Predictable declines in lung function occur with age, but the impact of aging with HIV on lung function remains largely unexplored. The Study of HIV Infection in the Etiology of Lung Disease (SHIELD) is an ongoing, prospective cohort of individuals with or at-risk for HIV that seeks to understand how HIV may impact lung function. SHIELD data indicate that HIV-infected persons have lower baseline lung function, measured as the forced expiratory volume in 1 second (FEV1), and that poorly controlled HIV plasma viremia is strongly associated with accelerated FEV1 decline over three years. We hypothesize that at older ages, HIV may accelerate the age-related decline in lung function, even among persons with well-controlled HIV disease, resulting in adverse clinical, functional and patient-reported outcomes. Further, we hypothesize that this process is driven at least in part by systemic inflammation and manifests with elastin degradation. By extending follow-up with regular interviews, spirometry, and blood collection on ~2000 well-characterized participants, SHIELD will accrue a decade of data, samples and endpoints allowing rigorous investigation of HIV, aging and lung function. We propose to systematically characterize the rates and predictors of lung function decline in our aging population of HIV-infected and comparable HIV-uninfected persons (Aim 1), to define the adverse clinical, functional, and patient-reported consequences associated with rapid lung function decline (Aim 2), and to delineate the contribution of systemic inflammation and elastin degradation to rapid lung function decline (Aim 3). Findings from the successful completion of these Aims will inform strategies for improving clinical management, developing interventions to slow lung function decline, and improving the healthy aging of persons living with HIV infection.
HIV infection appears to accelerate the age-related decline in lung function. By extending follow-up of a large well-characterized cohort of HIV-infected and comparable HIV-uninfected persons, this proposal will significantly advance our understanding of accelerated lung aging in HIV infection, identifying key risk factors, defining related consequences, and elucidating underlying mechanisms.
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