Clinical and pathologic features of familial interstitial pneumonia.
BACKGROUND
Several lines of evidence suggest that genetic factors and environmental exposures play a role in the development of pulmonary fibrosis.


OBJECTIVE
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.
Steele
Mark P
MP
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA. mark.steele@duke.edu
Speer
Marcy C
MC
Loyd
James E
JE
Brown
Kevin K
KK
Herron
Aretha
A
Slifer
Susan H
SH
Burch
Lauranell H
LH
Wahidi
Momen M
MM
Phillips
John A
JA
Sporn
Thomas A
TA
McAdams
H Page
HP
Schwarz
Marvin I
MI
Schwartz
David A
DA
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology; D017563:Lung Diseases, Interstitial / Q000209:etiology / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011859:Radiography; D012129:Respiratory Function Tests; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects