Elliot Israel, MD; Paul Rubin, MD; James P. Kemp, MD; Jay Grossman, MD; William Pierson, MD; Sheldon C. Siegel, MD; David Tinkelman, MD; John J. Murray, MD, PhD; William Busse, MD; Allen T. Segal, MD; James Fish, MD; Harold B. Kaiser, MD; Dennis Ledford, MD; Sally Wenzel, MD; Richard Rosenthal, MD; Judith Cohn, MD, PhD; Carmine Lanni, PhD; Helene Pearlman, MS; Peter Karahalios, MS; Jeffrey M. Drazen, MD
Israel E, Rubin P, Kemp JP, Grossman J, Pierson W, Siegel SC, et al. The Effect of Inhibition of 5-Lipoxygenase by Zileuton in Mild-to-Moderate Asthma. Ann Intern Med. 1993;119:1059-1066. doi: 10.7326/0003-4819-119-11-199312010-00001
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Published: Ann Intern Med. 1993;119(11):1059-1066.
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.
Randomized, double-blind, placebo-controlled study.
University hospitals and private allergy and pulmonary practices.
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.
Zileuton, 2.4 g/d or 1.6 g/d, or placebo for 4 weeks.
Airway function, -agonist use, and symptoms; inhibition of 5-lipoxygenase assessed by measurement of urinary leukotriene E4 (LTE4).
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 -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.
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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Pulmonary/Critical Care, Asthma.
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