Roflumilast, a phosphodiesterase 4 inhibitor, reduces airway hyperresponsiveness after allergen challenge
Date
2007
Authors
Louw C.
Williams Z.
Venter L.
Leichtl S.
Schmid-Wirlitsch C.
Bredenbroker D.
Bardin P.G.
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Background: Roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, is currently in clinical development for the treatment of asthma. Objectives: This pilot study examined the effect of roflumilast on allergen-induced airway hyperresponsiveness (AHR) to histamine challenge and asthmatic response to allergen challenge. Methods: In a randomized, double-blind, 2-period, crossover trial, 13 patients with mild allergic asthma [mean forced expiratory volume in 1 s (FEV1) % predicted = 86%] received a single dose of oral roflumilast 1,000 μg or placebo. Patients were administered roflumilast 60 min before allergen challenge, and asthmatic responses were assessed via change in FEV1 ≤9 h after allergen challenge. AHR to histamine provocation was measured before and repeated 24 h after allergen provocation. Patients inhaled histamine in doubling concentrations until attaining a decrease in FEV1 of ≤20% (PC20FEV1). Results: Roflumilast had no detectable bronchodilator activity 60 min after administration. Roflumilast significantly attenuated AHR compared with placebo, with a mean change in pre- to postallergen challenge PC20FEV 1 ratio of 1.23 ± 2.75 and 2.51 ± 2.95 for roflumilast and placebo, respectively (p = 0.002). During the late asthmatic response, roflumilast reduced the mean maximum decrease in FEV1 from 2 to 9 h after allergen challenge compared with placebo (p = 0.005). Additionally, FEV1 at 9 h after challenge was significantly higher in patients treated with roflumilast (p = 0.03). Early asthmatic responses to allergen challenge were not significantly reduced by the single dose of roflumilast. Conclusions: Roflumilast attenuated allergen-induced AHR in patients with mild asthma. These results support further investigation of roflumilast as an anti-inflammatory treatment of asthma. Copyright © 2006 S. Karger AG.
Description
Keywords
allergen, histamine, phosphodiesterase IV inhibitor, placebo, roflumilast, abdominal pain, adult, allergic asthma, article, bronchodilatation, clinical article, clinical trial, controlled clinical trial, controlled study, Dermatophagoides pteronyssinus, disease severity, dizziness, double blind procedure, drug activity, drug efficacy, drug fever, drug induced headache, forced expiratory volume, human, male, nausea, nervousness, prick test, priority journal, provocation test, pruritus, randomized controlled trial, side effect, single drug dose, somnolence, statistical significance, tachycardia, Administration, Oral, Adolescent, Adult, Allergens, Aminopyridines, Benzamides, Bronchial Hyperreactivity, Bronchial Provocation Tests, Cross-Over Studies, Cyclopropanes, Dose-Response Relationship, Drug, Double-Blind Method, Follow-Up Studies, Forced Expiratory Volume, Humans, Male, Middle Aged, Phosphodiesterase Inhibitors, Pilot Projects, Treatment Outcome
Citation
Respiration
74
4
74
4