Sex, HIV, and Air Pollution Effects on Post-TB Lung Disease (SHAPE PTLD) - Abstract Among the estimated 155 million TB survivors worldwide, a substantial proportion have post-tuberculosis lung disease (PTLD), characterized by persistent respiratory complaints, abnormal lung function, and/or chest X-ray abnormalities. Despite its prevalence, PTLD is poorly characterized and poorly understood. Our objectives are to establish a well-characterized PTLD cohort in a low-income and high-TB/HIV burden country and determine whether sex, HIV serostatus, and air pollution are associated with distinct lung function-chest CT PTLD phenotypes. This proposal builds upon a successful 17+ year collaboration in Kampala, Uganda. Our previous research found significant sex-based and HIV-specific differences in spirometry post-pneumonia, and preliminary data indicate similar trends in spirometry, total lung capacity (TLC), and diffusing capacity for carbon monoxide (DLco) post-TB. Specifically, post-TB women with HIV exhibited stronger trends towards abnormal spirometry, TLC, and DLco compared to post-TB men with HIV; this was not seen in post-TB persons without HIV or in persons without TB. Post-TB women with HIV also had significantly higher PM2.5 levels than their male counterparts. These findings support our central hypothesis that there are sex-based and HIV-specific differences in the lung function-chest CT presentations of PTLD and that women with HIV are at increased risk. We hypothesize that these sex and HIV differences are exacerbated by higher PM2.5 levels in women and an enhanced deleterious effect of PM2.5 exposure in HIV. To address this, we will enroll 650 post-TB and 165 non- TB adults. We will determine the impact of sex and HIV on lung function-CT findings and investigate whether sex or HIV modifies the associations between PM2.5 and PTLD. Aim 1: Determine the impact of sex and HIV on spirometry, TLC, and DLco in persons with and without TB at baseline (end of TB treatment for TB) and follow- up (2 years later). Hypothesis: Post-TB women with HIV will have higher odds of abnormal lung function than post-TB men with HIV; no such sex difference will be found in post-TB persons without HIV (primary hypothesis) or those without TB (secondary). Aim 2: Determine the impact of sex and HIV on CT findings using conventional chest radiologist interpretation and novel, automated AI algorithms in persons with and without TB at baseline and follow-up. Hypothesis: Post-TB women with HIV will have higher odds of emphysema, fibrosis, small airways disease, and vascular abnormalities on CT than post-TB men with HIV; no such sex difference will be found in post-TB persons without HIV or those without TB. Aim 3: Determine whether sex or HIV are effect modifiers of the relationship between PM2.5 and lung function-CT findings using short- and long-term PM2.5 measurements from personal samplers and residential satellite-based spatiotemporal models. Hypothesis: The relationships between PM2.5 and PTLD findings will be more pronounced among women compared to men and among persons with HIV compared to persons without HIV. This research will serve as a foundational study of PTLD, leading to advancements in its diagnosis and management, mechanistic studies, and targeted interventions in the future.
