2011 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, 2011 through March 31,2012
Project Amount: $25,000,000
RFA: Health Effects Institute (2010) RFA Text |  Recipients Lists
Research Category: Health Effects , Air Quality and Air Toxics , Air

Progress Summary:


The U.S. Environmental Protection Agency (U.S. EPA) has an intensive schedule of National Ambient Air Quality Standards (NAAQS) reviews, which by law are supposed to be completed every five years. The schedule of reviews for particulate matter (PM) and gases such as nitrogen dioxide and ozone is so full the process has come to be known as “all NAAQS all the time.”

These reviews are increasing the need for the type of informative science HEI provides. To propose and approve new NAAQS that result in improved health, EPA decision makers need to know the levels at which certain pollutants and mixes of pollutants cause adverse health effects. Such information is equally important to industry as it responds to rule changes with innovations intended to reduce the emissions of harmful toxics.

The Road Ahead for Air Quality

The revised nitrogen dioxide NAAQS includes a requirement for a new roadside monitoring system to detect and measure nitrogen dioxide emissions. This change will most likely place a brighter spotlight on vehicular emissions because of the increased surveillance — despite substantial improvements in emissions technologies in recent years.

A new ozone NAAQS increases the pressure to reduce levels of this difficult pollutant. New limits approach background concentrations, so that controlling ozone at this level will be challenging given current technologies. In 2008 new EPA rules potentially tripled the number of U.S. counties in violation of ground-level ozone standards. The upcoming review in 2013 may double that number again to 650 counties.

Science at the Ready

In response to increased regulatory pressure and in order to answer the call for objective scientific data, HEI has launched several investigative efforts to inform these complex future reviews.

In 2007, HEI launched a five-year comprehensive assessment of PM to determine which components of the mix of PM and gases found in air pollution may be the most toxic and at what levels they become hazardous.

This impartial program of systematic highquality science, called the National Particle Component Toxicity (NPACT) initiative, is advised by experts from government, industry, and environmental organizations. NPACT involves two coordinated multicity toxicologic and epidemiologic studies, directed by teams from New York University and the University of Washington. Both studies are examining the long-term cardiovascular effects of PM on mice and humans.

In November 2010 and May 2011, HEI’s NPACT advisory group met to review the progress of these two studies, which were designed to test whether some parts of PM are more toxic than others. HEI provided the NPACT advisory committee with updates on the progress of the studies and made plans for review and submission of the final reports to the committee by late 2011 in order to ensure that the results will be ready in time for the next round of NAAQS reviews in 2013. Final communications on NPACT from the HEI Review Committee will include concise summaries for federal, state, and local decision makers, as well as scientific details for technical staff.

In response to the tightening of ozone regulations in 2008, HEI began a study of the effects of ground-level ozone on cardiovascular health. This effort entails a series of multicenter human studies of ozone and PM designed specifically to develop important testing methods and uncover any health effects in order to inform future NAAQS reviews. The effects of ozone on the respiratory system have been studied extensively, but little is known about its effects on the cardiovascular system. In 2011, HEI selected three teams to examine the effects of ozone versus the broader mix of pollutants. Phase 1, which is just beginning, will expose adults from age 55 to 70 years with no evident cardiovascular disease to ozone in a laboratory setting. In Phase 2, participants will be exposed to the same levels of ozone but in the field, outside of the laboratory, where they will be in the presence of other, real-world pollutants.

The selected research teams, from the University of California–San Francisco, the University of North Carolina–Chapel Hill, and the University of Rochester, are conducting coordinated studies in a multicenter effort and have developed common hypotheses, protocols, and operations. To ensure consistency, analysis of data from all three teams will be completed by the New England Research Institutes.

To address the realities of air pollution and its health effects, HEI has also undertaken a novel effort to develop and evaluate new statistical techniques for analyzing multiple pollutants all at once. In the past, scientific studies have mirrored regulations, taking a one-pollutant-at-a-time look at health effects. However, pollutants may cause similar biologic responses through different mechanisms, and exposure to a mix of pollutants may be worse or possibly not as bad as exposure to one alone. Studying pollutants in isolation and in combination helps reveal root causes and the most hazardous combinations, but today’s statistics cannot really answer the questions. HEI hopes to innovate with a new generation of techniques that can get at the answers.

As a first step, HEI is funding three investigative teams to develop novel statistical methods. A team at Harvard University is developing a new framework built on model-based clustering methods to assess the collective effects of multiple airborne pollutants. Another team at Oregon State University is developing ways to cluster joint patterns of air pollution exposure into air pollution profiles. The team also hopes to connect these profiles to health outcomes. At the Texas A&M Transportation Institute, another team is developing statistical methods that consider source-specific exposures in the assessment of the health effects of multiple pollutants. The investigators from all three institutions are also exploring ways to test and validate their methods on real-world data, including data in the HEI Air Quality Database.

The Road Ahead in Europe

The European Union (E.U.) finalized its most recent integrated air pollution standards in 2008 and will review the scientific results and weigh the success of resulting interventions in 2013. At the kickoff meeting for the E.U. Air Quality Review, three major HEI studies were at the center of discussions of key new science helpful to decision makers. Those studies were published in Research Report 138, Health Effects of Real-World Exposure to Diesel Exhaust in Persons with Asthma, comparing effects on asthmatics walking in a London park away from traffic and on a busy London street; Research Report 140, Extended Analysis of the American Cancer Society Study of Particulate Air Pollution and Mortality, examining potential health  effects in the most extensive population studied to date; and Research Report 142, Air Pollution and Health: A European and North American Approach (APHENA), cofunded with the E.U., exploring ways to interpret data collected through different methods across geographic regions. These reports underscore the value HEI can bring to targeted and local investigations in many countries through its strategic science investments.


In theory, hot spots are obvious; any area with a high concentration of pollutants in the air qualifies. But in practice, as two recent HEI studies show, hot spots are anything but. The results of these studies suggest that there may be more than one way to define a hot spot.

And clear definitions matter because hot spots have become targets for new efforts aimed at reducing or eliminating them. Moreover, it is difficult to measure the health outcomes of hot spots and the interventions that alleviate them if the hot spots may or may not exist in the first place.

Hot Spot or Not: The Peace Bridge

Researcher John Spengler of the Harvard School of Public Health identified the U.S.–Canada border crossing at the Peace Bridge in Buffalo, N.Y., as a hot spot because it is a locale with elevated concentrations of pollutants coming from a local source: traffic.

Every day, 4000 trucks cross the Peace Bridge. Each truck requires an inspection, so traffic backs up at busy times, and trucks idle for long periods of time on the roadways. In an HEI-funded study, Spengler’s team measured more than a dozen toxic compounds both upwind and downwind of the inspection plaza and found that levels of air toxics and ultrafine particles rose in the adjoining neighborhood when the winds blew across the plaza in a certain direction.

However, in the view of HEI’s Review committee, the levels of mobile-source air toxics found by Spengler’s team at the Peace Bridge were not notably high relative to other U.S. locations, and on many days the winds blew away from the neighborhood, making it unclear whether the locale constitutes a genuine hot spot. Nevertheless, the committee found that Spengler developed and employed a novel mobile monitoring program that will help with future hot spot studies seeking to measure pollutant concentrations in neighborhoods and in small geographic areas.

Hot Spot or Not: Camden, N.J.

A study in Camden, N.J., by Paul J. Lioy of the Environmental and Occupational Health Sciences Institute of Piscataway, N.J., compared two nearby neighborhoods, one a presumed hot spot (containing industrial sites) and the other not (with no industrial sites). While the presumed hot spot had some consistently higher air toxics concentrations than the control site, the control site had higher concentrations of benzene, methyl tert-butyl ether, and other air toxics. Moreover, it had elevated air toxics levels compared with measurements made in other places in New Jersey and the United States.

It turns out that both sites qualify as hot spots. These findings can inform the design of future studies by illustrating how confirming an area as a hot spot is a crucial step that must take into consideration a variety of data and must be done before launching exposure and health effects studies.

The Road Ahead for Traffic and Hot Spot Studies

After publishing these hot spot studies in 2011 and a major HEI report on exposure and health effects of traffic in 2010 (Special Report 17, Traffic-Related Air Pollution: A Critical Review of the Literature on Emissions, Exposure, and Health Effects), HEI is bringing together in 2012 a set of experts and its Research Committee in a targeted workshop to define the next highly relevant research HEI should undertake in this important area.

Health Effects of New Fuel and Vehicle Technologies

In a significant move, President Barack Obama came together with the vehicle industry this past year to declare a new goal of reaching a standard of 54 mpg by 2025, a standard that few cars meet today. To reach it, automobile makers must increase fuel efficiency by 5% each year from 2017 to 2025.

New Engines

A major means of increasing fuel economy is the use of gasoline direct-injection technology in light-duty trucks. A potential side effect of this technology is an increase in ultrafine particle (UFP) emissions. Because data on UFPs are scant, HEI has begun a review of the literature in order to understand what is known about how mobile sources contribute to UFPs in the environment and to characterize the health effects of exposure to them. Results are expected in the spring of 2012.

In parallel, investigators implementing Phase 2 of HEI’s Advanced Collaborative Emissions Study (ACES) have launched an effort to evaluate emissions from 2010-model engines that use novel control techniques for PM and nitrogen oxides (NOx). For example, selective catalytic reduction introduces urea to control NOx emissions but may also result in the emission of new nitrogen compounds. The first results from this effort are expected in late 2012.

New Fuels

With pressure from new rules from the U.S. EPA and Department of Transportation, as well as new state rules in California that will require lower-carbon fuels, new alternatives to petroleum-based fuels are on the rise, including fuels derived from biologic sources, such as ethanol and biodiesel, and synthetically manufactured fuels, such as Fischer-Tropsch diesel. While these fuels have advantages — they may be renewable, provide some energy independence, and can lower some emissions — questions remain about whether the emissions they do produce have any unintended consequences.

To investigate, HEI’s Research Committee hopes to organize a multiparty, expert workshop to review the latest data from researchers who focus their investigations on these fuels. The outcomes of this workshop will help guide HEI’s future funding of biofuels research.

It’s Electric

Industry and research efforts to meet the new fuel efficiency goal include the introduction of hybrid and electric vehicles. HEI’s Special Committee on Emerging Technologies (SCET) has found that there are almost no published data on whether electric vehicles will expose drivers and passengers to electromagnetic fields. Similarly, there are few data on whether the use of lithium and other reactive metals in batteries could result in human exposures and subsequent health risks in the case of accidents and at the begining and end of the battery’s life cycle.

The HEI Research Committee is undertaking preliminary fact-finding efforts to review all relevant existing data and recommend whether there should be a research agenda to assess the risks of these new technologies.


To do their jobs effectively, government decision makers and industry leaders responsible for helping prevent the negative health effects of air toxics must have access to scientific evidence that gets down to the root causes of ill health due to air pollution.

HEI provides the kind of targeted science that constantly strives, using modern scientific methods and novel technologies, to root out the airborne causes of ill health. Equally important, HEI communicates its findings to key stakeholders so that they may make the most informed recommendations possible and the ones most likely to be effective.

The Word on Diesel

HEI Vice President Robert O’Keefe testified to the U.S. Senate in May 2011, sharing HEI’s latest findings on the health effects of diesel exhaust with the Subcommittee on Clean Air and Nuclear Safety. The hearing focused on encouraging the replacement of older diesel engines — engines so durable they are slow to be replaced — with newer, much cleaner diesel engines. HEI-funded investigators have been testing these newer engines in the Advanced Collaborative Emissions Study (ACES).

O’Keefe presented new data on the health effects of diesel exhaust from older engines and on the substantial improvements that come with newer diesel technologies. He reported that an HEI-funded study in London, involving 60 participants, found that shortterm exposures to older-engine diesel exhaust can reduce lung function in people with asthma. The testimony also included evidence from HEI-funded research that exposure to particulate air pollution is associated with premature mortality, particularly from heart disease, and that there is a small, but consistent, increase in lung cancer risk for workers exposed to these older engines.

Based on this and other evidence, the U.S. EPA has estimated that annually more than 20,000 premature deaths could be avoided in the United States by replacing diesel on-road and non-road engines that incorporate older technologies with new, cleaner ones.

The data on the new diesel engines bear this out, O’Keefe reported. According to the testing of new diesel technologies in Phase 1 of ACES, the new engines are substantially cleaner. Emissions of fine particles, carbon monoxide, and hydrocarbons from 2007-compliant heavy-duty engines were 90% lower than required. Unregulated emissions, such as ultrafine particles and air toxics, were 90% to 99% lower than emissions from 2004-compliant vehicles. “This substantial overcompliance with the stringent EPA standards is a remarkable achievement, and one that can be expected to make a significant contribution to improving public health as the older engines are replaced,” O’Keefe reported at the hearing.

The Word on Congestion Charging

To help reduce traffic congestion, one market economics approach imposes financial disincentives by charging drivers to enter restricted, congestion-prone areas. The idea is that the added fee represents the cost of potential negative outcomes, such as delays from congestion. The health effects of air pollution are not specifically targeted. But these interventions raise the question of whether there are measurable health benefits attributable to enactment of these schemes. The first step in answering this is to determine if the congestion charging programs produce an improvement in air quality.

In 2011, HEI released Research Report 155, The Impact of the Congestion Charging Scheme on Air Quality in London — a study of the largest example of such disincentives — and found that the scheme, while reducing traffic, had few air quality benefits.

The study, led by Frank Kelly of King’s College London and funded by HEI’s Health Outcomes research program, evaluated whether the London regulation resulted in changes in emissions, air quality, and the characteristics of PM linked to toxicity. Using one roadside and three urban background monitoring sites, researchers measured air pollutant concentrations during the two years before and after the scheme began. These measurements did not show significant reductions within the congestion charging zone, despite the predictions of models the researchers had developed, which anticipated that the scheme would result in substantial reductions — up to 20% in the case of NOx and PM.

The study was limited by the small number of monitoring sites, which reduced the precision of the measurements. In addition, during the first year of the study, unusual weather conditions in London led to periods of elevated pollution levels. Other changes, such as an increase in nitrogen dioxide levels possibly caused by an unrelated project involving diesel buses in the area, also influenced the measurements. Finally, the study concluded that the area of London in which congestion charging was imposed accounted for only 1.4% of Greater London, possibly too small an area to substantially influence air pollution levels.

This study suggests several lessons for future research on interventions expected to influence air quality. In addition to illustrating the challenges of detecting air quality improvements and accounting for confounding factors such as weather, it also highlights the importance of assessing the impact on air quality of an intervention first before attempting to assess its health effects.

On the Horizon: New Health Outcomes Research

HEI is launching new research to assess efforts to improve air quality as part of its Health Outcomes research agenda. HEI will fund 3 to 4 studies with $2.5 million over three years beginning in 2012. Funded projects will focus on national and regional interventions — including both regulatory and incentive-based actions — and their longer-term outcomes over a time frame of several years. The studies will also assess the effects of complex regulations that target large urban areas and will include efforts to develop new methods specifically designed to conduct this type of Health Outcomes research.


Estimates suggest that the demand for cars in China will be nine times higher in 2025 than in 2005, and five times higher in India, creating markets primed for expansion by worldwide automobile manufacturers. At the same time, concerns about air pollution from many sources are growing in these countries.

Regulations Based on Science

In 2009, India revised its NAAQS. Key features of the new standards included requirements that industrial areas meet the same air quality standards as residential areas, the addition of the regulation of fine PM (PM2.5, or PM with an aerodynamic diameter ≤ 2.5 μm), and inclusion of the regulation of other pollutants such as ozone, arsenic, nickel, and benzene.

While regulations such as these are a step forward, they have been based predominantly on World Health Organization guidelines and European air quality limits. They have not had the benefit of being informed by local studies that help regulators understand the challenges unique to the specific location.

For the past decade, with additional funding, HEI has been working to strengthen the quality of local scientific investigations into emissions, exposure, and health effects in China, India, Thailand, and other Asian countries. With the support of the Hewlett Foundation, the Asian Development Bank, and the U.S. Agency for International Development, HEI has increased the capacity for rigorous science in these emerging markets and has established key contacts with environmental agency leaders.

Looking ahead, HEI will continue to strengthen these efforts through targeted local science, particularly in India and China. HEI also has plans to provide key regulatory decision makers with timely communications of new, internationally relevant findings, such as the ACES findings on new cleaner diesel engines, and data on low-sulfur fuels and advanced fuel and engine technologies. The intention is to help build a base for more informed decisions about environmental regulations so that new rules make sense locally.

New Public Health Data in Asia

As examples of recent local scientific efforts in India, HEI published two Public Health and Air Pollution in Asia (PAPA) studies in March 2011 examining how short-term exposure to air pollution affects daily mortality in Chennai and Delhi. The studies, conducted by two separate research teams using rigorously coordinated methods, provide valuable epidemiologic evidence of the effects of short-term exposure to air pollution.

The Chennai investigators found that the relative risk for nonaccidental all-cause mortality increased 0.4% when PM10concentrations increased by 10 μg/m3 the previous day. Using a similar approach, the Delhi investigators found a 0.15% increase in the relative risk of mortality under the same conditions.

The PAPA protocol used in these two studies was previously employed in four other separately funded studies in cities in China and Thailand, demonstrating how HEI-funded research is increasing the capacity for quality science and providing a valuable foundation for further research in developing countries. 

These four earlier PAPA studies, published in 2010, as well as other multicity studies worldwide, including in Europe and North America, have found similar increases in risk. This consistency is of great scientific interest since concentrations of air pollutants are substantially higher in Asia than in Europe and North America; it lends support to the idea that people in these developing countries respond to air pollution in ways similar to those in the United States and Europe.

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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  • 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