Air Pollution's Impact on Lung Aging in HIV

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PROJECT SUMMARY Today, persons living with HIV (PLWH) face a disproportionate burden of chronic respiratory disease and accelerated lung aging. Despite advances in research that have increased our understanding of lung disease among PLWH, there are significant gaps in our knowledge of factors that impact lung health in this at-risk population. Worldwide ambient air pollution remains a significant, but modifiable, contributor to chronic respiratory morbidity and disease development. While translational studies suggest that HIV increases susceptibility to cigarette smoke, whether this applies to long-term ambient air pollution exposure has not been studied. To date, the impact of long-term air pollution exposure on lung aging in HIV remains unknown. The Study of HIV Infection in the Etiology of Lung Disease (SHIELD), a prospective cohort of 2600 individuals with or at-risk for HIV in Baltimore, MD, provides an ideal platform to efficiently answer questions about the impact of the environment on lung aging for PLWH. Building on the existing SHIELD cohort, we aim to determine if long-term ambient air pollution is a driver of accelerated lung aging in a high-risk population, and if PLWH are more susceptible to the respiratory health effects of pollutant exposure. The proposed research will uniquely characterize the interaction between the environment, HIV, and lung aging. We will add refined measures of long-term ambient air pollution with enhanced precision, in-depth CT phenotyping to capture early lung disease, and molecular markers of biologic aging and susceptibility to exposures, while leveraging longitudinal lung function data from a well-defined cohort of PLWH. We propose three aims to study the impact of long-term exposures on multidimensional (physiologic, radiographic, and biologic) lung aging among PLWH. (Aim 1) To determine the association between long-term ambient pollutant exposure and physiologic lung aging (trajectory of lung function decline) and health related quality of life for PLWH and comparable HIV-uninfected participants; (Aim 2) To define the impact of long-term pollutant exposure on CT measures of radiographic lung aging (small airways disease, air trapping, emphysema) among PLWH; (Aim 3) To determine the association between long-term pollutant exposure and accelerated “biologic” aging, measured via the epigenetic clock, a molecular marker of biologic responses and susceptibility to pollutant exposure. In all aims we will examine how HIV and markers of HIV control increase susceptibility to air pollution. This proposal will provide mentored training in the implementation of an environmental cohort study, the complexities of HIV-lung disease research, advanced biostatical methods, novel CT analysis techniques for lung phenotyping, and the application of epigenetic markers to describe biologic responses and susceptibility to exposures. The career development plan includes expert mentorship, formal coursework, and hands-on experience to facilitate Dr. Raju in achieving his career goal of becoming an independent physician scientist with expertise at the intersection of environmental health disparities, HIV, and lung health research.