The role of the phosphodiesterase-4 inhibitor, roflumilast, in chronic obstructive pulmonary disease.

9 inhibitors are attractive targets for drug devel‐ opment. PDE4, for example, is one of the main enzymes involved in meta bolism and inflamma‐ tion within the airways.6 Thus, there has been a considerable inter est in PDE4 inhibitors in air‐ way disease, first with cilomilast and current‐ ly with roflumilast. The previous smaller stud‐ ies with cilomilast showed a beneficial effect on lung function,7 while the studies with roflumi‐ last showed that exacerbations could also be re‐ duced, though these reductions were not consis‐ tent across exacerbation severities.8,9 However, a post ‐hoc analysis of the study by Calverley et al., published in 2007, suggested that roflumilast could reduce exacerbations in a subtype of COPD patients, namely patients with more severe airflow obstruction and more frequent exacerbations.9 Thus, in 2 further ran‐ domized controlled trials combined in a single paper and recently published, Calverley et al. de‐ scribe the effect of roflumilast on lung function and exacerbations in patients with FEV1 less than 50% predicted, chronic cough and sputum production, and at least 1 recorded COPD exac‐ erbation treated with oral corticosteroids and/ or treated in hospital in the past year.10 This is an inter esting design because COPD patients with a history of bronchitis and frequent ex‐ acerbation were for the first time recruited to a major trial, and we have shown that these pa‐ tients are more likely to have increased airway inflammation compared with patients with in‐ frequent exacerbations.11 This is also the group of patients with frequent exacerbations where one would expect anti ‐inflammatory therapies to have most effect and where the therapy can be most cost ‐effective by preventing hospital admission. When combined, the results of these studies showed that the prespecified primary endpoints EDITORIAL