Allergy Asthma Respir Dis.  2018 Jan;6(1):14-25. 10.4168/aard.2018.6.1.14.

The KAAACI Standardization Committee Report on the procedure and application of the bronchial provocation tests

• Lim KH
• Kim MH
• Yang MS
• Song WJ
• Jung JW
• Lee J
• Suh DI
• Shin YS
• Kwon JW
• Kim SH
• Kim SH
• Lee BJ
• Cho SH
• Korean Academy of Asthma, Allergy and Clinical Immunology Standardization Committee

• KMID: 2403181
• DOI: http://doi.org/10.4168/aard.2018.6.1.14

Abstract

Bronchial provocation tests are of value in the evaluation of airway hyperresponsiveness. Nonspecific bronchial challenge (methacholine, mannitol, exercise, etc.) is used when the symptoms, physical examination, and measurements of pulmonary function are unremarkable in the diagnosis of asthma, when a patient is suspected of having occupational asthma or exercise-induced bronchoconstriction (EIB), and when a screening test for asthma or EIB is required for some occupational groups in whom bronchospasm would pose an unacceptable hazard. Methacholine inhalation challenge is most widely used pharmacologic challenge and highly sensitive. For appropriate interpretation of the results of methacholine provocation, it is important to perform the test with the standardized protocol and to recognize that inhalation methods significantly influence the sensitivity of the procedure. Indirect challenges (e.g., mannitol and exercise) correlate with airway inflammation and are more specific but less sensitive for asthma. Indirect provocation tests are used to confirm asthma, to differentiate asthma from other airway diseases, and to evaluate EIB.

Keyword

Bronchial provocation tests; Methacholine; Mannitol; Exercise test

MeSH Terms

Asthma
Asthma, Occupational
Bronchial Provocation Tests*
Bronchial Spasm
Bronchoconstriction
Diagnosis
Exercise Test
Humans
Inflammation
Inhalation
Mannitol
Mass Screening
Methacholine Chloride
Occupational Groups
Physical Examination
Mannitol
Methacholine Chloride

Reference

1. Busse WW, Lemanske RF Jr. Asthma. N Engl J Med. 2001; 344:350–62.

2. Chapman DG, Irvin CG. Mechanisms of airway hyper-responsiveness in asthma: the past, present and yet to come. Clin Exp Allergy. 2015; 45:706–19.

3. Anderson SD, Brannan JD. Bronchial provocation testing: the future. Curr Opin Allergy Clin Immunol. 2011; 11:46–52.

4. Tiffeneau R, Beauvallet M. Epreuve de bronchoconstriction et de bron-chodilation par aerosols. Bull Acad Med. 1945; 129:165–8.

5. Cockcroft DW, Davis BE. Diagnostic and therapeutic value of airway challenges in asthma. Curr Allergy Asthma Rep. 2009; 9:247–53.

6. Cockcroft D, Davis B. Direct and indirect challenges in the clinical assessment of asthma. Ann Allergy Asthma Immunol. 2009; 103:363–9.

7. Cockcroft DW. Direct challenge tests: airway hyperresponsiveness in asthma: its measurement and clinical significance. Chest. 2010; 138(2 Suppl):18S–24S.

8. Anderson SD. Indirect challenge tests: Airway hyperresponsiveness in asthma: its measurement and clinical significance. Chest. 2010; 138(2 Suppl):25S–30S.

9. Coates AL, Wanger J, Cockcroft DW, Culver BH, Diamant Z, Gauvreau G, et al. ERS technical standard on bronchial challenge testing: general considerations and performance of methacholine challenge tests. Eur Respir J. 2017; 49(5):pii: 1601526.https://doi.org/10.1183/13993003.01526-2016.

10. Crapo RO, Casaburi R, Coates AL, Enright PL, Hankinson JL, Irvin CG, et al. 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.

11. Martin RJ, Wanger JS, Irvin CG, Bucher Bartelson B, Cherniack RM. Methacholine challenge testing: safety of low starting FEV1. Asthma Clinical Research Network (ACRN). Chest. 1997; 112:53–6.

12. Freezer NJ, Croasdell H, Doull IJ, Holgate ST. Effect of regular inhaled beclomethasone on exercise and methacholine airway responses in school children with recurrent wheeze. Eur Respir J. 1995; 8:1488–93.

13. Kim MH, Song WJ, Kim TW, Jin HJ, Sin YS, Ye YM, et al. Diagnostic properties of the methacholine and mannitol bronchial challenge tests: a comparison study. Respirology. 2014; 19:852–6.

14. Anderson SD, Charlton B, Weiler JM, Nichols S, Spector SL, Pearlman DS, et al. Comparison of mannitol and methacholine to predict exercise-induced bronchoconstriction and a clinical diagnosis of asthma. Respir Res. 2009; 10:4.

15. Kim CW. Bronchial asthma with negative methacholine challenge test. J Asthma Allergy Clin Immunol. 2012; 32:150–1.

16. Cockcroft DW, Davis BE, Todd DC, Smycniuk AJ. Methacholine challenge: comparison of two methods. Chest. 2005; 127:839–44.

17. Prieto L, Ferrer A, Domenech J, Pérez-Francés C. Effect of challenge method on sensitivity, reactivity, and maximal response to methacholine. Ann Allergy Asthma Immunol. 2006; 97:175–81.

18. Cockcroft DW, Davis BE. The bronchoprotective effect of inhaling methacholine by using total lung capacity inspirations has a marked influence on the interpretation of the test result. J Allergy Clin Immunol. 2006; 117:1244–8.

19. Todd DC, Davis BE, Hurst TS, Cockcroft DW. Dosimeter methacholine challenge: comparison of maximal versus submaximal inhalations. J Allergy Clin Immunol. 2004; 114:517–9.

20. Holzer K, Anderson SD, Douglass J. Exercise in elite summer athletes: Challenges for diagnosis. J Allergy Clin Immunol. 2002; 110:374–80.

21. Ban GY, Park HL, Hwang EK, Ye YM, Shin YS, Nahm DH, et al. Clinical characteristics of asthmatics having negative results to methacholine bronchial challenge. J Asthma Allergy Clin Immunol. 2012; 32:152–8.

22. Nair P, Martin JG, Cockcroft DC, Dolovich M, Lemiere C, Boulet LP, et al. Airway hyperresponsiveness in asthma: measurement and clinical relevance. J Allergy Clin Immunol Pract. 2017; 5:649–59.e2.

23. Dell SD, Bola SS, Foty RG, Marshall LC, Nelligan KA, Coates AL. Pro-vocative dose of methacholine causing a 20% drop in FEV1 should be used to interpret methacholine challenge tests with modern nebulizers. Ann Am Thorac Soc. 2015; 12:357–63.

24. Sverrild A, Porsbjerg C, Backer V. The use of inhaled mannitol in the diagnosis and management of asthma. Expert Opin Pharmacother. 2012; 13:115–23.

25. Porsbjerg C, Sverrild A, Backer V. The usefulness of the mannitol challenge test for asthma. Expert Rev Respir Med. 2013; 7:655–63.

26. Anderson SD, Brannan J, Spring J, Spalding N, Rodwell LT, Chan K, et al. A new method for bronchial-provocation testing in asthmatic subjects using a dry powder of mannitol. Am J Respir Crit Care Med. 1997; 156(3 Pt 1):758–65.

27. Brannan JD, Anderson SD, Perry CP, Freed-Martens R, Lassig AR, Charlton B, et al. The safety and efficacy of inhaled dry powder mannitol as a bronchial provocation test for airway hyperresponsiveness: a phase 3 comparison study with hypertonic (4.5%) saline. Respir Res. 2005; 6:144.

28. Miedinger D, Chhajed PN, Tamm M, Stolz D, Surber C, Leuppi JD. Diagnostic tests for asthma in firefighters. Chest. 2007; 131:1760–7.

29. Miedinger D, Mosimann N, Meier R, Karli C, Florek P, Frey F, et al. Asthma tests in the assessment of military conscripts. Clin Exp Allergy. 2010; 40:224–31.

30. Brannan JD, Koskela H, Anderson SD, Chew N. Responsiveness to mannitol in asthmatic subjects with exercise- and hyperventilation-induced asthma. Am J Respir Crit Care Med. 1998; 158:1120–6.

31. Holzer K, Anderson SD, Chan HK, Douglass J. Mannitol as a challenge test to identify exercise-induced bronchoconstriction in elite athletes. Am J Respir Crit Care Med. 2003; 167:534–7.

32. Porsbjerg C, Brannan JD. Alternatives to exercise challenge for the objective assessment of exercise-induced bronchospasm: eucapnic voluntary hyperpnoea and the osmotic challenge tests. Breathe. 2010; 7:52–63.

33. Brannan JD, Koskela H, Anderson SD, Chan HK. Budesonide reduces sensitivity and reactivity to inhaled mannitol in asthmatic subjects. Respirology. 2002; 7:37–44.

34. Koskela HO, Hyvärinen L, Brannan JD, Chan HK, Anderson SD. Sensitivity and validity of three bronchial provocation tests to demonstrate the effect of inhaled corticosteroids in asthma. Chest. 2003; 124:1341–9.

35. Leuppi JD, Salome CM, Jenkins CR, Anderson SD, Xuan W, Marks GB, et al. Predictive markers of asthma exacerbation during stepwise dose reduction of inhaled corticosteroids. Am J Respir Crit Care Med. 2001; 163:406–12.

36. Anderson WJ, Lipworth BJ. Relationship of mannitol challenge to methacholine challenge and inflammatory markers in persistent asthmatics receiving inhaled corticosteroids. Lung. 2012; 190:513–21.

37. Porsbjerg C, Brannan JD, Anderson SD, Backer V. Relationship between airway responsiveness to mannitol and to methacholine and markers of airway inflammation, peak flow variability and quality of life in asthma patients. Clin Exp Allergy. 2008; 38:43–50.

38. Sverrild A, Porsbjerg C, Thomsen SF, Backer V. Airway hyperresponsiveness to mannitol and methacholine and exhaled nitric oxide: a random-sample population study. J Allergy Clin Immunol. 2010; 126:952–8.

39. Kim KW. Clinical implication of mannitol challenge test and exaled nitric oxide in childhood asthma. Seoul: Ministry of Health & Welfare;2011.

40. Park TY, Yi MJ, Choi WH, Kim SY, Yu R, Ban JE, et al. Relationship between atopy and bronchial hyperresponsiveness to indirect stimuli in asthmatic children. Allergy Asthma Respir Dis. 2017; 5:83–91.

41. Anderson SD. Exercise-induced bronchoconstriction. Immunol Allergy Clin North Am. 2013; 33:xv–xvii.

42. Parsons JP, Hallstrand TS, Mastronarde JG, Kaminsky DA, Rundell KW, Hull JH, et al. An official American Thoracic Society clinical practice guideline: exercise-induced bronchoconstriction. Am J Respir Crit Care Med. 2013; 187:1016–27.

43. Pongdee T, Li JT. Exercise-induced bronchoconstriction. Ann Allergy Asthma Immunol. 2013; 110:311–5.

44. Park HK, Jung JW, Cho SH, Min KU, Kang HR. What makes a difference in exercise-induced bronchoconstriction: an 8 year retrospective analysis. PLoS One. 2014; 9:e87155.

45. Kippelen P, Anderson SD. Pathogenesis of exercise-induced bronchoconstriction. Immunol Allergy Clin North Am. 2013; 33:299–312. vii.

46. Anderson SD, Connolly NM, Godfrey S. Comparison of bronchoconstriction induced by cycling and running. Thorax. 1971; 26:396–401.

47. Choi IS, Ki WJ, Kim TO, Han ER, Seo IK. Seasonal factors influencing exercise-induced asthma. Allergy Asthma Immunol Res. 2012; 4:192–8.

48. Koh YI, Choi IS. Seasonal difference in the occurrence of exercise-induced bronchospasm in asthmatics: dependence on humidity. Respiration. 2002; 69:38–45.