As a potential effector in cAMP-driven and β2-adrenergic receptor-induced signalling and a newly discovered inhibitor of NF-κB-dependent inflammatory response, Epac1 down-regulation by cigarette smoke may provide an additional explanation for the variable anti-inflammatory capacities of β2-agonists in the treatment of COPD. This evidence concerns the gene NFKB1 and chronic obstructive pulmonary disease.