It was also shown that roflumilast N-oxide, an active metabolite of roflumilast (drug approved for COPD treatment) with potent, selective PDE4 inhibitory activity, significantly reduced TGF-β-Smad signaling in both human bronchial epithelial cells and alveolar epithelial type II cells [20,38]. The gene discussed is PDE4A; the disease is chronic obstructive pulmonary disease.