PDE4A and fibrosis: Nonspecific PDE4 inhibitors have been shown to inhibit development and therapeutically reduce fibrosis in multiple preclinical models of pulmonary fibrosis, including bleomycin.109, 110, 111However, the nonspecific PDE4 inhibitors' clinical utility has been hampered by adverse side effects, namely headaches, gastrointestinal, and psychiatric side effects.112Targeted PDE4B inhibition offers potent anti-fibrotic effects with a better side effect profile.