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

摘要

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.