title: Effects of single-dose zileuton on bronchial hyperresponsiveness in asthmatic patients treated with inhaled corticosteroids.
abstract: The aim of the study was to determine whether zileuton, an inhibitor of 5-lipoxygenase, attenuated bronchial hyperresponsiveness (BHR) in asthmatic subjects who had marked BHR during maintenance treatment with inhaled corticosteroids (ICS). In a randomized, double-blind, placebo-controlled, cross-over study, a challenge test with histamine (provocative concentration of histamine producing a 20% fall in forced expiratory volume in one second (FEV1) (PC20,Hist)) and with ultrasonically nebulized distilled water (UNDW) (provocative dose of UNDW producing a 20% fall in FEV1 (PD20,UNDW)) was performed in seven patients with asthma after intake of either 400 mg zileuton or placebo. All patients (mean age 33 yrs, mean FEV1 111% of predicted) had marked BHR, as indicated by a mean PD20,UNDW of 4.74 mL under treatment for at least 6 months with up to 800 microg ICS (mean 536 microg 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 nor placebo changed baseline airway calibre prior to provocation. Zileuton increased PC20,Hist from 0.99 to 5.64 mg x mL(-1) (2.1 doubling doses; 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 hyperresponsiveness to histamine and ultrasonically nebulized distilled water in asthmatic patients with marked bronchial hyperresponsiveness during treatment with inhaled corticosteroids.
authors.affiliation: Dept of Pulmonary Diseases, Academic Hospital Nijmegen, The Netherlands.
authors.forename: P N
authors.initials: PN
authors.lastname: Dekhuijzen
authors.forename: G P
authors.initials: GP
authors.lastname: Bootsma
authors.forename: P L
authors.initials: PL
authors.lastname: Wielders
authors.forename: L R
authors.initials: LR
authors.lastname: van den Berg
authors.forename: J
authors.initials: J
authors.lastname: Festen
authors.forename: C L
authors.initials: CL
authors.lastname: van Herwaarden
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D001249:Asthma / Q000175:diagnosis* / Q000188:drug therapy* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000188:drug therapy*; D001985:Bronchial Provocation Tests / Q000379:methods; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006632:Histamine; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016859:Lipoxygenase Inhibitors / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D012129:Respiratory Function Tests; D012680:Sensitivity and Specificity; D014867:Water
chemical_list: D000305:Adrenal Cortex Hormones; D016859:Lipoxygenase Inhibitors; D014867:Water; D006632:Histamine; C063449:zileuton; D006918:Hydroxyurea