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

摘要 慢性心脏代谢（CM）疾病，如高血压和2型糖尿病（T2 DM）， 与全球发病率和死亡率不成比例，而且越来越多的人认为， 影响。在此竞争性更新（AIRCMD）的前5年，我们执行了一项跨国 在空气污染暴露水平高的环境中进行合作，并证明短期内 暴露于黑碳和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。考虑到空气质量的改善需要几十年的时间， 在中国和印度这样的国家， 排除了基于美国的研究证明有意义的效果的能力，个人的功效- 最好在相关国家进行干预（例如，中国），环境水平高，公众 很可能从中受益。在这项竞争性更新中，我们提出了一项高影响力的干预性研究， 个人干预策略减轻PM2.5诱导的心脏代谢不良影响的有效性， 环境暴露水平高的环境。使用“简单”口罩（N95）减少空气 污染暴露在经历高空气污染水平的地区很普遍， 被这些环境中的游客所接受。在目标1中，作为对100名成年人的随机交叉研究的一部分， 代谢综合征，我们将证明一个简单的面罩（FM）干预的影响，而户外对 心脏代谢结局（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（无面罩）。次要终点将包括自动静息SBP、SNS活动（时间和 频域心率变异性[HRV]）和中心主动脉BP。在Aim 2中，无论是家用空气净化器 系统与HEPA过滤器[APHF]）联合FM与假过滤臂和无FM导线相比 在一项双盲交叉研究中， 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 使用和不使用安全的稳定同位素[13 C标记的口服葡萄糖]进行葡萄糖耐量试验， 对受益途径的见解。总的来说，这个项目的结果可能会提供关键的新数据， 个人干预策略的保护作用。

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.