Inhibition of exercise-induced bronchospasm by zileuton: a 5-lipoxygenase inhibitor.
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.
Meltzer
S S
SS
Division of Pulmonary and Critical Care Medicine, University of Maryland School of Medicine, Baltimore, 21201, USA.
Hasday
J D
JD
Cohn
J
J
Bleecker
E R
ER
D000328:Adult; D000420:Albuterol / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001250:Asthma, Exercise-Induced / Q000503:physiopathology / Q000517:prevention & control*; D001986:Bronchial Spasm / Q000503:physiopathology / Q000517:prevention & control*; D001993:Bronchodilator Agents / Q000627:therapeutic use; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D006918:Hydroxyurea / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000502:physiology; D020024:Leukotriene Antagonists; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors; D017997:Leukotriene C4 / Q000037:antagonists & inhibitors; D015289:Leukotrienes / Q000502:physiology; D016859:Lipoxygenase Inhibitors / Q000627:therapeutic use*; D014797:Vital Capacity / Q000187:drug effects
D018927:Anti-Asthmatic Agents; D001993:Bronchodilator Agents; D018836:Inflammation Mediators; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D007975:Leukotriene B4; D017997:Leukotriene C4; D000420:Albuterol; C063449:zileuton; D006918:Hydroxyurea