Exercise-induced bronchoconstriction in children: montelukast attenuates the immediate-phase and late-phase responses.
BACKGROUND
Montelukast, a leukotriene receptor antagonist, attenuates exercise-induced bronchoconstriction. We and others have shown that there is a late-phase response 3 to 8 hours after exercise in a subset of asthmatic patients.


OBJECTIVE
We sought to evaluate the protective effect of montelukast on immediate-phase and late-phase responses after exercise challenges.


METHODS
Twenty-two atopic asthmatic children aged 7 to 16 years with reproducible exercise-induced bronchoconstriction (minimum of 15% decrease of FEV(1) from baseline) were enrolled in this placebo-controlled crossover study. Exercise challenges were performed while breathing cold dry air, and FEV(1) measurements were taken up to 480 minutes after exercise. Patients underwent exercise challenges on a screening day and 1 week after placebo treatment. Subsequently, after a week with no treatment, pulmonary function was assessed after breathing dry cold air (control day). Finally, an exercise challenge was carried out after a week of treatment with montelukast.


RESULTS
Reproducible late-phase reactions occurred in 5 of 22 patients, which correlated with the extent of the immediate response (P <.05). After 1 week of treatment with montelukast, a significant decrease of immediate responses was observed. Montelukast treatment compared with placebo was associated with a lower mean maximum decrease of FEV(1) (mean +/- SEM: 17.3% +/- 2.4% and 35.1% +/- 2.6%, respectively), decrease of the area above the curve (267.8% +/- 42.7%/min and 868.0% +/- 103.8%/min, respectively), and shorter time for recovery (6.9 +/- 1.1 minutes and 30.9 +/- 4.0 minutes, respectively; P <.05). Treatment with montelukast also abolished late-phase responses.


CONCLUSIONS
Once daily treatment with oral montelukast attenuated the immediate-phase response and abolished the late-phase response induced by means of exercise challenge in asthmatic children.
Melo
Raul E
RE
Division of Allergy, Clinical Immunology, and Rheumatology, Department of Pediatrics, Federal University of São Paulo-Escola Paulista de Medicina, Rua dos Otonis 725, 04025-002 São Paulo, Brazil.
Solé
Dirceu
D
Naspitz
Charles K
CK
D000085:Acetates / Q000008:administration & dosage / Q000627:therapeutic use*; D000284:Administration, Oral; D000293:Adolescent; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology*; D016084:Bronchoconstriction / Q000187:drug effects*; D002648:Child; D018592:Cross-Over Studies; D003521:Cyclopropanes; D015444:Exercise; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D020024:Leukotriene Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D011804:Quinolines / Q000008:administration & dosage / Q000627:therapeutic use*; D013440:Sulfides
D000085:Acetates; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; C093875:montelukast