Sex, HIV, and Lung Health Across the Life Course: The Uganda Lung Health Study

About This Grant

PROJECT SUMMARY Chronic obstructive pulmonary disease (COPD) is the leading respiratory cause of death worldwide, and by 2050, sub-Saharan Africa (sSA) will bear the greatest COPD burden despite the lowest smoking rates in the world. HIV is an important yet underappreciated driver of COPD risk that leads to more aggressive and fatal disease, particularly among women, for reasons that have not been fully elucidated. The intersection between HIV, sex, and COPD risk is particularly important in sSA, where most of the global population with HIV lives, over half of whom are women and girls. Consequently, two major public health priorities include understanding the mechanisms of COPD in women with HIV in sSA and developing methods to identify at-risk individuals and interventions to prevent or reduce its impact on their health. To accomplish these priorities and respond to the growing epidemic, data are needed in this population prior to the development of COPD at potentially intervenable timepoints. Unfortunately, longitudinal lung health data prior to COPD and mechanistic data to elucidate pathobiology and identify at-risk populations are rarely available in sSA. This proposal is led by experts in adult and adolescent lung disease epidemiology, quantitative chest imaging analytics, proteomic biomarker science, and risk prediction scores in sSA. In this proposal, we will build upon our preliminary data that suggest that women with HIV have particularly elevated risk of HIV-associated lung disease by establishing the Uganda Lung Health Study, a cohort of 800 adolescents and adults that is evenly balanced by sex and HIV and spans the entire adult lifespan from 16 to 90 years of age. We will follow these 800 individuals with three annual study visits where we will collect post-bronchodilator spirometry, study questionnaires, blood samples, and non- contrast chest CT imaging to accomplish the following aims: Aim 1: To identify trajectories of lung dysfunction across the lifespan and their key risk factors in adolescent girls and women with HIV in Uganda. We will estimate lung function trajectories via group-based trajectory modeling using 2,400 spirometry measures from 16 to 90 years old. Our secondary outcomes are categorical lung dysfunction and parenchymal lung disease. Our primary predictors are HIV and sex, and we will also consider demographic, environmental, clinical, and HIV-specific factors. We will identify key risk factors through clinical prediction scores and clinical prediction algorithms. Aim 2: To identify candidate biological pathways that predict lung dysfunction among adolescent girls and women with HIV in Uganda. We will assess biological pathways using proteomic signatures, and will compare signatures predictive of abnormal lung function trajectory and parenchymal lung disease by sex and HIV serostatus, with the goal of motivating future work to develop HIV- and/or sex-specific interventions. Our work will provide insights into potentially targetable risks and biological pathways in Uganda and will guide mechanistic and intervention studies to preserve lung health among PWH, which is directly responsive to NHLBI, Office of AIDS Research, and Office of Research on Women’s Health research priorities.