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Previous Volume 339:147-152 July 16, 1998 Number 3 Next

	Full Text PDF Editorial by Hansen-Flaschen, J. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Patients with mild asthma frequently have only exercise-induced bronchoconstriction, a symptom of inadequate control of asthma. We evaluated the ability of montelukast, a leukotriene-receptor antagonist, to protect such patients against exercise-induced bronchoconstriction.

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 patients) or placebo (56 patients) once daily at bedtime for 12 weeks in a double-blind study. Treatment was followed by a two-week, single-blind washout period during which all patients received placebo. Exercise challenges were performed at base line; 20 to 24 hours after dosing at weeks 4, 8, and 12; and at the end of the washout period. The primary end point was the area under the curve for FEV₁ (expressed as the percent change from base-line values) in the first 60 minutes after exercise. This measure summarized the extent and duration of bronchoconstriction after exercise.

Results At 12 weeks, montelukast therapy offered significantly greater protection against exercise-induced bronchoconstriction than placebo therapy (expressed as the percentage of inhibition of the end points), as evidenced by the improvement in the area under the FEV₁ curve (degree of inhibition, 47.4 percent; P=0.002). Montelukast therapy was also associated with a significant improvement in the maximal decrease in FEV₁ after exercise (P=0.003) and the time 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 between 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 rescue therapy with a -agonist during or after exercise challenge. The rates of adverse events were similar in the two groups.

Conclusions As compared with placebo, once-daily treatment with montelukast provided significant protection against exercise-induced asthma over a 12-week period. Tolerance to the medication and rebound worsening of lung function after discontinuation of treatment were not seen.

Source Information

From the Departments of Pulmonary-Immunology and Biostatistics, Merck Research Laboratories, Rahway, N.J. (J.A.L., S.K., J.Z., B.C.S., T.F.R.); the University of Wisconsin, Madison (W.W.B.); the Colorado Allergy and Asthma Clinic, Aurora (D.P.); the AAAA Medical Research Group, Salt Lake City (E.A.B.); the Allergy and Asthma Medical Group and Research Center, San Diego, Calif. (J.K.); the University of Florida School of Pharmacy, Gainesville (L.H.); and International Medical Technical Consultants, Kansas City, Mo. (R.D.).

Address reprint requests to Dr. Reiss at Merck and Company, P.O. Box 2000, Rahway, NJ 07065-0914.

Full Text of this Article

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Exercise-Induced Asthma
Aziz I., Lipworth B. J., Dickey B. F., Adachi R., Honig P. K., Jenkins J. K., Stempel D. A., McFadden E.R., Strauss L., Nelson J. A., Reiss T. F., Hansen-Flaschen J.
Extract | Full Text  
N Engl J Med 1998; 339:1783-1786, Dec 10, 1998. Correspondence

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