Final Report: Great Lakes Air Center for Integrative Environmental Research (GLACIER)

EPA Grant Number: R834797
Center: Great Lakes Air Center for Integrative Environmental Research
Center Director: Harkema, Jack
Title: Great Lakes Air Center for Integrative Environmental Research (GLACIER)
Investigators: Brooks, Robert P. , Araujo, Jesus , Kaplan, Marianna J. , Oral, Elif
Institution: Michigan State University , The Ohio State University - Main Campus , University of California - Los Angeles , University of Michigan - Ann Arbor
EPA Project Officer: Ilacqua, Vito
Project Period: January 1, 2011 through December 31, 2015 (Extended to December 31, 2016)
Project Amount: $7,999,875
RFA: Clean Air Research Centers (2009) RFA Text |  Recipients Lists
Research Category: Health Effects , Air

Objective:

This final report provides 1) an annual update of the Great Lakes Air Center for Integrative Environmental Research (GLACIER) and 2) a summary of major accomplishments over the entire five-year funding period. GLACIER has been a multidisciplinary center with the objective to explore one of the most prevalent and important global health-environment interfaces: the inter-relationships between facets of the cardiometabolic syndrome (CMS) and air pollution. CMS is among the leading causes of death and threats to worldwide health. In tandem, exposure to air pollution, most notably fine particle matter (PM2.5), remains highly prevalent and ranks among the leading causes of global mortality. Our center’s overall hypothesis is that PM2.5 and ozone (O3) are 1) capable of eliciting multiple important adverse cardiometabolic health effects that are dependent on 2) the local multipollutant milieu, 3) an individual’s pre-existing cardiovascular (CV) and metabolic condition (susceptibility), and 4) the interactive toxicity of PM2.5 and O3 coexposure.

In conjunction with 3 core facilities (Administration, Exposure Characterization, and Biostatistics and Data Management) GLACIER consisted of 3 controlled exposure projects that each addressed specific aspects of the CMS-air pollution interface. The projects were scientifically integrated and interactive which fostered synergistic insights and cohesive synthesis of conclusions.

Project 1 aimed to elucidate in humans the mechanisms of adverse CMS responses and the concentration-response relationships of acute exposures to differing PM2.5 mixtures.

Project 2 aimed to determine the short-term CV, autonomic and airway toxicity in rats exposed to differing PM2.5 mixtures.

Project 3 expanded upon the main theme by determining the CMS toxicity of differing longer-term exposures in mice. Each project also investigated the role of pre-existing susceptibility and the comparative effects of PM2.5 mixtures derived from 2-3 dissimilar multipollutant milieus of regional importance (near-roadway, industrial, transported). Toxic effects of PM2.5, O3, each alone and in combination, were evaluated at each location. We addressed 1) temporal-response relationships to pollutant exposure and the development of CMS, 2) CMS effects of ozone and fine particle mixtures from three differing locations and their interactive toxicity, 3) the role of obesity and pre-existing cardiometabolic abnormalities in individual susceptibility, 4) concentration-response relationships for particles and O3, and 5) mechanisms whereby air pollutants elicit CV and metabolic health effects. Our results provided critical insights into the health effects of PM2.5, O3, and their coexposures in a multipollutant context.

GLACIER Exposure Core 

The GLACIER Air Pollution Center included three projects to assess the impacts of air pollution exposure at field study locations with specific types of air pollution emission source impacts. Our Center’s overall hypothesis was that primary air pollutants, fine particulate matter (PM2.5) and ozone (O3), are 1) capable of causing important adverse health effects that are 2) dependent on the local combinations of air pollutants, 3) a person’s pre-existing health condition, and 4) the interactive adverse effects of exposure to both PM2.5 and O3. As part of GLACIER, our Exposure Characterization Core (ECC) coordinated with and supported GLACIER Projects 1-3 to provide measurements  of air pollutant exposure.

Our previous work in human population studies, as well as human and animal studies of exposure to concentrated ambient particles (CAP) and ozone have demonstrated the critical importance of complete exposure characterization. Several of these studies have identified adverse health effects related to metabolic syndrome such as development of high blood pressure due to specific components of air pollution, as well as specific sources of air pollution. Because ambient PM is currently regulated on a mass basis, assuming all particles equally impact health, it was clear that in order to determine the most effective way in which to regulate PM and ensure that reductions in PM do in fact improve human health, additional studies were required.

The ECC was designed to investigate the components and sources of air pollution prominent across the Great Lakes region that are responsible for adverse health effects. The ECC was highly innovative in design by virtue of the use of mobile ambient particle concentrators coupled with mobile toxicological laboratories to evaluate the acute health effects of air pollution dominated by different chemical components and sources. These mobile labs were stationed in communities in Michigan (Detroit/Dearborn, and Dexter) for short-term exposure studies conducted in Projects 1 and 2, as well as two community locations in Columbus, OH, for long-term exposure studies in Project 3. The ECC specifically utilized these exposure sites in Michigan and Ohio primarily impacted by (1) near-roadway motor vehicle emissions, (2) industrial point sources, and (3) regionally transported air pollution (no local emission sources). The primary objectives of the ECC were to: characterize the chemical components of air pollution exposure, identify the sources of air pollution exposure, and  assess the air pollution components and sources responsible for the adverse cardiometabolic responses observed for each of Projects 1-3.

GLACIER BIOSTATISTICS AND DATA MANAGEMENT

The overarching thesis of the EPA Great Lakes Air Center for  Integrated  Environmental Research (GLACIER) is that the primary air pollutants, fine particulate matter (PM2.5) and ozone (O3), cause cardiometabolic health effects that are dependent on 1) the local multipollutant atmospheric milieu, 2) the individual’s pre-existing cardiovascular and metabolic condition, and 3) the interactive toxicity of PM2.5 and O3 coexposure. The objectives of the GLACIER Biostatistics and Data Management Core (BDMC) are to provide guidance for the statistical design and analysis of studies and data management services that allow for the integration of the data into a single  platform that facilitates timely analysis for GLACIER investigators and projects. In the modern era of environmental sciences research, research investigators are generating a vast amount of data on multiple pollutants, health outcomes with the goal of studying the health effects caused by an ensemble of pollutants. Although our understanding of the mechanisms in which multipollutant mixtures cause/affect/mediate chronic diseases remains in its infancy, a major goal of this core is to equip the investigators of GLACIER to face the challenges in exploring the intricacies of  statistical modeling for mixtures of pollutants. The Core, consisting of biostatisticians, experienced with working on problems relevant to environmental health sciences, will equip the investigator with state of the art statistical modeling techniques  to understand the generated data.

In addition, essential attention to data collection and management activities prior to and during the conduct of studies in a platform that allows collaborative interchange between the scientists at the source of the data and statisticians at the analytic end of the data provides the ability to analyze complex and rich data more fully and efficiently at the close of  each study.

Summary/Accomplishments (Outputs/Outcomes):

During Year 6 (no-cost extension year), there were no changes in our overall research objective or specific aims. GLACIER’s research projects/cores continued to build upon its many accomplishments since the last progress report in July 2016. These latest research accomplishments along with highlights of GLACIER’s accomplishments since its conception in 2011 are provided in this final report to the EPA. Separate written reports are presented for each of our research projects. In these reports, we briefly 1) review objectives of the specific research, 2) highlight major scientific accomplishments, and 3) provide a comprehensive list of our peer-reviewed publications and presentations given at national scientific meetings. Please note that progress regarding our intramural CLARC collaborative project with Harvard University is found in the report of Project 2.

On June 6 and 7, 2016, GLACIER hosted the final Clean Air Research Centers (CLARC) Annual Meeting that took place at the University of Michigan in Ann Arbor, MI. On the first day of this meeting, Center Directors from Harvard, SCAPE, CCAR and GLACIER provided an update of their individual center’s research activities in year 5 as well as highlighting major accomplishments and challenges, including collaborative inter-center research, over the past five years. Time was also provided for informal group discussions on this first day of the conference. On day two, oral reports on EPA intramural and collaborative research was provided by Dr. Kathie Dionisio and Dr. Robert Devlin. Talks on future directions for air pollution and health research at the EPA were given by Drs. Dan Costa, Scott Jenkins and Rich Cook. A panel discussion/critique on the successes and challenges of the CLARC program was provided by invited discussants, Drs. Jeff Brook (Health Canada), Bert Brunekreef (Utrecht University), Dan Costa (US EPA, Moderator), and Robert Devlin (US EPA). Ms. Kasey Baldwin and Amy Swagart from our Administrative Core did an outstanding job in making all the logistical arrangements for this successful meeting.

Conclusions:

GLACIER Exposure Core

Over several exposure studies conducted across a number of airsheds, in support of GLACIER Projects 1-3, ECC investigators were successful in quantitatively assessing and apportioning pollutant components and sources. This allowed an assessment of the components and sources responsible for the adverse health responses observed (detailed and illustrated throughout the list of GLACIER ECC publications and presentations below). For example:

  • We found PM2.5 mass in an urban/industrial airshed to be significantly associated with increased heart rate (HR), among a number of other cardiovascular (CV) outcomes, as part of a GLACIER Project 1 human exposure study. Trace elements as well as secondary aerosol, diesel/urban dust and iron/steel manufacturing factors partially explained these HR changes. However, trace element component analysis demonstrated additional associations with other CV responses including changes in blood pressure (BP), arterial compliance, autonomic balance and trends toward reductions in endothelial function. Two factors were related to BP changes (diesel/urban dust, motor vehicle) and trends toward impaired endothelial function (diesel/urban dust). This study indicated that composition of PM2.5 and its sources may contribute to CV health effects independently of PM2.5 mass.
  • As part of a GLACIER Project 2 animal exposure study conducted within the same urban/industrial airshed, we found PM2.5 mass to increase mean HR and BP.  Following components analysis, we found the CV responses to be driven by the elemental carbon (EC) component and its EC1 fraction, while by comparison, associations with organic carbon were negligible. These findings were the first to describe associations between acute cardiovascular responses and thermally resolved carbon subfractions.

Collectively, the GLACIER ECC findings across a number of studies in Projects 1-3 are of public health and regulatory importance by supporting the notion that the composition and likely sources of PM are important determinants of the adverse cardiovascular health effects of air pollution exposures.

It is also a noteworthy success that one of our graduate students, Pearl Nathan, who has conducted her doctoral research in close coordination with GLACIER ECC activities is expected to soon complete her Environmental Health Sciences dissertation, entitled Fine Bioaerosols in Ambient Air: Presence and Interactions across Urban and Rural Airsheds.

GLACIER BIOSTATISTICS AND DATA MANAGEMENT

The Biostatistics and Data Management Core collaborated extensively with investigators from Projects 1, 2 and 3 for quality control (QC) and analysis of their data from conducted studies  throughout the funding period. Nearly forty peer-reviewed papers were published over the entire reporting period in collaboration with center investigators including multiple significant methodology publications. Two other methodology papers are in submission. The Core statisticians met/communicated with members of the various projects and the Exposures Core on several occasions to discuss the intricacies of the data and to learn about past techniques that have  been used in the analyses of these data. Our goal was to produce clean and accurate analytic datasets that  are  transportable across projects and develop common methods to deal with the high frequency composition of particulate matter data across all projects in GLACIER. Dr. Bhramar Mukherjee provided statistical support for the investigators on Project 3 as well as leading a between center collaboration with Brent Coull from Harvard University School of Public Health on multiple pollutant distributed lag models. Dr. Lu Wang provided support for Project 1 (Brook) and Dr. Bin Nan provided support for Project 2 (Harkema).

In the initial phase of GLACIER the core supported the public access website (Great Lakes Air Center Exit) and the internal website deposition of study information and data. The data management aspect of the core, led by Dr. Cathie Spino performed QC efforts for datasets received from investigators and the Exposure Core, including assessment of outliers, data errors and distributions via graphical and numeric summaries of all data. QCed data and summaries are stored in a shared drive that was used by all Biostatistics and Data Management Core statisticians. A graduate student research assistant in Biostatistics supported the analysis throughout the funding period.


Journal Articles: 71 Displayed | Download in RIS Format

Other center views: All 147 publications 71 publications in selected types All 71 journal articles
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Journal Article Balasubramanian P, Sirivelu MP, Weiss KA, Wagner JG, Harkema JR, Morishita M, Mohankumar PS, Mohankumar SM. Differential effects of inhalation exposure to PM 2.5 on hypothalamic monoamines and corticotrophin releasing hormone in lean and obese rats. NeuroToxicology 2013;36:106-111. R834797 (2013)
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  • Journal Article Blazek A, Rutsky J, Osei K, Maiseyeu A, Rajagopalan S. Exercise-mediated changes in high-density lipoprotein: impact on form and function. American Heart Journal 2013;166(3):392-400. R834797 (2013)
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  • Journal Article Brandenberger C, Li N, Jackson-Humbles DN, Rockwell CE, Wagner JG, Harkema JR. Enhanced allergic airway disease in old mice is associated with a Th17 response. Clinical & Experimental Allergy 2014;44(10):1282-1292. R834797 (2014)
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  • Journal Article Brook RD, Rajagopalan S, Pope III CA, Brook JR, Bhatnagar A, Diez-Roux AV, Holguin F, Hong Y, Luepker RV, Mittleman MA, Peters A, Siscovick D, Smith SC, Whitsel L, Kaufman JD. Particulate matter air pollution and cardiovascular disease: an update to the scientific statement from the American Heart Association. Circulation 2010;121(21):2331-2378. R834797 (2016)
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  • Journal Article Brook RD, Rajagopalan S. Can what you breathe trigger a stroke within hours? Comment on "ambient air pollution and the risk of acute ischemic stroke". Archives of Internal Medicine 2012;172(3):235-236. R834797 (2014)
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  • Journal Article Brook RD, Bard RL, Kaplan MJ, Yalavarthi S, Morishita M, Dvonch JT, Wang L, Yang H-Y, Spino C, Mukherjee B, Oral EA, Sun Q, Brook JR, Harkema J, Rajagopalan S. The effect of acute exposure to coarse particulate matter air pollution in a rural location on circulating endothelial progenitor cells: results from a randomized controlled study. Inhalation Toxicology 2013;25(10):587-592. R834797 (2013)
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  • Journal Article Brook RD, Xu X, Bard RL, Dvonch JT, Morishita M, Kaciroti N, Sun Q, Harkema J, Rajagopalan S. Reduced metabolic insulin sensitivity following sub-acute exposures to low levels of ambient fine particulate matter air pollution. The Science of the Total Environment 2013;448:66-71. R834797 (2012)
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  • Journal Article Brook RD, Bard RL, Morishita M, Dvonch JT, Wang L, Yang HY, Spino C, Mukherjee B, Kaplan MJ, Yalavarthi S, Oral EA, Ajluni N, Sun Q, Brook JR, Harkema J, Rajagopalan S. Hemodynamic, autonomic, and vascular effects of exposure to coarse particulate matter air pollution from a rural location. Environmental Health Perspectives 2014;122(6):624-630. R834797 (2013)
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  • Journal Article Byrd JB, Morishita M, Bard RL, Das R, Wang L, Sun Z, Spino C, Harkema J, Dvonch JT, Rajagopalan S, Brook RD. Acute increase in blood pressure during inhalation of coarse particulate matter air pollution from an urban location. Journal of the American Society of Hypertension 2016;10(2):133-139. R834797 (2016)
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  • Journal Article Carey SA, Ballinger CA, Plopper CG, McDonald RJ, Bartolucci AA, Postlethwait EM, Harkema JR. Persistent rhinitis and epithelial remodeling induced by cyclic ozone exposure in the nasal airways of infant monkeys. American Journal of Physiology:Lung Cellular and Molecular Physiology 2011;300(2):L242-L254. R834797 (2014)
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  • Journal Article Deiuliis JA, Kampfrath T, Zhong J, Oghumu S, Maiseyeu A, Chen LC, Sun Q, Satoskar AR, Rajagopalan S. Pulmonary T cell activation in response to chronic particulate air pollution. American Journal of Physiology:Lung Cellular and Molecular Physiology 2012;302(4):L399-L409. R834797 (2014)
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  • Journal Article Fonken LK, Xu X, Weil ZM, Chen G, Sun Q, Rajagopalan S, Nelson RJ. Air pollution impairs cognition, provokes depressive-like behaviors and alters hippocampal cytokine expression and morphology. Molecular Psychiatry 2011;16(10):987-995. R834797 (2014)
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  • Journal Article Giorgini P, Rubenfire M, Das R, Gracik T, Wang L, Morishita M, Bard RL, Jackson EA, Fitzner CA, Ferri C, Brook RD. Higher fine particulate matter and temperature levels impair exercise capacity in cardiac patients. Heart 2015;101(16):1293-1301. R834797 (2014)
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  • Journal Article Giorgini P, Rubenfire M, Das R, Gracik T, Wang L, Morishita M, Bard RL, Jackson EA, Fitzner CA, Ferri C, Brook RD. Particulate matter air pollution and ambient temperature: opposing effects on blood pressure in high-risk cardiac patients. Journal of Hypertension 2015;33(10):2032-2038. R834797 (2014)
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  • Journal Article Gong Jr. H, Linn WS, Terrell SL, Clark KW, Geller MD, Anderson KR, Cascio WE, Sioutas C. Altered heart-rate variability in asthmatic and healthy volunteers exposed to concentrated ambient coarse particles. Inhalation Toxicology 2004;16(6-7):335-343. R834797 (2016)
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  • Journal Article Huang W, Wang L, Li J, Liu M, Xu H, Liu S, Chen J, Zhang Y, Morishita M, Bard RL, Harkema JR, Rajagopalan S, Brook RD. Short-term blood pressure responses to ambient fine particulate matter exposures at the extremes of global air pollution concentrations. American Journal of Hypertension 2018;31(5):590-599. R834797 (Final)
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  • Journal Article Hubbs AF, Mercer RR, Benkovic SA, Harkema J, Sriram K, Schwegler-Berry D, Goravanahally MP, Nurkiewicz TR, Castranova V, Sargent LM. Nanotoxicology--a pathologist's perspective. Toxicologic Pathology 2011;39(2):301-324. R834797 (2014)
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  • Journal Article Kamal AS, Rohr AC, Mukherjee B, Morishita M, Keeler GJ, Harkema JR, Wagner JG. PM2.5-induced changes in cardiac function of hypertensive rats depend on wind direction and specific sources in Steubenville, Ohio. Inhalation Toxicology 2011;23(7):417-430. R834797 (2014)
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  • Journal Article Liu C, Ying Z, Harkema J, Sun Q, Rajagopalan S. Epidemiological and experimental links between air pollution and type 2 diabetes. Toxicologic Pathology 2013;41(2):361-373. R834797 (2013)
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  • Journal Article Liu C, Xu X, Bai Y, Wang TY, Rao X, Wang A, Sun L, Ying Z, Gushchina L, Maiseyeu A, Morishita M, Sun Q, Harkema JR, Rajagopalan S. Air pollution-mediated susceptibility to inflammation and insulin resistance:influence of CCR2 pathways in mice. Environmental Health Perspectives 2014;122(1):17-26. R834797 (2013)
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  • Journal Article Liu C, Bai Y, Xu X, Sun L, Wang A, Wang TY, Maurya SK, Periasamy M, Morishita M, Harkema J, Ying Z, Sun Q, Rajagopalan S. Exaggerated effects of particulate matter air pollution in genetic type II diabetes mellitus. Particle and Fibre Toxicology 2014;11:27. R834797 (2014)
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  • Journal Article Liu C, Fonken LK, Wang A, Maiseyeu A, Bai Y, Wang T-Y, Maurya S, Ko Y-A, Periasamy M, Dvonch T, Morishita M, Brook RD, Harkema J, Ying Z, Mukherjee B, Sun Q, Nelson RJ, Rajagopalan S. Central IKKβ inhibition prevents air pollution mediated peripheral inflammation and exaggeration of type II diabetes. Particle and Fibre Toxicology 2014;11:53. R834797 (2014)
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  • Journal Article Maiseyeu A, Yang H-Y, Ramanathan G, Yin F, Bard RL, Morishita M, Dvonch JT, Wang L, Spino C, Mukherjee B, Badgeley MA, Barajas-Espinosa A, Sun Q, Harkema J, Rajagopalan S, Araujo JA, Brook RD. No effect of acute exposure to coarse particulate matter air pollution in a rural location on high-density lipoprotein function. Inhalation Toxicology 2014;26(1):23-29. R834797 (2014)
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  • Journal Article Maniar-Hew K, Postlethwait EM, Fanucchi MV, Ballinger CA, Evans MJ, Harkema JR, Carey SA, McDonald RJ, Bartolucci AA, Miller LA. Postnatal episodic ozone results in persistent attenuation of pulmonary and peripheral blood responses to LPS challenge. American Journal of Physiology:Lung Cellular and Molecular Physiology 2011;300(3):L462-L471. R834797 (2014)
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  • Journal Article Mathew AV, Yu J, Guo Y, Byun J, Chen YE, Wang L, Liu M, Bard RL, Morishita M, Huang W, Li J, Harkema JR, Rajagopalan S, Pennathur S, Brook RD. Effect of ambient fine particulate matter air pollution and colder outdoor temperatures on high-density lipoprotein function. The American Journal of Cardiology 2018;122(4):565-570. R834797 (Final)
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  • Journal Article Morishita M, Keeler GJ, Kamal AS, Wagner JG, Harkema JR, Rohr AC. Source identification of ambient PM2.5 for inhalation exposure studies in Steubenville, Ohio using highly time-resolved measurements. Atmospheric Environment 2011;45(40):7688-7697. R834797 (2014)
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  • Journal Article Morishita M, Keeler GJ, Kamal AS, Wagner JG, Harkema JR, Rohr AC. Identification of ambient PM2.5 sources and analysis of pollution episodes in Detroit, Michigan using highly time-resolved measurements. Atmospheric Environment 2011;45(8):1627-1637. R834797 (2014)
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  • Journal Article Morishita M, Bard RL, Kaciroti N, Fitzner CA, Dvonch T, Harkema JR, Rajagopalan S, Brook RD. Exploration of the composition and sources of urban fine particulate matter associated with same-day cardiovascular health effects in Dearborn, Michigan. Journal of Exposure Science & Environmental Epidemiology 2015;25(2):145-152. R834797 (2014)
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  • Journal Article Morishita M, Bard RL, Wang L, Das R, Dvonch JT, Spino C, Mukherjee B, Sun Q, Harkema JR, Rajagopalan S, Brook RD. The characteristics of coarse particulate matter air pollution associated with alterations in blood pressure and heart rate during controlled exposures. Journal of Exposure Science & Environmental Epidemiology 2015;25(2):153-159. R834797 (2014)
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  • Journal Article Munzel T, Sorensen M, Gori T, Schmidt FP, Rao X, Brook FR, Chen LC, Brook RD, Rajagopalan S. Environmental stressors and cardio-metabolic disease: part II–mechanistic insights. European Heart Journal 2017;38(8):557-564. R834797 (Final)
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  • Journal Article Newby DE, Mannucci PM, Tell GS, Baccarelli AA, Brook RD, Donaldson K, Forastiere F, Franchini M, Franco OH, Graham I, Hoek G, Hoffmann B, Hoylaerts MF, Kunzli N, Mills N, Pekkanen J, Peters A, Piepoli MF, Rajagopalan S, Storey RF, ESC Working Group on Thrombosis, European Association for Cardiovascular Prevention and Rehabilitation, ESC Heart Failure Association. Expert position paper on air pollution and cardiovascular disease. European Heart Journal 2015;36(2):83-93b. R834797 (2014)
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  • Journal Article Ong CB, Kumagai K, Brooks PT, Brandenberger C, Lewandowski RP, Jackson-Humbles DN, Nault R, Zacharewski TR, Wagner JG, Harkema JR. Ozone-induced type 2 immunity in nasal airways. Development and lymphoid cell dependence in mice. American Journal of Respiratory Cell and Molecular Biology 2016;54(3):331-340. R834797 (2014)
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  • Journal Article Pancras JP, Landis MS, Norris GA, Vedantham R, Dvonch JT. Source apportionment of ambient fine particulate matter in Dearborn, Michigan, using hourly resolved PM chemical composition data. The Science of the Total Environment 2013;448:2-13. R834797 (2013)
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  • Journal Article Rajagopalan S, Brook RD. Personalizing your airspace and your health. Journal of the American College of Cardiology 2015;65(21):2288-2290. R834797 (2014)
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  • Journal Article Rao X, Patel P, Puett R, Rajagopalan S. Air pollution as a risk factor for type 2 diabetes. Toxicological Sciences 2015;143(2):231-241. R834797 (2014)
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  • Journal Article Rao X, Montresor-Lopez J, Puett R, Rajagopalan S, Brook RD. Ambient air pollution:an emerging risk factor for diabetes mellitus. Current Diabetes Reports 2015;15(6):603. R834797 (2014)
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  • Journal Article Rohr AC, Kamal A, Morishita M, Mukherjee B, Keeler GJ, Harkema JR, Wagner JG. Altered heart rate variability in spontaneously hypertensive rats is associated with specific particulate matter components in Detroit, Michigan. Environmental Health Perspectives 2011;119(4):474-480. R834797 (2014)
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  • Journal Article Sun L, Liu C, Xu X, Ying Z, Maiseyeu A, Wang A, Allen K, Lewandowski RP, Bramble LA, Morishita M, Wagner JG, Dvonch JT, Sun Z, Yan X, Brook RD, Rajagopalan S, Harkema JR, Sun Q, Fan Z. Ambient fine particulate matter and ozone exposures induce inflammation in epicardial and perirenal adipose tissues in rats fed a high fructose diet. Particle and Fibre Toxicology 2013;10:43. R834797 (2013)
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  • Journal Article Wagner JG, Morishita M, Keeler GJ, Harkema JR. Divergent effects of urban particulate air pollution on allergic airway responses in experimental asthma:a comparison of field exposure studies. Environmental Health 2012;11:45 (13 pp.). R834797 (2014)
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  • Journal Article Wagner JG, Allen K, Yang HY, Nan B, Morishita M, Mukherjee B, Dvonch JT, Spino C, Fink GD, Rajagopalan S, Sun Q, Brook RD, Harkema JR. Cardiovascular depression in rats exposed to inhaled particulate matter and ozone: effects of diet-induced metabolic syndrome. Environmental Health Perspectives 2014;122(1):27-33. R834797 (2013)
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  • Journal Article Wagner JG, Kamal AS, Morishita M, Dvonch JT, Harkema JR, Rohr AC. PM2.5-induced cardiovascular dysregulation in rats is associated with elemental carbon and temperature-resolved carbon subfractions. Particle and Fibre Toxicology 2014;11:25 (10 pp.). R834797 (2014)
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  • Journal Article Wang Y, Eliot MN, Kuchel GA, Schwartz J, Coull BA, Mittleman MA, Lipsitz LA, Wellenius GA. Long-term exposure to ambient air pollution and serum leptin in older adults: results from the MOBILIZE Boston Study. Journal of Occupational and Environmental Medicine 2014;56(9):e73-e77. R834797 (2016)
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  • Journal Article Wold LE, Ying Z, Hutchinson KR, Velten M, Gorr MW, Velten C, Youtz DJ, Wang A, Lucchesi PA, Sun Q, Rajagopalan S. Cardiovascular remodeling in response to long-term exposure to fine particulate matter air pollution. Circulation:Heart Failure 2012;5(4):452-461. R834797 (2014)
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  • Journal Article Xu X, Liu C, Xu Z, Tzan K, Zhong M, Wang A, Lippmann M, Chen LC, Rajagopalan S, Sun Q. Long-term exposure to ambient fine particulate pollution induces insulin resistance and mitochondrial alteration in adipose tissue. Toxicological Sciences 2011;124(1):88-98. R834797 (2014)
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  • Journal Article Xu X, Liu C, Xu Z, Tzan K, Wang A, Rajagopalan S, Sun Q. Altered adipocyte progenitor population and adipose-related gene profile in adipose tissue by long-term high-fat diet in mice. Life Sciences 2012;90(25-26):1001-1009. R834797 (2014)
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  • Journal Article Xu Z, Xu X, Zhong M, Hotchkiss IP, Lewandowski RP, Wagner JG, Bramble LA, Yang Y, Wang A, Harkema JR, Lippmann M, Rajagopalan S, Chen L-C, Sun Q. Ambient particulate air pollution induces oxidative stress and alterations of mitochondria and gene expression in brown and white adipose tissues. Particle and Fibre Toxicology 2011;8:20 (14 pp.). R834797 (2014)
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  • Journal Article Ying Z, Xu X, Chen M, Liu D, Zhong M, Chen L-C, Sun Q, Rajagopalan S. A synergistic vascular effect of airborne particulate matter and nickel in a mouse model. Toxicological Sciences 2013;135(1):72-80. R834797 (2013)
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  • Journal Article Ying Z, Xu X, Bai Y, Zhong J, Chen M, Liang Y, Zhao J, Liu D, Morishita M, Sun Q, Spino C, Brook RD, Harkema JR, Rajagopalan S. Long-term exposure to concentrated ambient PM2.5 increases mouse blood pressure through abnormal activation of sympathetic nervous system:a role for hypothalamic inflammation. Environmental Health Perspectives 2014;122(1):79-86. R834797 (2013)
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  • Journal Article Yue W, Stolzel M, Cyrys J, Pitz M, Heinrich J, Kreyling WG, Wichmann H-E, Peters A, Wang S, Hopke PK. Source apportionment of ambient fine particle size distribution using positive matrix factorization in Erfurt, Germany. Science of the Total Environment 2008;398(1-3):133-144. R834797 (2016)
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  • Journal Article Zheng Z, Xu X, Zhang X, Wang A, Zhang C, Huttemann M, Grossman LI, Chen LC, Rajagopalan S, Sun Q, Zhang K. Exposure to ambient particulate matter induces a NASH-like phenotype and impairs hepatic glucose metabolism in an animal model. Journal of Hepatology 2013;58(1):148-154. R834797 (2014)
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  • Journal Article Zhong J, Allen K, Rao X, Ying Z, Braunstein Z, Kankanala SR, Xia C, Wang X, Bramble LA, Wagner JG, Lewandowski R, Sun Q, Harkema JR, Rajagopalan S. (2016) Repeated ozone exposure exacerbates insulin resistance and activates innate immune response in genetically susceptible mice. Inhalation Toxicology 2016;28(9):383-392. R834797 (Final)
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  • Journal Article Kumagai K, Lewandowski R, Jackson-Humbles DN, Li N, Van Dyken SJ, Wagner JG, Harkema JR (2016). Ozone-Induced Nasal Type 2 Immunity in Mice Is Dependent on Innate Lymphoid Cells. American Journal of Respiratory Cell and Molecular Biology 2016;54(6):782-791. R834797 (Final)
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  • Journal Article Ong CB, Kumagai K, Brooks PT, Brandenberger C, Lewandowski RP, Jackson-HumblesDN, Nault R, Zacharewski TR, Wagner JG, Harkema JR. (2016) Ozone-Induced Type 2 Immunity in Nasal Airways: Development and Lymphoid Cell Dependence in Mice. American Journal of Respiratory Cell and Molecular Biology 2016;54(3):331-340. R834797 (Final)
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  • Journal Article Ying Z, Allen K, Zhong J, Chen M, Williams KM, Wagner JG, Lewandowski R, Sun Q, Rajagopalan S, Harkema JR. Subacute inhalation exposure to ozone induces systemic inflammation but not insulin resistance in a diabetic mouse model. Inhalation Toxicology 2016;28(4):155-163. R834797 (Final)
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  • Journal Article Rajagopalan S, Brook RD. (2012) Air Pollution and Type II Diabetes:Mechanistic Insights Diabetes. 2012 Dec;61(12):3037-45. PMCID:PMC3501850. R834797C003 (Final)
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    Journal Article Xu X, Rao X, Wang TY, Jiang SY, Ying Z, Liu C, Wang A, Zhong M, Deiuliis JA, Maiseyeu A, Rajagopalan S, Lippmann M, Chen LC, Sun Q. (2012) Effect of co-exposure to nickel and particulate matter on insulin resistance and mitochondrial dysfunction in a mouse model. Part Fibre Toxicol. 2012 Nov 5;9:40. PMCID:PMC3545913. R834797C003 (Final)
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    Journal Article Münzel T, Sørensen M, Gori T, Schmidt FP, Rao X, Brook J, Chen LC, Brook RD, Rajagopalan S. (2016) Environmental stressors and cardio-metabolic disease:part I-epidemiologic evidence supporting a role for noise and air pollution and effects of mitigation strategies. Eur Heart J. 2016 Jul 26. pii:ehw269. PMID:27460892. R834797C003 (Final)
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    Journal Article Münzel T, Sørensen M, Gori T, Schmidt FP, Rao X, Brook FR, Chen LC, Brook RD, Rajagopalan S. (2016) Environmental stressors and cardio-metabolic disease:part II-mechanistic insights.Eur Heart J. 2016 Jul 26. pii:ehw294. [Epub ahead of print] PMID:27460891. R834797C003 (Final)
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    Journal Article Ying Z, Allen K, Zhong J, Chen M, Williams KM, Wagner JG, Lewandowski R, Sun Q, Rajagopalan S, Harkema JR. (2016) Subacute inhalation exposure to ozone induces systemic inflammation but not insulin resistance in a diabetic mouse model. Inhal Toxicol. 2016;28(4):155-63. PMCID:PMC4836866. R834797C003 (Final)
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    Journal Article Carll, A.P., Crespo, S.M., Filho, M.S., Zati, D.H., Coull, B.A., Diaz, E.A., Raimundo, R.D., Jaeger, T.N.G., Ricci-Vitor, A.L., Papapostolou, V., Lawrence, J.E., Garner, D.M., Perry, B.S., Harkema, J.R., and Godleski, J.J. (2017). Inhaled Ambient-level Traffic-derived Particulates Decrease Cardiac Vagal Influence and Baroreflexes and Increase Arrhythmia in a Rat Model of Metabolic Syndrome. Particle and Fibre Toxicology 14, 16. R834797C002 (Final)
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    Journal Article Zhong J, Allen K, Rao X, Ying Z, Braunstein Z, Kankanala SR, Xia C, Wang X, Bramble LA, Wagner JG, Lewandowski R, Sun Q, Harkema JR, Rajagopalan S (2016). Repeated ozone exposure exacerbates insulin resistance and activates innate immune response in genetically susceptible mice. Inhal Toxicol. 28(9):383-92. PubMed PMID:27240593. R834797C002 (2016)
    R834797C002 (Final)
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    Journal Article Subacute inhalation exposure to ozone induces systemic inflammation but not insulin resistance in a diabetic mouse model. Ying Z, Allen K, Zhong J, Chen M, Williams KM, Wagner JG, Lewandowski R, Sun Q, Rajagopalan S, Harkema JR. Inhal Toxicol. 2016;28(4):155-63. R834797C003 (2016)
    R834797C003 (Final)
    not available
    Journal Article Repeated ozone exposure exacerbates insulin resistance and activates innate immune response in genetically susceptible mice. Zhong J, Allen K, Rao X, Ying Z, Braunstein Z, Kankanala SR, Xia C, Wang X, Bramble LA, Wagner JG, Lewandowski R, Sun Q, Harkema JR, Rajagopalan S. Inhal Toxicol. 2016 Aug;28(9):383-92. R834797C003 (2016)
    R834797C003 (Final)
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    Supplemental Keywords:

    air toxics, metals exposure, SEAS, biostatistics, data management, modeling of multipollutant mixtures, high dimensional correlated data, Scientific Discipline, Air, ENVIRONMENTAL MANAGEMENT, HUMAN HEALTH, air toxics, Exposure, Health Risk Assessment, Biochemistry, Biology, Risk Assessment, ambient air quality, particulate matter, aerosol particles, susceptible populations, acute cardiovascualr effects, human exposure, physiology, cardiopulmonary, cardiotoxicity, acute exposure

    Relevant Websites:

    Great Lakes Air Center Exit

    Progress and Final Reports:

    Original Abstract
  • 2011 Progress Report
  • 2012 Progress Report
  • 2013 Progress Report
  • 2014 Progress Report
  • 2015 Progress Report
  • Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R834797C001 Cardiometabolic Effects of Exposure to Differing Mixtures and Concentrations of PM2.5 in Obese and Lean Adults
    R834797C002 Cardiometabolic, Autonomic, and Airway Toxicity of Acute Exposures to PM2.5 from Multipollutant Atmospheres in the Great Lakes Region
    R834797C003 Long Term Metabolic Consequences of Exposures to Multipollutant Atmospheres in the Great Lakes Region