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2001 Progress Report: Epidemiologic Study of Particulate Matter and Cardiopulmonary Mortality

EPA Grant Number: R827355C001
Subproject: this is subproject number 001 , established and managed by the Center Director under grant R827355
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Airborne PM - Northwest Research Center for Particulate Air Pollution and Health
Center Director: Koenig, Jane Q.
Title: Epidemiologic Study of Particulate Matter and Cardiopulmonary Mortality
Investigators: Kaufman, Joel D. , Checkoway, Harvey , Koenig, Jane Q. , Sheppard, Lianne , Siscovick, David
Current Investigators: Kaufman, Joel D. , Ishikawa, Naomi , Karr, Catherine , Miller, Kristine , Schreuder, Astrid , Shepherd, Kristine , Sheppard, Lianne , Siscovick, David , Sullivan, Jeff
Institution: University of Washington
EPA Project Officer: Stacey Katz/Gail Robarge,
Project Period: June 1, 1999 through May 31, 2004 (Extended to May 31, 2006)
Project Period Covered by this Report: June 1, 2001 through May 31, 2002
Project Amount: Refer to main center abstract for funding details.
RFA: Airborne Particulate Matter (PM) Centers (1999)
Research Category: Particulate Matter

Description:

Objective:

The main objective of this research project (for Years 1 through 3 of the project) is to investigate the associations between ambient particulate matter (PM) exposure and cardiopulmonary disease risks. The objectives have been addressed mainly through the use of case-crossover study designs. In Years 4 and 5 of the project, the epidemiology project objectives are being expanded to consider PM health outcomes in multicity settings.

We are initiating a new project to assess the effect of long-term exposure to fine PM air pollution and other pollutants on the incidence of cardiovascular events in the Women’s Health Initiative (WHI) Observational Study, adjusting for potential confounders and assessing effect modifiers. The assessment of effect modification by subject characteristics may provide insight into susceptibility to, or mechanisms of, PM health effects.

Progress Summary:

We completed a second analysis of cardiac arrest deaths and PM exposure in Seattle. One manuscript has been provisionally accepted. As with the first study (Levy, et al., 2001), we found no significant association in the total number of cases between primary cardiac arrest and air pollution; however, we found a significant association in current smokers, a finding that warrants further investigation.

A second effort of the epidemiology group is an analysis of subjects outcomes in the Myocardial Infarction Triage and Intervention (MITI) study of 6,000 confirmed cases of MI in Seattle between 1989 and 1991. We will examine the effects of short-term exposure to PM2.5 and onset of MI and compare our results with those of Peters, et al. (2001), who found an association between a cardiac event and exposure to PM2.5 2 hours prior to the event.

As the third component of our epidemiology work, Dr. Joel Kaufman initiated an analysis of relationships between cardiac events and air pollution in a large ongoing cohort study, WHI. This study is examining the effects of chronic exposure.

Background

Outdoor airborne PM exposures have been associated with various health outcomes including premature mortality from cardiovascular and respiratory diseases. Although much of the epidemiologic evidence relies on time-series analyses from single cities and chiefly provides information on acute PM effects, a few studies have attempted to assess long-term health effects of air pollution by studying cohorts with populations in multiple locations. Two of these studies (the Harvard Six Cities Study and the American Cancer Society Study) and their subsequent re-analyses and one smaller additional cohort study (Adventist Health Study of Smog, AHSMOG) have found associations between mortality and combustion-source air pollutants (especially fine PM, sulfate, and sulfur dioxide). Cardiopulmonary mortality accounted for the largest proportion of excess mortality attributable to PM in these studies. The two major studies found significant relative risks of cardiopulmonary mortality with an order of magnitude of approximately 1.3 associated with long-term exposure to a fine PM increment of approximately 25 µg/m3. Given the widespread and anthropogenic nature of these exposures, the public health implication of a small excess risk is great.

These prior studies provide insight into mortality only. Substantial questions remain regarding the ability of these studies to either adequately assign exposure levels or to control for potential confounding. Two of the studies included a very small number of geographic locations. Some of the findings also were sensitive to small changes in statistical methods and leave open to question whether the effects are related to PM, other pollutants, or other unmeasured environmental factors. As a result, the effect of PM and other pollutants on the development of cardiovascular disease in a well-characterized cohort remains of substantial interest. Additional information on this subject is of critical importance to environmental priority setting and decisionmaking. The WHI Observational Study cohort represents a tremendous resource for this study.

The goal of this study is to assess the effect of long-term exposure to fine particulate matter air pollution and other pollutants on the incidence of cardiovascular events in the WHI Observational Study, adjusting for potential confounders and assessing effect modifiers. Assessment of effect modification by subject characteristics may provide insight into susceptibility to, or mechanisms of, PM health effects. The study aims to determine the association between medium-term exposure to fine particulate air pollution and incident cardiovascular events and total mortality in 50-79 year old women, using proportional hazards modeling. The effects of other pollutants also will be considered. In addition, this study aims to determine the degree to which subject characteristics (including sedentary lifestyle and prior health conditions) modify the relationship between air pollution and cardiovascular events.

Summary of Proposed Methods

Exposure Assignment. We will assign exposures to cohort members based on geographic location of residence, using the U.S. Environmental Protection Agency (EPA) National Aerometric Database for air pollution exposures. At the simplest level, exposure levels could be based on time at annual average exposures at the associated clinical center. However, the study would be substantially improved by assigning a more precise exposure estimate based on the residence location and determination of time in residence at specific locations. The incorporation of geographic residence history in the questionnaire may improve this. Approximately 24 of the clinical centers coincide with cities assessed in a recent large-scale analysis of time-series PM health effects that may facilitate exposure assignments in these cities. In addition to average exposure to PM during the time of followup, analyses also will assign exposures based on shorter timeframes.

Outcome Assessment. This research project will focus on incident coronary heart disease and stroke events, along with all deaths from nonaccidental causes.

Analytic Approach. The overall approach would use a proportional hazards model. This permits the assessment of the effects of the exposures of interest along with potential effect modifiers and confounders. We will conduct an analysis using events recorded to date, with an additional analysis at the conclusion of the observation period. In addition to the pollutant exposures, variables of interest will include age, other health conditions (e.g., preexisting cardiovascular disease and diabetes), smoking status, time spent outdoors (to the extent calculable) or exercising, medications and supplements, occupation and employment status, socioeconomic factors (income, educational attainment), and findings of the core physical and blood examinations. The strength of the association also will be assessed in relation to the contribution of sources of particulate exposures in the communities (fuel oil, industrial sources, gasoline or diesel combustion, wood smoke, etc.) Depending on the detail possible in exposure assignments, special analyses may be necessary to assess: (1) the degree of exposure uniformity in the communities under study; and (2) the need for assessing regional or spatial autocorrelation in the exposure data.

Strengths and Limitations

One advantage of the WHI cohort is that, in addition to the sheer size of the cohort, WHI represents a well-characterized set of subjects with careful data collection and followup procedures, studied in a relatively large number of geographical locations, providing for contrasts in several pollutant and climatic characteristics of interest. In comparison to previous studies, this cohort also has detailed information on subject health conditions and nonfatal cardiovascular events.

Exposure assignment in an air pollution study without personal air sampling results is limited by the availability of routine monitoring data and the need to make ecological assumptions. However, previous studies showing effects have suffered from the same problem and exposure homogeneity in a community is not an unreasonable assumption. Improvements in available environmental monitoring data during the last several years in the region of most clinical centers should ensure data of adequate quality. Combined with improved exposure modeling techniques, we can anticipate less measurement error than in previous studies.

Role of Clinical Coordinating Center (CCC)

In addition to the involvement of Dr. Anderson as a co-investigator, center programming time also would be required. To preserve the confidentiality of potentially identifiable information (e.g., address, age, and health events within the WHI research program), staff in the CCC would be involved in linking exposure information to health outcome data.

Future Activities:

Future activities will include accomplishment of the goals of the chronic study using the WHI cohort, completion of the MITI study, continued research and publication of associations between severity of cystic fibrous, and annual air pollution concentrations.


Journal Articles on this Report: 5 Displayed | Download in RIS Format

Other subproject views: All 20 publications 13 publications in selected types All 13 journal articles
Other center views: All 191 publications 97 publications in selected types All 94 journal articles

Type Citation Sub Project Document Sources
Journal Article Levy D, Sheppard L, Checkoway H, Kaufman J, Lumley T, Koenig J, Siscovick D. A case-crossover analysis of particulate matter air pollution and out-of-hospital primary cardiac arrest. Epidemiology 2001;12(2):193-199. R827355 (2004)
R827355 (Final)
R827355C001 (2000)
R827355C001 (2001)
  • Abstract from PubMed
  • Full-text: Wolters Kluwer Full Text
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  • Other: Wolters Kluwer PDF
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  • Journal Article Levy D, Lumley T, Sheppard L, Kaufman J, Checkoway H. Referent selection in case-crossover analyses of acute health effects of air pollution. Epidemiology 2001;12(2):186-192. R827355 (2004)
    R827355 (Final)
    R827355C001 (2000)
    R827355C001 (2001)
    R825173 (1999)
    R825173 (2000)
  • Abstract from PubMed
  • Full-text: Wolters Kluwer Full Text
    Exit EPA Disclaimer
  • Other: Wolters Kluwer PDF
    Exit EPA Disclaimer
  • Journal Article Lumley T, Sheppard L. Assessing seasonal confounding and model selection bias in air pollution epidemiology using positive and negative control analyses. Environmetrics 2000;11(6):705-717. R827355 (2001)
    R827355 (Final)
    R827355C001 (2000)
    R827355C001 (2001)
    R827355C009 (Final)
    R825173 (1999)
  • Abstract: InterScience Abstract
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  • Other: InterScience PDF
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  • Journal Article Sheppard L, Kaufman J. Sorting out the role of air pollutants in asthma initiation. (Editorials) Epidemiology 2000;11(2):100-101. R827355 (2004)
    R827355 (Final)
    R827355C001 (1999)
    R827355C001 (2001)
    R827355C009 (Final)
  • Abstract from PubMed
  • Full-text: Wolters Kluwer Full Text
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  • Journal Article Sheppard L, Levy D, Checkoway H. Correcting for the effects of location and atmospheric conditions on air pollution exposures in a case-crossover study. Journal of Exposure Science and Environmental Epidemiology 2001;11(2):86-96. R827355 (2004)
    R827355 (Final)
    R827355C001 (2001)
    R827355C009 (Final)
    R825173 (1999)
    R825173 (2000)
  • Abstract from PubMed
  • Full-text: Nature Publishing Group Full Text
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  • Other: Nature Publishing Group PDF
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  • Supplemental Keywords:

    ambient particles, fine particles, combustion, health, exposure, biostatistics, susceptibility. , Air, Geographic Area, Scientific Discipline, Health, RFA, PHYSICAL ASPECTS, Susceptibility/Sensitive Population/Genetic Susceptibility, Toxicology, indoor air, Risk Assessments, genetic susceptability, Northwest, Health Risk Assessment, Physical Processes, Incineration/Combustion, Epidemiology, air toxics, Children's Health, Atmospheric Sciences, Biochemistry, particulate matter, Environmental Chemistry, Allergens/Asthma, State, aerosols, combustion contaminants, exposure assessment, incineration, risk assessment, California (CA), PAHs, exposure and effects, environmental hazard exposures, allergen, ambient air quality, cardiovascular disease, health effects, hydrocarbons, indoor air quality, inhalation, mortality, allergens, epidemelogy, air quality, ambient air, cardiopulmonary response, hazardous air pollutants, indoor environment, atmospheric aerosols, assessment of exposure, cardiopulmonary responses, combustion, harmful environmental agents, human health risk, particle exposure, toxics, epidemeology, mortality studies, acute cardiovascular effects, air pollutants, biostatistics, human health effects, particulates, sensitive populations, biological response, ambient particle health effects, air pollution, airborne pollutants, airway disease, atmospheric chemistry, biological markers, children, exposure, children's vulnerablity, human susceptibility, ambient aerosol, asthma, health risks, human exposure, Human Health Risk Assessment, morbidity, animal model, airway inflammation, particle transport

    Progress and Final Reports:
    1999 Progress Report
    2000 Progress Report
    Original Abstract
    2002 Progress Report
    2003 Progress Report
    Final Report


    Main Center Abstract and Reports:
    R827355    Airborne PM - Northwest Research Center for Particulate Air Pollution and Health

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R827355C001 Epidemiologic Study of Particulate Matter and Cardiopulmonary Mortality
    R827355C002 Health Effects
    R827355C003 Personal PM Exposure Assessment
    R827355C004 Characterization of Fine Particulate Matter
    R827355C005 Mechanisms of Toxicity of Particulate Matter Using Transgenic Mouse Strains
    R827355C006 Toxicology Project -- Controlled Exposure Facility
    R827355C007 Health Effects Research Core
    R827355C008 Exposure Core
    R827355C009 Statistics and Data Core
    R827355C010 Biomarker Core
    R827355C011 Oxidation Stress Makers

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    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.


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