A systematic review 1 including 11 studies (including 8 in which the asthma was experimentally induced) was abstracted in DARE. According to the results from 8 trials, zafirlukast antagonizes exercise-induced bronchoconstriction, and blocks both early- and late-phase responses following allergen provocation in patients with atopic asthma. Two multicentre trials found that 20 mg of zafirlukast twice daily significantly reduced symptoms of asthma. A multicentre trial found that both zafirlukast and chromolyn were significantly more effective than placebo with the two drug treatments exhibiting comparable efficacy. Zafirlukast was well tolerated.
Fifty clinical centers randomly allocated 681 patients with chronic, stable asthma to receive placebo or montelukast after demonstrating a forced expiratory volume in 1 second 50% to 85% of the predicted value 2. Twenty-three percent of the patients used concomitant inhaled corticosteroids. Montelukast improved airway obstruction (forced expiratory volume in 1 second, morning and evening peak expiratory flow rate) and patient-reported end points (daytime asthma symptoms, "as-needed" beta-agonist use, nocturnal awakenings) (P<.001 compared with placebo). Montelukast provided near-maximal effect in these end points within the first day of treatment. Tolerance and rebound worsening of asthma did not occur. Montelukast improved outcome end points, including asthma exacerbations, asthma control days (P<.001 compared with placebo), and decreased peripheral blood eosinophil counts (P<.001 compared with placebo). The incidence of adverse events and discontinuations from therapy were similar in the montelukast and placebo groups.
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 were assigned to receive 10 mg of montelukast (54 patients) or placebo (56 patients) once daily at bedtime for 12 weeks in a double-blind study 3. Treatment was followed by a two-week, single-blind washout period during which all patients received placebo. 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).
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