PDE4A and chronic bronchitis: In a pooled analysis of two 1-year, placebo-controlled, double-blind, multicenter studies, roflumilast (a PDE-4 inhibitor) was associated with a 17 % reduction in the rate of moderate-to-severe exacerbations compared with placebo in patients with severe COPD, chronic bronchitis and a history of previous exacerbation (p < 0.0003) (Table 4) [97].