Dunne AE, et al. - Given that neutrophilic inflammation is characteristic of chronic obstructive pulmonary disease (COPD), researchers investigated if roflumilast (PDE4 inhibitor) directly influenced neutrophil migration. They isolated blood-derived neutrophils from nonsmokers, smokers, and patients with COPD. Using Boyden chambers, they measured chemotaxis. Enhanced chemotactic responses toward both CXCL1 and leukotriene B4 were demonstrated by neutrophils from patients with COPD vs control cells. In a concentration-dependent manner, both the active metabolite roflumilast N-oxide and rolipram inhibited chemotaxis, with no variation in responsiveness between subjects. According to the findings, via a cAMP-mediated mechanism requiring activation of Epac1, direct inhibition of neutrophil chemotaxis by roflumilast was evident. COPD neutrophilic inflammation could be attenuated by Epac1 activators.