Clinical and Pathologic Features of Familial Interstitial Pneumonia

Telomere Shortening in Familial and Sporadic Pulmonary Fibrosis

“…Other mutation carriers within the same family have been diagnosed with nonspecific interstitial pneumonitis, granulomatous lung disease, and coal worker pneumoconiosis. Similarly, the occurrence of pathologic findings of diverse subtypes of nonusual interstitial pneumonitis in the same family has been reported for other cohorts of familial pulmonary fibrosis kindreds (30,31). Granulomatous lung disease, as seen in the proband of family F106, has been associated with telomerase mutations earlier; we previously described one of the affected individuals in family F71 with chronic hypersensitivity whose open lung biopsy showed usual interstitial pneumonitis with features of noncaseating granulomas (2).…”

“…Smoking is a known risk factor for IPF (32) and for the development of interstitial lung disease in at-risk individuals in kindreds with the familial form of the disease (30,31). Those with mutations in TERT or TERC had a lower cumulative amount of cigarette smoking than those without mutations, 12.5 versus 19.2 pack-years.…”

Gene Expression Profiling of Familial and Sporadic Interstitial Pneumonia

“…First, it is well known that a substantial number of patients have histologic evidence of both UIP and NSIP in the same lung (6). Moreover, we have found that a substantial portion of the families with familial IIP had several radiographic or histologic patterns of IIP (most often including UIP and NSIP), suggesting that the different histologic types of IIP may be related etiologically and even pathogenically (7). Although more research is needed, multiple lines of evidence suggest that UIP and NSIP do not always represent distinct forms of IIP.…”

“…Although these diseases are thought to be clinically distinct (5), the transcriptional features of the different types of IIP have received little attention. In fact, two publications (6,7) indicate that these distinct clinical-pathologic processes (UIP and NSIP) appear to be related etiologically and pathogenically.…”

“…Finally, variability in the development of pulmonary fibrosis in response to fibrogenic agents has been reported in workers exposed to similar concentrations of asbestos (21,22) as well as in inbred strains of mice challenged with either asbestos (23,24) or bleomycin (25,26). We have reported more than 100 families with two or more cases of IIP and found that familial IIP is pleiotropic and appears to be caused by an interaction between a specific environmental exposure and a gene (or genes) that predisposes to the development of several subtypes of IIP (7). However, the transcriptional features that distinguish familial from nonfamilial (or sporadic) interstitial lung disease have not been established.…”