%0 Journal Article %A R. A. McIvor %T Future options for disease intervention: important advances in phosphodiesterase 4 inhibitors %D 2007 %R 10.1183/09059180.00010504 %J European Respiratory Review %P 105-112 %V 16 %N 105 %X Current drug treatments for chronic obstructive pulmonary disease (COPD) focus on managing symptoms of the disease and include short- and long-acting β2-agonists, anticholinergic agents (ipratroprium, tiotropium), methylxanthines (theophylline) and inhaled corticosteroids (ICS). Cyclic nucleotide phosphodiesterases (PDEs) play a key role in cell signalling by degrading cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate. PDE4 is expressed in inflammatory cells and inhibition of this enzyme enhances the anti-inflammatory effects of cAMP in all key cells involved in COPD. Two PDE4 inhibitors, roflumilast and cilomilast, have been extensively evaluated in patients with COPD. Results from patients with moderate-to-severe and severe-to-very severe COPD have shown that roflumilast significantly improves forced expiratory volume in one second (FEV1) and significantly decreases exacerbations, particularly in patients with severe disease. Roflumilast is well tolerated with a low incidence of gastrointestinal adverse events that declines with continued treatment. Clinical trials with cilomilast have produced more varied results. Significant improvements in FEV1 and reductions in exacerbation rates versus placebo were observed in two of four trials. Cilomilast also has a high risk for gastrointestinal adverse events that does not appear to dissipate over 24 weeks of treatment. While further research is needed to fully determine the place in chronic obstructive pulmonary disease therapy for phosphodiesterase 4 inhibitors, they have several important potential benefits in the treatment of this disease, including convenient once-daily oral administration and freedom from adverse effects associated with corticosteroids. The fact that phosphodiesterase 4 inhibitors have potent anti-inflammatory effects and are administered orally, thereby reaching the systemic circulation, may decrease the severity of systemic comorbidities in chronic obstructive pulmonary disease patients. %U https://err.ersjournals.com/content/errev/16/105/105.full.pdf