PDE4A and chronic obstructive pulmonary disease: Following observations that PDE4 inhibition in rodents reduced tobacco smoke-mediated neutrophil influx in BAL, reduced lung parenchyma infiltration of neutrophils, macrophages and lymphocytes, and inhibited endothelial-neutrophil cell interactions [22, 23], initial studies of roflumilast in populations with COPD focused on its anti-inflammatory effects.