@article {Grootendorst1081, author = {Diana C Grootendorst and Stefanie A Gauw and Renate M Verhoosel and Peter J Sterk and Jeannette J Hospers and Dirk Bredenbr{\"o}ker and Thomas D Bethke and Pieter S Hiemstra and Klaus F Rabe}, title = {Reduction in sputum neutrophil and eosinophil numbers by the PDE4 inhibitor roflumilast in patients with COPD}, volume = {62}, number = {12}, pages = {1081--1087}, year = {2007}, doi = {10.1136/thx.2006.075937}, publisher = {BMJ Publishing Group Ltd}, abstract = {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 (FEV1) 61.0 (12.6)\% predicted) received 500 μg 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 α2-macroglobulin in sputum and the release of tumour necrosis factor α from blood cells were significantly reduced by roflumilast compared with placebo treatment (p\<0.05 for all). Post-bronchodilator FEV1 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 FEV1.}, issn = {0040-6376}, URL = {https://thorax.bmj.com/content/62/12/1081}, eprint = {https://thorax.bmj.com/content/62/12/1081.full.pdf}, journal = {Thorax} }