Final Report: Health Effects of Ambient Air PM in Controlled Human Exposures

EPA Grant Number: R827351C004
Subproject: this is subproject number 004 , established and managed by the Center Director under grant R827351
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: EPA NYU PM Center: Health Risks of PM Components
Center Director: N/A
Title: Health Effects of Ambient Air PM in Controlled Human Exposures
Investigators: Gordon, Terry , Chen, Lung Chi , Reibman, Joan
Institution: New York University School of Medicine
EPA Project Officer: Chung, Serena
Project Period: June 1, 1999 through May 31, 2005 (Extended to May 31, 2006)
RFA: Airborne Particulate Matter (PM) Centers (1999) RFA Text |  Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air

Objective:

The original hypothesis of this Project was that concentrated ambient particulate matter (PM) will produce acute adverse respiratory and cardiovascular health outcomes in volunteers under controlled exposure conditions. In Year 02, the project was changed and we examined whether the stimulation of epithelial cells by ambient particles results in the release of cytokines which can upregulate antigen presentation by dendritic cells. As a follow-up to these in vitro studies, we coordinated a multi-Center collaboration which examined the in vitro and in vivo effects of size-segregated particles collected at geographically diverse sites throughout the United States.

Summary/Accomplishments (Outputs/Outcomes):

In Vitro Studies with Airway Epithelial Cells

Drs. Reibman, Chen, and Gordon concentrated their efforts on an examination of in vitro responses of human bronchial epithelial cells to size-fractionated ambient PM. Because of the significant association between ambient PM and exacerbation of allergic asthma, we examined the potential for airway epithelial cells (primary culture) to modulate the immune system. Size-fractionated ambient PM was collected with a MOUDI impactor for 2 week intervals throughout the year, and used to treat human bronchial epithelial cells obtained from normal human volunteers. The fraction of particles less than 0.18 μm produced a dose-dependent increase in GM-CSF released from the epithelial cells. GM-CSF is a cytokine that can elicit inflammation in the airways via an effect on eosinophils and can also modulate immune responses via effects on dendritic cells. There was no change in secreted GM-CSF in cells treated with larger size ambient particles or equivalent doses of control particles, thus suggesting that the human epithelial cell response was not due to a general particle effect. Moreover, treatment of epithelial cells with endotoxin had no effect on GM-CSF. Further experiments with inhibitors demonstrated that MAPK pathways are involved in the ambient particle effects on GM-CSF secretion by epithelial cells.

Multi-Site Ambient PM Study (MAPS)

The overall objective of the interdisciplinary MAPS study was to pool resources from multiple Centers to collect particles from several different geographical regions, characterize their physical and chemical properties, and make them available to investigators for in vitro and animal toxicology studies. The results of these studies will be used to relate health effects with PM components and ultimately sources. Recent studies suggest that PM derived from different sources may differ in toxicity and that specific PM components may serve as markers for different sources, suggesting an alternative, more efficient way of regulating PM. To directly study this issue, airborne particles in the ultrafine, fine, and coarse thoracic size ranges were collected in eight different locations in the U.S. and Europe. The sites were selected to take advantage of regional differences in PM sources and components. Weekly samples were collected for a period of a month in each location, using a 3 stage particle impactor, developed at Harvard’s U.S. Environmental Protection Agency (EPA) Center, which is capable of collecting 15 to 100 mg of material at 3 size fractions during a weekly sampling interval. The particles have been assayed for a number of chemical components in collaboration with EPA’s National Health and Environmental Effects Research Laboratory (NHEERL) and made available to investigators in several different laboratories. Several studies have been completed and results presented so far demonstrate clear particle size and source dependent differences in toxicity. At least four manuscripts (U.S. EPA, University of Rochester, and New York University [NYU]) are in preparation for submission.

Conclusions:

Our in vitro studies have clearly demonstrated that particle toxicity is dependent on the source of particles and the size of particles. These findings are important for consideration by policy makers in setting regulations for airborne particles.

Technical Report:

Long Version of Final Report (PDF) (2 pp, 24.5 K, About PDF)


Journal Articles on this Report : 3 Displayed | Download in RIS Format

Other subproject views: All 3 publications 3 publications in selected types All 3 journal articles
Other center views: All 111 publications 100 publications in selected types All 88 journal articles
Type Citation Sub Project Document Sources
Journal Article Gordon T, Reibman J. Cardiovascular toxicity of inhaled ambient particulate matter. Toxicological Sciences 2000;56(1):2-4. R827351 (Final)
R827351C004 (2002)
R827351C004 (Final)
R826244 (1999)
R826244 (2000)
R826244 (Final)
  • Abstract from PubMed
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  • Journal Article Reibman J, Hsu Y, Chen LC, Kumar A, Su WC, Choy W, Talbot A, Gordon T. Size fractions of ambient particulate matter induce granulocyte macrophage colony-stimulating factor in human bronchial epithelial cells by mitogen-activated protein kinase pathways. American Journal of Respiratory Cell and Molecular Biology 2002;27(4):455-462. R827351 (2003)
    R827351 (Final)
    R827351C004 (2002)
    R827351C004 (Final)
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  • Journal Article Reibman J, Hsu Y, Chen LC, Bleck B, Gordon T. Airway epithelial cells release MIP-3α/CCL20 in response to cytokines and ambient particulate matter. American Journal of Respiratory Cell and Molecular Biology 2003;28(6):648-654. R827351 (2003)
    R827351 (Final)
    R827351C003 (2003)
    R827351C003 (Final)
    R827351C004 (2002)
    R827351C004 (Final)
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  • Supplemental Keywords:

    particle size; allergic asthma; GM-CSF,, RFA, Health, PHYSICAL ASPECTS, Scientific Discipline, Air, ENVIRONMENTAL MANAGEMENT, particulate matter, Environmental Chemistry, Health Risk Assessment, Risk Assessments, Physical Processes, Environmental Monitoring, Risk Assessment, ambient air quality, atmospheric particulate matter, particulates, air toxics, atmospheric particles, chemical characteristics, toxicology, ambient air monitoring, acute cardiovascular effects, airborne particulate matter, ozone, environmental risks, exposure, Sulfur dioxide, air pollution, aerosol composition, atmospheric aerosol particles, human exposure, PM, exposure assessment

    Relevant Websites:

    Long Version of Final Report (PDF) (2 pp, 24.5 K, About PDF)
    http://www.med.nyu.edu/environmental/ exit 

EPA
    https://www.epa.gov/research-grants/

    Progress and Final Reports:

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

  • Main Center Abstract and Reports:

    R827351    EPA NYU PM Center: Health Risks of PM Components

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R827351C001 Exposure Characterization Error
    R827351C002 X-ray CT-based Assessment of Variations in Human Airway Geometry: Implications for Evaluation of Particle Deposition and Dose to Different Populations
    R827351C003 Asthma Susceptibility to PM2.5
    R827351C004 Health Effects of Ambient Air PM in Controlled Human Exposures
    R827351C005 Physicochemical Parameters of Combustion Generated Atmospheres as Determinants of PM Toxicity
    R827351C006 Effects of Particle-Associated Irritants on the Cardiovascular System
    R827351C007 Role of PM-Associated Transition Metals in Exacerbating Infectious Pneumoniae in Exposed Rats
    R827351C008 Immunomodulation by PM: Role of Metal Composition and Pulmonary Phagocyte Iron Status
    R827351C009 Health Risks of Particulate Matter Components: Center Service Core
    R827351C010 Lung Hypoxia as Potential Mechanisms for PM-Induced Health Effects
    R827351C011 Urban PM2.5 Surface Chemistry and Interactions with Bronchoalveolar Lavage Fluid (BALF)
    R827351C012 Subchronic PM2.5 Exposure Study at the NYU PM Center
    R827351C013 Long Term Health Effects of Concentrated Ambient PM2.5
    R827351C014 PM Components and NYC Respiratory and Cardiovascular Morbidity
    R827351C015 Development of a Real-Time Monitoring System for Acidity and Soluble Components in Airborne Particulate Matter
    R827351C016 Automated Real-Time Ambient Fine PM Monitoring System