Selective phosphodiesterase-4 inhibitors in chronic obstructive lung disease.
OBJECTIVE
Chronic obstructive pulmonary disease (COPD) is a disease state characterized by airflow limitation that is usually progressive. In addition, an abnormal inflammatory response of the lungs to noxious particles or gases can be seen throughout the airways, parenchyma, and pulmonary vasculature. So far, anti-inflammatory medications (eg, inhaled corticosteroids) have failed to show a major effect on the decline of lung function in COPD patients. Novel anti-inflammatory therapies such as selective phosphodiesterase 4 (PDE4) inhibitors are in clinical development. Their potential role in the management of COPD is described in this review.


RESULTS
Some of the selective PDE4 inhibitors have demonstrated in vitro and in vivo anti-inflammatory activity on cells commonly linked to airway inflammation in COPD, such as neutrophils. While these agents seem to offer only a modest improvement in lung function compared with other bronchodilators, their anti-inflammatory effects appear to provide some substantial benefits in reducing exacerbations and improving health-related quality of life.


CONCLUSIONS
Based on the available data, the second generation of selective PDE4 inhibitors will likely provide additional therapeutic options for the management of COPD. These agents may become an important tool in the treatment of this disease, since they target three important components of COPD: airway obstruction, inflammation, and structural changes.
Soto
Francisco J
FJ
Division of Pulmonary and Critical Care Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. fsoto@mail.mcw.edu
Hanania
Nicola A
NA
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000577:Amides / Q000627:therapeutic use; D000631:Aminopyridines / Q000627:therapeutic use; D001549:Benzamides / Q000627:therapeutic use; D002264:Carboxylic Acids / Q000627:therapeutic use; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D003509:Cyclohexanecarboxylic Acids; D003521:Cyclopropanes / Q000627:therapeutic use; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology; D008168:Lung / Q000201:enzymology; D009570:Nitriles / Q000627:therapeutic use; D009712:Nucleotides, Cyclic / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism
C470045:AWD 12-281; D000577:Amides; D000631:Aminopyridines; D001549:Benzamides; D002264:Carboxylic Acids; D003509:Cyclohexanecarboxylic Acids; D003521:Cyclopropanes; D007211:Indoles; D009570:Nitriles; D009712:Nucleotides, Cyclic; D010726:Phosphodiesterase Inhibitors; C424423:Roflumilast; C433247:Cilomilast; D010727:Phosphoric Diester Hydrolases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4