The primary objective of the translational core is to provide patient access and quality data collection. In order to constuct clinical cohorts for translational investigations, we have chosen to use two populations enriched for pulmonary arterial hypertension - COPD and HIV. Both COPD and HIV+ patients develop pulmonary hypertension at a rate significantly greater than the general population. Morbidity and mortality are also greatly increased in dually affected persons. Through our ongoing clinical studies, we have access to well-charaterized research subjects who are at risk for pulmonary arterial hypertension (PAH). Available cohorts include an Emphysema Registry, Lung Tissue Research Consortium participante, smokers enrolled in our COPD Specialized Center of Clinically Oriented Research grant, and HIV-infected and HIV-uninfected controls from local and multicenter trials. Together, these populations comprise over 2000 research subjects. The human core will support goals of all projects by identifying and characterizing populations to be used for evaluating mechanistic pathways in various PAH sub-phenotypes and by establishing clinical cohorts in whom to test novel therapeutic agents. The core will provide expertise in population screening, use of biomarkers, genomics, computed tomography, Doppler-echocardiography, and right heart catheterization in order to identify and characterize the subphenotypes of PAH in COPD and HIV. The core will supply imaging, catheterization, biobanking, and bioinformatics and statistical support for all Projects. Importantly, the clinical core will synergize with the pre-clinical core to translate findings from bench-to-bedside. The core will meet its goals by addressing the following Specific Aims:
Specific Aim 1 : To establish a cohort exhibiting the PAH phenotype from our diverse patient populations in order to support the Research Projects in translational investigations and to assess utility of plasma NT-proBNP as a biomarker of PAH.
Specific Aim 2 : To assist program investigators in testing novel therapeutic interventions in pulmonary arterial hypertension.
Specific Aim 3. To establish a biorepository for mechanistic studies of PAH sub-phenotypes.

Public Health Relevance

Both COPD and HIV-infected patients are disproportionally affected by pulmonary arterial hypertension (PAH). Little work has been done to understand these particular phenotypes of PAH. Establishing a cohort in whom to explore mechanisms of disease pathogenesis and for testing of novel therapeutics would have a large public health impact for these populations and others who suffer from PAH.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
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Special Emphasis Panel (ZHL1-CSR-A)
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University of Pittsburgh
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