PDE4A and chronic obstructive pulmonary disease: A pooled analysis of the Roflumilast in the Prevention of COPD Exacerbations While Taking Appropriate Combination Treatment (REACT) and the Roflumilast Effect on Exacerbations in Patients on Dual Therapy (RE2SPOND) RCTs [54] documented that the phosphodiesterase (PDE4) inhibitor roflumilast 500 μg QD reduced the rate of moderate to severe exacerbations in men with COPD (RR 0.82, 95%CI 0.73–0.93; P < 0.01 vs. PCB), while women showed only a numerical decrease after 1 year of therapy.