Skip to main content
British Journal of Sports Medicine logoLink to British Journal of Sports Medicine
. 2005 Apr;39(4):232–236. doi: 10.1136/bjsm.2004.014282

Effects of montelukast on airway narrowing from eucapnic voluntary hyperventilation and cold air exercise

K Rundell 1, B Spiering 1, J Baumann 1, T Evans 1
PMCID: PMC1725192  PMID: 15793094

Abstract

Background: Exercise induced bronchoconstriction (EIB) is common in elite athletes. Eucapnic voluntary hyperventilation (EVH) is a laboratory test recommended for the identification of EIB in athletes, secondary to a field exercise challenge. Montelukast attenuates EIB, but its protective effect against airway narrowing from EVH has not been investigated.

Objective: To examine the effectiveness of montelukast after exercise and after EVH.

Methods: A randomised, placebo controlled, double blind, crossover study was performed with 11 physically active EIB positive subjects (eight men, three women; mean (SD) age 22.8 (6.8) years). Six hours before each of the following challenges 10 mg montelukast or placebo was ingested: (a) a six minute, cold air (–3°C) maximal effort work accumulation cycle ergometer exercise; (b) EVH, breathing 5% CO2 compressed air at 85% maximal voluntary ventilation for six minutes. Spirometry was performed before and 5, 10, and 15 minutes after the challenge. At least 48 hours was observed between challenges.

Results: No differences in forced expiratory volume in one second (FEV1) were found after the two challenges. Exercise and EVH resulted in falls in FEV1 of 22.4 (18.0) and 25.6 (16.8) respectively. Falls in FEV1 after montelukast were less than after placebo (10.6 (10.6) and 14.3 (11.3) after exercise and EVH respectively; p<0.05). Montelukast provided protection against bronchoconstriction (59% and 53%; p<0.05) for eight exercising subjects and 10 EVH subjects; no protection was afforded for three exercising and one EVH challenged subject.

Conclusions: Both exercise and EVH were potent stimuli of airway narrowing. A single dose of montelukast provided reasonable protection in attenuating bronchoconstriction from either exercise or EVH. The similar protection by montelukast suggests that EVH is a suitable laboratory surrogate for EIB evaluation.

Full Text

The Full Text of this article is available as a PDF (88.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson S. D., Argyros G. J., Magnussen H., Holzer K. Provocation by eucapnic voluntary hyperpnoea to identify exercise induced bronchoconstriction. Br J Sports Med. 2001 Oct;35(5):344–347. doi: 10.1136/bjsm.35.5.344. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anderson S. D., Daviskas E. The mechanism of exercise-induced asthma is ... J Allergy Clin Immunol. 2000 Sep;106(3):453–459. doi: 10.1067/mai.2000.109822. [DOI] [PubMed] [Google Scholar]
  3. Argyros G. J., Roach J. M., Hurwitz K. M., Eliasson A. H., Phillips Y. Y. Eucapnic voluntary hyperventilation as a bronchoprovocation technique: development of a standarized dosing schedule in asthmatics. Chest. 1996 Jun;109(6):1520–1524. doi: 10.1378/chest.109.6.1520. [DOI] [PubMed] [Google Scholar]
  4. Beck K. C., Offord K. P., Scanlon P. D. Bronchoconstriction occurring during exercise in asthmatic subjects. Am J Respir Crit Care Med. 1994 Feb;149(2 Pt 1):352–357. doi: 10.1164/ajrccm.149.2.8306029. [DOI] [PubMed] [Google Scholar]
  5. Burdet L., de Muralt B., Schutz Y., Fitting J. W. Thermogenic effect of bronchodilators in patients with chronic obstructive pulmonary disease. Thorax. 1997 Feb;52(2):130–135. doi: 10.1136/thx.52.2.130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cheng H., Leff J. A., Amin R., Gertz B. J., De Smet M., Noonan N., Rogers J. D., Malbecq W., Meisner D., Somers G. Pharmacokinetics, bioavailability, and safety of montelukast sodium (MK-0476) in healthy males and females. Pharm Res. 1996 Mar;13(3):445–448. doi: 10.1023/a:1016056912698. [DOI] [PubMed] [Google Scholar]
  7. Crapo R. O., Casaburi R., Coates A. L., Enright P. L., Hankinson J. L., Irvin C. G., MacIntyre N. R., McKay R. T., Wanger J. S., Anderson S. D. 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 Jan;161(1):309–329. doi: 10.1164/ajrccm.161.1.ats11-99. [DOI] [PubMed] [Google Scholar]
  8. Dahlén S. E., Dahlén B., Eliasson E., Johansson H., Björck T., Kumlin M., Boo K., Whitney J., Binks S., King B. Inhibition of allergic bronchoconstriction in asthmatics by the leukotriene-antagonist ICI-204,219. Adv Prostaglandin Thromboxane Leukot Res. 1991;21A:461–464. [PubMed] [Google Scholar]
  9. Drazen J. M. Leukotrienes as mediators of airway obstruction. Am J Respir Crit Care Med. 1998 Nov;158(5 Pt 3):S193–S200. doi: 10.1164/ajrccm.158.supplement_2.13tac180. [DOI] [PubMed] [Google Scholar]
  10. Finnerty J. P., Wood-Baker R., Thomson H., Holgate S. T. Role of leukotrienes in exercise-induced asthma. Inhibitory effect of ICI 204219, a potent leukotriene D4 receptor antagonist. Am Rev Respir Dis. 1992 Apr;145(4 Pt 1):746–749. doi: 10.1164/ajrccm/145.4_Pt_1.746. [DOI] [PubMed] [Google Scholar]
  11. Helenius I. J., Tikkanen H. O., Haahtela T. Occurrence of exercise induced bronchospasm in elite runners: dependence on atopy and exposure to cold air and pollen. Br J Sports Med. 1998 Jun;32(2):125–129. doi: 10.1136/bjsm.32.2.125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Holzer Karen, Anderson Sandra D., Douglass Jo. Exercise in elite summer athletes: Challenges for diagnosis. J Allergy Clin Immunol. 2002 Sep;110(3):374–380. doi: 10.1067/mai.2002.127784. [DOI] [PubMed] [Google Scholar]
  13. Hurwitz K. M., Argyros G. J., Roach J. M., Eliasson A. H., Phillips Y. Y. Interpretation of eucapnic voluntary hyperventilation in the diagnosis of asthma. Chest. 1995 Nov;108(5):1240–1245. doi: 10.1378/chest.108.5.1240. [DOI] [PubMed] [Google Scholar]
  14. Israel E., Dermarkarian R., Rosenberg M., Sperling R., Taylor G., Rubin P., Drazen J. M. The effects of a 5-lipoxygenase inhibitor on asthma induced by cold, dry air. N Engl J Med. 1990 Dec 20;323(25):1740–1744. doi: 10.1056/NEJM199012203232505. [DOI] [PubMed] [Google Scholar]
  15. Jones T. R., Labelle M., Belley M., Champion E., Charette L., Evans J., Ford-Hutchinson A. W., Gauthier J. Y., Lord A., Masson P. Pharmacology of montelukast sodium (Singulair), a potent and selective leukotriene D4 receptor antagonist. Can J Physiol Pharmacol. 1995 Feb;73(2):191–201. doi: 10.1139/y95-028. [DOI] [PubMed] [Google Scholar]
  16. Kikawa Y., Hosoi S., Inoue Y., Saito M., Nakai A., Shigematsu Y., Hirao T., Sudo M. Exercise-induced urinary excretion of leukotriene E4 in children with atopic asthma. Pediatr Res. 1991 May;29(5):455–459. doi: 10.1203/00006450-199105010-00009. [DOI] [PubMed] [Google Scholar]
  17. Leff J. A., Busse W. W., Pearlman D., Bronsky E. A., Kemp J., Hendeles L., Dockhorn R., Kundu S., Zhang J., Seidenberg B. C. Montelukast, a leukotriene-receptor antagonist, for the treatment of mild asthma and exercise-induced bronchoconstriction. N Engl J Med. 1998 Jul 16;339(3):147–152. doi: 10.1056/NEJM199807163390302. [DOI] [PubMed] [Google Scholar]
  18. Manning P. J., Watson R. M., Margolskee D. J., Williams V. C., Schwartz J. I., O'Byrne P. M. Inhibition of exercise-induced bronchoconstriction by MK-571, a potent leukotriene D4-receptor antagonist. N Engl J Med. 1990 Dec 20;323(25):1736–1739. doi: 10.1056/NEJM199012203232504. [DOI] [PubMed] [Google Scholar]
  19. Melo Raul E., Solé Dirceu, Naspitz Charles K. Exercise-induced bronchoconstriction in children: montelukast attenuates the immediate-phase and late-phase responses. J Allergy Clin Immunol. 2003 Feb;111(2):301–307. doi: 10.1067/mai.2003.66. [DOI] [PubMed] [Google Scholar]
  20. Peroni Diego G., Piacentini Giorgio L., Ress Michela, Bodini Alessandro, Loiacono Attilio, Aralla Raffaele, Boner Attilio L. Time efficacy of a single dose of montelukast on exercise-induced asthma in children. Pediatr Allergy Immunol. 2002 Dec;13(6):434–437. doi: 10.1034/j.1399-3038.2002.02078.x. [DOI] [PubMed] [Google Scholar]
  21. Reiss T. F., Sorkness C. A., Stricker W., Botto A., Busse W. W., Kundu S., Zhang J. Effects of montelukast (MK-0476); a potent cysteinyl leukotriene receptor antagonist, on bronchodilation in asthmatic subjects treated with and without inhaled corticosteroids. Thorax. 1997 Jan;52(1):45–48. doi: 10.1136/thx.52.1.45. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rundell K. W., Im J., Mayers L. B., Wilber R. L., Szmedra L., Schmitz H. R. Self-reported symptoms and exercise-induced asthma in the elite athlete. Med Sci Sports Exerc. 2001 Feb;33(2):208–213. doi: 10.1097/00005768-200102000-00006. [DOI] [PubMed] [Google Scholar]
  23. Rundell K. W., Wilber R. L., Szmedra L., Jenkinson D. M., Mayers L. B., Im J. Exercise-induced asthma screening of elite athletes: field versus laboratory exercise challenge. Med Sci Sports Exerc. 2000 Feb;32(2):309–316. doi: 10.1097/00005768-200002000-00010. [DOI] [PubMed] [Google Scholar]
  24. Rundell Kenneth W., Anderson Sandra D., Spiering Barry A., Judelson Daniel A. Field exercise vs laboratory eucapnic voluntary hyperventilation to identify airway hyperresponsiveness in elite cold weather athletes. Chest. 2004 Mar;125(3):909–915. doi: 10.1378/chest.125.3.909. [DOI] [PubMed] [Google Scholar]
  25. Sterk P. J., Fabbri L. M., Quanjer P. H., Cockcroft D. W., O'Byrne P. M., Anderson S. D., Juniper E. F., Malo J. L. 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. 1993 Mar;16:53–83. [PubMed] [Google Scholar]
  26. Sue-Chu M., Sandsund M., Holand B., Bjermer L. Montelukast does not affect exercise performance at subfreezing temperature in highly trained non-asthmatic endurance athletes. Int J Sports Med. 2000 Aug;21(6):424–428. doi: 10.1055/s-2000-3838. [DOI] [PubMed] [Google Scholar]
  27. Szczeklik Andrew, Stevenson Donald D. Aspirin-induced asthma: advances in pathogenesis, diagnosis, and management. J Allergy Clin Immunol. 2003 May;111(5):913–922. doi: 10.1067/mai.2003.1487. [DOI] [PubMed] [Google Scholar]
  28. Villaran C., O'Neill S. J., Helbling A., van Noord J. A., Lee T. H., Chuchalin A. G., Langley S. J., Gunawardena K. A., Suskovic S., Laurenzi M. Montelukast versus salmeterol in patients with asthma and exercise-induced bronchoconstriction. Montelukast/Salmeterol Exercise Study Group. J Allergy Clin Immunol. 1999 Sep;104(3 Pt 1):547–553. doi: 10.1016/s0091-6749(99)70322-2. [DOI] [PubMed] [Google Scholar]
  29. Weiler J. M., Layton T., Hunt M. Asthma in United States Olympic athletes who participated in the 1996 Summer Games. J Allergy Clin Immunol. 1998 Nov;102(5):722–726. doi: 10.1016/s0091-6749(98)70010-7. [DOI] [PubMed] [Google Scholar]
  30. Weiler J. M., Ryan E. J., 3rd Asthma in United States olympic athletes who participated in the 1998 olympic winter games. J Allergy Clin Immunol. 2000 Aug;106(2):267–271. doi: 10.1067/mai.2000.108605. [DOI] [PubMed] [Google Scholar]
  31. Wilber R. L., Rundell K. W., Szmedra L., Jenkinson D. M., Im J., Drake S. D. Incidence of exercise-induced bronchospasm in Olympic winter sport athletes. Med Sci Sports Exerc. 2000 Apr;32(4):732–737. doi: 10.1097/00005768-200004000-00003. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Sports Medicine are provided here courtesy of BMJ Publishing Group

RESOURCES