Phosphodiesterase 4-selective inhibition: novel therapy for the inflammation of COPD.
Chronic obstructive pulmonary disease (COPD), which is increasing in prevalence and a leading cause of death worldwide, is characterised by an 'abnormal' inflammatory response. There is a predominance of CD8(+) T cells, CD68(+) macrophages and, in exacerbations-neutrophils, in both conducting airways and lung parenchyma. Smoking is the most common etiological factor leading to COPD and smoking cessation is the most effective approach to the management of COPD, but it does not resolve the underlying inflammation of COPD, which persists, even in ex-smokers. The presence of mucosal inflammation serves as the rationale for anti-inflammatory therapy. However, while there are reductions in the numbers of mast cells following treatment with inhaled steroids, CD8(+), CD68(+) cells and neutrophils are refractory to such treatment, highlighting a need for additional, more targeted interventions. Phosphodiesterase 4 (PDE4) inhibitors are a promising and novel drug class that have potent activity against several key components of the inflammatory process in COPD. A recently published study has shown that the selective PDE4 inhibitor, cilomilast, reduces the numbers of bronchial mucosal CD8(+) and CD68(+) cells and neutrophils. This review focuses on the nature of the inflammation in COPD and considers how selective PDE4 inhibitors may optimize and advance our treatment of this chronic condition.
Jeffery
Peter
P
Lung Pathology, Imperial College London, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK. p.jeffery@imperial.ac.uk
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D002986:Clinical Trials as Topic; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D006801:Humans; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D011014:Pneumonia / Q000188:drug therapy* / Q000503:physiopathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D006113:United Kingdom / Q000453:epidemiology
D010726:Phosphodiesterase Inhibitors; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4