Epidemiological and animal studies have identified many potential mechanisms by which airborne particles may impact health. However, the relative importance of these potential pathways remains not well understood. Our competing renewal is a molecular epidemiologic study with the overall goal to investigate distinct biologic pathways that mediate the detrimental effects of exposure to particulate matter (PM), building upon our productive studies in this population during our last funding period. We have focused on particles from fossil fuel power plants and welding fume as a model to evaluate the health effects of metallic particles. We will test hypotheses regarding these exposures using three endpoints for hypothesis testing: 1) autonomic function, as measured by heart rate variability (HRV);2) vascular function, as measured by blood pressure and arterial stiffness;and 3) epigenetic changes, measured by global methylation in DNA from peripheral blood and nasal mucosa brushings of exposed individuals. We will investigate potential PM mechanisms in a cohort of particle- exposed workers with well characterized exposure to PM2.5. We have shown that inhaled PM is associated with heart rate variability changes, and evidence of oxidative DNA damage, as well as systemic inflammation. Moreover, we have shown that metallic fume exposure produces systemic changes in gene expression in peripheral blood of exposed individuals. This cohort is advantageous because of the direct access to the environment in which to measure personal exposures directly and accurately and the high rate of participation and cooperation. To test our hypotheses, our first aim will assess how short-term (hours) exposure to particles (PM) affects cardiac autonomic function (as measured by changes in heart rate variability;HRV);and vascular function as measured by changes in blood pressure and arterial stiffness measured by Pulse Wave Analysis (PWA).
Our second aim will assess whether long-term (years) PM exposure to metallic PM is associated with increased risk of impaired vascular function, and systemic inflammation.
Our third aim will assess personal PM exposure in relation to epigenetic changes in peripheral blood and in nasal epithelial brushings, as measured by epigenome-wide DNA methylation.
Our fourth aim i s exploratory in which we will mine data mining from our existing gene expression results, and further assess the relationship between plasma profiles and the observed autonomic, vascular and inflammatory responses to PM. We will assess specific candidate biomarkers of early and chronic responses to metal-rich particulate exposures based on global gene expression profiles among this cohort. Our multidisciplinary team, combined with an established population, allows a unique opportunity to combine innovative methods with established epidemiologic methods for investigating particulate-associated cardiovascular and systemic effects in humans.

Public Health Relevance

The mechanisms linking PM inhalation into the lung to adverse health outcomes, including cardiovascular diseases, have not been completely understood. In this study, we will investigate potential PM mechanisms in construction workers with well characterized exposure to PM with aerodynamic diameters <2.5

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES009860-12
Application #
8650872
Study Section
Cardiovascular and Sleep Epidemiology (CASE)
Program Officer
Dilworth, Caroline H
Project Start
1999-03-01
Project End
2015-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
12
Fiscal Year
2014
Total Cost
$388,018
Indirect Cost
$141,270
Name
Harvard University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02115
Fan, Tianteng; Fang, Shona C; Cavallari, Jennifer M et al. (2014) Heart rate variability and DNA methylation levels are altered after short-term metal fume exposure among occupational welders: a repeated-measures panel study. BMC Public Health 14:1279
Grashow, Rachel; Zhang, Jinming; Fang, Shona C et al. (2014) Toenail metal concentration as a biomarker of occupational welding fume exposure. J Occup Environ Hyg 11:397-405
Wong, Jason Y Y; De Vivo, Immaculata; Lin, Xihong et al. (2014) The association between global DNA methylation and telomere length in a longitudinal study of boilermakers. Genet Epidemiol 38:254-64
Wong, Jason Y Y; De Vivo, Immaculata; Lin, Xihong et al. (2014) The relationship between inflammatory biomarkers and telomere length in an occupational prospective cohort study. PLoS One 9:e87348
Grashow, Rachel; Zhang, Jinming; Fang, Shona C et al. (2014) Inverse association between toenail arsenic and body mass index in a population of welders. Environ Res 131:131-3
Wong, Jason Y Y; De Vivo, Immaculata; Lin, Xihong et al. (2014) Cumulative PM(2.5) exposure and telomere length in workers exposed to welding fumes. J Toxicol Environ Health A 77:441-55
Zhang, Jinming; Fang, Shona C; Mittleman, Murray A et al. (2013) Secondhand tobacco smoke exposure and heart rate variability and inflammation among non-smoking construction workers: a repeated measures study. Environ Health 12:83
Wei, Yongyue; Wang, Zhaoxi; Chang, Chiung-yu et al. (2013) Global metabolomic profiling reveals an association of metal fume exposure and plasma unsaturated fatty acids. PLoS One 8:e77413
Laohaudomchok, Wisanti; Lin, Xihong; Herrick, Robert F et al. (2011) Toenail, blood, and urine as biomarkers of manganese exposure. J Occup Environ Med 53:506-10
Lee, Mi-Sun; Magari, Shannon; Christiani, David C (2011) Cardiac autonomic dysfunction from occupational exposure to polycyclic aromatic hydrocarbons. Occup Environ Med 68:474-8

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