2013 Progress Report: Health Effects Institute (2010-2015)

EPA Grant Number: R834677
Center: Health Effects Institute (2005 — 2010)
Center Director: Greenbaum, Daniel S.
Title: Health Effects Institute (2010-2015)
Investigators: Greenbaum, Daniel S.
Institution: Health Effects Institute (HEI)
EPA Project Officer: Chung, Serena
Project Period: April 1, 2010 through March 31, 2015
Project Period Covered by this Report: April 1, 2013 through March 31,2014
Project Amount: $25,000,000
RFA: Health Effects Institute (2010) RFA Text |  Recipients Lists
Research Category: Health Effects , Air Quality and Air Toxics , Air



 For 33 years, the Health Effects Institute has been fielding the United States’, and the world’s, toughest questions about the effects of air pollution on health. All told, HEI has funded more than 330 research projects in North America, Europe, Asia, and Latin America and published more than 260 reports that have informed policy and industry decisions about carbon monoxide, air toxics, nitrogen oxides, diesel exhaust, ozone, particulate matter (PM), and other pollutants. The answers HEI provides are uniquely trusted, not only because they are grounded in peer-reviewed science, but also because HEI continually strives to improve the quality of its data by recruiting expert teams, applying updated methods, and scrutinizing the scientific process.

Answering the Call at Home

In the wake of the June 2012 designation of diesel exhaust as a carcinogen by the World Health Organization’s (WHO’s) International Agency for Research on Cancer, the U.S. Environmental Protection Agency (EPA) and HEI’s industry sponsors asked HEI to revisit and update its 1999 assessment of diesel exhaust data. In response, in March 2013, HEI formed the HEI Diesel Epidemiology Panel. This multidisciplinary panel of experts will review the latest epidemiologic evidence and consider its strengths and weaknesses for use in assessing how diesel exhaust affects the risk of lung cancer.

Not only does the EPA call on HEI for scientific review, but it also asks for advice. In July 2013, the EPA’s Office of Research and Development solicited HEI’s expertise on how to protect the privacy of study participants while still making their medical data available for scientific inquiry. The request, which also went out to the American Cancer Society and Harvard University, stated that “the EPA recognizes that such institutions are the best source for helping us better understand what technical options may be available.” HEI has responded with advice and an assured commitment to data transparency.

Answering the Call Abroad

As the HEI model for scientific inquiry continues to prove to be effective and reliable, HEI is positioning itself for the future by strengthening its scientific expertise and methods in core areas, as well as its active participation in the evolving global conversation about the health effects of air pollution. For instance, in January 2013, HEI co-organized a meeting in Brussels, along with the European Commission and the WHO, to review the latest scientific findings on air quality and health, with the goal of helping the European Union make decisions about how to update Europe’s air quality policies.

In another example, in October 2012, delegates from the Japan Automobile Manufacturers Association visited HEI to share research results from the Japan Automotive Research Institute. During their visit, they also learned about HEI’s latest findings regarding diesel and PM and received HEI’s expert input on their plans for new studies.

Answering the Call of Peers

The HEI approach has been so successful that groups outside of HEI’s traditional area of expertise have approached HEI to determine if its model can be applied to science used to guide public policy in other areas. For instance, the Shale Gas Roundtable in Pennsylvania, in an effort to evaluate the health and environmental effects of a burgeoning shale gas industry in the state, investigated several research approaches to inform its plans. The diverse Roundtable members — from government, academia, NGOs, and industry — found only one that passed muster, that of HEI.

In an August 2013 report, Deliberations, Findings, and Recommendations, the Roundtable announced the selection of HEI’s approach as a model for its own research fund: “HEI’s nonpartisan approach, independent structure, history, and activities informed the Roundtable members’ thinking on unconventional oil and gas research issues and aided in the development of the proposal. . . . It will be essential for diverse stakeholders to be able to trust the rigor and independence of the process and resulting agenda.” 

Progress Summary:


With decades of experience studying the health effects of exposure to diesel exhaust, HEI is continually being called on to report its latest findings and to explore new methods of assessing risk.

New Diesel Advances

HEI’s Advanced Collaborative Emissions Study (ACES) is the most comprehensive study ever undertaken to characterize the emissions of new-technology diesel engines and to examine health risks associated with exposure. The latest ACES findings from Phases 2 and 3 were presented at HEI’s 27th Annual Conference in San Francisco in April 2013.

In Phase 2 of the study, which ended in December 2012, investigators characterized emissions from three heavy-duty engines designed to meet the 2010 U.S. EPA standards for emission of nitrogen oxides and particulate matter (PM), among other pollutants. The new engines were found to be extremely effective at reducing nitrogen oxides and PM, and emissions from all three engines were substantially lower than the 2010 standard, results that were published in November 2013.

In ACES Phase 3, investigators studied the effects of chronic exposure of rats to 2007-compliant diesel engine exhaust. While the final report is due out in 2014, initial results suggest that exposure produced few health effects in rats after up to 30 months. In May 2013, to further substantiate the ACES Phase 3 findings, HEI invited a group of expert pathologists to provide peer review of the pathology findings of the study, and their review will be included in HEI’s broader, detailed review of the report.

Turning Over the Fleet

Substantial progress has been made in replacing older diesel engines with new technology in North America and Europe, with as many as 30% of the diesel on the road in the United States now meeting 2007 standards, according to a presentation by HEI President Dan Greenbaum at HEI’s Annual Conference. But progress remains slow in other places, where the ultralow-sulfur fuel is not available. For instance, in Mexico, PM released from many sources including older diesel engines burning higher-sulfur fuel remains a problem that contributes, according to the latest calculation of the Global Burden of Disease for outdoor air pollution, to an estimated 20,500 premature deaths each year.

Mexican authorities addressed this and other air quality issues at the multinational Climate and Clean Air Coalition meeting in Mexico City in July 2013. HEI presented data showing that 64% of people in Mexico City live close enough to roads to be exposed to high levels of traffic-related air pollution, but also noted, based on its ACES study, just how much cleaner emissions could be if low-sulfur fuel were available.

At the meeting, Mexico’s Ministry of Environment described plans to regulate diesel PM emissions through the proven solutions of using low-sulfur fuel and employing particulate filters to eliminate 90% of diesel PM emissions.

Revisiting Risk

In 1999, HEI published a Special Report, Diesel Emissions and Lung Cancer, that concluded that existing data from studies of the health effects of diesel exhaust exposure could not support a quantitative assessment of the health risks of diesel exposure. Since then, new studies examining the association between exposure to diesel exhaust and lung cancer have been published, including studies of miners and of trucking industry employees in the United States. Investigators in these newer studies have made more extensive efforts to estimate historical exposures. In view of these new data and at the request of the U.S. EPA and industry sponsors, HEI initiated the Diesel Epidemiology Project in 2013 and assembled a panel of experts to evaluate whether evidence from these new studies can be used in a quantitative assessment of the cancer risks associated with exposure to diesel exhaust. HEI’s Diesel Epidemiology Panel has held several meetings to evaluate the studies and in March 2014 will hold a public workshop to hear presentations and receive input from investigators who carried out the new studies.

One of the key questions to be answered by the Panel is whether the data from these new studies will allow government officials to calculate the risks of diesel exhaust exposure at levels similar to those encountered in the general environment where traffic is present or in occupational settings. Panel deliberations will continue following the 2014 workshop and will conclude with a final report.

Tackling Tough Questions About Traffic Exposure

Many issues complicate the accuracy and reliability of metrics used to estimate personal exposure to pollutants from traffic, ranging from weather and geography to the presence of other sources of pollution and the type of exposure model used. In view of this situation, HEI convened a group of experts in 2012 to help the HEI Research Committee identify the top-priority needs for more effective ways to estimate individual and community exposures to traffic pollutants.

In response to a January 2013 request for applications, researchers submitted a host of proposals for studies to identify novel measures for assessing exposure to near-road, traffic-related pollution, evaluate which variables best explain how traffic pollution concentration levels vary in time and space, and improve the models used to estimate exposure to traffic pollution in health-related studies, from which HEI will make a selection.


HEI has continued its research efforts to understand the complex mixture of air pollutants by carrying out new projects to better characterize particles and ozone and to understand their health effects.

Answers from NPACT

Particulate matter (PM) is a complex mixture of particles of different sizes and chemical composition. One long-standing question from industry and policy makers is whether some components of the PM mixture are more toxic than others and therefore deserving of priority efforts for control. In 2007, to answer this and other questions about multipollutant components of PM, HEI launched its National Particle Component Toxicity (NPACT) initiative.

In October 2013, HEI released the results of two major NPACT studies (Lippmann et al. and Vedal et al.), each comprising both epidemiology and toxicology studies. The Lippmann study found that particles associated with coal combustion, residual oil combustion, traffic, and metals are the most consistently associated with adverse health effects. In its analyses, the Vedal study found strong evidence for associations of fine PM, organic carbon, and sulfur with subclinical and clinical cardiovascular outcomes. In addition, the toxicologic component provided strong evidence for the effects of mixed vehicular engine emissions and, to a lesser extent, exhaust gas on vascular markers.

However, according to the HEI NPACT Review Panel — a group of experts in medicine, epidemiology, toxicology, statistics, atmospheric chemistry, and exposure — the studies, the most comprehensive of their kind to date, did not provide compelling evidence to exclude any specific source, component, or size class of PM as a contributor to PM toxicity. Additional research is needed before it can be concluded that targeting specific sources or components of fine PM will protect public health more effectively than the current practice of targeting fine PM mass as a whole.

Contributing to the Conversation on Ultrafine Particles

In January 2013, HEI released an HEI Perspective, Understanding the Health Effects of Ambient Ultrafine Particles, written by a panel of experts who reviewed some 300 toxicologic studies in animals, controlled human exposure studies, and epidemiologic studies. The panel found that ultrafine particles (those ≤ 0.1 μm in size) had been shown to behave differently in the body from larger particles, but are not likely to be responsible for all of the adverse affects associated with ambient pollutants, including fine PM. The findings are consistent with the EPA’s decision not to set a new standard for the control of ultrafine particles in its 2012 National Ambient Air Quality Standards for PM.

Changing the Debate on Ozone

Scientific evidence suggests that ozone exposure may have effects in the airways that could lead to systemic inflammation and potentially to adverse cardiovascular effects in humans. However, to date there have been few controlled studies of human exposure to ozone that have evaluated effects on the cardiovascular system.

HEI responded to this research need with its Multicenter Ozone Study in Elderly Subjects (MOSES). Investigators in this study are examining the results of exposing healthy volunteers, ages 55 to 75, to two different near-ambient levels of ozone and to clean air. The research is being conducted at clinical centers at the University of California–San Francisco, the University of North Carolina–Chapel Hill, and the University of Rochester. Researchers are looking to see if ozone exposure has effects on autonomic balance, cardiovascular function, vascular function, and clotting variables.

Recruitment continues, with 44 participants enrolled and tested as of the end of 2013. Testing and analysis will continue for approximately two years, with results potentially ready for review in late 2015.


For more than a decade, HEI has extended its research, with supplemental funding, to help inform air quality decisions in Europe, Asia, and elsewhere. This global reach began at the urging of HEI sponsors and the World Health Organization (WHO) and continues today with activities that are helping to guide the decisions of public and industry leaders worldwide.

HEI in Europe: Talking about the Year of Air

When the European Commission declared 2013 as the “Year of Air,” it made a commitment to focus on improving air quality in Europe. To meet this goal, the European Commission, the WHO, and HEI joined forces to organize a conference in January 2013 that would facilitate open and transparent discussion of the latest scientific findings on the health effects of air pollution and inform regulatory and other policy decisions concerning air quality controls.

The event, held in Brussels, Belgium, featured speakers from across Europe as well as representatives from the WHO Regional Office for Europe, the U.S. EPA, and HEI, all presenting the latest scientific evidence to help the European Commission answer pressing questions relating to decisions about how to update Europe’s air quality policies. Specifically, the Commission wanted to know if there were levels of major pollutants below which there were no adverse health effects and if there were specific sizes or types of particulate matter associated with adverse health effects.

The evidence presented included a substantial review of HEI’s NPACT findings as well as HEI’s ultrafine particle research results. The meeting drew 200 attendees, including representatives of European member states, environmentalists, and industry, and included a special briefing for the Committee on the Environment, Public Health, and Food Safety of the European Parliament.

Assessing the Global Burden of Disease

In December 2012, The Lancet published an analysis titled “The 2010 Global Burden of Disease,” which concluded that a large burden of disease in many parts of the world can be traced back to air pollution. The analysis, based on the largest global database ever assembled to estimate premature death from risks such as smoking, diet, alcohol, AIDS, and pollution, was conducted by an international team that included HEI Principal Scientist Aaron Cohen.

The study found that exposure to particulate matter is among the top 10 global risk factors, contributing to 3.2 million premature deaths worldwide and 74 million years of healthy life lost in 2010. Approximately two-thirds of those deaths are estimated to have occurred in the developing countries of Asia.

To bring these results to the attention of the Indian and Chinese public health and policy communities, HEI received foundation support to organize workshops in Delhi in February 2013 and in Beijing in March. The workshops resonated with these communities, as severe air pollution episodes have become increasingly common in Asia. In China, air pollution is exacerbated by the burning of significant amounts of low-grade coal in power plants, coupled with rapidly rising levels of energy consumption.

The workshops drew large crowds of prominent local medical and air pollution researchers, representatives from regulatory agencies, and the media, including Chinese and Indian news outlets, the New York Times, the BBC, and the Wall Street Journal. In an interview with National Public Radio, HEI Vice President Robert O’Keefe reported seeing positive reactions from the Chinese government in response, such as the establishment of a nationwide air pollution monitoring network. “For the first time, the Chinese government is providing transparent [information on] levels of air pollution that the public can actually see,” said O’Keefe. 

Journal Articles: 5 Displayed | Download in RIS Format

Other center views: All 69 publications 62 publications in selected types All 5 journal articles
Type Citation Sub Project Document Sources
Journal Article Greenbaum D, Shaikh R. First steps toward multipollutant science for air quality decisions. Epidemiology 2010;21(2):195-197. R834677 (Final)
  • Abstract from PubMed
  • Full-text: LWW-Full Text HTML
  • Other: LWW-Full Text PDF
  • Journal Article Meng Q, Hackfeld LC, Hodge RP, Walker VE. Comparison of mutagenicity of stereochemical forms of 1,2,3,4-diepoxybutane at HPRT and TK loci in human cells. Environmental and Molecular Mutagenesis 2003;41(36 Supplement):77. R834677C150 (Final)
    not available
    Journal Article Meng Q, Redetzke DL, Hackfeld LC, Hodge RP, Walker DM, Walker VE. Mutagenicity of stereochemical configurations of 1,2-epoxybutene and 1,2:3,4-diepoxybutane in human lymphoblastoid cells. Chemico-Biological Interactions 2007;166(1-3):207-218. R834677C150 (Final)
  • Abstract from PubMed
  • Abstract: ScienceDirect-Abstract
  • Journal Article van Erp AM, Kelly FJ, Demerjian KL, Pope III CA, Cohen AJ. Progress in research to assess the effectiveness of air quality interventions towards improving public health. Air Quality, Atmosphere & Health 2012;5(2):217-230. R834677 (Final)
  • Abstract: Springer-Abstract
  • Journal Article van Erp AM, Cohen AJ, Shaikh R, O’Keefe R. Recent progress and challenges in assessing the effectiveness of air quality interventions toward improving public health: the HEI experience. EM Magazine 2012;10:22-28. R834677 (Final)
  • Full-text: EM Magazine-Full Text PDF
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    Progress and Final Reports:

    Original Abstract
  • 2010 Progress Report
  • 2011 Progress Report
  • 2012 Progress Report
  • Final Report
  • Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R834677C149 Development and Application of a Sensitive Method to Determine Concentrations of Acrolein and Other Carbonyls in Ambient Air
    R834677C150 Mutagenicity of Stereochemical Configurations of 1,3-Butadiene Epoxy Metabolites in Human Cells
    R834677C151 Biologic Effects of Inhaled Diesel Exhaust in Young and Old Mice: A Pilot Project
    R834677C152 Evaluating Heterogeneity in Indoor and Outdoor Air Pollution Using Land-Use Regression and Constrained Factor Analysis
    R834677C153 Improved Source Apportionment and Speciation of Low-Volume Particulate Matter Samples
    R834677C155 The Impact of the Congestion Charging Scheme on Air Quality in London
    R834677C156 Concentrations of Air Toxics in Motor Vehicle-Dominated Environments
    R834677C158 Air Toxics Exposure from Vehicle Emissions at a U.S. Border Crossing: Buffalo Peace Bridge Study
    R834677C159 Role of Neprilysin in Airway Inflammation Induced by Diesel Exhaust Emissions
    R834677C160 Personal and Ambient Exposures to Air Toxics in Camden, New Jersey
    R834677C162 Assessing the Impact of a Wood Stove Replacement Program on Air Quality and Children’s Health
    R834677C163 The London Low Emission Zone Baseline Study
    R834677C165 Effects of Controlled Exposure to Diesel Exhaust in Allergic Asthmatic Individuals
    R834677C168 Evaluating the Effects of Title IV of the 1990 Clean Air Act Amendments on Air Quality
    R834677C172 Potential Air Toxics Hot Spots in Truck Terminals and Cabs
    R834677C173 Detection and Characterization of Nanoparticles from Motor Vehicles
    R834677C174 Cardiorespiratory Biomarker Responses in Healthy Young Adults to Drastic Air Quality Changes Surrounding the 2008 Beijing Olympics