CLINICAL CHARACTERIZATION OF FAMILIAL SPONTANEOUS PNEUMOTHORAX

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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. It has been estimated that approximately 10% of individuals who have a spontaneous pneumothorax have a positive family history of the disorder. In recent years it has become evident that in some families the pneumothorax is a manifestation of a known monogenic disease, such as alpha-1-antitrypsin deficiency or Marfan syndrome. In other families, no known disease can explain the pneumothoraces. We propose that familial spontaneous pneumothorax is a disease distinct from other monogenic disorders. To test this hypothesis, we have collected a number of families with this disorder; affected individuals who do not have any of the laboratory or clinical features of alpha-1-antitrypsin deficiency, Marfan syndrome, or any other known disorder associated with spontaneous pneumothoraces. In the largest family we have ruled out two genetic loci associated with spontaneous pneumothoraces. We propose a number of tests for affected individuals and those at-risk for developing the disease that will provide detailed clinical characterization of the features of this disease. First, we will perform detailed physical exams with special attention toward the musculoskeletal, dermatologic, and pulmonary systems. Given the known association between spontaneous pneumothorax and an asthenic body habitus, anthropometric measurements of height, arm span, weight, sitting height, upper arm and upper leg lengths will be taken and compared with NHANES III norms. Alpha-1-antitrypsin quantitative measurements will be determined. Pulmonary function tests including spirometry, body plethysmography, and diffusion capacity will measure physiologic respiratory mechanics. Computed tomography (CT) scans of the chest will be taken in an effort to visualize the peripheral, subpleural blebs or holes in the lung that are the hallmark of this disorder. These proposed characteristics may identify individuals who have an intermediate phenotype, related family members who have normal spirometry and radiographic evidence of localized emphysematous-lesions of the lung not explained by a significant smoking history. The proposed detailed clinical characterization of this disorder will be essential for determining the molecular basis of this disorder by using genetic methods in the future.