Given our current state of knowledge, it is clear that further pre-clinical research is necessary to determine the exact role(s) of individual PDE4 isoforms (e.g., those encoded by PDE4A vs. PDE4B vs. PDE4D, and the various isoforms encoded by each of these genes) in critical aspects of the pathogenesis of COPD, such as small airway inflammation, mucus hypersecretion, the activation and tissue effects of neutrophils and macrophages, and the production of various cytokines. Here, PDE4A is linked to chronic obstructive pulmonary disease.