Bosentan et fibrose pulmonaire

Abstract

Diseases with pulmonary fibrosis belong to the group of fibrosing interstitial lung diseases (ILD). Idiopathic pulmonary fibrosis (IPF) characterized by a histopathologic pattern of usual interstitial pneumonia is the most frequent and the most severe form of idiopathic ILDs. No treatment has demonstrated to improve survival in IPF. Treatments currently being studied reflect the crucial role of the interaction between alveolar epithelial cells and myofibroblasts. Endothelin-1 promotes fibrogenesis in vitro. The endothelin receptor antagonist bosentan has antifibrotic properties in vitro and in animal models. The clinical trial BUILD-1 demonstrated lack of improvement of the 6-minute walking distance by bosentan in IPF, with a non significant trend towards improved progression-free survival, and improvement of overall survival in patients with a biopsy-confirmed diagnosis of IPF and (or) with little honeycombing on chest imaging. Clinically significant ILD occurs in about a quarter of patients with systemic sclerosis, mostly with a histopathological pattern of nonspecific interstitial pneumonia with frequent fibrosis. Chest imaging initially shows ground glass opacities, which evolve toward fibrosis. Short term and mild efficacy of cyclophosphamide does not seem is not maintained at two years. In the clinical trial BUILD-2, bosentan did not significantly improve systemic sclerosis associated ILD. Further studies are needed concerning the effect of bosentan on survival in IPF early in the course of the disease, and in deteriorating ILD associated with systemic sclerosis.