Antifibrotic Therapy for Idiopathic Pulmonary Fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial pneumonia characterized by a poor response to therapy and a dismal prognosis. Historically, the fibrotic process in IPF has been thought to be preceded by a chronic inflammatory process that injures the lung and causes irreversible fibrosis. This notion has led to an emphasis on antiinflammatory therapy with corticosteroids and immunosuppressive agents (azathioprine or cyclophosphamide). However, several studies have shown little or no benefit with these drugs in addition to potentially harmful side effects. A search for additional therapies has focused on strategies to abrogate fibroblast proliferation and collagen deposition. Unfortunately, certain antifibrotic agents such as colchicine and D-penicillamine, which showed initial promise in preclinical studies, were not shown to be efficacious in patients with IPF. In a recent open-label study, pirfenidone appeared to stabilize pulmonary function and impact favorably on survival in patients with IPF. However, a more definitive study is required to confirm these findings. Exciting research has further defined the fibrotic process as one involving cytokine mediators, alveolar epithelial cell injury, and fibroblast apoptosis. In a preliminary study, interferon gamma was shown to improve or stabilize lung function in steroid-recalcitrant IPF, findings that warrant confirmation in a larger clinical trial. Furthermore, a phase II clinical trial evaluating the efficacy of interferon beta was recently completed with results soon to be available. Agents widely used in clinical practice may have a role in the treatment of IPF. For example, angiotensin-converting enzyme inhibitors, such as captopril, may protect the alveolar epithelium, whereas lovastatin, a cholesterol-lowering agent, may induce fibroblast apoptosis. With new understanding of the regulation of injury, repair, and fibrogenesis, novel therapies will continue to be discovered.