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

HIV 感染与肺部疾病病因学研究 (SHIELD) 空气：空气污染对 HIV 呼吸系统健康的影响

• 批准号: 10462663
• 负责人: Gregory D Kirk
• 金额: $ 108.63万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-20 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10462663
• 关键词: Acute; Address; Air; Air Movements; Air Pollution; Albumins; Baltimore; Biological; Biometry; Chronic; Chronic lung disease; Climate; Data; Development; Dose; Environmental Exposure; Environmental Health; Etiology; Exposure to; Face; Funding; Gases; HIV; HIV Infections; HIV Seronegativity; Health; Home; Hospitalization; Household; Household Air Pollution; Immunologics; Impairment; Individual; Indoor Air Pollution; Inflammation; Inflammatory; Intervention; Life Expectancy; Link; Liquid substance; Longitudinal Studies; Lung; Lung diseases; Mass Spectrum Analysis; Measurement; Measures; Monitor; Morbidity - disease rate; Nasal Epithelium; National Heart, Lung, and Blood Institute; Nicotine; Nitrogen Dioxide; Oxidative Stress; Ozone; Participant; Particulate Matter; Persons; Physiological; Pollution; Population; Predisposition; Prevalence; Prospective cohort; Pulmonary Function Test/Forced Expiratory Volume 1; Pulmonology; Quality of life; Research; Research Personnel; Resolution; Respiratory Disease; Respiratory Tract Infections; Risk; Risk Factors; Serum; Subgroup; Symptoms; Urine; Vulnerable Populations; age related; airway epithelium; airway obstruction; ambient air pollution; antiretroviral therapy; biobank; biological adaptation to stress; chronic respiratory disease; cigarette smoke; cohort; comorbidity; environmental tobacco smoke; experience; fine particles; health care service utilization; healthy aging; high risk population; improved; indoor pollutant; innovation; insight; lung health; lung injury; modifiable risk; molecular marker; mortality; multidisciplinary; novel marker; novel strategies; particle; pollutant; pulmonary function; pulmonary function decline; respiratory; respiratory health; respiratory morbidity; response; therapeutic target; therapy development

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.

联合抗逆转录病毒疗法显着提高了艾滋病毒感染者 (PLWH) 的生存率。和 随着预期寿命的延长，艾滋病毒感染者现在面临着与年龄相关的合并症的显着发病率，包括更大的并发症 慢性呼吸道疾病流行，肺功能加速下降。引起肺部损伤的是 有毒颗粒，包括香烟烟雾和空气污染，使环境长期存在。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、慢性肺病和呼吸系统疾病的发展有关 住院治疗。虽然艾滋病毒被假设会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，污染对感染者肺部疾病风险的影响也是未知的。 HIV 感染与肺部疾病病因学研究 (SHIELD) 是一项持续进行的前瞻性队列研究，涵盖了超过 2600 名艾滋病毒感染者或有感染艾滋病毒风险的人为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疾病。神盾局已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缺乏的风险增加 交换，加速肺功能下降，并增加呼吸道疾病发病率。然而，贡献 环境暴露导致 PLWH 呼吸道疾病发病率过高的原因尚不清楚。为了解决这一差距，我们 提议扩展 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对健康的影响，并且污染物暴露会导致 PLWH 中过度的肺功能损害和呼吸系统发病率。三个独立但 互补的目标建立在神盾局团队的长期经验之上，并增加了 研究人员正在研究室外和家庭空气污染对弱势群体健康的影响。目标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部疾病的影响 艾滋病病毒感染者和未感染艾滋病毒的参与者的功能下降。目标 2 将确定关联 家庭空气污染与艾滋病病毒感染者呼吸道疾病之间的关系。目标 3 将表征生物 对空气污染暴露的反应，评估艾滋病毒是否与内部暴露剂量增加有关 和/或过度的氧化宿主气道和全身反应。我们将通过以下方式应用新颖的方法 用白蛋白加合物质谱法评估分子标记。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。这些目标的成功完成将推动 我们对空气污染对艾滋病毒影响的机制和影响的理解。此外，我们的研究结果可以 确定高危人群的治疗目标并指导干预措施的制定以改善 PLWH 的呼吸健康和健康老龄化。