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 (FEV(1)) % predicted = 86%] received a single dose of oral roflumilast 1,000 microg or placebo. Patients were administered roflumilast 60 min before allergen challenge, and asthmatic responses were assessed via change in FEV(1) <or=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 FEV(1) of <or=20% (PC(20)FEV(1)). 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 PC(20)FEV(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 FEV(1) from 2 to 9 h after allergen challenge compared with placebo (p = 0.005). Additionally, FEV(1) 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 (c) 2006 S. Karger AG, Basel.
RCT Entities:
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 (FEV(1)) % predicted = 86%] received a single dose of oral roflumilast 1,000 microg or placebo. Patients were administered roflumilast 60 min before allergen challenge, and asthmatic responses were assessed via change in FEV(1) <or=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 FEV(1) of <or=20% (PC(20)FEV(1)). 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 PC(20)FEV(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 FEV(1) from 2 to 9 h after allergen challenge compared with placebo (p = 0.005). Additionally, FEV(1) 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 (c) 2006 S. Karger AG, Basel.
Authors: T E Albertson; M Schivo; N Gidwani; N J Kenyon; M E Sutter; A L Chan; S Louie Journal: Clin Rev Allergy Immunol Date: 2015-02 Impact factor: 8.667
Authors: Monalisa F Azevedo; Fabio R Faucz; Eirini Bimpaki; Anelia Horvath; Isaac Levy; Rodrigo B de Alexandre; Faiyaz Ahmad; Vincent Manganiello; Constantine A Stratakis Journal: Endocr Rev Date: 2013-12-05 Impact factor: 19.871
Authors: Hussam A Murad; Hamed S Habib; Misbahuddin M Rafeeq; Mansour I Sulaiman; Amer S Abdulrahman; Mohamad Nidal Khabaz Journal: Exp Biol Med (Maywood) Date: 2017-01-05
Authors: Madhur D Shastri; Wai Chin Chong; Kamal Dua; Gregory M Peterson; Rahul P Patel; Malik Q Mahmood; Murtaza Tambuwala; Dinesh K Chellappan; Nicole G Hansbro; Shakti D Shukla; Philip M Hansbro Journal: Inflammopharmacology Date: 2020-11-05 Impact factor: 4.473
Authors: Thomas Trian; Janette K Burgess; Kyoko Niimi; Lyn M Moir; Qi Ge; Patrick Berger; Stephen B Liggett; Judith L Black; Brian G Oliver Journal: PLoS One Date: 2011-05-17 Impact factor: 3.240
Authors: Michael R Edwards; Fabrizio Facchinetti; Maurizio Civelli; Gino Villetti; Sebastian L Johnston Journal: Pharmacol Res Perspect Date: 2016-01-15