PM Health Outcomes
PM Health Outcomes
Exposure to outdoor air pollutants is often difficult to avoid. The air we breathe may contain contaminants that are harmful to the lungs and sometimes to organs such as the heart and brain or biological systems.
Impacts on the lungs may take several forms. Short-term effects include deficits in lung function that can limit breathing, especially in exercise. Irritants like ozone, acidic gases, and toxic components of particulate matter (PM) may cause airway constriction or chest tightening that is uncomfortable or limiting to normal activity. These changes in lung function sometimes have underlying lung tissue inflammation which over the long term may lead to chronic lung disease.
Individuals with underlying lung disease are most susceptible to the impacts of air pollutants. And effects may be greater for those who have genetic sensitivities to air pollutants, although the science of genetic factors is still being explored.
Recently, PM has been linked to adverse cardiac effects. Individuals with pre-existent cardiopulmonary diseases or the aged are thought to be most at risk from PM exposure.
Cardiac events may be mediated through vascular or blood clotting effects, but much remains uncertain. What is known is that people at higher risk can die after exposure to PM or develop life-threatening health problems that lead to hospitalization or medical interventions.
Science provides the foundation for much of our knowledge about the health outcomes of air pollutants, particularly ozone, PM, and other common air pollutants or criteria pollutants regulated by EPA.
Health effects research is focused on several critical areas:
- Health effects resulting from different sizes of PM
- Health effects resulting from different chemical make-ups or composition of PM
- Relationship between PM and asthma
- Toxic mechanisms that trigger biological processes that lead to PM’s effects
- Susceptible populations at greater risk from PM exposure
Outdoor air pollution particles are currently divided into three classes based on their size:
- Coarse particulate matter (PM) consists of particles with a diameter between 2.5 and 10 micrometers (µm) and deposit efficiently along the airways. Particles larger than 10 µm are generally not inhalable into the lungs.
- Fine PM consists of particles with a diameter less than 2.5 µm and can be inhaled deeply into the lungs.
- Ultrafine particles, the smallest, consist of particles with a diameter smaller than 0.1 µm and have widespread deposition within the respiratory tract.
It is not well understood whether particles with different size ranges have different abilities to cause adverse health effects.
The U.S. Environmental Protection Agency currently regulates PM on the basis of mass in both the fine and coarse size ranges. More than 150 epidemiology studies have demonstrated an association between fine PM and acute mortality and morbidity.
A smaller number of studies have linked exposure to coarse PM with increased mortality and morbidity. However, uncertainty about the effects of coarse PM derived from different sources has led EPA to ask for science to address the question of differential toxicity from coarse PM of urban areas versus PM of rural areas. There is also concern that because of the high concentration of biological compounds present in coarse PM, compared with smaller size fractions, asthmatics may be a particularly susceptible subpopulation to coarse particles.
In addition, there is concern that there may be adverse health effects associated with exposure to ultrafine particles, which, if established, could potentially lead EPA to propose a a PM standard for these smaller particles.
Because of these uncertainties, regulators and scientists both believe there is more to learn about the adverse health effects of different sized PM, especially as the composition of these particles varies.
Researchers are conducting a comprehensive and integrated research program to compare the cardiovascular and pulmonary responses of humans or appropriate animal models to different sizes of PM. Both EPA scientists as well as academic researchers funded by the Agency are engaged in these studies.
The research program includes studies which:
- Compare the cardiovascular and pulmonary response of healthy human volunteers or animal models exposed to coarse, fine, and ultrafine particles.
- Determine if people with pre-existing cardiovascular or pulmonary disease such as asthma are especially susceptible to one or all of the particle sizes.
- Compare the cardiovascular and pulmonary response to coarse PM originating from urban and rural areas.
- Identify the underlying cellular and molecular mechanisms by which each size fraction causes adverse health effects.
- Characterize the relative toxicities of coarse, fine, and ultrafine PM from several different geographical areas that have different sources of PM pollution. The chemical composition of these size ranges can simultaneously be associated with the health outcomes.
- Characterize the relative toxicity of different particle sizes from real world sources, notably near highly trafficked roadways.
- Conduct epidemiological field studies to assess size related health impacts on selected populations of high risk. especially near roadways.
Application and Impact
Research to expand our knowledge about the health effects associated with exposure to different size particles will provide important information that will allow EPA to set PM standards which are optimally protective of human health.
The research will help EPA regulators:
- Determine if it is appropriate to regulate particles based on the number of particles rather than size.
- Assess whether ultrafine particles should be regulated.
- Assist with making decisions on where to position air quality monitors to obtain the data that best represents human health risks.
Gilmour, MI, et al. Comparative Toxicity of Size Fractionated Airborne Particulate Matter Obtained from Different Cities in the USA. Inhalation Toxicology, 2007; 1:7-16.
Graff, DW, et al. Assessing the Role of Particulate Matter Size and Composition on Gene Expression in Pulmonary Cells. Inhalation Toxicology, 2007; 1:23-8.
Samet, JM, et al. A Comparison of Studies on the Effects of Controlled Exposure to Fine, Coarse and Ultrafine Ambient Particulate Matter from a Single Location. Inhalation Toxicology, 2007; 1:29-32.
Frampton M.W., et al. Inhalation of Ultrafine Particles alters Blood Leukocyte Expression of Adhesion Molecules in Humans. Environmental Health Perspectives, 2006; 114(1): 51-58.
Peng R.D., et al. Coarse particulate matter air pollution and hospital admissions for cardiovascular and respiratory diseases among Medicare patients. Journal of the American Medical Association, 2008; 299(18): 2172-9.
Robert Devlin (firstname.lastname@example.org), Ph.D., National Health and Environmental Effects Research Laboratory, EPA's Office of Research and Development, 919-966-6255.
M. Ian Gilmour (email@example.com), Ph.D., National Health and Environmental Effects Research Laboratory, 919-541-0015.
The U.S. Environmental Protection Agency currently regulates particulate matter (PM) on the basis of mass in specific size ranges. However, PM not only exists in different sizes, but each size range varies in chemical composition.
Scientists and policymakers want to know how particles vary in toxicity, depending on both size and composition, especially from sources that emit combustion by-products into the air. Are there specific chemical profiles responsible for PM-related cardiovascular and respiratory problems and possibly other adverse effects?
Research has contributed significantly to the understanding of health effects of PM and findings have been used to establish the Agency's regulations for PM.
As part of the program's comprehensive and multidisciplinary approach to studying PM, researchers are characterizing both outdoor (ambient) particles in various sizes and particles derived from varied sources. The research objectives are to identify which particles are most toxic, what attribute(s) of the particles confer toxicity, and what are the associated health outcomes.
Health scientists use a variety of research approaches including the use of samples obtained from various EPA studies. Samples are used to systematically address health questions based on cell assays, and/or laboratory and clinical studies.
The specific scientific questions with this effort include:
- What health effects are associated with PM of differing composition?
- What new biomarkers that indicate health impacts can be linked to specific PM components and associated gases that coexist with PM?
- What is the comparative toxicity of PM from different locations, and varied seasonal and climate conditions?
- What is the comparative toxicity of PM from defined sources (e.g., diesel exhaust, automotive traffic, coal emissions, ship-stack emissions, incinerators, wood smoke, etc)?
- What PM components and associated gases are responsible for differing toxicity of complex combustion emissions and how can they be used to link sources and processes to health effects?
Application and Impact:
EPA research provides crucial information on the toxicity of various types of PM, based on their components and sources. The studies also elucidate the mechanisms by which PM components may be linked to specific adverse health effects.
Taken together, this information improves the ongoing assessment of the current mass-based standards (PM2.5 and PM10) aids deliberations regarding the utility of component- or source-based PM regulations and control strategies.
Research has demonstrated that:
- PM toxicity varies by size and composition with both bioavailable metals and organic chemicals playing a role in the health outcomes.
- Diesel particulates obtained from different engines can have diverse chemical signatures which can affect particle toxicity, mutagenicity and allergic potentials.
- Particle-associated metals exert their toxicity in part due to their bioavailability and pro-oxidant potential.
- Size fractionated ambient (outdoor) particulate samples obtained from various cities across the United States have different chemical makeup and accompanying toxicity profiles.
- Ultrafine particles collected in Los Angeles were significantly higher in organic and elemental carbon than fine or coarse particles, and were also more potent in inducing oxidative stress in in vitro tests using mouse and human cell lines.
- Analysis of Medicare hospitalization data indicates that East-West coast differences in PM composition appear to be associated with rates of hospitalization for cardiovascular and respiratory causes.
- Analysis of data from 25 U.S. communities found an increase in mortality associated with fine PM, and the association was increased when the PM contained higher proportions of certain species, such as aluminum, arsenic, sulfate, silicon and nickel.
Araujo JA, Barajas B, Kleinman M, Wang X, Bennett BJ, Gong KW, Navab M, Harkema J, Sioutas C, Lusis AJ, Nel AE (2008) Ambient particulate pollutants in the ultrafine range promote early atherosclerosis and systemic oxidative stress. Circ Res. 2008 Mar 14;102(5):589-96.
Gilmour MI., McGee, J, Duvall, RM., Dailey, L., Daniels, M., Boykin E., Cho, SH., Doerfler, D., Gordon, T., & Devlin, RB. (2007) Comparative Toxicity of Size Fractionated Airborne Particulate Matter Obtained from Different Cities in the USA. Inhalation Toxicology. 19 (Supp). 1-10.
Franklin M., Koutrakis P., and Schwartz J. (2008) The Role of Particle Composition on the Association Between PM2.5 and Mortality. Epidemiology 19: 680–689.
M. Ian Gilmour (Gilmour.firstname.lastname@example.org), National Health and Environmental Effects Research Laboratory, EPA's Office of Research and Development, 919-541-0015.
It is estimated that over 20 million Americans suffer from asthma. This includes almost two million emergency department visits, 5,000 deaths, and a financial cost of $14 billion each year.
Asthma has been identified as a serious and growing health problem by the U.S. Department of Health and Human Services. Air pollution, both outdoor and indoor, is a significant risk factor for the exacerbation of asthma. In addition, because asthmatics may have difficulty clearing pollutants from their airways, they may be at an increased risk of non-respiratory effects of air pollutants such adverse effects on cardiac health.
Though it has been firmly established that air pollution can initiate asthma attacks, its role in causing asthma in the first place is still unclear. At greatest risk may be individuals who are exposed to pollutants in the womb or at a young age. The elderly who have asthma on top of already age-related loss of function may also be at greater risk. The Office of Research and Development (ORD) in the U.S. Environmental Protection Agency has a research program dedicated to resolving these uncertainties about asthma.
Research is conducted in several main areas:
- Induction and exacerbation of asthma
- Susceptibility factors contributing to asthma
- Risk assessment issues related to induction, exacerbation, and susceptibility
ORD addresses key issues to understand the role of pollutants on asthma, including:
- Determining the critical time window of exposure that predisposes one to asthma
- Understanding the key biological pathways by which air pollutants cause asthma
- Identifying the factors that make asthmatics more vulnerable to the effects of air pollutants
A major epidemiological research project sponsored by ORD is the Detroit Children's Health study, which is providing data on the association between exposure of air pollutants, particularly particulate matter (PM), and adverse health outcomes. The study is examining whether long-term, early-life exposures to mobile-source emissions, particularly diesel exhaust particles, play a key role in the induction of allergic asthma in school children.
Asthma research is also focused on:
- Exploring the association between exposure to mobile sources in the womb or early in life and its role in induction of asthma in children and in the elderly
- Exploring the mechanisms by which air pollutants impact respiratory and cardiac health in asthmatics
- Understanding the effects of outdoor air pollution on moderate and severe asthma subjects
- Understanding the acute effects of exposure to different sizes of particulate matter (PM) on cardiopulmonary function, biomarkers of inflammation, and other factors in mild to moderate asthmatics
- Identifying biomarkers unique to elderly asthmatics, which differs from younger asthmatics following air pollutant exposure
Application and Impact
Asthma research at ORD is leading to the development of new scientific methods, models, and data that is helping to assess the risks of asthma from exposure to air pollutants.
The research has contributed to the development by EPA of regulatory standards for two high-priority air pollutants--ozone and particulate matter. Studies have also supported health assessments for diesel emissions.
Among other contributions, research showed that residual oil fly ash from oil combustion in power plants causes immune system changes that make mice more sensitive to dust mite allergens. Residual oil fly ash often contains nickel as well as vanadium and iron. Each metal could cause the mice to develop a stronger allergy to dust mites. This may help explain why some geographic regions have higher rates of asthma.
ORD's Asthma Research Strategy:
ORD's Asthma Research Highlights:
Gong, H. Jr., Linn, W.S., Clark, K.W., Anderson, K.R., Sioutas, C., Alexis, N.E., Cascio, W.E., Devlin, R.B. Exposures of Healthy and Asthmatic Volunteers to Concentrated Ambient Ultrafine Particles in Los Angeles. Inhal. Toxicol. 2008 Apr; 20(6):533-45.
Yeatts, K., Svendsen, E., Creason, J., Alexis, N., Herbst, M., Scott, J., Kupper, L., Williams, R., Neas, L., Cascio, W., Devlin, R.B., and Peden, D.B. Coarse Particulate Matter (PM2.5-10) Affects Heart Rate Variability, Blood Lipids, and Circulating Eosinophils in Adults with Asthma. Environ. Health Perspect. 2007 May; 115(5):709-14.
David Diaz-Sanchez (email@example.com), National Health and Environmental Effects Research Laboratory, EPA’s Office of Research and Development, 919-966-0676.
Exposure to airborne particle pollutants, known as particulate matter (PM), has been linked with health hazards, including heart disease, diminished lung function, and lung cancer. While these adverse health connections have been proven through extensive scientific research, the underlying mechanisms for these effects have been harder to identify.
PM is a complex and varying mixture that can include thousands of organic and inorganic compounds, derived from both anthropogenic (human-made) and natural sources. Epidemiological evidence suggests that, rather than causing specific diseases, PM exposure is linked to exacerbations of and increased predisposition to a wide range of common adverse cardiovascular and pulmonary effects in humans. As a further complication, there appears to be great variability in the human effects of PM exposure from person to person—variations that are not well understood presently. In addition, much uncertainty remains regarding the specific toxic agents in PM and their toxicological effects on humans.
Currently, there is not enough data to provide a full assessment of the risks to human health that PM exposure entails, especially given the wide range of individual responses to these airborne pollutants. Understanding the toxicity of PM at the cellular and molecular level is essential for the U.S. Environmental Protection Agency to better protect exposed populations.
Researchers are working in close partnership with EPA's regulatory programs and other organizations outside the Agency to identify, characterize, and model the cellular and molecular events that lead to adverse reactions to airborne pollutant exposure. This research effort seeks to answer relevant scientific questions about the nature of ambient particulate matter and its toxicity in humans.
These questions include, but are not limited to:
- What are the earliest molecular events that define lung cellular responses to PM exposure?
- What are the physical and chemical properties of PM that are associated with adverse reactions?
- Is it possible to develop predictive mathematical models of the activation of cellular responses to PM inhalation?
The answers to these questions are being pursued through research studies using advanced cellular, biochemical and molecular biology approaches. Ultimately, these efforts will provide the basis for the generation of reliable models for predicting the effects of airborne particulate pollution across the widely varied ranges of PM and the populations that it affects.
Application and Impact
Filling the knowledge gaps surrounding the adverse effects of airborne contaminants at the cellular and molecular levels will enable EPA to develop and implement regulatory measures to mitigate the adverse effects of PM exposure on human health with greater accuracy and efficiency.
Specifically, EPA expects this research effort to achieve the following:
- Elucidate critical cellular and molecular events that underlie adverse cellular responses to PM exposure
- Identify critical physicochemical properties of PM types that are responsible for adverse health effects
- Aid in the translation of laboratory data in cells and laboratory animals to the human situation
- Develop a predictive computational model of the intracellular pathways that lead to adverse cellular responses to PM inhalation. These models can be used for risk assessment in support of protective regulatory strategies
Cao D, Bromberg PA, Samet JM. Cox-2 expression induced by diesel particles involves chromatin modification and degradation of hdac1. Am J Respir Cell Mol Biol 2007;37(2):232-239.
Kim YM, Cao D, Reed W, Wu W, Jaspers I, Tal T, Bromberg PA, Samet JM. Zn2+-induced nf-kappab-dependent transcriptional activity involves site-specific p65/rela phosphorylation. Cell Signal 2007;19(3):538-546.
Tal TL, Graves LM, Silbajoris R, Bromberg PA, Wu W, Samet JM. Inhibition of protein tyrosine phosphatase activity mediates epidermal growth factor receptor signaling in human airway epithelial cells exposed to zn2+. Toxicol Appl Pharmacol 2006;214(1):16-23.
James M. Samet (firstname.lastname@example.org), National Health and Environmental Effects Research Laboratory, EPA's Office of Research and Development, 919-966-0665.
Urmila Kodavanti (email@example.com), National Health and Environmental Effects Research Laboratory, 919-541-4963.
The Clean Air Act requires the U.S. Environmental Protection Agency to set air pollution standards to protect human health. However, there is wide disparity in people’s susceptibility to air pollutants and the intensities of their reactions to them.
The National Ambient Air Quality Standards (NAAQS) are designed to protect the most vulnerable populations from outdoor air pollutants. Identifying these groups more precisely and understanding why they are more susceptible is of great importance to scientists and policy makers.
While multiple studies suggest a direct relation between outdoor air pollution and an increased risk of cardiopulmonary events or diseases, segments of the population appear far more vulnerable or responsive to these pollutants. The elderly and the very young, for example, have been found to be more vulnerable to pollution's effects.
The collective evidence garnered from epidemiological, clinical, and toxicological studies indicates a range of responsiveness that can vary in both kind and degree. In fact, sensitivity can be several-fold higher in the case of particulate matter (PM) or ozone. Characterization of this enhanced sensitivity and its underlying causes will aid in the development of appropriate standards or intervention strategies to mitigate risk to more susceptible populations.
Researchers provide the science to better define the individual elements that lead to higher susceptibility to air pollution. Primary elements for consideration include (but are not limited to) differences in dose, age, disease, behaviors such as exercise, or genetic predispositions.
ORD researchers are studying how and why these characteristics contribute to an increased risk of adverse effects in response to air pollutants. Other factors such as socio-economic status and living conditions are also being examined.
ORD research activities include the following:
- Studying the airborne contaminant effects on adult and pediatric populations
- Investigating differences between elderly versus younger asthmatics and appropriate animal models in response to ozone and PM exposures
- Evaluating the use of antioxidants to mitigate the effects of PM in healthy young and elderly individuals
- Investigating animal models of defined sensitivities to assess the impact of pollutants or their causation of chronic cardiopulmonary diseases
- Identifying adverse health effects of PM on people and animal models with underlying cardiopulmonary and related diseases
- Identifying the genes involved with increased susceptibility to air pollutants
- Identifying changes to respiratory and cardiac cells in human, animal and in vitro models exposed to PM
Application and Impact
Research by the Clean Air Research Program is improving the ability of EPA and others to identify and characterize populations more susceptible to airborne contamination. As susceptible populations are better defined, and the root biological mechanisms of higher susceptibility are revealed, information on specific risk factors is used to advise susceptible individuals on ways to protect their health. This information is also used to evaluate and develop air pollution policies and guidelines. For example, research has:
Supported a decision by California to pass legislation restricting the location of new schools near major roadways
Supported New York City’s rule that bus fleets must convert to clean diesel fuel sources
Provided the scientific foundation for the development of guidelines by the National Asthma Education and Prevention Program (NAEPP), which recommends clinicians advise asthma patients to avoid exertion outdoors when levels of air pollution are high. URL: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm
Provided scientific data used to develop protocols for conducting the National Children's Study
Selgrade MK, Plopper CG, Gilmour MI, Conolly RB, Foos BS. Assessing the health effects and risks associated with children's inhalation exposures—asthma and allergy. J Toxicol Environ Health A. 2008;71(3):196-207.
Alexeeff SE, Litonjua AA, Wright RO, et al. Ozone Exposure, Antioxidant Genes, and Lung Function in an Elderly Cohort: VA Normative Aging Study. Occupational and Environmental Medicine 2008;doi:10.1136/oem.2007.035253.
O'Neill MS, Veves A, Sarnat JA, Zanobetti A, et al. 2007. Air pollution and inflammation in type 2 diabetes: a mechanism for susceptibility. Occup Environ Med 64: 373-379.
David Diaz-Sanchez (firstname.lastname@example.org), National Health and Environmental Effects Research Laboratory, EPA’s Office of Research and Development, 919-966-0676