A Specific LTD4/LTE4receptor Antagonist Improves Pulmonary Function in Patients with Mild, Chronic Asthma

LY171883 is a new selective LTD4/LTE4-receptor antagonist. To evaluate the efficacy of LY171883, we studied 138 nonsmoking asthmatic patients, 18 to 65 yr old, in a double-blind, randomized block-design study. All patients were required to demonstrate a greater than or equal to 15% increase in FEV1 after inhaled bronchodilator use and were then randomly assigned to either LY171883 (600 mg) or placebo twice daily for 6 weeks. Assessment of efficacy was measured by inhaled metaproterenol use (mg/wk), symptoms, twice-daily peak expiratory flow, and weekly FEV1 measurements. LY171883-treated patients had improved FEV1 values upon completion of the treatment period compared with placebo recipients (p = 0.003). Metaproterenol use decreased in both groups, but treatment differences, though not statistically significant, favored LY171883 (p = 0.089). Of patients who used at least 23 mg/wk of metaproterenol (36 inhalations) at initiation of the study, those who received LY171883 used significantly less metaproterenol than those who received placebo (p = 0.007). LY171883 was well tolerated and reduced the need for a bronchodilator drug while improving pulmonary function. Results of this study support the hypothesis that leukotrienes LTD4 and/or LTE4 may be important in the pathogenesis of asthma in humans.