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Public Health Air Quality: Health Effects
by
C. Arden Pope

Introduction

Ambient air pollution has long been implicated as a contributor to adverse health effects. Severe air-pollution episodes in the early and mid–20th century demonstrated that extreme exposure to air pollution can result in serious illness or death. Beginning around 1990 there was a dramatic growth in epidemiological research regarding the contribution of air-pollution exposure to cardiopulmonary disease and mortality. Daily time-series and related studies indicate that short-term exposure exacerbates existing cardiovascular and pulmonary disease and increases the risk of becoming symptomatic, requiring medical attention, or even of dying. Population-based cross-sectional studies and cohort-based studies indicate that long-term repeated exposures increase the risk of chronic pulmonary and cardiovascular disease and death. Various intervention or natural-experiment studies have provided both indirect and direct evidence that public-policy efforts that reduce air pollution can result in improved health. Toxicological research, in concert with epidemiological research, has attempted to elucidate mechanistic pathways that link exposure to air pollution and cardiopulmonary disease and mortality. This research suggests that general mechanistic pathways include pulmonary and systemic oxidative stress and inflammation, enhanced initiation and progression of atherosclerosis, and altered cardiac autonomic function. Attempts to evaluate the constituents or characteristics of air pollution most responsible for these health effects have generally implicated combustion-related fine particles and associated air pollutants as being largely responsible.

General Overviews

By the 1970s and 1980s there was general agreement on a link between respiratory and cardiovascular diseases and very high concentrations of air pollution, but, as discussed in Holland, et al. 1979, there was a prevailing view that compelling evidence of significant health effects at low to moderate levels of pollution exposure was lacking. During the relatively short period of the early to mid-1990s, several epidemiological research studies reported air-pollution health effects at unexpectedly low concentrations of air pollution, and a sudden increase of subsequent research has provided additional evidence. Articles and books reviewing this literature, such as Bascom, et al. 1996 and Holgate, et al. 1999, increasingly began to suggest that there was growing consistent and coherent evidence that air pollution, common in modern cities, contributed to respiratory disease. Other reviewers, including Vedal 1997, emphasized inconsistencies, disagreements in interpretation, and gaps in knowledge. Phalen 2002 also emphasized that gaps in knowledge remained but further highlighted the lack of consensus regarding the appropriate public-policy response. However, recent reviews such as Brunekreef and Holgate 2002 and Pope and Dockery 2006 have reflected the swelling evidence base and growing consensus that significant, relevant, and biologically plausible health effects of air pollution occur, even at common levels of exposure. The updated scientific statement from the American Heart Association (Brook, et al. 2010) reviews the mounting evidence that ambient air pollution contributes to cardiovascular disease.

  • Bascom, R., P. A. Bromberg, D. L. Costa, R. Devlin, D. W. Dockery, M. W. Frampton, W. Lambert, J. M Samet, F. E. Speizer, and M. Utell. 1996. Health effects of outdoor air pollution. American Journal of Respiratory and Critical Care Medicine 153:3–50.

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    An authoritative report from the American Thoracic Society that addressed the health effects of a wide range of air pollutants. They documented various health effects of particulate matter, sulfur dioxide, nitrogen dioxide, ozone, and other pollutants, including at moderate levels of exposure.

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  • Brook, Robert, Sanjay Rajagopalan, C. Arden Pope III, Jeffrey R. Brook, Aruni Bhatnagar, Ana V. Diez-Roux, Fernando Holguin, Yuling Hong, Russell V. Luepker, Murray A. Mittleman, Annette Peters, David Siscovick, Sidney C. Smith Jr., Laurie Whitsel, and Joel D. Kaufman. 2010. Particulate matter air pollution and cardiovascular disease: An update to the scientific statement from the American Heart Association. Circulation 121:2331–2378.

    DOI: 10.1161/CIR.0b013e3181dbece1Save Citation »Export Citation »E-mail Citation »

    This updated American Heart Association scientific statement provides a relatively comprehensive review and evaluation of the recent but rapidly growing epidemiological, toxicological, and related research. It concludes that the overall evidence is consistent with a causal relationship between fine particulate pollution exposure and cardiovascular disease morbidity and mortality.

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  • Brunekreef, Bert, and Stephen T. Holgate. 2002. Air pollution and health. Lancet 360:1233–1242.

    DOI: 10.1016/S0140-6736(02)11274-8Save Citation »Export Citation »E-mail Citation »

    A relatively concise review that primarily addresses the health effects of particulate matter, ozone, and nitrogen dioxide.

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  • Holgate, Stephen T., Jonathan M. Samet, Hillel S. Koren, and Robert L. Maynard, eds. 1999. Air pollution and health. San Diego, CA: Academic.

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    A large (1,065 pages, forty-four chapters, and sixty-eight contributing authors) book edited by eminent air-pollution and health scientists, intended to provide inclusive coverage of air pollution issues in one volume. It covers a broad range of air pollutants and issues and provides evidence that air pollution continues to be a public health concern worthy of further research and public-policy efforts.

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  • Holland, W. W., A. E. Bennett, I. R. Cameron, C. du V. Florey, S. R. Leeder, R. S. F. Schilling, A. V. Swan, and R. E. Waller. 1979. Health effects of particulate pollution: reappraising the evidence. American Journal of Epidemiology 110:525–659.

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    A special authoritative report by eminent British researchers on health effects of particulate-matter air pollution that filled the entire issue of the journal. They concluded that there were significant health effects at very high exposures, but that there was not compelling evidence of substantive health effects at low to moderate levels of exposure.

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  • Phalen, Robert F. 2002. The particulate air pollution controversy: A case study and lessons learned. Boston: Kluwer Academic.

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    A relatively concise book (128 pages) written by a well-respected inhalation toxicologist that is skeptical of how air-pollution science is being used to motivate environmental and public-health policy. It contains a review of the particulate-air-pollution and health science and addresses scientific and public-health controversies and limitations surrounding this literature.

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  • Pope, C. Arden, III, and Douglas W. Dockery. 2006. Health effects of fine particulate air pollution: Lines that connect. Journal of the Air & Waste Management Association 56:709–742.

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    An invited critical review that focused on knowledge gained in the previous ten years. It concluded that, although important gaps in scientific knowledge remain, recent research has connected many of the gaps and has provided persuasive evidence that common exposures to fine particulate and related air pollution contribute to adverse cardiopulmonary health.

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  • Vedal, Sverre. 1997. Ambient particles and health: Lines that divide. Journal of the Air & Waste Management Association 47:551–581.

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    An invited critical review of particulate air pollution and health literature written by a well-respected expert in the field. In addition to providing an insightful review of the literature, major sources of controversy and important gaps in knowledge are discussed and evaluated in terms of their scientific and public-policy importance.

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Early Severe Episodes

Several extreme air-pollution episodes, often referred to as “killer smog” episodes, occurred in the early to mid-20th century. They demonstrated convincingly that extreme levels of air pollution, even for just a few days, can contribute substantially to cardiovascular and respiratory disease and death and served as primary motivation for subsequent air pollution research and for air pollution control efforts in the United Kingdom, United States, and elsewhere. Firket 1931 reports on the first of these well-documented severe air-pollution episodes that occurred in Meuse Valley, Belgium, in 1930. Schrenk, et al. 1948 provides a report of another major episode that occurred in Donora, Pennsylvania, in 1948. Contemporaneous and recent retrospective analyses of the most dramatic and famous episode, which occurred in London in 1952 are provided by Logan 1953 and Bell, et al. 2004, respectively.

  • Bell, Michelle L., Devra L. Davis, and Tony Fletcher. 2004. A retrospective assessment of mortality from the London smog episode of 1952: The role of influenza and pollution. Environmental Health Perspectives 112:6–8.

    DOI: 10.1289/ehp.6539Save Citation »Export Citation »E-mail Citation »

    This retrospective analysis of the 1952 London smog episode concludes that only a fraction of the excess mortality that followed the episode can be attributed to influenza. If the delayed effects of exposure to the episodes are accounted for, excess deaths attributed to the episode would be approximately twelve thousand, versus the approximately four thousand originally estimated.

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  • Firket, J. 1931. The cause of the symptoms found in the Meuse valley during the fog of December. Bulletin De l’Academie Royale de Medecine de Belgique 11:683–741.

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    A research report on the dramatic health impacts of the severe air pollution episode that occurred in the industrialized Meuse Valley during 1–5 December 1930. During the episode there were approximately sixty deaths (ten times the expected number) and much illness, with severe coughing and breathlessness being common symptoms.

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  • Logan, W. P. D. 1953. Mortality in the London fog incident, 1952. Lancet 264:336–338.

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    A concise report on the mortality effects associated with the severe air-pollution episode that occurred in London on 5–9 December 1952—probably the most dramatic, well-documented, and public-policy-influencing severe air-pollution episode in history. This report concludes that the four-day episode was responsible for approximately four thousand excess deaths.

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  • Schrenk, H. H., Harry Heimann, George D. Clayton, W. M. Gafafer, and Harry Wexler. 1949. Air pollution in Donora, Pa.: Epidemiology of the unusual smog episode of October 1948. Washington, DC: Government Printing Office.

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    A public health bulletin and research report of the severe air-pollution episode that occurred in industrial community of Donora, Pennsylvania, on 27–31 October 1948. There were approximately twenty excess deaths and wide-scale illness in the community attributed to the episode.

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Short-Term Exposure

Since the early 1990s, many epidemiological studies of air pollution have evaluated associations between day-to-day changes in various health endpoints and day-to-day changes in air-pollution concentrations. The most common health endpoint used in these studies has been population-based daily mortality counts or specific mortality events. However, there have also been many studies that have evaluated daily changes in various respiratory and cardiovascular morbidity health endpoints. These studies are typically referred to as short-term exposure studies or acute-exposure studies.

Mortality

Numerous daily time-series mortality studies have evaluated changes in daily death counts associated with day-to-day changes in air pollution at relatively low and common levels of pollution, even while controlling for weather variables, seasonality, long-term time trends, and other time-dependent factors. Changes in daily mortality counts were associated with changes in various indexes of air pollution, especially inhalable or fine particulate-matter air pollution. Analyses of cause-specific mortality counts indicated that air pollution was most strongly associated with respiratory- and cardiovascular-disease mortality. There was substantial skepticism regarding several early single-city studies, but, as reported by Samet, et al. 1995, the early research could be independently validated and replicated. There have since been many other single-city studies, as reviewed by Anderson, et al. 2005. More recently, the single-city time-series results have been largely superseded by several large multicity studies with greater statistical power and analytic rigor, and with less potential of city-selection bias. Samet, et al. 2000, Peng, et al. 2005, Bell, et al. 2004, and Zanobetti and Schwartz 2009 are representative reports of key large US-based studies. Analitis, et al. 2006 reports the results of a similar European-based multicity study. Somoli, et al. 2008 presents results from the largest coordinated multicity study using cities from across the United States, Canada, and Europe.

  • Analitis, Antonis, Klea Katsouyanni, Konstantina Dimakopoulou, Evanglia Samoli, Aristidis K. Nikoloulopoulos, Yannis Petasakis, Giota Touloumi, Joel Schwartz, Hugh Ross Anderson, Koldo Cambra, Francesco Forastiere, Denis Zmirou, Judith M. Vonk, Luke Clancy, Bohumir Kriz, Janos Bobvos, and Juha Pekkanen. 2006. Short-term effects of ambient particles of cardiovascular and respiratory mortality. Epidemiology 17:230–233.

    DOI: 10.1097/01.ede.0000199439.57655.6bSave Citation »Export Citation »E-mail Citation »

    The results from a large European-based multicity study, Air Pollution and Health: a European Approach (APHEA2). Respiratory and cardiovascular disease deaths were associated with measures of particulate-matter air pollution.

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  • Anderson, H. Ross, Richard W. Atkinson, Janet L. Peacock, Michael J. Sweeting, and Louise Marston. 2005. Ambient particulate matter and health effects: Publication bias in studies of short-term associations. Epidemiology 16:155–163.

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    This paper reported the results of a comprehensive meta-analysis of previously published short-term exposure and mortality studies; it also evaluated the existence of publication bias. It found some evidence of publication bias, but even after correction for this bias, positive and precisely estimated associations between particulate-matter air pollution and mortality remained.

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  • Bell, Michelle L., Aidan McDermott, Scott L. Zeger, Jonathan M. Samet, and Francesca Dominici. 2004. Ozone and short-term mortality in 95 U.S. urban communities, 1987–2000. Journal of the American Medical Association 292:2372–2378.

    DOI: 10.1001/jama.292.19.2372Save Citation »Export Citation »E-mail Citation »

    Using data from the National Morbidity, Mortality, and Air Pollution Study for ninety-five US cities, the authors evaluated daily changes in cardiovascular and respiratory mortality counts and daily changes in air pollution with a focus on the effect of ozone exposure while controlling for the particulate-matter effect. An ozone effect that appeared to be independent of particulate matter was observed.

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  • Peng, Roger D., Francesca Dominici, Roberto Pastor-Barriuso, Scott L. Zeger, and Jonathan M. Samet. 2005. Seasonal analyses of air pollution and mortality in 100 U.S. cities. American Journal of Epidemiology 161:585–594.

    DOI: 10.1093/aje/kwi075Save Citation »Export Citation »E-mail Citation »

    A report on a substantial analysis of a large US-based multicity study, the National Morbidity and Mortality Air Pollution Study (NMMAPS). Bayesian semiparametric hierarchical models for estimating time-varying effects were developed. Significant pollution-mortality associations were observed but were affected by season and geographic region.

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  • Samet, Jonathan M., Francesca Dominici, Frank C. Curriero, Ivan Coursac, and Scott L. Zeger. 2000. Fine particulate air pollution and mortality in 20 U.S. cities, 1987–1994. New England Journal of Medicine 343:1742–1749.

    DOI: 10.1056/NEJM200012143432401Save Citation »Export Citation »E-mail Citation »

    A report of a US-based multicity daily time-series study of air pollution and associated mortality. All-cause, cardiovascular, and respiratory deaths were consistently associated with fine particulate-matter air pollution. Weaker associations were observed for ozone.

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  • Samet, Jonathan M., Scott L. Zeger, and Kiros Berhane. 1995. “Particulate air pollution and daily mortality: replication and validation of selected studies: The Phase I Report of the Particulate Epidemiology Evaluation Project.” Health Effects Institute: Cambridge, MA.

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    This report presents the replication and validation of several key early daily time-series mortality studies. Although this report did not resolve all of the controversies surrounding the interpretation and use of these studies, the authors were largely able to validate and replicate the results originally reported.

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  • Samoli, Evangelia, Roger Peng, Tim Ramsay, Marina Pipikou, Giota Touloumi, Francesca Dominici, Rick Burnett, Aaron Cohen, Daniel Krewski, Jon Samet, and Klea Katsouyanni. 2008. Acute effect of ambient particulate matter on mortality in Europe and North America: Results from the APHENA study. Environmental Health Perspectives 116:1480–1486.

    DOI: 10.1289/ehp.11345Save Citation »Export Citation »E-mail Citation »

    Data for cities across the United States, Canada, and Europe were combined and analyzed using a common protocol. Particulate matter–mortality associations were observed across all regions, but the role of copollutants, in terms of providing primary effects or effect modification, was somewhat different across the regions.

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  • Zanobetti, Antonella, and Joel Schwartz. 2009. The effect of fine and coarse particulate air pollution on mortality: A national analysis. Environmental Health Perspectives 117:898–903.

    DOI: 10.1289/ehp.0800108Save Citation »Export Citation »E-mail Citation »

    This report presents the results of a large multicity study of 112 US cities. All-cause, cardiovascular, and respiratory disease mortality were most strongly associated with fine particulate air pollution. Weaker, but positive, associations were observed with coarse particles.

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Cardio-Respiratory Morbidity

By the mid-1990s various panel and related studies had observed that short-term exposures to particulate-matter air pollution were associated with transient declines in lung function and increases in respiratory symptoms, as reviewed by Dockery and Pope 1994. Gold, et al. 2000 presents an excellent example of numerous studies that have also demonstrated that short-term elevations in air pollution result in reductions in various measures of heart rate variability, suggesting that air pollution contributes to reduced cardiac autonomic function. Dominici, et al. 2006 and Bell, et al. 2008 provide examples of numerous studies that have reported associations between daily changes in short-term air-pollution exposures and respiratory and cardiovascular hospitalizations, similar to those observed with respiratory and cardiovascular mortality. Further evidence that air pollution affects cardiovascular disease comes from studies that focus on specific, well-defined, serious cardiovascular disease events. Key examples include reports of pollution-related triggering of myocardial infarction by Peters, et al. 2001 and Peters, et al. 2004, pollution-related triggering of ischemic heart disease events more broadly defined by Pope, et al. 2006, and air-pollution associations with ischemic-stroke hospital admissions by Wellenius, et al. 2005.

  • Bell, Michelle L., Keita Ebisu, Roger D. Peng, Jemma Walker, Jonathan M. Samet, Scott L. Zeger, Francesca Dominici. 2008. Seasonal and regional short-term effects of fine particles on hospital admissions in 202 US counties, 1999–2005. American Journal of Epidemiology 168:1301–1310.

    DOI: 10.1093/aje/kwn252Save Citation »Export Citation »E-mail Citation »

    Using a large database of US Medicare enrollees, the authors explored the link between daily changes in fine particulate air pollution and respiratory and cardiovascular hospitalizations. Associations between hospitalization and air pollution were observed, as were seasonal and regional variations in the effect.

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  • Dockery, D. W., and C. A. Pope III. 1994. Acute respiratory effects of particulate air pollution. Annual Review of Public Health 15:107–132.

    DOI: 10.1146/annurev.pu.15.050194.000543Save Citation »Export Citation »E-mail Citation »

    This article provides a review of the then available literature regarding the acute respiratory effects of exposure to ambient particulate air pollution. It also evaluates the coherency and consistency of epidemiologic data.

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  • Dominici, Francesca, Roger D. Peng, Michelle L. Bell, Luu Pham, Aidan McDermott, Scott L. Zeger, and Jonathan M. Samet. 2006. Fine particulate air pollution and hospital admission for cardiovascular and respiratory diseases. Journal of the American Medical Association 295:1127–1134.

    DOI: 10.1001/jama.295.10.1127Save Citation »Export Citation »E-mail Citation »

    This study used US Medicare records for 11.5 million enrollees living in 204 counties with adequate air pollution monitoring. Short-term exposure to fine particulate-matter air pollution was associated with hospital admissions for cardiovascular and respiratory diseases.

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  • Gold, Diane R., Augusto Litonjua, Joel Schwartz, Eric Lovett, Andrew Larson, Bruce Nearing, George Allen, Monique Verrier, Rebecca Cherry, and Richard Verrier. 2000. Ambient pollution and heart rate variability. Circulation 101:1267–1273.

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    This is just one of many studies that found that short-term exposure to air pollution (typically fine particulate matter and/or ozone) was associated with reductions in various measures of heart-rate variability, suggesting that air pollution contributes to a loss of cardiac autonomic function.

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  • Peters, Annette, Douglas W. Dockery, James E. Muller, and Murray A. Mittleman. 2001. Increased particulate air pollution and the triggering of myocardial infarction. Circulation 103:2810–2815.

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    Data from myocardial-infarction patients in the greater Boston area and case-crossover analysis were used to evaluate the role of short-term air-pollution exposure in triggering myocardial infarction. An increased risk of myocardial infarction onset associated with exposure to fine particulate air pollution was observed.

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  • Peters, Annette, Stephanie von Klot, Margit Heier, Ines Trentinaglia, Allmut Hörmann, H. Erich Wichmann, and Hannelore Löwel. 2004. Exposure to traffic and the onset of myocardial infarction. New England Journal of Medicine 351:1721–1729.

    DOI: 10.1056/NEJMoa040203Save Citation »Export Citation »E-mail Citation »

    Data from a myocardial-infarction registry in Augsburg, Germany, and case-crossover analysis were used to evaluate the role of exposure to traffic in triggering myocardial infarction. An association was observed between the onset of myocardial infarction and one-hour-previous exposure to traffic.

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  • Pope, C. Arden, III, Joseph B. Muhlestein, Heidi T. May, Dale G. Renlund, Jeffrey L. Anderson, and Benjamin D. Horne. 2006. Ischemic heart disease events triggered by short-term exposure to fine particulate air pollution. Circulation 114:2443–2448.

    DOI: 10.1161/CIRCULATIONAHA.106.636977Save Citation »Export Citation »E-mail Citation »

    Acute ischemic heart disease events were explored using a cardiac catheterization registry from the Wasatch Front region in Utah. Short-term fine particulate-matter exposure contributed to the risk of these events, especially for patients with angiographically demonstrated coronary-artery disease.

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  • Wellenius, Gregory A., Joel Schwartz, and Murray A. Mittleman. 2005. Air pollution and hospital admissions for ischemic and hemorrhagic stroke among Medicare beneficiaries. Stroke 36:2549–2553.

    DOI: 10.1161/01.STR.0000189687.78760.47Save Citation »Export Citation »E-mail Citation »

    Analyses of stroke hospitalization records among Medicare recipients in nine US cities. Elevated particulate-matter air pollution was associated with increased risk of ischemic, but not hemorrhagic, stroke.

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Long-Term Exposure

To fully understand the health effects of air pollution, it is critical to evaluate effects of long-term or chronic exposure to air pollution. There are several basic study designs that have evaluated associations between spatial differences in long-term average air-pollution concentrations and spatial differences in mortality rates and/or risk of mortality. These designs include population-based cross-sectional studies and prospective and retrospective cohort studies that use well-developed formal survival analyses and related data-analytic approaches. Prospective cohort, panel, and related studies have also evaluated long-term exposure on various morbidity outcomes. The long-term exposure studies have generally found larger effects of air pollution than observed in the short-term exposure studies.

Population-Based Studies

As early as the 1970s, population-based cross-sectional studies such as Lave and Seskin 1977 indicated that across US metropolitan areas long-term average concentrations of fine particulate matter and sulfur oxide air pollution were associated with mortality rates. Although various studies, including Ozkaynak and Thurston 1987 and Lipfert and Morris 2002, subsequently replicated these results using data sets for later time periods, the population-based cross-sectional results were discounted because of concerns that they could not control for cigarette smoking and other individual risk factors.

  • Lave, Lester B., and Eugene P. Seskin. 1977. Air pollution and human health. Baltimore: Johns Hopkins Univ. Press.

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    Pioneering, but highly controversial, national cross-sectional regression analysis of annual mortality rates and air pollution. Mortality rates were found to be associated with total suspended particulate matter and sulfates.

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  • Lipfert, F. W., and S. C. Morris. 2002. Temporal and spatial relations between age specific mortality and ambient air quality in the United States: Regression results for counties, 1960–97. Occupational Environmental Medicine 59:156–174.

    DOI: 10.1136/oem.59.3.156Save Citation »Export Citation »E-mail Citation »

    Cross-sectional regression analysis of mortality rates and air pollution, similar to previous studies, was conducted. However, these regressions were conducted using data for five different time periods, with the strongest associations observed for the earlier periods.

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  • Özkaynak, Halûk, and George D. Thurston. 1987. Associations between 1980 U.S. mortality rates and alternative measures of airborne particle concentration. Risk Analysis 7:449–461.

    DOI: 10.1111/j.1539-6924.1987.tb00482.xSave Citation »Export Citation »E-mail Citation »

    An excellent example of a population-based study of mortality rates and air pollution using cross-sectional regression analysis. The innovation in this paper is the consideration of particle-size, composition, and source information. The results suggest that fine and sulfate particles, particles from iron/steel emissions, and particles from coal combustion are most significantly associated with mortality.

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Cohort Studies

Some of the most compelling evidence that long-term exposure to air pollution contributes to mortality risk is provided by prospective cohort-studies studies that use formal survival analysis and control for individual differences in multiple confounding variables and various cardiopulmonary risk factors. The “Harvard Six-Cities” study reported by Dockery, et al. 1993 and the American Cancer Society study reported by Pope et al. 2002 were two prominent prospective cohort mortality studies which have undergone substantial scrutiny, independent reanalysis, and extended analyses. Miller, et al. 2007 and Zeger, et al. 2008 are excellent examples of more recent US-based cohort mortality studies, and Gehring, et al. 2006 and Naess, et al. 2007 are excellent examples of European-based cohort mortality studies. Overall, these studies generally find that mortality risk is significantly associated with air pollution, and that the effect estimates for long-term exposure are much larger than what had been observed from the studies of short-term exposure. The causes of death most consistently and strongly associated with air pollution include cardiovascular-disease death, although excess death from lung cancer and nonmalignant respiratory diseases were sometimes observed. The pollutants most consistently and strongly associated with mortality risk include fine particulate-matter pollution, but associations with sulfur and nitrogen oxides are also reported. Jerrett, et al. 2009 reports that even after controlling for the effects of fine particulate pollution, long-term ozone exposures are significantly associated with respiratory mortality.

  • Beelen, Rob, Gerard Hoek, Piet A. van den Brandt, R. Alexandra Goldbohm, Paul Fischer, Leo J. Schouten, Michael Jerrett, Edward Hughes, Ben Armstrong, and Bert Brunekreef. 2008. Long-term effects of traffic-related air pollution on mortality in a Dutch cohort (NLCS-AIR study). Environmental Health Perspectives 116:196–202.

    DOI: 10.1289/ehp.10767Save Citation »Export Citation »E-mail Citation »

    A large ongoing Dutch cohort study on diet and cancer was linked with estimated ambient air pollution exposures. Elevated levels of traffic-related air pollution and traffic-exposure variables were associated with increased mortality risk.

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  • Dockery, Douglas W., C. Arden Pope III, Xiping Xu, John D. Spengler, James H. Ware, Martha E. Fay, Benjamin G. Ferris, and Frank E. Speizer. 1993. An association between air pollution and mortality in six U.S. cities. New England Journal of Medicine 329:1753–1759.

    DOI: 10.1056/NEJM199312093292401Save Citation »Export Citation »E-mail Citation »

    The original report of the first major prospective cohort mortality study. Commonly referred to as the Harvard Six-Cities study, it is a well-designed study. It reported that long-term exposures to fine and sulfate particulate pollution were associated with increased risk of cardiopulmonary-disease death. This study has undergone substantial scrutiny and independent reanalysis, and the results have been reproducible and robust.

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  • Gehring, Ulrike, Joachim Heinrich, Ursula Krämer, Veit Grote, Matthias Hochadel, Dorothea Sugiri, Martin Kraft, Knut Rauchfuss, Hans George Eberwein, and H.-Erich Wichmann. 2006. Long-term exposure to ambient air pollution and cardiopulmonary mortality in women. Epidemiology 17:545–551.

    DOI: 10.1097/01.ede.0000224541.38258.87Save Citation »Export Citation »E-mail Citation »

    This paper presents results of a study of cardiopulmonary mortality in a cohort of women in Germany. Cardiopulmonary mortality was associated with air pollution (particulate matter and nitrogen dioxide) and with living in close proximity to a major roadway.

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  • Jerrett, Michael, Richard T. Burnett, C. Arden Pope III, Kazuhiko Ito, George Thurston, Daniel Krewski, Yuanli Shi, Eugenia Calle, and Michael Thun. 2009. Long-term ozone exposure and mortality. New England Journal of Medicine 360:1085–1095.

    DOI: 10.1056/NEJMoa0803894Save Citation »Export Citation »E-mail Citation »

    This is an extended analysis of the American Cancer Society cohort study that observed typical cardiovascular associations with fine particulate-matter air pollution. This study, however, also observed that long-term ozone exposure was associated with nonmalignant respiratory mortality, even while controlling for fine particulate exposure.

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  • Miller, Kristin A., David S. Siscovick, Lianne Sheppard, Kristen Shepherd, Jeffrey H. Sullivan, Garnet L. Anderson, and Joel D. Kaufman. 2007. Long-term exposure to air pollution and incidence of cardiovascular events in women. New England Journal of Medicine 356:447–458.

    DOI: 10.1056/NEJMoa054409Save Citation »Export Citation »E-mail Citation »

    Linking monitored air pollution data with data from the Women’s Health Initiative Observational Study, the authors evaluated effects of air pollution on risk of fatal and nonfatal cardiovascular events in a cohort of postmenopausal women without previous cardiovascular disease. Long-term fine particulate exposure was associated with incidence of cardiovascular disease and death.

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  • Naess, Øyvind, Per Nafstad, Geir Aamodt, Bjørgulf Claussen, and Pål Rosland. 2007. Relation between concentration of air pollution and cause-specific mortality: Four-year exposures to nitrogen dioxide and particulate matter pollutants in 470 neighborhoods in Oslo, Norway. American Journal of Epidemiology 165:435–443.

    DOI: 10.1093/aje/kwk016Save Citation »Export Citation »E-mail Citation »

    All inhabitants of Oslo, Norway, aged fifty-one to ninety years, were followed up as a cohort. Ambient air-pollution exposure across 470 administrative neighborhoods was estimated for inhalable and fine particulate pollution and for nitrogen dioxide. All-cause, chronic obstructive pulmonary-disease, cardiovascular, and lung-cancer mortality were associated with all three markers of exposure.

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  • Pope, C. Arden, III, Richard T. Burnett, Michael J. Thun, Eugenia E. Calle, Daniel Krewski, Kazuhiko Ito, and George D. Thurston. 2002. Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution. Journal of the American Medical Association 287:1132–1141.

    DOI: 10.1001/jama.287.9.1132Save Citation »Export Citation »E-mail Citation »

    A report of an extended analysis of the American Cancer Society prospective cohort study that observed that long-term exposure to fine and sulfate particulate pollution were associated with increased risk of death. The increased risk of death was primarily due to nonmalignant cardiopulmonary-disease deaths, but air pollution was also significantly associated with risk of lung-cancer mortality. This study has undergone substantial scrutiny, independent reanalysis, and multiple extended analyses, but the results have been reproducible and robust.

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  • Zeger, Scott L., Francesca Dominici, Aidan McDermott, and Jonathan M. Samet. 2008. Mortality in the Medicare population and chronic exposure to fine particulate air pollution in urban centers (2000–2005). Environmental Health Perspectives 116:1614–1619.

    DOI: 10.1289/ehp.11449Save Citation »Export Citation »E-mail Citation »

    US Medicare data were linked with air-pollution data to create a very large retrospective cohort study. Long-term exposure to fine particulate-matter air pollution was associated with mortality risk in the eastern and central regions, but not in the western United States.

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Cardio-Respiratory Morbidity

Various studies suggest that long-term exposure to air pollution may contribute to the initiation and progression of cardiopulmonary disease. Raizenne, et al. 1996, Dockery, et al. 1996, and Ackermann-Liebrich, et al. 1997 provide representative examples of cross-sectional studies of air pollution that suggest that long-term exposures to air pollution are associated with reduced levels of lung function and increased respiratory symptoms. Reports of the prominent Southern California Children’s Health Study, including Gauderman, et al. 2004 and Gauderman, et al. 2007, present results that indicate that children living in cities with higher levels of air pollution or children exposed to more traffic-source pollution by living nearer to major roadways apparently have slower lung development as indicated by greater deficits in lung-function growth. Similarly, Kunzli, et al. 2010, Hoffmann, et al. 2007, and Allen, et al. 2009 report the results of studies that provide evidence that air-pollution exposure, as indicated by community-level exposures or by proximity to traffic sources, contributes to the progression of cardiovascular disease, especially atherosclerosis.

  • Ackermann-Liebrich, U., P. Leuenberger, J. Schwartz, C. Schindler, C. Monn, G. Bolognini, J. P. Bongard, O. Brandli, G. Domenighetti, S. Elsasser, L Grize, W. Karrer, R. Keller, H. Keller-Wossidlo, N. Kunzli, B. W. Martin, T. C Medici, A. P. Perruchoud, M. H. Schoni, J. M. Tschopp, B. Villiger, B. Wuthrich, J. P. Zellweger, and E. Zemp. 1997. Lung function and long term exposure to air pollutants in Switzerland: Study on Air Pollution and Lung Diseases in Adults (SAPALDIA) Team. American Journal of Respiratory and Critical Care Medicine 155:122–129.

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    Lung function was studied in a cross-sectional population-based sample of adults living in eight areas of Switzerland. Statistically significant, consistent negative associations between lung function and measures of air pollution from fossil-fuel combustion (inhalable particulate matter, sulfur dioxide, nitrogen dioxide) were observed.

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  • Allen, Ryan W., Michael H. Criqui, Ana V. Diez Roux, Matthew Allison, Steven Shea, Robert Detrano, Lianne Sheppard, Nathan D. Wong, Karen Hinckley Stukovksy, and Joel D. Kaufman. 2009. Fine particulate matter air pollution, proximity to traffic, and aortic atherosclerosis. Epidemiology 20:254–264.

    DOI: 10.1097/EDE.0b013e31819644ccSave Citation »Export Citation »E-mail Citation »

    In one of multiple air-pollution and related studies of adults from the Multi-Ethnic Study of Atherosclerosis, abdominal aortic calcium was associated with long-term fine particulate-matter air-pollution exposure.

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  • Dockery, Douglas W., Joan Cunningham, Andrew I. Damokosh, Lucas M. Neas, John D. Spengler, Petros Koutrakis, James H. Ware, Mark Raizenne, and Frank E. Speizer. 1996. Health effects of acid aerosols on North American children: Respiratory symptoms. Environmental Health Perspectives 104:500–505.

    DOI: 10.2307/3432990Save Citation »Export Citation »E-mail Citation »

    Associations between air pollution and respiratory symptoms were explored using data collected on children living in twenty-four communities in the United States and Canada. Symptoms of bronchitis, but generally not other respiratory symptoms, were associated with higher levels of inhalable particles, fine particles, sulfate particles, and fine-particle strong acidity.

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  • Gauderman, W. James, Edward Avol, Frank Gilliland, Hita Vora, Duncan Thomas, Kiros Berhane, Rob McConnell, Nino Kuenzli, Fred Lurmann, Edward Rappaport, Helene Margolis, David Bates, and John Peters. 2004. The effect of air pollution on lung development from 10 to 18 years of age. New England Journal of Medicine 351:1057–1067.

    DOI: 10.1056/NEJMoa040610Save Citation »Export Citation »E-mail Citation »

    This paper reports results of a prospective study of lung-function growth in children from schools in twelve southern California communities. Children living in cities with higher levels of various measures of air pollution (nitrogen dioxide, acid vapor, fine particulate matter, elemental carbon) had clinically significant deficits in lung-function growth.

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  • Gauderman, W. James, Hita Vora, Rob McConnell, Kiros Berhane, Frank Gilliland, Duncan Thomas, Fred Lurmann, Edward Avol, Nino Kunzli, Michael Jerrett, and John Peters. 2007. Effect of exposure to traffic on lung development from 10 to 18 years of age: A cohort study. Lancet 369:571–577.

    DOI: 10.1016/S0140-6736(07)60037-3Save Citation »Export Citation »E-mail Citation »

    This paper reports additional results of the prospective study of lung-function growth in children from schools in twelve southern California communities (see Gauderman, et al. 2004). It further found greater deficits in lung-function growth for children exposed to more local traffic-source pollution by living nearer to major roadways—independent of regional air quality.

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  • Hoffmann, B., S. Moebus, S. Möhlenkamp, A. Stang, N. Lehmann, N. Dragano, A. Schmermund, M. Memmesheimer, K. Mann, R. Erbel, K.-H. Jöckel. 2007. Residential exposure to traffic is associated with coronary atherosclerosis. Circulation 116:489–496.

    DOI: 10.1161/CIRCULATIONAHA.107.693622Save Citation »Export Citation »E-mail Citation »

    This paper presents the results of a population-based sample of subjects from Germany. Exposure to traffic-source pollution, as indicated by proximity to major roadways, was associated with increased coronary-artery calcification—again suggesting that air pollution exposure may accelerate the progression of atherosclerosis.

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  • Künzli, Nino, Michael Jerrett, Raquel Garcia-Esteban, Xavier Basageña, Bernardo Beckermann, Frank Gilliland, Merce Medina, John Peters, Howard N. Hodis, and Wendy J. Mack. 2010. Ambient air pollution and the progression of atherosclerosis in adults. PLoS ONE 5.2: 1–10.

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    This paper evaluates a potential link between exposure to air pollution and change in carotid-artery intima-media thickness, using a noninvasive technique to evaluate the burden of subclinical vascular (atherosclerotic) disease. Although there were major limitations to this study, the results suggest that air pollution may contribute to the progression of vascular disease.

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  • Raizenne, Mark, Lucas M. Neas, Andrew I. Damokosh, Douglas W. Dockery, John D. Spengler, Petros Koutrakis, James H. Ware, and Frank E. Speizer. 1996. Health effects of acid aerosols on North American children: Pulmonary function. Environmental Health Perspectives 104:506–514.

    DOI: 10.2307/3432991Save Citation »Export Citation »E-mail Citation »

    Associations between air pollution and lung function were explored using data collected on children living in twenty-four communities in the United States and Canada. Small but significant reductions in lung function were observed for children living in communities with higher levels of inhalable particles, fine particles, and fine-particle strong acidity.

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Intervention/Natural-Experiment Studies

Studies that have exploited changes in air-pollution exposures that occurred due to specific interventions provided evidence regarding the potential health benefits from specific intervention-induced reductions in air pollution. Some of these studies are referred to as “natural” interventions studies. They are studies of specific but unplanned interventions, such as the intermittent operation of a steel mill, as analyzed and reported by Pope 1989, and an economic recession that induced differential reductions in air pollution across the United States, as analyzed and reported by Chay and Greenstone 2003. Similar studies evaluate changes in exposure due to planned interventions, such as an analysis of the Dublin Coal Ban reported by Clancy, et al. 2002 and sulfur restrictions in fuel in Hong Kong, as analyzed and reported by Hedley, et al. 2002. Pope, et al. 2009 evaluates changes in life expectancies related to substantial differential changes in air pollution across metropolitan areas that occurred because of public-policy clean-air efforts and other factors. The number of intervention studies are limited, but they have provided additional evidence of adverse human-health effects of air pollution and have added important and, in some cases, unique additional evidence.

  • Chay, Kenneth Y., and Michael Greenstone. 2003. The impact of air pollution on infant mortality: Evidence from geographic variation in pollution shocks induced by a recession. Quarterly Journal of Economics 118:1121–1167.

    DOI: 10.1162/00335530360698513Save Citation »Export Citation »E-mail Citation »

    Substantial variation in pollution reductions was induced by the 1981–1982 recession in the United States. This paper reports that differential changes in particulate-matter air pollution were associated with differential changes in infant mortality.

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  • Clancy, Luke, Pat Goodman, Hamish Sinclair, and Douglas W. Dockery. 2002. Effect of air-pollution control on death rates in Dublin, Ireland: An intervention study. Lancet 360:1210–1214.

    DOI: 10.1016/S0140-6736(02)11281-5Save Citation »Export Citation »E-mail Citation »

    A ban on coal sales in Dublin resulted in a large, sudden decrease in ambient level of particulate air pollution. This paper reports subsequent reductions in respiratory and cardiovascular death rates larger than would be predicted based on daily time-series mortality studies, but smaller than predicted based on the cohort studies of long-term exposure.

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  • Hedley, Anthony Johnson, Chit-Ming Wong, Thuan Quoc Thach, Stefan Ma, Tai-Hing Lam, and Hugh Ross Anderson. 2002. Cardiorespiratory and all-cause mortality after restrictions on sulphur content of fuel in Hong Kong: An intervention study. Lancet 360:1646–1652.

    DOI: 10.1016/S0140-6736(02)11612-6Save Citation »Export Citation »E-mail Citation »

    Sharp restrictions on the sulfur content of fuel oil used for road vehicles and power plants in Hong Kong resulted in an immediate reduction in ambient sulfur dioxide. This paper reports that there was a reduction in seasonal deaths, especially respiratory and cardiovascular deaths, immediately following the sulfur restrictions.

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  • Pope, C. Arden, III. 1989. Respiratory disease associated with community air pollution and a steel mill, Utah Valley. American Journal of Public Health 79:623–628.

    DOI: 10.2105/AJPH.79.5.623Save Citation »Export Citation »E-mail Citation »

    This paper reports the first of several studies that opportunistically utilized a unique natural experiment in Utah Valley. The intermittent operation of the major source of local air pollution, a large integrated steel mill, was associated with substantial changes in local air pollution and pediatric respiratory hospital admissions.

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  • Pope, C. Arden, III, Majid Ezzati, and Douglas W. Dockery. 2009. Fine-particulate air pollution and life expectancy in the United States. New England Journal of Medicine 360:376–386.

    DOI: 10.1056/NEJMsa0805646Save Citation »Export Citation »E-mail Citation »

    Over the last several decades in the Unites States, efforts to improve air quality (and other factors) have resulted in differential reductions in pollution. The study reported in this paper uses this nationwide effort as a natural experiment and finds that larger reductions in air pollution were associated with larger increases in life expectancies, even controlling for socioeconomic, demographic, and smoking variables.

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Adverse Birth and Pregnancy Outcomes

There is growing evidence that air pollution is a risk factor for increased mortality in infants and young children. Reviews of studies of air pollution and infant mortality such as Glinianaia, et al. 2004, Tong, et al. 2004, and Lacasaña, et al. 2005 generally conclude that air-pollution exposure is most strongly and consistently associated with post-neonatal respiratory mortality, with less compelling evidence of a link between air pollution and SIDS. There are also contemporary studies, as reviewed by Lacasaña, et al. 2005, American Academy of Pediatrics Committee on Environmental Health 2004, Maisonet, et al. 2004, and Šrám, et al. 2005, that have evaluated potential links between air pollution and pregnancy outcomes such as birth weight, premature birth, fetal growth, intrauterine mortality, birth defects, and lymphocyte immunophenotypes in cord and maternal blood at delivery. Stillerman, et al. 2008 provides a review of the literature pertaining to adverse pregnancy outcomes and broader environmental exposures, including ambient air pollution and secondhand cigarette smoke. These reviews are not entirely consistent in their conclusions regarding the various pregnancy outcomes. They do suggest, however, that there is evidence of some effects of ambient air pollution, but that these effects remain poorly understood.

  • American Academy of Pediatrics Committee on Environmental Health. 2004. Ambient air pollution: Health hazards to children Pediatrics 114:1699–1707.

    DOI: 10.1542/peds.2004-2166Save Citation »Export Citation »E-mail Citation »

    This policy statement from the American Academy of Pediatrics provides a succinct review of the literature and makes various conclusions and recommendations. It concludes that air pollution has significant and diverse health effects in children, but it does not do a good job of outlining and delineating specific infant or birth health outcomes.

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  • Glinianaia, Svetlana V., Judith Rankin, Ruth Bell, Tanja Pless-Mulloli, and Denise Howel. 2004. Does particulate air pollution contribute to infant death? A systematic review. Environmental Health Perspectives 112:1365–1370.

    DOI: 10.1289/ehp.6857Save Citation »Export Citation »E-mail Citation »

    This paper presents a systematic review of the literature that addresses the effects of particulate-matter air pollution on infant mortality. At the time, fifteen relevant studies were reviewed. The authors concluded that there were substantial inconsistencies and uncertainties, but the evidence suggested that particulate air pollution contributed to some subgroups of infant mortality.

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  • Lacasaña, Marina, Ana Esplugues, and Ferran Ballester. 2005. Exposure to ambient air pollution and prenatal and early childhood health effects. European Journal of Epidemiology 20:183–199.

    DOI: 10.1007/s10654-004-3005-9Save Citation »Export Citation »E-mail Citation »

    This paper reports the findings of a review of the evidence of air-pollution impact on infant death and various pregnancy outcomes published during the 1994–2003 period. It concludes that there are relatively consistent findings that particulate pollution is associated with post-neonatal mortality (especially for respiratory diseases), but inconsistent evidence of associations with the various pregnancy outcomes.

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  • Maisonet, Mildred, Adolfo Correa, Dawn Misra, and Jouni J. K. Jaakkola. 2004. A review of the literature on the effects of ambient air pollution on fetal growth. Environmental Research 95:106–115.

    DOI: 10.1016/j.envres.2004.01.001Save Citation »Export Citation »E-mail Citation »

    This paper presents the results of a systematic review of the literature pertaining to the effects of air pollution on fetal growth. The authors conclude that small air-pollution effects were apparent for preterm delivery and intrauterine growth restriction, but not for low birth weight.

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  • Šrám, Radim J., Blanka Binková, Jan Dejmek, and Martin Bobak. 2005. Ambient air pollution and pregnancy outcomes: A review of the literature. Environmental Health Perspectives 113:375–382.

    DOI: 10.1289/ehp.6362Save Citation »Export Citation »E-mail Citation »

    This is a relatively comprehensive review of the recent air-pollution and pregnancy-outcome literature. The authors conclude that there is relatively compelling evidence that particulate-matter air pollution contributes to post-neonatal respiratory mortality. The evidence is only suggestive for certain pregnancy outcomes such as birth weight, preterm births, and intrauterine growth retardation. For birth defects the evidence is insufficient.

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  • Stillerman, Karen Perry, Donald R. Mattison, Linda C. Giudice, and Tracey J. Woodruff. 2008. Environmental exposures and adverse pregnancy outcomes: A review of the science. Reproductive Sciences 15:631–650.

    DOI: 10.1177/1933719108322436Save Citation »Export Citation »E-mail Citation »

    This report reviews the literature on adverse pregnancy outcomes and broader environmental exposures. The authors conclude that both environmental tobacco smoke and ambient air pollution are risk factors for reduced birth weight and preterm birth.

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  • Tong, Shilu, and Paul Colditz. 2004. Air pollution and sudden infant death syndrome: A literature review. Paediatric and Perinatal Epidemiology 18:327–335.

    DOI: 10.1111/j.1365-3016.2004.00565.xSave Citation »Export Citation »E-mail Citation »

    A systematic review of the literature that addresses the effects of air pollution on sudden infant death syndrome is presented. Nine relevant studies were reviewed. The authors surmise that the evidence at this time is inadequate to conclude that air pollution contributes to SIDS.

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Biological Mechanisms/Toxiciology

Toxicological research, in concert with epidemiological and related research, has attempted to elucidate mechanistic pathways that link exposure to air pollution and cardiopulmonary disease and mortality. As early as 1995, Seaton, et al. 1995 featured the proposition that inhalation of urban air pollution, which contains extremely large numbers of ultrafine particles, may provoke pulmonary and systemic inflammation, increase blood coagulability, and contribute to cardiovascular deaths. However, as more toxicological studies have been conducted, some reviews of the studies, including Lippmann and Schlesinger 2000 and Green and Armstrong 2003, have concluded that the toxicological evidence of effects of air pollution is inconsistent with the epidemiological evidence and generally not supportive of health effects at moderate exposures. Schlesinger, et al. 2006 continues to emphasize that there are unquestionably substantial gaps in knowledge about the relative toxicity of various pollutants from various sources. However, coherence between specific epidemiological results and toxicologically inspired pathophysiological pathways has been reported by Pope, et al. 2004, and several recent reviews such as Simkhovich, et al. 2008, Brook, et al. 2009, and Brook, et al. 2010 conclude that there is now evidence for multiple general mechanistic pathways that are “biologically plausible” and are supported by toxicological evidence. These include pollution-induced pulmonary and systemic oxidative stress and inflammation, enhanced initiation and progression of atherosclerosis, altered cardiac autonomic function, and direct translocation of ultrafine particles into the circulation.

  • Brook, Robert, Sanjay Rajagopalan, C. Arden Pope III, Jeffrey R. Brook, Aruni Bhatnagar, Ana V. Diez-Roux, Fernando Holguin, Yuling Hong, Russell V. Luepker, Murray A. Mittleman, Annette Peters, David Siscovick, Sidney C. Smith Jr., Laurie Whitsel, and Joel D. Kaufman. 2010. Particulate matter air pollution and cardiovascular disease: An update to the scientific statement from the American Heart Association. Circulation 121:2331–2378.

    DOI: 10.1161/CIR.0b013e3181dbece1Save Citation »Export Citation »E-mail Citation »

    This updated American Heart Association scientific statement provides a relatively authoritative and comprehensive review that integrates evidence from epidemiology, controlled clinical studies, and toxicology. It concludes that there is evidence for multiple biological mechanisms through which particulate-matter air pollution can exacerbate existing cardiovascular disease, trigger acute disease events, and instigate or accelerate chronic disease.

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  • Brook, Robert D., Bruce Urch, J. Timothy Dvonch, Robert L. Bard, Mary Speck, Gerald Keeler, Masako Morishita, Frank J. Marsik, Ali S. Kamal, Niko Kaciroti, Jack Harkema, Paul Corey, Frances Silverman, Diane R. Gold, Greg Wellenius, Murray A. Mittleman, Sanjay Rajagopalan, and Jeffrey R. Brook. 2009. Insights into the mechanisms and mediators of the effects of air pollution exposure on blood pressure and vascular function in healthy humans. Hypertension 54:659–667.

    DOI: 10.1161/HYPERTENSIONAHA.109.130237Save Citation »Export Citation »E-mail Citation »

    This paper presents the results of a novel controlled human study of exposure to fine particulate pollution and ozone. The authors provide credible mechanistic evidence of links between the inhalation of fine particulate pollution and the triggering of acute cardiovascular events.

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  • Green, Laura C., and Sarah R. Armstrong. 2003. Particulate matter in ambient air and mortality: Toxicologic perspectives. Regulatory Toxicology and Pharmacology 38:326–335.

    DOI: 10.1016/S0273-2300(03)00099-0Save Citation »Export Citation »E-mail Citation »

    This is a selective review and evaluation of the literature from a toxicological perspective that is integrated with the epidemiological findings and focuses on particulate-matter air pollution. The authors conclude that epidemiologic findings of mortality effects at low to moderate levels of exposure, and air-quality standards based on these findings, are not sufficiently supported by toxicology.

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  • Lippmann, M., and R. B. Schlesinger. 2000. Toxicological bases for the setting of health-related air pollution standards. Annual Review of Public Health 21:309–333.

    DOI: 10.1146/annurev.publhealth.21.1.309Save Citation »Export Citation »E-mail Citation »

    This is a selective review and evaluation of the relevant literature and a thoughtful discussion of how to integrate information from epidemiology, controlled clinical studies, and animal toxicology in the context of establishing health-related air-pollution standards. It concludes that the toxicological bases for particulate-matter standards are weaker than for ozone.

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  • Pope, C. Arden III, Richard T. Burnett, George D. Thurston, Michael J. Thun, Eugenia E. Calle, Daniel Krewski, and John J. Godleski. 2004. Cardiovascular mortality and long-term exposure to particulate air pollution: Epidemiological evidence of general pathophysiological pathways of disease. Circulation 109:71–77.

    DOI: 10.1161/01.CIR.0000108927.80044.7FSave Citation »Export Citation »E-mail Citation »

    An extended analysis of the American Cancer Society Prospective cohort study that evaluated alternative general pathophysiological pathways of disease. The results are consistent with suggested mechanistic pathways such as systemic inflammation, accelerated atherosclerosis, and altered cardiac autonomic function.

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  • Seaton, A., D. Godden., W. MacNee, and K. Donaldson. 1995. Particulate air pollution and acute health effects. Lancet 345:176–178.

    DOI: 10.1016/S0140-6736(95)90173-6Save Citation »Export Citation »E-mail Citation »

    This short paper briefly outlined the epidemiological evidence that exposure to urban air pollution contributed to cardiovascular and respiratory disease. It provided an early authoritative hypothesis regarding general mechanistic pathways that pointed the way to much subsequent research.

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  • Schlesinger, R. B., N. Kunzli, G. M. Hidy, T. Gotschi, and M. Jerret. 2006. The health relevance of ambient particulate matter characteristics: Coherence of toxicological and epidemiological inferences. Inhalation Toxicology 18:95–125.

    DOI: 10.1080/08958370500306016Save Citation »Export Citation »E-mail Citation »

    This paper further explores the potential coherence of the toxicological and epidemiological findings. It explores the relevant progress in knowledge that is being made but indicates that the question of toxic properties and relative contribution to health outcomes of various types and sources of pollution remains largely unresolved.

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  • Simkhovich, Boris Z., Michael T. Kleinman, and Robert A. Kloner. 2008. Air pollution and cardiovascular injury: Epidemiology, toxicology, and mechanisms. Journal of the American College of Cardiology 52:719–726.

    DOI: 10.1016/j.jacc.2008.05.029Save Citation »Export Citation »E-mail Citation »

    This paper briefly discusses the epidemiological and toxicological evidence of air pollution and cardiovascular injury. It concludes that there is evidence of major mechanisms of inhalation-mediated cardiovascular toxicity, including activation of pro-inflammatory pathways and translocation of ultrafine particles into the circulation.

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LAST MODIFIED: 02/23/2011

DOI: 10.1093/OBO/9780199756797-0122

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