Study of HIV Infection in the Etiology of Lung Disease (SHIELD) AIR: Air Pollution Impact on Respiratory Health in HIV

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Combination antiretroviral therapy has dramatically improved survival for persons living with HIV (PLWH). With increased life expectancy, PLWH now face significant morbidity from age-related comorbidities, including greater prevalence of chronic respiratory diseases and accelerated decline in lung function. Lung injury is caused and perpetuated by noxious particles, including cigarette smoke and air pollution. Air pollution, including fine particulate matter (PM2.5) and nitrogen dioxide (NO2), has been shown to elicit inflammatory and oxidative stress responses, and is linked to impairment in lung function, development of chronic lung disease, and respiratory hospitalizations. While HIV is hypothesized to increase susceptibility to cigarette smoke, whether this extends to other pollutants remains unknown, as is the contribution of pollution to the risk for lung disease among PLWH. The Study of HIV Infection in the Etiology of Lung Disease (SHIELD) is an ongoing, prospective cohort of over 2600 individuals with or at-risk for HIV that has made significant contributions to our understanding of HIV- associated lung function impairment and respiratory morbidity. SHIELD has demonstrated that HIV leads to unique physiologic changes in the lung, including increased risk for airflow obstruction and deficiencies in gas exchange, accelerated decline in lung function, and increased respiratory morbidity. However, the contribution of environmental exposures to excess respiratory morbidity among PLWH is unknown. To address this gap, we propose to extend SHIELD to address our overarching hypothesis that PLWH represent a population that is uniquely susceptible to the health effects of air pollution and that pollutant exposure contributes to the excess lung function impairment and respiratory morbidity among PLWH. Three independent but complementary aims build upon the long-standing experience of the SHIELD cohort and add the expertise of investigators in studying health effects of outdoor and household air pollution in vulnerable populations. Aim 1 will define the impact of outdoor air pollution exposure to both acute and chronic respiratory morbidity and lung function decline among PLWH and comparable HIV-uninfected participants. Aim 2 will determine the association between household air pollution and respiratory morbidity among PLWH. Aim 3 will characterize biologic response to air pollution exposure, assessing whether HIV is associated with increased internal dose of exposure and/or exaggerated oxidative host airway and systemic response. We will apply novel approaches through molecular markers assessed with albumin adductome mass spectrometry. In all aims, we will examine how HIV and markers of HIV control influence susceptibility to pollution. Successful completion of these aims will advance our understanding of mechanisms and impact of air pollution in the setting of HIV. Further, our findings could identify therapeutic targets among high-risk populations and guide development of interventions to improve respiratory health and healthy aging among PLWH.