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

联合抗逆转录病毒疗法大大提高了艾滋病毒感染者的生存率。与 随着预期寿命的增加，PLWH现在面临着与年龄相关的合并症的显著发病率，包括更大的 慢性呼吸道疾病的流行和肺功能的加速下降。造成肺损伤， 有害颗粒，包括香烟烟雾和空气污染。空气污染，包括罚款 颗粒物（PM2.5）和二氧化氮（NO2）已被证明会引起炎症和氧化应激 反应，并与肺功能受损，慢性肺部疾病的发展和呼吸系统疾病有关。 住院治疗虽然艾滋病毒被假设为增加对香烟烟雾的易感性，但这是否会延伸到 其他污染物仍然未知，污染对感染者肺病风险的影响也是未知的。 HIV感染在肺部疾病病因学中的研究（SHIELD）是一项正在进行的前瞻性队列研究， 2600名艾滋病毒感染者或有感染艾滋病毒风险的人为我们了解艾滋病毒做出了重大贡献- 相关的肺功能损害和呼吸系统疾病。神盾局已经证明，艾滋病毒导致 肺部独特的生理变化，包括气流阻塞和气体不足的风险增加 交换，肺功能加速下降，呼吸系统发病率增加。然而，贡献 目前尚不清楚艾滋病毒携带者在环境中暴露于过量呼吸道疾病的可能性。为了弥补这一差距，我们 我建议扩展SHIELD，以解决我们的总体假设，即PLWH代表的人群， 特别容易受到空气污染的健康影响，污染物暴露有助于 PLWH的肺功能损害和呼吸系统疾病的发生率。三个独立但 补充性目标建立在盾牌部队长期积累的经验基础上，并增加了以下方面的专门知识： 研究户外和家庭空气污染对脆弱人群健康的影响。要求1 将定义室外空气污染暴露对急性和慢性呼吸道疾病和肺的影响。 PLWH和类似的未感染HIV的参与者的功能下降。目标2将决定协会 家庭空气污染与艾滋病毒携带者呼吸道疾病发病率之间的关系。目标3将描述生物 对空气污染暴露的反应，评估艾滋病毒是否与暴露的内部剂量增加有关 和/或过度的氧化宿主气道和全身反应。我们将采用新的方法， 用白蛋白内包体质谱法评估分子标志物。在所有目标中，我们将研究艾滋病毒如何 艾滋病毒控制的标志物影响对污染的敏感性。这些目标的顺利实现将推动 我们对艾滋病毒环境中空气污染的机制和影响的理解。此外，我们的发现可能 确定高危人群的治疗目标，指导制定干预措施， 呼吸系统健康和健康老龄化。

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.