EFFECTS OF SINGLE-DOSE ZILEUTON ON BRONCHIAL HYPERRESPONSIVENESS IN ASTHMATIC-PATIENTS TREATED WITH INHALED CORTICOSTEROIDS

The aim of the study was to determine whether zileuton, an inhibitor o f 5-lipoxygenase, attenuated bronchial hyperresponsiveness (BHR) in as thmatic subjects who had marked BHE during maintenance treatment with inhaled corticosteroids (ICS). In a randomized, double-blind, placebo- controlled, cross-over study, a challenge test with histamine (provoca tive concentration of histamine producing a 20% fall in forced expirat ory volume in one second (FEV1) (PC20,Hist)) and with ultrasonically n ebulized distilled mater (UNDW) (provocative dose of UNDW producing a 20% fall in FEV1 (PD20,UNDW)) was performed in seven patients with ast hma after intake of either 400 mg zileuton or placebo, All patients (m ean age 33 yrs, mean lipoxygenase inhibitor FEV1 111% of predicted) ha d marked BHR, as indicated by a mean PD20,UNDW of 4.74 mL under treatm ent for at least 6 months with up to 800 mu g ICS (mean 536 mu g daily ), On four different occasions, separated by at least 5 days, two UNDW and two histamine challenge tests were performed in random order 3 h after a morning dose of either zileuton or placebo, Neither zileuton n or placebo changed baseline airway calibre prior to provocation, Zileu ton increased PC20,Hist from 0.99 to 5.64 mg.mL(-1) (2.1 doubling dose s; p<0.03 compared to placebo), and increased PD20,UNDW from 3.10 to 9 .31 mL (1.3 doubling doses; p<0.05 compared to placebo), In conclusion , a single dose of 400 mg zileuton attenuates bronchial hyperresponsiv eness to histamine and ultrasonically nebulized distilled water in ast hmatic patients with marked bronchial hyperresponsiveness during treat ment with inhaled corticosteroids.