Phosphodiesterase 4 inhibitors: a new class of agents for the treatment of chronic obstructive pulmonary disease
Chronic inflammation is a hallmark of chronic obstructive pulmonary disease (COPD) and there is an unmet medical need for anti-inflammatory agents that target the inflammatory pathways underlying COPD. The degradation of 3′, 5′-cyclic adenosine monophosphate (cAMP) is modulated by phosphodiesterase (PDE) and has been identified as a putative target to reduce chronic inflammation in obstructive airway diseases. The PDE inhibitors, particularly inhibitors of the subtype PDE4, represent a new class of anti-inflammatory agents that have the potential to directly modulate the inflammatory pathophysiology underlying COPD, a limitation of current pharmacologic therapies. These agents modulate cAMP-mediated inflammation by targeting the cAMPhydrolysing isozyme, PDE4, which is expressed in many immune effector cells implicated in the pathogenesis of COPD. Thus, targeted inhibition of PDE4 provides the rationale for the design of new drugs for the treatment of COPD.