MONTELUKAST, A LEUKOTRIENE-RECEPTOR ANTAGONIST, FOR THE TREATMENT OF MILD ASTHMA AND EXERCISE-INDUCED BRONCHOCONSTRICTION

Background Patients with mild asthma frequently have only exercise-ind uced bronchoconstriction, a symptom of inadequate control of asthma. W e evaluated the ability of montelukast, a leukotriene-receptor antagon ist, to protect such patients against exercise-induced bronchoconstric tion. Methods We randomly assigned 110 patients (age, 15 to 45 years) with mild asthma and a decrease in the forced expiratory volume in one second (FEV1) of at least 20 percent after exercise on two occasions during a placebo run-in period to receive 10 mg of montelukast (54 pat ients) or placebo (56 patients) once daily at bedtime for 12 weeks in a double-blind study. Treatment was followed by a two-week, single-bli nd washout period during which all patients received placebo. Exercise challenges were performed at base line; 20 to 24 hours after dosing a t weeks 4, 8, and 12; and at the end of the washout period. The primar y end point was the area under the curve for FEV1 (expressed as the pe rcent change from base-line values) in the first 60 minutes after exer cise. This measure summarized the extent and duration of bronchoconstr iction after exercise. Results At 12 weeks, montelukast therapy offere d significantly greater protection against exercise-induced bronchocon striction than placebo therapy (expressed as the percentage of inhibit ion of the end points), as evidenced by the improvement in the area un der the FEV1 curve (degree of inhibition, 47.4 per cent; P = 0.002). M ontelukast therapy was also associated with a significant improvement in the maximal decrease in FEV1 after exercise (P = 0.003) and the tim e from the maximal decrease in FEV1 to the return of lung function to within 5 percent of pre-exercise values (P = 0.04). The differences be tween groups in the various measures of lung function were similar at 4, 8, and 12 weeks; there was no evidence of rebound worsening of lung function in the montelukast group after the washout period. After 12 weeks of treatment, patients in the montelukast group were more likely to rate their asthma control as better and less likely to require res cue therapy with a beta-agonist during or after exercise challenge. Th e rates of adverse events were similar in the two groups. Conclusions As compared with placebo, once-daily treatment with montelukast provid ed significant protection against exercise-induced asthma over a 12-we ek period. Tolerance to the medication and rebound worsening of lung f unction after discontinuation of treatment were not seen. (N Engl J Me d 1998;339:147-52.) (C)1998, Massachusetts Medical Society.