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1 December 1993 | Volume 119 Issue 11 | Pages 1059-1066
Objective: To evaluate the effectiveness of inhibiting the formation of the 5-lipoxygenase products of arachidonic acid by the 5-lipoxygenase inhibitor zileuton in the treatment of mild-to-moderate asthma.
Design: Randomized, double-blind, placebo-controlled study.
Setting: University hospitals and private allergy and pulmonary practices.
Patients: A total of 139 persons with asthma who had a forced expiratory volume in 1 second (FEV1) of 40% to 75% of the predicted value and who were not being treated with inhaled or oral steroids.
Intervention: Zileuton, 2.4 g/d or 1.6 g/d, or placebo for 4 weeks.
Measurements: Airway function, ß-agonist use, and symptoms; inhibition of 5-lipoxygenase assessed by measurement of urinary leukotriene E4 (LTE4).
Results: Zileuton produced a 0.35-L (95% CI, 0.25 to 0.45 L) increase in the FEV1 within 1 hour of administration (P < 0.001 compared with placebo), equivalent to a 14.6% increase from baseline. After 4 weeks of zileuton therapy, airway function and symptoms improved, with the greatest improvements occurring in the 2.4 g/d group: This group's FEV1 increased by 0.32 L (CI, 0.16 to 0.48 L), a 13.4% increase, compared with a 0.05-L (CI, –0.10 to 0.20 L) increase in patients taking placebo (P = 0.02). Symptoms and frequency of ß-agonist use also decreased with zileuton, 2.4 g/d. The mean urinary LTE4 level decreased by 39.2 pg/mg creatinine (CI, 18.1 to 60.4 pg/mg creatinine) and 26.5 pg/mg creatinine (CI, 6.6 to 46.5 pg/mg creatinine) in the 2.4 g/d and 1.6 g/d groups, respectively, compared with a slight increase in the placebo group (P = 0.007 and P = 0.05). No difference was noted in the number of adverse events among treatment groups.
Conclusions: Inhibition of 5-lipoxygenase can improve airway function and decrease symptoms and medication use in patients with asthma, suggesting that this inhibition can be useful therapy for asthma. Also, 5-lipoxygenase products may mediate part of the baseline airway obstruction in patients with mild-to-moderate asthma.
Author and Article Information
Request for Reprints: Elliot Israel, MD, Pulmonary and Critical Care Division, Beth Israel Hospital, 330 Brookline Avenue, Boston, MA 02215.
ARTICLE
The Effect of Inhibition of 5-Lipoxygenase by Zileuton in Mild-to-Moderate Asthma
Acknowledgments: The authors thank Vivian Simonelli and Carmen Hall for assistance with manuscript preparation.
Grant Support: In part by a grant from Abbott Laboratories. The study was designed by the investigators, and data collection and entry were done by the investigators. Data coding and initial analysis were done by Abbott Laboratories.
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