CHARACTERIZATION OF FAMILIAL IDIOPATHIC PULMONARY FIBROSIS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Idiopathic pulmonary fibrosis (IPF) is a well defined clinical entity that has characteristic clinical, radiographic, and physiologic characteristics. It occurs at a frequency of approximately 13-20 per 100,000. It is the most deadly of the idiopathic pneumonias with no known cure and few treatments. The familial form of the disease is even more rare, accounting for 0.5-3.7% of all the cases of IPF. The molecular basis of the familial form of the disease is unknown. The largest reported families with this disease exhibit vertical transmission, male to male transmission, and variable penetrance. We hypothesize that familial idiopathic pulmonary fibrosis is a rare disease displaying an autosomal dominant pattern of inheritance with variable penetrance. To test this hypothesis we have established a collection of families with familial idiopathic pulmonary fibrosis (IPF) through patient contact and referrals. This proposal seeks to characterize affected and at-risk family members by clinical methods. We propose using the GCRC resources to facilitate characterization of subjects. Each partcipant will undergo a physical exam, submit blood for routine analyses, have pulmonary function testing, a high-resolution CT (HRCT) scan, and undergo bronchoscopy to evaluate bronchoalveolar lavage fluid for markers of inflammation and fibrosis. The pulmonary function testing will include spirometry, body plethysmography, diffusion capacity measurement, and oxygen desaturation with exercise. HRCT scans of the chest will be obtained to evaluate for the characteristic findings of IPF. This is a novel type of study using our unique resources of families with familial IPF. If the pattern of inheritance is indeed autosomal dominant with reduced penetrance, then this type of screening of adult at-risk individuals may identify some with early findings of the disease or those with an intermediate phenotype of the disease. These studies will directly complement our attempts to identify the genetic basis of this disease by classical linkage techniques.