Familial interstitial lung disease and new insights on molecular biology and pathogenesis

Familial idiopathic pulmonary fibrosis is defined as interstitial fibrosis affecting two or more family members, and constitutes 2-20% of all cases of idiopathic pulmonary fibrosis. Investigation of the genetics of familial idiopathic interstitial fibrosis will hopefully provide insight into pathogenesis as well as provide potential targets for therapy. Telomerase mutations, mutations of surfactant genes and mutations of MUC5B have been most commonly reported. However, 80% of familial cases remain without an identifiable mutation, and pathogenesis remains poorly understood. A shift away from an inflammatory driven pathogenesis to one of abnormal wound healing has occurred, with injury to alveolar epithelium and aberrant fibroproliferation likely underlying the process. Such aberrant wound healing likely occurs in a background of genetic predisposition and exposure to environmental stressors. An additional theory of traction related injury has also been proposed.