Inflammation, Aging, Microbes, Obstructive Lung Disease and Diffusion Abnormalities (I AM OLD-DA) Study - Diversity Supplement

摘要（多样性增刊）

ABSTRACT (Diversity Supplement) Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality in persons with HIV, and its clinical significance is increasing as the HIV+ population ages. New therapies to treat or prevent this growing problem will require improved mechanistic insights. However, our current understanding of the pathogenesis underlying HIV+ COPD is limited, but both HIV-related and COPD-specific mechanisms are hypothesized. The I AM OLD-DA Study seeks to improve our understanding using a novel, established multinational (US and Uganda) cohort of HIV+ persons. The study is measuring HIV-related and COPD-specific markers of immune activation, inflammation, lung injury, and cellular aging in blood and performing lung function testing. It is examining the associations between the selected markers and lung function (spirometry and diffusion capacity for carbon monoxide, DLco). Our central hypothesis is that: (1) different pathogenic mechanisms underlie abnormal spirometry and abnormal DLco and (2) different pathogenic mechanisms underlie COPD/emphysema (i.e., abnormal spirometry and abnormal DLco) and isolated reductions in DLco (i.e., abnormal DLco with normal spirometry), referred to as iso↓DLco hereafter. To test this hypothesis, we proposed three Aims, the first two of which are detailed here and are part of this Diversity Supplement proposal: Aim 1: To test the hypothesis that persistent abnormalities in markers of immune activation, inflammation, lung injury, and cellular aging measured in peripheral blood are associated with subsequent changes (declines) in FEV1/FVC and FEV1. Aims 2A and 2B: To test the hypothesis that persistent abnormalities in the same markers measured in peripheral blood are associated with subsequent changes (declines) in DLco and that the markers associated with diffusion abnormalities in COPD/emphysema will be different from the markers associated with iso↓DLco. This Diversity Supplement to the I AM OLD-DA Study will support a meritorious post-baccalaureate scholar from an under-privileged background who seeks a future career as a physician-scientist and will provide him with essential research training, mentoring, and hands-on experience in support of his application to medical school. Diversity Supplement Aim 1: To test the hypothesis that persistent elevations in plasma IL-6 and hsCRP (non- specific markers of inflammation previously associated with abnormal spirometry) are associated with subsequent declines in spirometry: FEV1/FVC and FEV1. Aim 2A: To test the hypothesis that persistent elevations in plasma pulmonary and activation-regulated chemokine (PARC/CCL-18) and club cell secretory protein-16 (CC-16) (previously associated with abnormal DLco) are associated with subsequent declines in DLco. Aim 2B: To test the hypothesis that persistent elevations in plasma soluble tumor necrosis factor receptor 2 (sTNFR-II) and interferon gamma-inducible protein-10 (IP-10) (previously associated with abnormal iso↓DLco) are associated with subsequent changes (declines) in iso↓DLco. The success of these aims will both improve our current understanding of HIV+ COPD and benefit this meritorious post-baccalaureate scholar.