PDE4A and chronic obstructive pulmonary disease: In the past two decades, many PDE inhibitors have been developed, including sildenafil (PDE5 inhibitor) [5], roflumilast (PDE4 inhibitor) [6], and milrinone (PDE3 inhibitor) [7], which were approved for the treatments of erectile dysfunction [8], chronic obstructive pulmonary disease (COPD) [6], and congestive heart failure [9], respectively .