Final Report: Examining Conditions That Predispose Towards Acute Adverse Effects of Particulate Exposures

EPA Grant Number: R827353C004
Subproject: this is subproject number 004 , established and managed by the Center Director under grant R827353
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Harvard Particle Center
Center Director: Koutrakis, Petros
Title: Examining Conditions That Predispose Towards Acute Adverse Effects of Particulate Exposures
Investigators: Schwartz, Joel , Zanobetti, Antonella , Wellenius, Gregory , O'Neill, M.
Institution: Harvard T.H. Chan School of Public Health , Harvard University
EPA Project Officer: Chung, Serena
Project Period: June 1, 1999 through May 31, 2005 (Extended to May 31, 2006)
Project Amount: Refer to main center abstract for funding details.
RFA: Airborne Particulate Matter (PM) Centers (1999) RFA Text |  Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air

Objective:

Theme II: Identifying Populations Susceptible to the Health Effects of Particulate Air Pollution

Identification of populations that are especially susceptible to particulate matter (PM) health effects can further our understanding of biologic mechanisms of heart and lung disease attributable to PM. This area of our work has focused on testing the hypothesis that patients with pre-existing respiratory, cardiovascular or diabetic conditions have an enhanced mortality response to particle exposures.

Summary/Accomplishments (Outputs/Outcomes):

As part of this research effort, we previously reported that socio-economic factors were not modifiers of the risk of PM associated mortality (Zanobetti and Schwartz, 2000), although there was some increased risk in females. The same pattern held true for hospital admissions for heart and lung disease (Zanobetti, et al., 2000a). In contrast, we found that respiratory illness modified the risk of cardiovascular hospital admissions associated with PM (Zanobetti, et al., 2000b) and that heart failure modified the risk of PM-associated chronic obstructive pulmonary disease (COPD) admissions.

Additional work by our group has shown that individuals with diabetes are at higher risk from exposure to PM. We have published several papers addressing this issue. We published two studies suggesting that diabetes is an effect modifier (Zanobetti and Schwartz, 2001; 2002). One paper examined effect modification by concurrent diagnosis of diabetes overall and by age group in four US cities (Zanobetti and Schwartz, 2002), concluding that individuals with diabetes have twice the risk of a PM10-associated cardiovascular admission compared to those without the disease.

To further examine susceptibility by diabetes observed in these population studies, we obtained clinical information to gain insights on potential biological mechanisms. With researchers at the Joslin Diabetes Center and Beth Israel/Deaconess Hospital, we analyzed the relationship between air pollution and both inflammation and vascular reactivity in over 200 greater-Boston residents participating in clinical trials. We used particle data (PM2.5, particle number [PN], black carbon (BC), and SO42-) measured at the Harvard School of Public Health (HSPH) site established by the PM center. Both BC and SO42- particles appeared to have effects on vascular reactivity and endothelial function, especially among people with diabetes. (O’Neill, et al., 2005b) Additional analyses have shown associations between increased particle levels and blood markers of inflammation, including ICAM-1, VCAM-1, and von Willibrand’s factor, and a manuscript has been accepted for publication in Occupational and Environmental Medicine (O’Neill, et al., 2007).

We continued to explore factors influencing vulnerability to temperature-related mortality. Data on air pollution compiled for PM center projects have been used to control for confounding. In a study of seven US cities, lower educational attainment, black race, and dying outside a hospital were markers of vulnerability to death on extreme temperature days, controlling for PM10 exposure (O’Neill, et al., 2003c). In a follow-up analysis, we found that air conditioning prevalence explained some of the observed racial disparities in heat-related mortality in four of these cities (O’Neill, et al., 2005c). An additional analysis found that air pollution and epidemics were important confounders of temperature and mortality associations and suggested inclusion of PM10, O3, and epidemic periods in future analyses that can be used in forecasting health impacts of climate change. (O’Neill, et al., 2005a).

Furthermore, we conducted mortality follow-ups of subjects whose potentially predisposing conditions were identified for use in hospital admissions data. These analyses used the case-crossover approach. We completed a methodological paper examining the potential for bias and confounding in that approach and developed new statistical methods to address these problems (Bateson and Schwartz, 2001). The newly developed methods estimate and subtract biases from health risk estimates. We also conducted simulations showing our method has correct coverage probabilities, but a paper has not been submitted for review (Bateson and Schwartz, in preparation).

Mixed models are another group of analysis methods that represent an important tool for determining whether persons with certain characteristics are more susceptible to the effects of airborne particles. However, classic mixed regression programs are linear models, whereas we know that season and weather effects on health are often nonlinear. These have often been addressed using nonparametric smoothing. To enhance our ability to assess sensitivity while maintaining good covariate control, we developed an additive mixed model, which combines the attributes of both approaches (Coull, et al., 2001).

The case-crossover approach was also used to examine the PM10-associated risk of emergency hospitalization for myocardial infarction during 1985-1999 among elderly residents of twenty-one US cities. Results from this study showed increased risk of hospitalization for myocardial infarction for diabetics. Effect sizes were roughly doubled in persons with COPD or concurrent pneumonia compared to those without (Zanobetti, et al., 2004).

More recently we examined the association of PM2.5 and changes in blood markers of cardiovascular risk, including lipid profiles and markers of acute systemic inflammation, in the VA Normative Aging Study. For the same outcomes the associations were not as strong in the group taking statins (Zeka, et al., 2006).

Conclusions:

A number of factors were found to increase the effects of particulate matter on morbidity and mortality. Socioeconomic status (SES) was not identified as a modifier of PM mortality or hospital admissions for heart and lung disease. Pre-existing respiratory illness modified the effects of PM-related cardiovascular hospital admissions, and in turn, heart failure increased the risk of PM-related COPD hospital admissions. Individuals with diabetes had double the risk of PM-related cardiovascular hospital admissions. Controlling for respiratory epidemics does not change the effect size estimates for PM on mortality. Race and SES indicators were modifiers of mortality on extreme temperature days.

References:

Bateson T, Schwartz J. Selection bias and confounding in case-crossover analyses of environmental time-series data. Epidemiology 2001;12(6):654-661.

Coull BA, Schwartz J, Wand MP. Respiratory health and air pollution: additive mixed model analyses. Biostatistics 2001;2:337-349.

O’Neill MS, Zanobetti A, Schwartz J. Modifiers of the temperature and mortality association in seven US cities. American Journal of Epidemiology 2003c;157(12):1074-1082.

O’Neill MS, Hajat S, Zanobetti A, Ramirez-Aguilar M, Schwartz J. Impact of control for air pollution and respiratory epidemics on the estimated associations of temperature and daily mortality. International Journal of Biometeorology 2005a;50(2):121-129.

O’Neill MS, Veves A, Zanobetti A, Sarnat JA, Gold DR, Economides PA, Horton ES, Schwartz J. Diabetes enhances vulnerability to particulate air pollution-associated impairment in vascular reactivity and endothelial function. Circulation 2005b;111(22):2913-2920.

O’Neill MS, Zanobetti A, Schwartz J. Disparities by race in heat-related mortality in four US cities: the role of air conditioning prevalence. Journal of Urban Health 2005c;82(2):191-197.

O’Neill MS, Veves A, Sarnat JA, Zanobetti A, Gold DR, Economides PA, Horton E, Schwartz J. Air pollution and inflammation in type 2 diabetes: a mechanism for susceptibility. Occupational and Environmental Medicine 2007;64:373-379.

Zanobetti A, Schwartz J. Race, gender, and social status as modifiers of the effects of PM10 on mortality. Journal of Occupational and Environmental Medicine 2000;42(5):469-474.

Zanobetti A, Schwartz J. Are diabetics more susceptible to the health effects of airborne particles? American Journal of Respiratory and Critical Care Medicine 2001;164(1):831-833.

Zanobetti A, Schwartz J. Cardiovascular damage by airborne particles: are diabetics more susceptible? Epidemiology 2002;13(5):588-592.

Zanobetti A, Schwartz J, Dockery D. Airborne particles are a risk factor for hospital admissions for heart and lung disease. Environmental Health Perspectives 2000a;108:1071-1077.

Zanobetti A, Schwartz J, Gold D. Are there sensitive subgroups for the health effects of airborne particles? Environmental Health Perspectives 2000b;108:841-845.

Zanobetti A, Canner M, Stone P, Schwartz J, Sher D, Eagan-Bengston E, Gates K, Hartley L, Suh H, Gold D. Ambient pollution and blood pressure in cardiac rehabilitation patients. Circulation 2004;110(15):2184-2189.

Zeka A, Sullivan JR, Vokonas PS, Sparrow D, Schwartz J. Inflammatory markers and particulate air pollution: characterizing the pathway to disease. International Journal of Epidemiology 2006;35(5):1347-1354.


Journal Articles on this Report : 33 Displayed | Download in RIS Format

Other subproject views: All 34 publications 34 publications in selected types All 33 journal articles
Other center views: All 200 publications 198 publications in selected types All 197 journal articles
Type Citation Sub Project Document Sources
Journal Article Bateson TF, Schwartz J. Selection bias and confounding in case-crossover analyses of environmental time-series data. Epidemiology 2001;12(6):654-661. R827353 (Final)
R827353C004 (2002)
R827353C004 (2003)
R827353C004 (2004)
R827353C004 (Final)
R827353C005 (2001)
R827353C005 (2002)
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R827353C005 (Final)
  • Abstract from PubMed
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  • Abstract: Epidemiology-Abstract
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  • Journal Article Braga ALF, Zanobetti A, Schwartz J. The effect of weather on respiratory and cardiovascular deaths in 12 U.S. cities. Environmental Health Perspectives 2002;110(9):859-863. R827353 (Final)
    R827353C004 (2002)
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    R827353C004 (Final)
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  • Journal Article Braga ALF, Zanobetti A, Schwartz J. The time course of weather-related deaths. Epidemiology 2001;12(6):662-667. R827353 (Final)
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  • Journal Article Coull BA, Schwartz J, Wand MP. Respiratory health and air pollution:additive mixed model analyses. Biostatistics 2001;2(3):337-349. R827353 (Final)
    R827353C004 (2000)
    R827353C004 (2001)
    R827353C004 (Final)
  • Abstract from PubMed
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  • Journal Article Dockery DW, Luttmann-Gibson H, Rich DQ, Link MS, Mittleman MA, Gold DR, Koutrakis P, Schwartz JD, Verrier RL. Association of air pollution with increased incidence of ventricular tachyarrhythmias recorded by implanted cardioverter defibrillators. Environmental Health Perspectives 2005;113(6):670-674. R827353 (Final)
    R827353C004 (Final)
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  • Journal Article Medina-Ramon M, Zanobetti A, Cavanagh DP, Schwartz J. Extreme temperatures and mortality:assessing effect modification by personal characteristics and specific cause of death in a multi-city case-only analysis. Environmental Health Perspectives 2006;114(9):1331-1336. R827353 (Final)
    R827353C004 (Final)
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  • Journal Article O'Neill MS, Jerrett M, Kawachi I, Levy JI, Cohen AJ, Gouveia N, Wilkinson P, Fletcher T, Cifuentes L, Schwartz J, Workshop on Air Pollution and Socioeconomic Conditions. Health, wealth, and air pollution:advancing theory and methods. Environmental Health Perspectives 2003;111(16):1861-1870. R827353 (Final)
    R827353C004 (2003)
    R827353C004 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Journal Article O'Neill MS, Zanobetti A, Schwartz J. Modifiers of the temperature and mortality association in seven US cities. American Journal of Epidemiology 2003;157(12):1074-1082. R827353 (Final)
    R827353C004 (2003)
    R827353C004 (Final)
  • Abstract from PubMed
  • Full-text: AJE-Full Text HTML
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  • Journal Article O'Neill MS, Veves A, Zanobetti A, Sarnat JA, Gold DR, Economides PA, Horton ES, Schwartz J. Diabetes enhances vulnerability to particulate air pollution-associated impairment in vascular reactivity and endothelial function. Circulation 2005;111(22):2913-2920. R827353 (Final)
    R827353C004 (2003)
    R827353C004 (2004)
    R827353C004 (Final)
  • Abstract from PubMed
  • Full-text: Circulation-Full Text HTML
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  • Abstract: Circulation-Abstract
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  • Journal Article O'Neill MS, Zanobetti A, Schwartz J. Disparites by race in heat-related mortality in four US cities:the role of air conditioning prevalence. Journal of Urban Health 2005;82(2):191-197. R827353 (Final)
    R827353C004 (Final)
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  • Abstract from PubMed
  • Associated PubMed link
  • Abstract: Springer-Abstract
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  • Journal Article O'Neill MS, Hajat S, Zanobetti A, Ramirez-Aguilar M, Schwartz J. Impact of control for air pollution and respiratory epidemics on the estimated associations of temperature and daily mortality. International Journal of Biometeorology 2005;50(2):121-129. R827353 (Final)
    R827353C004 (2003)
    R827353C004 (2004)
    R827353C004 (Final)
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  • Journal Article O'Neill MS, Veves A, Sarnat JA, Zanobetti A, Gold DR, Economides PA, Horton ES, Schwartz J. Air pollution and inflammation in type 2 diabetes:a mechanism for susceptibility. Occupational and Environmental Medicine 2007;64(6):373-379. R827353 (Final)
    R827353C004 (Final)
    R832416 (2008)
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  • Full-text: OEM-Full Text HTML
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  • Journal Article O'Neill MS. Air conditioning and heat-related health effects. Applied Environmental Science and Public Health 2003;1(1):9-12. R827353 (Final)
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    Journal Article Peters A, Dockery DW, Muller JE, Mittleman MA. Increased particulate air pollution and the triggering of myocardial infarction. Circulation 2001;103(23):2810-2815. R827353 (Final)
    R827353C004 (2002)
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    R827353C004 (Final)
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  • Full-text: Circulation-Full Text HTML
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  • Journal Article Rich DQ, Schwartz J, Mittleman MA, Link M, Luttmann-Gibson H, Catalano PJ, Speizer FE, Dockery DW. Association of short-term ambient air pollution concentrations and ventricular arrhythmias. American Journal of Epidemiology 2005;161(12):1123-1132. R827353 (Final)
    R827353C004 (Final)
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  • Journal Article Rich DQ, Mittleman MA, Link MS, Schwartz J, Luttmann-Gibson H, Catalano PJ, Speizer FE, Gold DR, Dockery DW. Increased risk of paroxysmal atrial fibrillation episodes associated with acute increases in ambient air pollution. Environmental Health Perspectives 2006;114(1):120-123. R827353 (Final)
    R827353C004 (Final)
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  • Journal Article Schwartz J. Assessing confounding, effect modification, and thresholds in the association between ambient particles and daily deaths. Environmental Health Perspectives 2000;108(6):563-568. R827353 (Final)
    R827353C004 (2003)
    R827353C004 (Final)
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  • Journal Article Schwartz J. Who is sensitive to extremes of temperature? A case-only analysis. Epidemiology 2005;16(1):67-72. R827353 (Final)
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  • Journal Article Wellenius GA, Schwartz J, Mittleman MA. Air pollution and hospital admissions for ischemic and hemorrhagic stroke among Medicare beneficiaries. Stroke 2005;36(12):2549-2553. R827353 (Final)
    R827353C004 (2004)
    R827353C004 (Final)
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  • Journal Article Wellenius GA, Bateson TF, Mittleman MA, Schwartz J. Particulate air pollution and the rate of hospitalization for congestive heart failure among Medicare beneficiaries in Pittsburgh, Pennsylvania. American Journal of Epidemiology 2005;161(11):1030-1036. R827353 (Final)
    R827353C004 (2004)
    R827353C004 (Final)
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  • Journal Article Wellenius GA, Schwartz J, Mittleman MA. Particulate air pollution and hospital admissions for congestive heart failure in seven United States cities. The American Journal of Cardiology 2006;97(3):404-408. R827353 (Final)
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    R832416 (2008)
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  • Journal Article Zanobetti A, Schwartz J. Race, gender, and social status as modifiers of the effects of PM10 on mortality. Journal of Occupational and Environmental Medicine 2000;42(5):469-474. R827353 (Final)
    R827353C004 (Final)
  • Abstract from PubMed
  • Full-text: ResearchGate-Abstract & Full Text
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  • Abstract: JOEM-Abstract
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  • Journal Article Zanobetti A, Schwartz J, Dockery DW. Airborne particles are a risk factor for hospital admissions for heart and lung disease. Environmental Health Perspectives 2000;108(11):1071-1077. R827353 (Final)
    R827353C004 (2000)
    R827353C004 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
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  • Journal Article Zanobetti A, Schwartz J, Gold D. Are there sensitive subgroups for the health effects of airborne particles? Environmental Health Perspectives 2000;108(9):841-845. R827353 (Final)
    R827353C004 (2000)
    R827353C004 (Final)
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  • Journal Article Zanobetti A, Wand MP, Schwartz J, Ryan LM. Generalized additive distributed lag models:quantifying mortality displacement. Biostatistics 2000;1(3):279-292. R827353 (Final)
    R827353C004 (2000)
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    R827353C004 (Final)
  • Abstract from PubMed
  • Full-text: Biostatistics-Full Text PDF
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  • Abstract: Biostatistics-Abstract
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  • Journal Article Zanobetti A, Schwartz J. Are diabetics more susceptible to the health effects of airborne particles? American Journal of Respiratory and Critical Care Medicine 2001;164(5):831-833. R827353 (Final)
    R827353C004 (2001)
    R827353C004 (Final)
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  • Journal Article Zanobetti A, Schwartz J, Samoli E, Gryparis A, Touloumi G, Atkinson R, Le Tertre A, Bobros J, Celko M, Goren A, Forsberg B, Michelozzi P, Rabczenko D, Aranguez Ruiz E, Katsouyanni K. The temporal pattern of mortality responses to air pollution:a multicity assessment of mortality displacement. Epidemiology 2002;13(1):87-93. R827353 (Final)
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  • Full-text: Epidemiology-Full Text HTML
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  • Journal Article Zanobetti A, Schwartz J. Cardiovascular damage by airborne particles:are diabetics more susceptible? Epidemiology 2002;13(5):588-592. R827353 (Final)
    R827353C004 (2001)
    R827353C004 (2002)
    R827353C004 (2003)
    R827353C004 (Final)
    R827353C005 (2003)
    R827353C005 (Final)
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  • Full-text: Epidemiology-Full Text HTML
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  • Journal Article Zanobetti A, Schwartz J, Samoli E, Gryparis A, Touloumi G, Peacock J, Anderson RH, Le Tertre A, Bobros J, Celko M, Goren A, Forsberg B, Michelozzi P, Rabczenko D, Hoyos SP, Wichmann HE, Katsouyanni K. The temporal pattern of respiratory and heart disease mortality in response to air pollution. Environmental Health Perspectives 2003;111(9):1188-1193. R827353 (Final)
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  • Journal Article Zanobetti A, Schwartz J. The effect of particulate air pollution on emergency admissions for myocardial infarction:a multicity case-crossover analysis. Environmental Health Perspectives 2005;113(8):978-982. R827353 (Final)
    R827353C004 (2004)
    R827353C004 (Final)
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  • Journal Article Zanobetti A, Schwartz J. Air pollution and emergency admissions in Boston, MA. Journal of Epidemiology & Community Health 2006;60(10):890-895. R827353 (Final)
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    R832416 (2008)
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  • Journal Article Zeka A, Zanobetti A, Schwartz J. Individual-level modifiers of the effects of particulate matter on daily mortality. American Journal of Epidemiology 2006;163(9):849-859. R827353 (Final)
    R827353C004 (Final)
    R832416 (2008)
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  • Journal Article Zeka A, Sullivan JR, Vokonas PS, Sparrow D, Schwartz J. Inflammatory markers and particulate air pollution:characterizing the pathway to disease. International Journal of Epidemiology 2006;35(5):1347-1354. R827353 (Final)
    R827353C004 (Final)
    R827353C010 (Final)
    R832416 (2008)
    R832416 (2009)
    R832416C001 (2009)
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  • Supplemental Keywords:

    RFA, Health, Scientific Discipline, Air, Geographic Area, particulate matter, Toxicology, air toxics, Environmental Chemistry, Epidemiology, State, Risk Assessments, Microbiology, Susceptibility/Sensitive Population/Genetic Susceptibility, Environmental Microbiology, Environmental Monitoring, Children's Health, genetic susceptability, tropospheric ozone, Atmospheric Sciences, Molecular Biology/Genetics, Biology, Environmental Engineering, ambient air quality, health effects, interindividual variability, molecular epidemiology, monitoring, particulates, risk assessment, sensitive populations, chemical exposure, air pollutants, cardiopulmonary responses, health risks, human health effects, indoor exposure, lung, stratospheric ozone, ambient air monitoring, exposure and effects, ambient air, ambient measurement methods, exposure, pulmonary disease, Utah (UT), developmental effects, epidemelogy, biological response, respiratory disease, air pollution, ambient monitoring, children, Human Health Risk Assessment, Massachusetts (MA), particle exposure, lung cancer, biological mechanism , cardiopulmonary response, human exposure, inhalation, pulmonary, susceptibility, Illinois (IL), particulate exposure, assessment of exposure, ambient particle health effects, elderly, indoor air, inhaled, Connecticut (CT), atmospheric monitoring, epidemeology, human susceptibility, environmental health hazard, inhalation toxicology, cardiopulmonary, indoor air quality, inhaled particles, human health, air quality, cardiovascular disease, dosimetry, human health risk, respiratory

    Relevant Websites:

    http://www.hsph.harvard.edu/epacenter/epa_center_99-05/index.html Exit

    Progress and Final Reports:

    Original Abstract
  • 1999 Progress Report
  • 2000 Progress Report
  • 2001 Progress Report
  • 2002 Progress Report
  • 2003 Progress Report
  • 2004 Progress Report

  • Main Center Abstract and Reports:

    R827353    Harvard Particle Center

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R827353C001 Assessing Human Exposures to Particulate and Gaseous Air Pollutants
    R827353C002 Quantifying Exposure Error and its Effect on Epidemiological Studies
    R827353C003 St. Louis Bus, Steubenville and Atlanta Studies
    R827353C004 Examining Conditions That Predispose Towards Acute Adverse Effects of Particulate Exposures
    R827353C005 Assessing Life-Shortening Associated with Exposure to Particulate Matter
    R827353C006 Investigating Chronic Effects of Exposure to Particulate Matter
    R827353C007 Determining the Effects of Particle Characteristics on Respiratory Health of Children
    R827353C008 Differentiating the Roles of Particle Size, Particle Composition, and Gaseous Co-Pollutants on Cardiac Ischemia
    R827353C009 Assessing Deposition of Ambient Particles in the Lung
    R827353C010 Relating Changes in Blood Viscosity, Other Clotting Parameters, Heart Rate, and Heart Rate Variability to Particulate and Criteria Gas Exposures
    R827353C011 Studies of Oxidant Mechanisms
    R827353C012 Modeling Relationships Between Mobile Source Particle Emissions and Population Exposures
    R827353C013 Toxicological Evaluation of Realistic Emissions of Source Aerosols (TERESA) Study
    R827353C014 Identifying the Physical and Chemical Properties of Particulate Matter Responsible for the Observed Adverse Health Effects
    R827353C015 Research Coordination Core
    R827353C016 Analytical and Facilities Core
    R827353C017 Technology Development and Transfer Core