Air Pollution-Related Illness: Effects of Particles

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Science  06 May 2005:
Vol. 308, Issue 5723, pp. 804-806
DOI: 10.1126/science.1108752

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Worldwide epidemiological studies show a consistent increase in cardiac and respiratory morbidity and mortality from exposure to particulate matter [HN1] (PM) (13). PM is a key ingredient of polluted air and is estimated to kill more than 500,000 people each year (4). To prevent this staggering loss of life we must understand the characteristics of the toxic particles and gain insight into how these characteristics are related to adverse health effects [HN2] (5). As our understanding increases, we can use this knowledge to develop biomarkers in the hope of identifying susceptible individuals and reducing their exposure to PM.

PM is composed of solid and liquid particles that come from sources such as vehicle exhaust, road dust, smokestacks, forest fires, windblown soil, volcanic emissions, and sea spray (6). Particle size, surface area, and chemical composition determine the health risk posed by PM (7). PM can be classified into coarse, fine, or ultrafine particles (6). Coarse particles, which have a diameter of more than 2.5 μm, are mostly derived from soil and sea salts. Fine particles (0.1 to 2.5 μm in diameter) and ultrafines (<0.1 μm in diameter) [HN3] are predominantly derived from combustion of fossil fuel (see the first figure). Combustion particles have a core of elemental carbon that is coated with a layer of chemicals, including organic hydrocarbons, metals, nitrates, and sulfates. All of these components may play a role in particle toxicity (7).

Dangerous dirt.

(Left) Electron micrograph of a fine mode particle collected by an impactor from air outside an engineering laboratory at the University of California, Los Angeles. A halo surrounds residues of what are probably inorganic salts and polar organic compounds dissolved in the original aqueous droplet. Sootlike particles are also present. (Right) Aggregates of ultrafine particles collected on the last stage of an eight-stage impactor. These are soot particles emitted from diesel engine sources such as buses. More volatile particles may have evaporated in the electron microscope.


Currently, government and air-quality monitoring agencies track and regulate 10-μm-diameter (PM10) and 2.5-μm-diameter (PM2.5) particles. Unfortunately, the unregulated ultrafine particles are potentially the most dangerous. Ultrafines are the major component in vehicle emissions—the largest source of air pollution in urban areas (8)—and they have the largest surface area and highest content of potentially toxic hydrocarbons among all PM sources. They can also penetrate deeper into lung tissue than fine or coarse particles (8).

Pulmonary effects of PM [HN4] include the triggering of inflammation [HN5] in the smaller airways, which can lead to the exacerbation of asthma and chronic bronchitis, airway obstruction, and decreased gas exchange (1, 2, 9). PM can also interfere with the clearance and inactivation of bacteria in lung tissue. More recently, there has been a growing awareness that PM is a cardiovascular risk factor [HN6] that is associated with heart attacks, stroke, heart rhythm disturbances, and sudden death (3).

A number of mechanisms have been proposed to explain the adverse health impact of PM (5). Effects of PM that have experimental support are inflammation, cytokine [HN7] and chemokine [HN8] release, production of white blood cells, oxygen free-radical production in the lungs, endotoxin-mediated cellular and tissue responses, stimulation of irritant receptors, and covalent modification of key cellular enzymes (5, 9). Best characterized in humans are the effects of PM on airway inflammation (10). In human and animal studies, inhalation of particles elicits proinflammatory effects, cytokine production, and enhancement of allergic responses in the upper and lower airways (911). PM exposure is likely linked to inflammation through the generation of reactive oxygen species [HN9] and oxidative stress [HN10] (9, 1214). Although there is still debate about which particle components are responsible for producing reactive oxygen species, there is accumulating evidence that pro-oxidative organic hydrocarbons, such as polycyclic aromatic hydrocarbons and quinones, and transition metals, such as copper, vanadium, chromium, nickel, cobalt, and iron, play a role (15, 16). The particle provides a template for electron transfer to molecular oxygen in these reduction and oxidation (redox) cycling events (7). In addition, target cells, such as airway epithelial cells and macrophages, generate reactive oxygen species in response to particle uptake by biologically catalyzed redox reactions that occur in the cell membrane and mitochondria (9, 13, 15). The second figure shows mitochondrial damage to a macrophage caused by ultrafine particles.

Reactive oxygen species can damage cellular proteins, lipids, membranes, and DNA. To defend against this damage, cells use up their stores of a key antioxidant, glutathione [HN11]. The glutathione depletion can induce a state of cellular stress, called oxidative stress, that triggers an increase in the production of antioxidant enzymes through activation of a transcription factor Nrf2 (17). Failure to overcome oxidative stress leads to the activation of additional intracellular signaling cascades that regulate the expression of cytokine and chemokine genes (14, 16). These products are produced locally in target tissues as well as systemically, and lead to widespread proinflammatory effects remote from the site of damage.

Toxic particles.

The effect of ultrafine particles (UFP) in a macrophage cell line. (Left) An untreated macrophage with healthy mitochondria (M). (Right) The same cell type treated with ambient ultrafine particles, collected in the Los Angeles basin. The enlarged images show that the untreated cell has healthy mitochondria with cristae, whereas the treated cell has damaged mitochondria that lack cristae. The vacuolar structures in the treated cell each represent a mitochondrion with included particles (P). Whether the particles gain access to and then damage the mitochondria or gain access to already damaged mitochondria is unknown. [Modified from (15)]

Some individuals may be more prone to the development of inflammation, asthma, and allergic responses, because of mutations in the genes involved in the induction of the antioxidant defense (18). Other conditions that predispose to PM susceptibility include old age, preexisting chronic heart and lung disease, and diabetes mellitus, all of which are associated with oxidative stress and inflammation.

Although oxidative stress and inflammation may explain aspects of cardiovascular disease such as the growth of atherosclerotic plaques, other adverse outcomes, such as sudden death, may result from altered autonomic regulation of heart rate and changes in the clotting abilities of the blood (3). Although the cause of altered autonomic nervous activity is unknown, the systemic release of cytokines from the lung and vasculature may affect the production of clotting factors and anticoagulant enzymes in the liver. This could lead to the formation of a dense clot on top of a ruptured atherosclerotic plaque, the pathological hallmark of fatal heart attacks. The role of adsorbed particle chemicals in these cardiovascular events is uncertain. However, it is noteworthy that the ultrafine particles may gain access to the systemic circulation by penetrating alveolar membranes in lung tissue (19).

Public concern about the adverse health impact of PM should drive future research. We need to determine which chemical components are most important and whether, in addition to the PM mass, we also need to monitor particle number when considering the effects of ultrafine particles. Products of oxidative stress, inflammation, or tissue damage can be used as biomarkers for early indication of adverse effects of PM exposure. These biomarkers could be monitored in population studies to find susceptible subsets and to determine whether regulatory efforts are sufficient to protect against PM-induced or PM-exacerbated disease.

HyperNotes Related Resources on the World Wide Web

General Hypernotes

Dictionaries and Glossaries

An atmospheric chemistry and air quality glossary is provided by the Department of Chemistry, Sam Houston State University, Huntsville, TX.

An air quality glossary is provided by the U.S. National Park Service.

A dictionary of aerosol science is provided by the Aerosols Online Web site.

The On-line Medical Dictionary is provided by CancerWeb.

Web Collections, References, and Resource Lists

The Google Directory provides links to Internet resources on air quality.

MedlinePlus provides a collection of links to Internet resources on air pollution and health.

Specialized Information Services at the National Library of Medicine (NLM) provide a collection of Internet links on outdoor air pollution.

AIRNET, a European network project on air quality and health, offers links to Internet resources.

The World Bank's New Ideas in Pollution Regulation Web site provides links to Internet resources on industrial pollution and related topics.

Sites Related to Aerosols and Atmospheric Chemistry is provided by the AIDA-Server of the Atmospheric Aerosol Research Department, Institute for Meteorology and Climate Research, Karlsruhe, Germany.

The Northwest Center for Particulate Matter and Health at the University of Washington makes available a collection of links to Internet resources.

The National Environmental Respiratory Center provides a collection of Internet links.

PSIgate provides annotated links to Internet educational resources on the atmosphere.

Online Texts and Lecture Notes

The Office of Air and Radiation of the U.S. Environmental Protection Agency (EPA) provides Air Pollution Trends and AIRLinks to topical information on air and radiation issues.

AIRNow is a cross-agency U.S. Government Web site with information on air quality issues.

The Encyclopedia of the Atmospheric Environment is provided by the Atmosphere, Climate and Environment Information Programme of Manchester Metropolitan University, UK.

The University of Michigan's Global Change Curriculum offers a presentations on urban atmospheric pollution and particulate matter.

R. Foust, Department of Chemistry, Northern Arizona University, makes available lecture notes for a course on environmental chemistry.

I. N. Sokolik, School of Earth and Atmospheric Sciences, Georgia Institute of Technology, offers lecture notes for a course on air chemistry and pollution.

General Reports and Articles

Environmental Health Perspectives from the National Institute of Environmental Health Sciences of the National Institutes of Health is a monthly journal of peer-reviewed research and news on the impact of the environment on human health. Collections of Environews articles on air pollution and particulate matter are available.

Ambient Particular Matter: An Overview is an online science assessment document provided by the Meteorological Service of CANADA.

The National Library for the Environment makes available in PDF format a January 2005 report from the Congressional Research Service titled “Particulate matter air quality standards: Background and current developments.”

The Clean Air Task Force issued a February 2005 report titled Diesel and Health in America: The Lingering Threat.

The 2004 report titled Research Priorities for Airborne Particulate Matter: IV. Continuing Research Progress is available from the National Academies Press. The three earlier reports in the series are also available.

The EPA's Office of Air and Radiation makes available the report titled “The particle pollution report: Current understanding of air quality and emissions through 2003.”

The 25 March 2005 issue of Science had an Enhanced Perspective by D. M. Murphy titled “Something in the air” and a News Focus article by J. Kaiser titled “Mounting evidence indicts fine-particle pollution” (with a sidebar titled “How dirty air hurts the heart”).

The Health Effects Institute makes available in PDF format a 2004 report titled “Time-series analysis of air pollution and mortality: A statistical review” and a March 2005 report titled “Particulate air pollution and nonfatal cardiac events, Part I.” Among the other publications available are two perspectives: “Airborne particles and health: HEI epidemiologic evidence” and “Understanding the health effects of components of the particulate matter mix: Progress and next steps” (6).

Numbered Hypernotes

1. Particulate matter in the air. AIRNow defines particle pollution. The Minnesota Pollution Control Agency offers definitions of particulate matter and fine particulate matter. The New Zealand Ministry for the Environment offers a presentation on particle size. Wikipedia has an article about particulates in the air. An introduction to particulates is provided by the Encyclopedia of the Atmospheric Environment. R. Foust provides lecture notes on particles in the atmosphere for a course on environmental chemistry. The Southern California Environmental Report Card 2001 from the UCLA Institute of the Environment includes a section by W. C. Hinds titled “Particulate air pollution.” FindArticles makes available the 1994 Environment article titled “Air pollution in the world's megacities” (4).

2. Particulate matter and health. R. Foust provides lecture notes on health effects of atmospheric particulates for a course on environmental chemistry. The 9 December 1993 issue of the New England Journal of Medicine had an article by D. W. Dockery et al. titled “An association between air pollution and mortality in six U.S. cities” (1). The 14 December 2000 issue of the New England Journal of Medicine had an article by J. M. Samet et al. titled “Fine particulate air pollution and mortality in 20 U.S. cities, 1987-1994” (2). The EPA Office of Air and Radiation provides a fact sheet on health and environmental effects of particulate matter and a presentation titled “How particulate matter affects the way we live and breathe.” The Minnesota Department of Health offers a fact sheet on particulate matter and health. The Natural Resources Defense Council (NRDC) provides a FAQ on particulate pollution and health. The WHO Regional Office for Europe offers in PDF format a fact sheet titled “Particulate matter air pollution: How it harms health” and a June 2004 report titled “Health aspects of air pollution.” The August 2000 issue of Environmental Health Perspectives had an article by C. A. Pope III titled “Epidemiology of fine particulate air pollution and human health: Biologic mechanisms and who's at risk?”

3. Fine and ultrafine particles. The EPA Office of Air and Radiation offers information on fine particles. The Tennessee Valley Authority offers a presentation titled “Dust in the wind: The challenge of fine particles” and a presentation titled “Chemical composition of fine particles.” The 15 March 2002 issue of Science had a News of the Week article by S. Pyne titled “Small particles add up to big disease risk.” The National Institute of Environmental Health Sciences issued a 5 March 2002 press release titled “Link strengthened between lung cancer, heart deaths and tiny particles of soot, dust.” The August 2002 issue of Environmental Health Perspectives had a news article by E. Hood titled “Particulate matter—A particular concern” and an editorial by G. Oberdörster and M. J. Utell titled “Ultrafine particles in the urban air: To the respiratory tract—and beyond?” (8). The vol. 39, no. 3, 2003 issue of the Annali dell'Istituto Superiore di Sanità had an article (PDF format) by K. Donaldson and V. Stone titled “Current hypotheses on the mechanisms of toxicity of ultrafine particles.” The March 2001 issue of the European Respiratory Journal had an article by P. Penttinen et al. titled “Ultrafine particles in urban air and respiratory health among adult asthmatics”; the April 2001 issue had an article by A. Sydbom et al. titled “Health effects of diesel exhaust emissions.” The October 2004 issue of Environmental Health Perspectives had an article by T. Xia et al. titled “Quinones and aromatic chemical compounds in particulate matter induce mitochondrial dysfunction: Implications for ultrafine particle toxicity.”

4. Particulate matter and the lungs. The Canadian Centre for Occupational Health and Safety offers a fact sheet on particulates and the respiratory system. The American Lung Association offers a particle pollution fact sheet. The 2 August 2003 issue of Science News had an article by J. Raloff titled “Air sickness: How microscopic dust particles cause subtle but serious harm.” The May 2003 issue of Environmental Health Perspectives had an article by A. Churg et al. titled “Chronic exposure to high levels of particulate air pollution and small airway remodeling.” The NRDC makes available a Winter 2003 article by K. Eisele titled “With every breath you take” about air pollution and asthma.

5. An introduction to inflammation is provided by H. Ibelgaufts' Cytokines Online Pathfinder Encyclopaedia (COPE). Kimball's Biology Pages offers a presentation on inflammation. The 15 August 2001 issue of the American Journal of Respiratory and Critical Care Medicine had an article by A. J. Ghio and R. B. Devlin titled “Inflammatory lung injury after bronchial instillation of air pollution particles” (10).

6. Particulates as cardiovascular risk factors. The American Heart Association provides a presentation titled “Air Pollution, heart disease and stroke.” The 1 June 2004 issue of Circulation had an article by R. D. Brook et al. titled “Air pollution and cardiovascular disease: A statement for healthcare professionals from the Expert Panel on Population and Prevention Science of the American Heart Association” (3). The 6 January 2004 issue of Circulation had an article by C. A. Pope III et al. titled “Cardiovascular mortality and long-term exposure to particulate air pollution: Epidemiological evidence of general pathophysiological pathways of disease” and a perspective article by R. L. Johnson, Jr. titled “Relative effects of air pollution on lungs and heart.” The 20 August 2002 issue of Circulation had an editorial by R. L. Verrier, M. A. Mittleman, and P. H. Stone titled “Air pollution: An insidious and pervasive component of cardiac risk” and an article by J. Pekkanen et al. titled “Particulate air pollution and risk of ST segment depression during repeated submaximal exercise tests among subjects with coronary heart disease: The ULTRA Study.” The 29 January 2002 issue of Circulation had an article by A. Nemmar et al. titled “Passage of inhaled particles into the blood circulation in humans” (19).

7. Cytokines. Cytokine is defined in the On-line Medical Dictionary. A cytokine tutorial is included in the Immunology Book Case provided by the Dalhousie University Faculty of Medicine. H. Ibelgaufts' COPE provides an introduction to cytokines. J. Decker, Department of Veterinary Science and Microbiology, University of Arizona, offers lecture notes on cytokines for an immunology course. A presentation on cytokines is provided by A. G. Izaguirre, Department of Pathology and Laboratory Medicine, University of Medicine and Dentistry of New Jersey.

8. Chemokine is defined in the On-line Medical Dictionary. H. Ibelgaufts' COPE includes an entry on chemokines. The Department of Biology, Davidson College, NC, makes available a lecture series on chemokines.

9. Reactive oxygen species. An introduction to reactive oxygen is provided by the Companion Web site for the third edition of Biochemistry by Mathews, van Holde, and Ahern. Kimball's Biology Pages provides information on reactive oxygen species. R&D Systems offers a mini-review on reactive oxygen species. G. Buettner and L. Oberley, Free Radical and Radiation Biology Graduate Program, University of Iowa College of Medicine, make available in PDF format 2001 student papers and 2003 student papers prepared for a graduate course on free radicals in biology and medicine. The August 2002 issue of Environmental Health Perspectives had an article by S. A. Gurgueira et al. titled “Rapid increases in the steady-state concentration of reactive oxygen species in the lungs and heart after particulate air pollution inhalation” (12).

10. Oxidative stress. Oxidative stress is defined in the On-line Medical Dictionary and in D. Glick's Glossary of Biochemistry and Molecular Biology. Sigma-Aldrich offers an introduction to oxidative stress. For a biochemistry course, H. Jakubowski, Chemistry Department, College of Saint Benedict/Saint John's University, St. Joseph, MN, makes available lecture notes on the chemistry of dioxygen that include a discussion of oxidative stress. The 12 December 2003 issue of the Journal of Biological Chemistry had an article by G. G. Xiao et al. titled “Use of proteomics to demonstrate a hierarchical oxidative stress response to diesel exhaust particle chemicals in a macrophage cell line” (14). The April 2003 issue of Environmental Health Perspectives had an article by N. Li et al. titled “Ultrafine particulate pollutants induce oxidative stress and mitochondrial damage” (15).

11. Glutathione. Glutathione is defined in the BioTech Life Sciences Dictionary. Wikipedia has an entry on glutathione. The Biochemistry companion Web site has an entry on glutathione. An annotated image of glutathione is provided by the Molecular Expressions Web site. Information on glutathione function is provided by M. King's Medical Biochemistry Page. The Society for Free Radical Biology and Medicine's Virtual Free Radical School makes available in PDF format presentations on glutathione regulation and glutathione synthesis.

12. André Nel is in the Division of Clinical Immunology and Allergy, Department of Medicine, University of California, Los Angeles.

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