Idiopathic pulmonary fibrosis (IPF) is a disease of unknown etiology that is characterized by the insidious development of lung fibrosis ultimately leading to distortion of the lung architecture, respiratory failure, and death. IPF is one of several entities associated with pulmonary fibrosis called the idiopathic interstitial pneumonias (IIP). Based on the histopathologic features of the fibrotic process, it is possible to identify four distinct entities: usual interstitial pneumonia (UIP) (synonymous with IPF), nonspecific interstitial pneumonia (NSIP), desquamative interstitial pneumonia DIP), and acute interstitial pneumonia (AIP) (Hamman-Rich lung). Each type appears to have different clinical progression and a different response to anti-inflammatory therapy. Our overall objective is to elucidate the molecular pathogenesis of IPF (UIP) by identifying factors that determine host susceptibility to this disease. We hypothesize that patients who develop pulmonary fibrosis, have a genetic propensity to abnormal lung repair that leads to fibrosis after acute lung injury. We further hypothesize that these genetic susceptibilities may determine if the pathologic process in the lung after an insult becomes UIP, AIP, NSIP, or DIP. To explore these hypotheses we propose to characterize the genetic polymorphisms in candidate genes involved in inflammation, matrix turnover, fibroblast proliferation and differentiation, and epithelial cell proliferation; and to correlate this with indices of disease progression.
