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The Proceedings of the American Thoracic Society 3:546 (2006)
© 2006 The American Thoracic Society
doi: 10.1513/pats.200603-051MS
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Phosphodiesterase 4 Inhibitors in Chronic Obstructive Pulmonary Disease

James F. Donohue

University of North Carolina, UNC School of Medicine, Chapel Hill, North Carolina

Correspondence and requests for reprints should be addressed to James F. Donohue, CB #7020, 420 Burnett-Womack Bldg., UNC School of Medicine, Chapel Hill, NC, USA 27599-7020. E-mail: Jdonohue{at}med.unc.edu

Chronic inflammation of the airway is a key component in the development and progression of chronic obstructive pulmonary disease (COPD). Increased cyclic adenosine monophosphate (cAMP), an intracellular second messenger that regulates various proinflammatory responses, decreases inflammatory cell function. Phosphodiesterase 4 (PDE4) degrades cAMP and is expressed in all airway inflammatory cells involved in the pathogenesis of COPD. Therefore, PDE4 is a logical target for the development of antiinflammatory treatments for COPD. Preclinical studies of PDE4 inhibitors have shown promising antiinflammatory effects. In addition, PDE4 inhibitors have demonstrated efficacy in clinical trials of patients with COPD. In a 24-wk study in patients with moderate to severe COPD, lung function (forced expiratory volume in 1 second [FEV1]) significantly improved from baseline in patients administered the oral PDE4 inhibitor roflumilast 500 µg/d compared with placebo (p < 0.0001). Patients treated with roflumilast experienced 34% fewer exacerbations and an approximately twofold greater improvement in health-related quality of life (measured by St. George's Respiratory Questionnaire) compared with patients receiving placebo. In a 12-wk study of the PDE4 inhibitor cilomilast 15 mg twice daily, patients with COPD experienced improvements in lung hyperinflation, including decreases from baseline compared with placebo in total lung capacity (–250 ml; p = 0.036), functional residual capacity (–290 ml; p = 0.022), residual volume (–390 ml; p = 0.005), and an increase from baseline in slow vital capacity (110 ml; p = 0.080) versus placebo. The antiinflammatory properties and clinical efficacy of PDE4 inhibitors support further development of these agents for the treatment of COPD.

FOOTNOTES

Conflict of Interest Statement: J.F.D. has consulted for Altana and GlaxoSmithKline on PDE4 Inhibitions. For this he received a total of $4,000 from Altana and a total of $6,000 from GlaxoSmithKline.

(Received in original form March 17, 2006; accepted in final form March 28, 2006)





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