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.

Public Health Relevance

Air pollution is a serious worldwide health problem that contributes more to cardiovascular morbidity and mortality than what was previously appreciated. We have previously demonstrated an important role of air pollution towards the development of diabetes mellitus (high blood sugar) and hypertension (high blood pressure). In this proposal, we will evaluate the effect of personalized interventions to lower air pollution associated health risk and understand the mechanistic pathways of benefit. The study results will be important in the effort to help combat and prevent the health problems caused by exposure to air pollution.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES019616-09
Application #
9985121
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Nadadur, Srikanth
Project Start
2011-02-04
Project End
2021-07-31
Budget Start
2020-08-01
Budget End
2021-07-31
Support Year
9
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
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Brook, Robert D; Rajagopalan, Sanjay (2017) ""Stressed"" About Air Pollution: Time for Personal Action. Circulation 136:628-631
Liu, Cuiqing; Xu, Xiaohua; Bai, Yuntao et al. (2017) Particulate Air pollution mediated effects on insulin resistance in mice are independent of CCR2. Part Fibre Toxicol 14:6
Qiu, Yining; Zheng, Ze; Kim, Hyunbae et al. (2017) Inhalation Exposure to PM2.5 Counteracts Hepatic Steatosis in Mice Fed High-fat Diet by Stimulating Hepatic Autophagy. Sci Rep 7:16286
Brook, Robert D; Sun, Zhichao; Brook, Jeffrey R et al. (2016) Extreme Air Pollution Conditions Adversely Affect Blood Pressure and Insulin Resistance: The Air Pollution and Cardiometabolic Disease Study. Hypertension 67:77-85
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Ying, Zhekang; Xie, Xiaoyun; Bai, Yuntao et al. (2015) Exposure to concentrated ambient particulate matter induces reversible increase of heart weight in spontaneously hypertensive rats. Part Fibre Toxicol 12:15
Rao, Xiaoquan; Patel, Priti; Puett, Robin et al. (2015) Air pollution as a risk factor for type 2 diabetes. Toxicol Sci 143:231-41
Rao, Xiaoquan; Montresor-Lopez, Jessica; Puett, Robin et al. (2015) Ambient air pollution: an emerging risk factor for diabetes mellitus. Curr Diab Rep 15:603
Morishita, Masako; Bard, Robert L; Kaciroti, Niko et al. (2015) Exploration of the composition and sources of urban fine particulate matter associated with same-day cardiovascular health effects in Dearborn, Michigan. J Expo Sci Environ Epidemiol 25:145-52

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