ASPIRE: Air Pollution: Strategies for Personalized Intervention to Reduce Exposure

ASPIRE：空气污染：减少接触的个性化干预策略

• 批准号: 9754146
• 负责人: Robert Daniel Brook
• 金额: $ 29.85万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-04 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9754146
• 关键词: Acute; Adopted; Adult; Air; Air Pollutants; Air Pollution; Area; Autonomic nervous system; Biological; Biological Markers; Blood Glucose; Blood Pressure; Carbon Black; Cardiovascular system; China; Chronic; Cities; Country; Cross-Over Studies; Data; Developing Countries; Development; Diabetes Mellitus; Disease; Double-Blind Method; Environment; Environmental Risk Factor; Exposure to; Fasting; Filtration; Frequencies; Future; Glucose; Guidelines; Health; Health Benefit; Home environment; Homeostasis; Hour; Hypertension; India; Individual; Inflammation; Institutes; Insulin; Insulin Resistance; Intervention; Intervention Studies; Investigation; Investments; Joints; Label; Lipids; Measures; Mediating; Metabolic; Metabolic dysfunction; Metabolic syndrome; Michigan; Modeling; Morbidity - disease rate; Nature; Non-Insulin-Dependent Diabetes Mellitus; OGTT; Oral; Outcome; Parents; Particulate Matter; Pathway interactions; Pattern; Plasma; Population; Public Health; Randomized; Rest; Risk; Role; Sampling; Single-Blind Study; Sympathetic Nervous System; System; Time; TimeLine; Translating; Travel; United States; Universities; Visit; World Health Organization; adipokines; arm; base; burden of illness; cardiometabolic risk; cardiometabolism; cardiovascular health; circulating biomarkers; combat; efficacy testing; experience; global environment; glucose metabolism; heart rate variability; high efficiency particulate air filter; indexing; insight; insulin sensitivity; metabolomics; mortality; oral glucose tolerance; patient subsets; personalized intervention; personalized strategies; prevent; primary endpoint; protective effect; secondary endpoint; stable isotope; success; traffic-related air pollution

ABSTRACT Chronic cardiometabolic (CM) diseases such as hypertension and type 2 diabetes (T2DM) contribute disproportionately to global morbidity and mortality, and are increasing believed to have multiple environmental influences. In the previous 5 years of this competitive renewal (AIRCMD), we executed a multinational collaborative in an environment with high levels of air pollution exposure and demonstrated that short-term exposure to black carbon and PM2.5 results in elevations in blood pressure (BP) and insulin sensitivity through sympathetic nervous system (SNS) mechanisms. Given the fact that improvements in air quality are decades away in countries like China and India and that prevailing low levels of air pollution in the United States preclude the ability of US based studies to demonstrate a meaningful effect, the efficacy of personal- intervention is best performed in relevant countries (e.g., China) where ambient levels are high, and the public is likely to derive benefit. In this competing renewal, we propose a high impact interventional study that will test the efficacy of personal intervention strategies to mitigate PM2.5-induced adverse cardiometabolic effects in environments with high levels of ambient exposures. The use of “simple” facemasks (N95) to reduce air pollution exposure is widespread across regions experiencing high air pollution levels, and is commonly adopted by visitors to these environments. In Aim 1, as part of a randomized crossover study of 100 adults with metabolic syndrome, we will demonstrate the impact of a simple facemask (FM) intervention while outdoors on cardio-metabolic outcomes (primary endpoints: 24-hour ambulatory systolic blood pressure [ASBP] and insulin resistance (IR) by fasting homeostasis model assessment of insulin resistance [HOMA-IR]) compared to control (no facemask). Secondary end-points will include automated resting SBP, SNS activity (time and frequency domain heart rate variability [HRV]), and central aortic BP. In Aim 2, whether in-home air purifier system with HEPA filters [APHF]) in conjunction with a FM compared to a sham filtration arm and no FM leads to improvements in the same cardio-metabolic outcomes, in a double-blinded cross-over study will be carried out. In an exploratory Aim 3 we will elucidate the potential pathways of benefit using circulating adipokines, oral glucose tolerance testing with and without a safe stable isotope [13C-labeled oral glucose] to provide new insights on pathways of benefit. Collectively, the results from this project are likely to provide critical new data on protective effects of personal intervention strategies.

抽象的 高血压和 2 型糖尿病 (T2DM) 等慢性心脏代谢 (CM) 疾病会导致 与全球发病率和死亡率不成比例，并且越来越多地被认为与多种环境因素有关 影响。在本次竞争性更新 (AIRCMD) 的前 5 年中，我们执行了一项跨国 在空气污染程度高的环境中进行协作，并证明短期内 接触黑碳和 PM2.5 会导致血压 (BP) 和胰岛素敏感性升高 交感神经系统（SNS）机制。鉴于空气质量的改善需要数十年的时间 中国和印度等国家的空气污染普遍较低 排除美国研究证明有意义的效果、个人效果的能力 干预最好在环境水平较高且公众 有可能获得利益。在这次竞争更新中，我们提出了一项高影响力的干预研究，该研究将测试 个人干预策略在减轻 PM2.5 引起的不良心脏代谢影响方面的功效 环境暴露水平较高的环境。使用“简单”口罩（N95）来减少空气 污染暴露在空气污染水平较高的地区普遍存在，并且通常 被这些环境的游客所采用。在目标 1 中，作为随机交叉研究的一部分，该研究对 100 名成年人进行了 代谢综合征，我们将展示在户外时简单的口罩 (FM) 干预的影响 心脏代谢结果（主要终点：24 小时动态收缩压 [ASBP] 和胰岛素 通过空腹稳态模型评估胰岛素抵抗[HOMA-IR]）与 控制（不戴口罩）。次要终点将包括自动静息收缩压、SNS 活动（时间和 频域心率变异性 [HRV]）和中央主动脉血压。目标2、是否家用空气净化器 带有 HEPA 过滤器 [APHF] 的系统与 FM 结合使用，与假过滤臂且无 FM 引线相比 为了改善相同的心脏代谢结果，将进行双盲交叉研究 出去。在探索性目标 3 中，我们将阐明使用循环脂肪因子、口服脂肪因子的潜在益处途径。 使用和不使用安全稳定同位素 [13C 标记的口服葡萄糖] 进行葡萄糖耐量测试，以提供新的 对利益途径的见解。总的来说，该项目的结果可能会提供重要的新数据 个人干预策略的保护作用。