted or has muscular fatigue or weakness.
  • Methacholine at sometimes can stimulate the upper airway responses sufficiently enough to cause violent coughing which can make spirometry difficult or impossible.[17]

References

  1. Aaron SD, Vandemheen KL, Boulet LP, McIvor RA, Fitzgerald JM, Hernandez P; et al. (2008). "Overdiagnosis of asthma in obese and nonobese adults". CMAJ. 179 (11): 1121–31. doi:10.1503/cmaj.081332. PMC 2582787. PMID 19015563.
  2. Aaron SD, Vandemheen KL, FitzGerald JM, Ainslie M, Gupta S, Lemière C; et al. (2017). "Reevaluation of Diagnosis in Adults With Physician-Diagnosed Asthma". JAMA. 317 (3): 269–279. doi:10.1001/jama.2016.19627. PMID 28114551.
  3. Cockcroft DW, Ruffin RE, Dolovich J, Hargreave FE (1977) Allergen-induced increase in non-allergic bronchial reactivity. Clin Allergy 7 (6):503-13. PMID: 589783
  4. 4.0 4.1 4.2 Crapo RO, Casaburi R, Coates AL, Enright PL, Hankinson JL, Irvin CG et al. (2000) 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 161 (1):309-29. PMID: 10619836
  5. Laprise C, Laviolette M, Boutet M, Boulet LP (1999) Asymptomatic airway hyperresponsiveness: relationships with airway inflammation and remodelling. Eur Respir J 14 (1):63-73. PMID: 10489830
  6. Weiss ST, Van Natta ML, Zeiger RS (2000) Relationship between increased airway responsiveness and asthma severity in the childhood asthma management program. Am J Respir Crit Care Med 162 (1):50-6. PMID: 10903219
  7. Juniper EF, Frith PA, Hargreave FE (1981) Airway responsiveness to histamine and methacholine: relationship to minimum treatment to control symptoms of asthma. Thorax 36 (8):575-9. PMID: 7031972
  8. Cockcroft DW, Killian DN, Mellon JJ, Hargreave FE (1977) Bronchial reactivity to inhaled histamine: a method and clinical survey. Clin Allergy 7 (3):235-43. PMID: 908121
  9. Lee P, Abisheganaden J, Chee CB, Wang YT (2001) A new asthma severity index: a predictor of near-fatal asthma? Eur Respir J 18 (2):272-8. PMID: 11529284
  10. Rubinfeld AR, Pain MC (1976) Perception of asthma. Lancet 1 (7965):882-4. PMID: 58147
  11. Irwin RS, Curley FJ, French CL (1990) Chronic cough. The spectrum and frequency of causes, key components of the diagnostic evaluation, and outcome of specific therapy. Am Rev Respir Dis 141 (3):640-7. PMID: 2178528
  12. Vandenplas O, Malo JL (1997) Inhalation challenges with agents causing occupational asthma. Eur Respir J 10 (11):2612-29. PMID: 9426105
  13. 13.0 13.1 Goldstein MF, Pacana SM, Dvorin DJ, Dunsky EH (1994) Retrospective analyses of methacholine inhalation challenges. Chest 105 (4):1082-8. PMID: 8162729
  14. 14.0 14.1 Sterk PJ, Fabbri LM, Quanjer PH, Cockcroft DW, O'Byrne PM, Anderson SD et al. (1993) Airway responsiveness. Standardized challenge testing with pharmacological, physical and sensitizing stimuli in adults. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. Eur Respir J Suppl 16 ():53-83. PMID: 8499055
  15. Covar RA, Colvin R, Shapiro G, Strunk R (2006) Safety of methacholine challenges in a multicenter pediatric asthma study. J Allergy Clin Immunol 117 (3):709-11. DOI:10.1016/j.jaci.2006.01.010 PMID: 16522478
  16. Goldstein MF, Veza BA, Dunsky EH, Dvorin DJ, Belecanech GA, Haralabatos IC (2001) Comparisons of peak diurnal expiratory flow variation, postbronchodilator FEV(1) responses, and methacholine inhalation challenges in the evaluation of suspected asthma. Chest 119 (4):1001-10. PMID: 11296161
  17. Christopher KL, Wood RP, Eckert RC, Blager FB, Raney RA, Souhrada JF (1983) Vocal-cord dysfunction presenting as asthma. N Engl J Med 308 (26):1566-70. DOI:10.1056/NEJM198306303082605 PMID: 6406891

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