The leukotriene D4-receptor antagonist zafirlukast attenuates exercise-induced bronchoconstriction in children

Objective: To determine the effects of zafirlukast on exercise-induced bronchoconstriction in children. Study design: Exercise challenges were done 4 hours after single oral doses of zafirlukast or placebo were administered in asthmatic children (6 to 14 years) treated with beta(2)-agonists alone. Subjects randomized to treatment had a 220% decrease in forced expiratory volume in 1 second (FEV1) after a screening challenge. In a randomized, double-blind, 3-way, crossover design, group 1 (n = 20) received placebo and 5 and 20 mg zafirlukast, and group 2 (n = 19) received placebo and 10 and 40 mg zafirlukast. Maximal percentage fall in FEV1, area under the curve, and time to recovery of FEV1 to within 5% of baseline after the challenge were compared with analysis of variance. Results: Mean values for maximal fall in FEV1 ranged from -8.7% +/-1.7% to -11.1% +/- 1.9% after zafirlukast compared with -17.1% +/- 1.8% and -16.3% +/- 1.9% after placebo. Differences from placebo for fall in FEV1 and area under the curve were significant (P less than or equal to .05) after 5, 20, and 40 mg zafirlukast and approached significance (P less than or equal to .08) after 10 mg zafirlukast. After all zafirlukast doses, recovery times (means of 5 to 7 minutes) decreased significantly (P less than or equal to .05) and by approximately half compared with placebo (11 and 14 minutes). Safety assessments did not differ among treatments. Conclusion: Four hours after dosing, zafirlukast attenuated exercise-induced bronchoconstriction in children.