Pathophysiology of idiopathic pulmonary fibrosis

Despite renewed interest in IPF, the precise biological mechanisms underlying the development of pulmonary fibrosis and irreversible lung destruction remain elusive. Inflammation seems to play a minor role at initial onset. Excessive apoptosis of alveolar epithelial cells in this setting suggests that IPF may result from repeated alveolar epithelial cell injury and activation. This would induce the recruitment, proliferation and activation of mesenchymal cells, leading to the formation of fibroblastic foci and abnormal accumulation of extracellular matrix. The fibroblastic foci are inter-connected in a three-dimensional reticulum. Circulating mesenchymal precursors called fibrocytes, and transdifferentiation of epithelial cells, endothelial cells and/or mesothelial cells, may all contribute to fibroblast accumulation in the lung.