The effect of inhibition of 5-lipoxygenase by zileuton in mild-to-moderate asthma.

Abstract

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, beta-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 beta-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.

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@article{Israel1993TheEO, title={The effect of inhibition of 5-lipoxygenase by zileuton in mild-to-moderate asthma.}, author={Elliot Israel and Paul D Rubin and James P Kemp and Jamie Grossman and Wesley Pierson and Subhadra Siegel and David G. Tinkelman and John J. Murray and William W. Busse and Anat Segal and James E. Fish and Harold B . Kaiser and Dennis Keith Ledford and SE Wenzel and Richard R. Rosenthal and John Cohn and Carmine Lanni and Helene Pearlman and Panagiotis Karahalios and Jeffrey M . Drazen}, journal={Annals of internal medicine}, year={1993}, volume={119 11}, pages={1059-66} }