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.