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显著提高了艾滋病毒携带者(PLWH)的存活率。使用 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严重发病率，包括 慢性呼吸系统疾病的流行和肺功能加速下降。肺损伤是由 有害颗粒物，包括香烟烟雾和空气污染，使其永久化。空气污染，包括罚款 颗粒物(PM2.5)和二氧化氮(NO2)已被证明会引发炎症和氧化应激 反应，并与肺功能受损、慢性肺部疾病和呼吸系统疾病的发展有关 住院治疗。虽然艾滋病毒被认为会增加对吸烟的易感性，但这是否延伸到 其他污染物仍然未知，污染对PLWH中肺部疾病风险的贡献也是未知的。 HIV感染在肺部疾病病因学中的研究(SHIELD)是一项正在进行的、具有前瞻性的队列研究 2600名艾滋病毒携带者或有艾滋病毒风险的人，他们对我们对艾滋病毒的了解做出了重大贡献- 相关的肺功能损害和呼吸系统发病率。Shield已经证明艾滋病毒会导致 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，并增加呼吸道发病率。然而，这一贡献 在PLWH中暴露于过量呼吸道发病率的环境风险尚不清楚。为了解决这一差距，我们 建议扩展Shield以解决我们的总体假设，即PLWH代表的人口 对空气污染对健康的影响是独一无二的，接触污染物有助于 PLWH患者的过度肺功能损害和呼吸系统并发症。三个独立的但 互补的目标建立在盾牌队列的长期经验基础上，并增加了 调查人员在研究室外和家庭空气污染对脆弱人群的健康影响。目标1 将确定室外空气污染暴露对急性和慢性呼吸道发病率和肺部的影响 在PLWH和类似的未感染艾滋病毒的参与者中，功能下降。目标2将确定这种联系 家庭空气污染与PLWH的呼吸道发病率之间的关系。目标3将描述生物的特征 对空气污染暴露的反应，评估艾滋病毒是否与增加的内部暴露剂量有关 和/或夸大氧化宿主呼吸道和全身反应。我们将通过以下方式应用新方法 白蛋白加合物组质谱鉴定分子标志物。在所有目标中，我们将检查艾滋病毒是如何 艾滋病毒控制的标志物影响对污染的敏感性。这些目标的成功实现将推进 我们对空气污染在艾滋病毒感染背景下的机制和影响的理解。此外，我们的发现可能 在高危人群中确定治疗目标，并指导制定干预措施，以改善 长春市妇幼保健院的呼吸健康与健康老龄化

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.