The influence of air pollution on lung health among people living with HIV.

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SUMMARY/ABSTRACT Significance: Chronic obstructive pulmonary disease (COPD) is a leading cause of global mortality, and women are at particular risk. Women who smoke have higher COPD risk, faster disease progression, and rising mortality rates compared to men who smoke, even at similar levels of tobacco exposure. Among those who have never smoked, COPD is more prevalent among women. HIV is an important non-tobacco related driver of COPD risk, and over half the global population with HIV are women and girls, but how HIV-associated COPD risk differs among women is unknown. Mechanisms driving the accentuated COPD risk among women are an area of active investigation, but changes in sex hormones during the menopausal transition may play a key mechanistic role. Women with HIV may have more advanced reproductive aging than women without HIV, which may further compound the COPD risk in this vulnerable population. Women have historically been underrepresented in COPD studies and studies of HIV-associated lung disease, so a deeper understanding of the influence of reproductive aging on lung health among women is essential to ensure the most comprehensive care of women aging with HIV. Our overarching objective is to characterize reproductive aging and its associated effects on lung health among HIV+ and HIV- women in Uganda. Innovation: Distinct advantages include: 1) A strategic focus on women in a resource-limited setting, where most global COPD mortality occurs and most women living with HIV reside, and thus our study cohort is representative of the environmental, occupational, and infectious exposures for most women affected by the confluence of the COPD and HIV epidemics, 2) Leveraging a well- characterized cohort in a global setting with 7 years of lung function and stored blood samples, allowing us to conduct advanced statistical analyses characterizing complex relationships, and 3) A novel biomarker-based approach to defining reproductive aging that prospectively identifies women approaching menopause. Investigators: Dr. Markella Zanni, an endocrinologist with expertise in hormonal mechanisms of non- communicable comorbidities among people with HIV, joins my mentorship team to guide aspects related to reproductive aging. Approach: We will leverage 7 years of stored blood samples to characterize reproductive aging among 126 women with and without HIV in the parent K23 cohort and pair these data with historic lung function data to test the following Specific Aims: 1) Using previously-collected demographic and health history data, I will identify predictors of advanced reproductive aging; and 2) Using historic lung function data, I will determine whether advanced reproductive aging modifies or mediates the relationship between HIV and lung function decline. Impact: These data will complement my K23-funded work by providing a deeper characterization of HIV and lung health among women, will inform future R01 proposals designed to test interventions to mitigate menopause-related lung dysfunction, and will establish a biorepository of reproductive aging data that can be used to study the influence of sex/gender on other health outcomes in sub-Saharan Africa.