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.

抗逆转录病毒疗法的联合疗法大大提高了HIV患者（PLWH）的生存率。和 预期寿命提高，PLWH现在面临着与年龄相关的合并症的显着发病率，包括更大的合并症 慢性呼吸道疾病的患病率和肺功能的加速下降。引起肺损伤， 被有害颗粒（包括香烟烟雾和空气污染）永久存在。空气污染，包括罚款 颗粒物物质（PM2.5）和二氧化氮（NO2）已被证明引起炎症和氧化应激 反应，与肺功能损害，慢性肺部疾病的发展和呼吸有关 住院。虽然假设艾滋病毒以增加对香烟烟雾的敏感性，但是否扩展到 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如此。 肺病病因（SHIELD）中HIV感染的研究是一个持续的，前瞻性的人群 有2600名患有艾滋病毒或高危艾滋病毒的人为我们对艾滋病毒的理解做出了重大贡献 相关的肺功能障碍和呼吸道发病率。盾牌证明了艾滋病毒导致 肺部独特的生理变化，包括增加气流阻塞的风险和气体缺陷 交换，加速肺功能下降以及呼吸发病率的增加。但是，贡献 PLWH中呼吸道发病过多的环境暴露是未知的。为了解决这个差距，我们 提议扩展盾牌，以解决我们的总体假设，即PLWH代表了一个人口 特别容易受到空气污染的健康影响，污染物的暴露有助于 PLWH之间的肺功能障碍和呼吸道发病率过多。三个独立但 互补的目标是基于盾牌队列的长期经验，并增加了专业知识 研究人员研究弱势群体对户外和家庭空气污染的健康影响。目标1 将定义室外空气污染暴露于急性和慢性呼吸道发病率和肺部的影响 PLWH和可比的HIV未感染参与者的功能下降。 AIM 2将确定关联 在家庭空气污染和PLWH之间的呼吸发病率之间。 AIM 3将表征生物学 对空气污染暴露的反应，评估HIV是否与内部剂量增加有关 和/或夸张的氧化宿主气道和全身响应。我们将采用新颖的方法 用白蛋白加合体质谱法评估的分子标记物。总的来说，我们将研究艾滋病毒 艾滋病毒控制的标记会影响污染的易感性。这些目标的成功完成将促进 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 确定高风险人群之间的治疗目标，并指导开发干预措施以改善 PLWH中的呼吸健康和健康衰老。