BACKGROUND:Roflumilast is a targeted oral once-daily administered phosphodiesterase 4 (PDE4) inhibitor with clinical efficacy in chronic obstructive pulmonary disease (COPD). Results from in vitro studies with roflumilast indicate that it has anti-inflammatory properties that may be applicable for the treatment of COPD. METHODS: In a crossover study, 38 patients with COPD (mean (SD) age 63.1 (7.0) years, post-bronchodilator forced expiratory volume in 1 s (FEV(1)) 61.0 (12.6)% predicted) received 500 microg roflumilast or placebo once daily for 4 weeks. Induced sputum samples were collected before and after 2 and 4 weeks of treatment. Differential and absolute cell counts were determined in whole sputum samples. Markers of inflammation were determined in sputum supernatants and blood. Spirometry was performed weekly. RESULTS:Roflumilast significantly reduced the absolute number of neutrophils and eosinophils/g sputum compared with placebo by 35.5% (95% CI 15.6% to 50.7%; p = 0.002) and 50.0% (95% CI 26.8% to 65.8%; p<0.001), respectively. The relative proportion of sputum neutrophils and eosinophils was not affected by treatment (p>0.05). Levels of soluble interleukin-8, neutrophil elastase, eosinophil cationic protein and alpha(2)-macroglobulin in sputum and the release of tumour necrosis factor alpha from blood cells were significantly reduced by roflumilast compared with placebo treatment (p<0.05 for all). Post-bronchodilator FEV(1) improved significantly during roflumilast compared with placebo treatment with a mean difference between treatments of 68.7 ml (95% CI 12.9 to 124.5; p = 0.018). CONCLUSION:PDE4 inhibition by roflumilast treatment for 4 weeks reduced the number of neutrophils and eosinophils, as well as soluble markers of neutrophilic and eosinophilic inflammatory activity in induced sputum samples of patients with COPD. This anti-inflammatory effect may in part explain the concomitant improvement in post-bronchodilator FEV(1).
RCT Entities:
BACKGROUND:Roflumilast is a targeted oral once-daily administered phosphodiesterase 4 (PDE4) inhibitor with clinical efficacy in chronic obstructive pulmonary disease (COPD). Results from in vitro studies with roflumilast indicate that it has anti-inflammatory properties that may be applicable for the treatment of COPD. METHODS: In a crossover study, 38 patients with COPD (mean (SD) age 63.1 (7.0) years, post-bronchodilator forced expiratory volume in 1 s (FEV(1)) 61.0 (12.6)% predicted) received 500 microg roflumilast or placebo once daily for 4 weeks. Induced sputum samples were collected before and after 2 and 4 weeks of treatment. Differential and absolute cell counts were determined in whole sputum samples. Markers of inflammation were determined in sputum supernatants and blood. Spirometry was performed weekly. RESULTS:Roflumilast significantly reduced the absolute number of neutrophils and eosinophils/g sputum compared with placebo by 35.5% (95% CI 15.6% to 50.7%; p = 0.002) and 50.0% (95% CI 26.8% to 65.8%; p<0.001), respectively. The relative proportion of sputum neutrophils and eosinophils was not affected by treatment (p>0.05). Levels of soluble interleukin-8, neutrophil elastase, eosinophil cationic protein and alpha(2)-macroglobulin in sputum and the release of tumour necrosis factor alpha from blood cells were significantly reduced by roflumilast compared with placebo treatment (p<0.05 for all). Post-bronchodilator FEV(1) improved significantly during roflumilast compared with placebo treatment with a mean difference between treatments of 68.7 ml (95% CI 12.9 to 124.5; p = 0.018). CONCLUSION:PDE4 inhibition by roflumilast treatment for 4 weeks reduced the number of neutrophils and eosinophils, as well as soluble markers of neutrophilic and eosinophilic inflammatory activity in induced sputum samples of patients with COPD. This anti-inflammatory effect may in part explain the concomitant improvement in post-bronchodilator FEV(1).
Authors: A Di Stefano; A Capelli; M Lusuardi; G Caramori; P Balbo; F Ioli; S Sacco; I Gnemmi; P Brun; I M Adcock; B Balbi; P J Barnes; K F Chung; C F Donner Journal: Clin Exp Allergy Date: 2001-06 Impact factor: 5.018
Authors: Gavin C Donaldson; Terence A R Seemungal; Irem S Patel; Angshu Bhowmik; Tom M A Wilkinson; John R Hurst; Peter K Maccallum; Jadwiga A Wedzicha Journal: Chest Date: 2005-10 Impact factor: 9.410
Authors: Fabienne Gally; Y Peter Di; Sean K Smith; Maisha N Minor; Yang Liu; Donna L Bratton; S Courtney Frasch; Nicole M Michels; Stephanie R Case; Hong Wei Chu Journal: Am J Pathol Date: 2011-05 Impact factor: 4.307
Authors: J Michael Wells; Patricia L Jackson; Liliana Viera; Surya P Bhatt; Joshua Gautney; Guy Handley; R Wilson King; Xin Xu; Amit Gaggar; William C Bailey; Mark T Dransfield; J Edwin Blalock Journal: Am J Respir Crit Care Med Date: 2015-10-15 Impact factor: 21.405