2001 Progress Report: Health Effects of Ambient Air PM in Controlled Human ExposuresEPA 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
Current 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)
Project Period Covered by this Report: June 1, 2001 through May 31, 2002
RFA: Airborne Particulate Matter (PM) Centers (1999) RFA Text | Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air
The main objective of this research project was to determine whether concentrated ambient particulate matter (PM) will produce acute adverse respiratory and cardiovascular health outcomes in volunteers under controlled exposure conditions. In Project Year 2, the project was stopped (with agreement from the External Advisory Committee), 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.
The exposure of human subjects to PM was terminated largely for two reasons. First, the centrifugal concentrator that was used in the initial animal studies by Drs. Gordon, Nadziejko, and Chen fell into disrepair. Repeated attempts to salvage the original concentrator were unsuccessful and the concentrator achieved concentration factors of three to five instead of the original 10fold concentration factor. A virtual impactor concentrator designed by Project Investigator Sioutas recently was purchased by the New York University (NYU) PM Center and will be used in animal studies, but it has not been established whether this new concentrator would be satisfactory for a human exposure study at NYU. Second, reports from the laboratories at the U.S. Environmental Protection Agency (EPA), University of Southern California, and University of Rochester have provided evidence that few, if any, significant effects are observed in normal, healthy subjects exposed to concentrated ambient PM at concentrations greater than those we originally proposed. Thus, our small project, with 10 healthy subjects exposed to concentrated ambient PM, was unlikely to be fruitful. Therefore, with the agreement of the External Advisory Committee, the project was terminated and the Center resources were made available for research needs.
Due to the fact that the human exposure project was not progressing during Year 2, Drs. Reibman, Chen, and Gordon concentrated their efforts on examining the in vitro response 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 Micro-Orifive Uniform Deposit Impactor for 2-week intervals throughout the year and was 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 granulocyte and macrophage-colony stimulating factor (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 also can 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 carbon or Mount St. Helen dust 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. Additional experiments with inhibitors demonstrated that mitogen-activated protein kinase pathways are involved in the ambient particle effects on GM-CSF secretion by epithelial cells. This research has resulted in publication of a manuscript (in press) and was used as preliminary data in a successful National Institute of Environmental Health Sciences (NIEHS) grant application by Dr. Reibman in Project Year 2. These studies have progressed under Dr. Reibman’s NIEHS grant.
Journal Articles:No journal articles submitted with this report: View all 3 publications for this subproject
Supplemental Keywords:particulate matter, PM, PM components, exposure, epidemiology, human exposure, respiratory, cardiovascular, epithelial cell, asthma., RFA, Health, Scientific Discipline, PHYSICAL ASPECTS, Air, ENVIRONMENTAL MANAGEMENT, particulate matter, Environmental Chemistry, Health Risk Assessment, Risk Assessments, Environmental Monitoring, Physical Processes, 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
Progress and Final Reports:Original Abstract
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