The Molecular Pathology of Pulmonary Fibrosis

The connective tissue in normal lung confers mechanical strength and elastic recoil properties that allow the lung to undergo repeated cycles of expansion and relaxation. Pulmonary fibrosis develops as a consequence of a wide variety of insults to the lung. Heterogeneity among patients with pulmonary fibrosis may also be reflected in the activity and rate of progression of disease. Intraalveolar connective tissue may also be present, and in some instances, it is the predominant finding. In advanced stages of pulmonary fibrosis, the normal architecture of the lung is partially obliterated: the alveoli are replaced by dense, disorganized connective tissue, and the terminal airways are dilated and thickened, giving the lung a “honeycomb” appearance. The pivotal role of lung connective tissue in the pathogenesis of pulmonary fibrosis has been appreciated for some time. Diverse experimental approaches, utilizing model systems of varying levels of biological complexity, have been employed in investigations aimed at elucidating the biochemical basis of pulmonary fibrosis.