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

摘要 慢性心脏代谢性疾病，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，并越来越多地被认为有多种环境因素 影响。在此次竞争更新的前5年(AIRCMD)中，我们执行了一项跨国公司 在空气污染暴露水平较高的环境中合作，并展示了短期内 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。考虑到几十年来空气质量的改善 在中国和印度这样的国家，以及美国普遍存在的低水平空气污染 排除了以美国为基础的研究证明有意义的影响的能力，个人- 干预最好在环境水平较高的相关国家(如中国)进行，公众 很可能会从中受益。在这一竞争性的更新中，我们提出了一项高影响力的干预性研究，将测试 个人干预策略对减轻PM2.5引起的心脏代谢不良影响的有效性 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，而且通常 被这些环境的访问者采用。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，我们将演示简单的面罩(FM)干预在户外对 心脏代谢结果(主要终点：24小时动态收缩压和胰岛素 通过空腹稳态模型评估胰岛素抵抗[HOMA-IR])与 对照(不戴口罩)。次要终端将包括自动静息SBP、SNS活动(时间和 频域心率变异性[HRV])和中央动脉血压。在目标2中，无论是家里的空气净化器 带有HEPA过滤器的系统[APHF])与假过滤臂和无FM引线相比 为了改善相同的心脏代谢结果，将进行一项双盲交叉研究 出去。在探索性目标3中，我们将阐明使用口服循环脂肪因子的潜在益处途径。 使用和不使用安全稳定的同位素[13C标记的口服葡萄糖]进行葡萄糖耐量测试提供新的 对受益途径的洞察。总体而言，该项目的结果可能会提供关键的新数据 关于个人干预策略的保护效果。

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.