Montelukast, a Leukotriene-Receptor Antagonist, for the Treatment of Mild Asthma and Exercise-Induced Bronchoconstriction
Jonathan A. Leff, M.D., William W. Busse, M.D., David Pearlman, M.D., Edwin A. Bronsky, M.D., James Kemp, M.D., Leslie Hendeles, Pharm.D., Robert Dockhorn, M.D., Sudeep Kundu, Ph.D., Ji Zhang, Ph.D., Beth C. Seidenberg, M.D., and Theodore F. Reiss, M.D.
Background Patients with mild asthma frequently have only exercise-inducedbronchoconstriction, a symptom of inadequate control of asthma.We evaluated the ability of montelukast, a leukotriene-receptorantagonist, to protect such patients against exercise-inducedbronchoconstriction.
Methods We randomly assigned 110 patients (age, 15 to 45 years)with mild asthma and a decrease in the forced expiratory volumein one second (FEV1) of at least 20 percent after exercise ontwo occasions during a placebo run-in period to receive 10 mgof montelukast (54 patients) or placebo (56 patients) once dailyat bedtime for 12 weeks in a double-blind study. Treatment wasfollowed by a two-week, single-blind washout period during whichall patients received placebo. Exercise challenges were performedat base line; 20 to 24 hours after dosing at weeks 4, 8, and12; and at the end of the washout period. The primary end pointwas the area under the curve for FEV1 (expressed as the percentchange from base-line values) in the first 60 minutes afterexercise. This measure summarized the extent and duration ofbronchoconstriction after exercise.
Results At 12 weeks, montelukast therapy offered significantlygreater protection against exercise-induced bronchoconstrictionthan placebo therapy (expressed as the percentage of inhibitionof the end points), as evidenced by the improvement in the areaunder the FEV1 curve (degree of inhibition, 47.4 percent; P=0.002).Montelukast therapy was also associated with a significant improvementin the maximal decrease in FEV1 after exercise (P=0.003) andthe time from the maximal decrease in FEV1 to the return oflung function to within 5 percent of pre-exercise values (P=0.04).The differences between groups in the various measures of lungfunction were similar at 4, 8, and 12 weeks; there was no evidenceof rebound worsening of lung function in the montelukast groupafter the washout period. After 12 weeks of treatment, patientsin the montelukast group were more likely to rate their asthmacontrol as better and less likely to require rescue therapywith a -agonist during or after exercise challenge. The ratesof adverse events were similar in the two groups.
Conclusions As compared with placebo, once-daily treatment withmontelukast provided significant protection against exercise-inducedasthma over a 12-week period. Tolerance to the medication andrebound worsening of lung function after discontinuation oftreatment 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.
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.
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N Engl J Med 1998;
339:1783-1786, Dec 10, 1998.
Correspondence
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-agonist during or after exercise challenge. The rates of adverse events were similar in the two groups. 
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