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Clinical and pathologic features of familial interstitial pneumonia Steele MP; Speer MC; Loyd JE; Brown KK; Herron A; Slifer SH; Burch LH; Wahidi MM; Phillips JA 3rd; Sporn TA; McAdams HP; Schwarz MI; Schwartz DAAm J Respir Crit Care Med 2005[Nov]; 172 (9): 1146-52RATIONALE: Several lines of evidence suggest that genetic factors and environmental exposures play a role in the development of pulmonary fibrosis. OBJECTIVES: We evaluated families with 2 or more cases of idiopathic interstitial pneumonia among first-degree family members (familial interstitial pneumonia, or FIP), and identified 111 families with FIP having 309 affected and 360 unaffected individuals. METHODS: The presence of probable or definite FIP was based on medical record review in 28 cases (9.1%); clinical history, diffusing capacity of carbon monoxide (DL(CO)), and chest X-ray in 16 cases (5.2%); clinical history, DL(CO), and high-resolution computed tomography chest scan in 191 cases (61.8%); clinical history and surgical lung biopsy in 56 cases (18.1%); and clinical history and autopsy in 18 cases (5.8%). RESULTS: Older age (68.3 vs. 53.1; p < 0.0001), male sex (55.7 vs. 37.2%; p < 0.0001), and having ever smoked cigarettes (67.3 vs. 34.1%; p < 0.0001) were associated with the development of FIP. After controlling for age and sex, having ever smoked cigarettes remained strongly associated with the development of FIP (odds ratio(adj), 3.6; 95% confidence interval, 1.3-9.8). Evidence of aggregation of disease was highly significant (p < 0.001) among sibling pairs, and 20 pedigrees demonstrated vertical transmission, consistent with autosomal dominant inheritance. Forty-five percent of pedigrees demonstrated phenotypic heterogeneity, with some pedigrees demonstrating several subtypes of idiopathic interstitial pneumonia occurring within the same families. CONCLUSIONS: These findings suggest that FIP may be caused by an interaction between a specific environmental exposure and a gene (or genes) that predisposes to the development of several subtypes of idiopathic interstitial pneumonia.|Adult[MESH]|Age Factors[MESH]|Aged[MESH]|Aged, 80 and over[MESH]|Female[MESH]|Genetic Predisposition to Disease[MESH]|Humans[MESH]|Lung Diseases, Interstitial/etiology/*genetics/*pathology[MESH]|Lung/diagnostic imaging/*pathology/physiopathology[MESH]|Male[MESH]|Middle Aged[MESH]|Radiography[MESH]|Respiratory Function Tests[MESH]|Risk Factors[MESH]|Sex Factors[MESH]|Smoking/adverse effects[MESH] |
