The proposal will allow the candidate the opportunity to attain the following objectives: 1) To complete didactic training in clinical research, advanced statistical techniques, and epidemiology by obtaining a Masters Degree through the Clinical Research Training Program, 2) To gain laboratory experience in molecular techniques, 3) To become an independent clinical investigator focusing on the molecular epidemiology of Pneumocystis carinii and its effects on pulmonary function. The candidate will draw on the complementary expertise of 2 mentors. Joel Weissfeld, MD, MPH is an expert in epidemiology and clinical trials. Karen Norris, PhD is an expert in the molecular biology of Pneumocystis carinii. A Career Development Committee will contribute both research and career guidance. The University of Pittsburgh is a unique setting for the training of clinical researchers because of the wealth of resources available through the Pulmonary Division, the Graduate School of Public Health, the Clinical Research Training Program, and the Center for Human Genetics. The proposal will examine the molecular epidemiology of P. carinii colonization and its clinical significance. The use of the polymerase chain reaction (PCR) to detect low levels of P. carinii has improved our ability to identify colonization. We are interested in understanding the nature of P. carinii colonization and investigating its effects on pulmonary function. Preliminary data suggest that colonization may be prevalent among the HIV-infected population and in those with severe emphysema, but the clinical significance of such colonization is unknown. Subjects with HIV infection are at increased risk of emphysema, and those who have had PCP develop permanent airways obstruction. The presence of P. carinii in the lungs produces inflammatory changes similar to those seen in emphysema. The project will use PCR to compare rates of colonization among HIV-infected subjects, subjects undergoing lung transplantation for emphysema or for causes other than emphysema, and normals. Clinical predictors of colonization will then be examined. Finally, degree of airways obstruction and worsening over time will be compared based on colonization status among HIV-infected subjects and smokers. This study may potentially identify a novel, treatable risk factor for susceptibility to emphysema. In addition, greater insight into the epidemiology of colonization may aid in understanding the transmission and prevention of P. carinii.
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