TITLE

Reduction in sputum neutrophil and eosinophil numbers by the PDE4 inhibitor roflumilast in patients with COPD

AUTHOR(S)
Grootendorst, Diana C.; Gauw, Stefanie A.; Verhoosel, Renate M.; Sterk, Peter J.; Hospers, Jeannette J.; Bredenbröker, Dirk; Bethke, Thomas D.; Hiemstra, Pieter S.; Rabe, Klaus F.
PUB. DATE
December 2007
SOURCE
Thorax;Dec2007, Vol. 62 Issue 12, p1081
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
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 (1 2.6)% 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 easinophils 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 FE1 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.
ACCESSION #
27885456

 

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