title: Pathogenesis of idiopathic pulmonary fibrosis: review of recent findings.
abstract: Idiopathic pulmonary fibrosis (IPF) is likely to result from the interaction between environmental exposures, including cigarette smoke, and genetic predisposition. This review focuses on clues provided by recent genetic association studies and other selected data and hypotheses. In IPF, association with surfactant mutations has highlighted the importance of type II epithelial cells, while shortened telomeres in some patients suggest that accelerated aging may play a role in the pathogenesis of lung fibrosis, possibly by affecting the renewal/differentiation potential of epithelial cells. The finding that a common variant in mucin 5B predisposes individuals to both familial and sporadic IPF suggests a hitherto under-investigated role of bronchiolar cells and mucins. Although the pathogenetic link between mucins and lung fibrosis is not known, it is possible that MUC5B overexpression interferes with physiological mucosal host defense, with reduced clearance of micro-organisms or inorganic noxious agents, or induction of endoplasmic reticulum stress. Other components of innate and adaptive immunity are likely to be involved in IPF pathogenesis/progression. Finally, the importance of the clotting cascade in IPF pathogenesis has been confirmed by a recent epidemiological study, in which patients with IPF were almost five times more likely than general population controls to have at least one inherited or acquired clotting defect.
authors.affiliation: Interstitial Lung Disease Unit, Royal Brompton Hospital and National Heart and Lung Institute Imperial College London, Emmanuel Kaye Building, 1B Manresa Road, London SW3 6LR UK.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Renzoni
authors.affiliation: Department of Medicine, Division of Pulmonary, Allergy and Critical Care, Emory University 1365 Clifton Rd NE Rm A 4319, Atlanta, GA 30322 USA.
authors.forename: Veeraraghavan
authors.initials: V
authors.lastname: Srihari
authors.affiliation: Respiratory Medicine Department, Ospedale "Le Scotte", University of Siena, viale Bracci 53100 Siena Italy.
authors.forename: Piersante
authors.initials: P
authors.lastname: Sestini