Selective phosphodiesterase-4 (PDE-4) inhibitors in COPD

Chronic obstructive pulmonary disease (COPD) is a worldwide health problem resulting in significant morbidity and mortality; however, it could not be understood totally so far. Treatment options for the disease are quite limited and there is an urgent need for new treatment strategies. Among new therapeutic agents that are under development, a group of significant importance is phosphodiesterase-4 (PDE-4) inhibitors shown to have antiinflammatory actions. Phosphodiesterases are the enzymes responsible from the breakdown and inactivation of cyclic adenosine monophosphate (cAMP) which is an intracellular second messenger molecule. They are present in several structural and inflammatory cells, in these cells the inactivation of cAMP results in a proinflammatory cascade. So, in COPD which goes together with chronic inflammation, prevention of cAMP inactivation via phosphodiesterase enzyme inhibition made phosphodiesterase enzymes potential targets. Main phosphodiesterase playing a part in COPD is PDE-4 which is predominantly present in inflammatory cells and airway smooth muscle cells. The studies therefore focused on inhibitors selective to PDE-4 subtype. The two selective PDE-4 inhibitors that are at Phase III clinical trial stage are cilomilast and roflumilast. The studies have demonstrated that antiinflammatory effects of cilomilast and roflumilast positively contribute to the respiratory function, frequency of exacerbations and quality of life of COPD patients. Despite we need new studies to evaluate the influence of these agents on the natural course of COPD as well as their long-term safety; we can certainly comment that cilomilast and roflumilast are promising hope in COPD treatment by their clinical and antiinflammatory effects.