SS Meltzer, JD Hasday, J Cohn and ER Bleecker
Division of Pulmonary and Critical Care Medicine, University of Maryland School of Medicine, Baltimore, 21201, USA.

Recent evidence suggests that leukotrienes may have a causative role in exercise-induced asthma. Twenty-four subjects with exercise-induced asthma received either 600 mg zileuton, a 5-lipoxygenase inhibitor, or a placebo four times daily for 2 d prior to exercise challenge (a total of nine doses). The last dose was administered in the laboratory 2 h before the exercise challenge. There was no bronchodilation after nine doses of the 5-lipoxygenase inhibitor (p=0.95). The administration of zileuton inhibited bronchospasm after exercise challenge by 40.75% as compared with placebo. Five minutes after the completion of exercise, the zileuton group's FEV1 was 85.76% of the preexercise value, compared with 73.92% of the preexercise value in the placebo group (p<0.01). The maximum percent change in baseline FEV1 after zileuton was a 15.58% decrement from the preexercise level, as compared with a 28.1% decrease after placebo (p<0.001). Five minutes after exercise, the FVC after zileuton was 92.76% of the preexercise value, as compared with 86.26% after placebo (p<0.05). This is the first study in which a 5- lipoxygenase inhibitor has been shown to attenuate exercise-induced asthma. These results suggest that leukotrienes are important biochemical mediators in the development of exercise-induced bronchospasm, and that leukotriene inhibit may have a role in the treatment of this disorder.

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