Grantee Research Project Results
1999 Progress Report: Health Effects of Ambient Air PM in Controlled Human Exposures
EPA Grant Number: R827351C004Subproject: 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: Health Effects Institute (2000 — 2005)
Center Director: Greenbaum, Daniel S.
Title: Health Effects of Ambient Air PM in Controlled Human Exposures
Investigators: Gordon, Terry , Reibman, Joan
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, 1999 through May 31, 2000
RFA: Airborne Particulate Matter (PM) Centers (1999) RFA Text | Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air
Objective:
The overall objective of this research project is to determine whether coexposure to concentrated ambient particulate matter (PM) and the gaseous pollutant ozone causes synergy in the acute respiratory and cardiovascular health outcomes epidemiologically associated with PM exposure. During Year 1 of the project, our specific objectives were to: (1) receive Institutional Review Board approval for the human exposure protocol; (2) validate the centrifugal concentrator exposure system; (3) perform quality assurance on electrocardiogram (EKG) data acquisition; and (4) begin the PM exposures with normal subjects.
Because of the unexpected delay in validating the particle concentrator, additional studies were conducted to examine the effect of size-segregated ambient particles on cytokine production by primary human bronchial epithelial cells in culture.
Progress Summary:
Construction and high-speed balancing of the new centrifugal concentrator have been completed. Assembly of the complete concentrator system and calibration of all flow parameters also have been completed. We encountered several problems during the testing phase, including balancing problems, particle generation by the concentrator, leakage of lubricant from a faulty bearing, overheating, and control of the motor that turns the centrifugal concentrator. The underlying cause of each problem was diagnosed and fixed— rebalancing by J&S Precision Balancing, Inc.; cleaning the centrifugal concentrator and removal of all balancing weights/material; replacement of bearings with bearings using low-migration lubricant; rebalancing and new bearings solved the heating problem; and a new, state-of-the-art motor controller (KB Electronics) permits a slow start of the rotating drum and precise speed control.
Unfortunately, we found that the centrifugal concentrator did not concentrate ambient PM or sodium chloride particles. Every possible aspect of the problem was examined, and as far as we could determine, all construction criteria of the original design had been met. The drum was pressure tested in water to determine whether the porosity of the fritted drum was uniform along the axis of rotation. It was immediately apparent that one-half inch sections at each end of the rotating drum were so “leaky” that air would pass through these regions rather than uniformly along the drum surface, thereby short circuiting the entire process of particle concentration. The fritted metal drum then was rolled so that the pores within five-eighths of an inch of the end of the drum were closed and finally (and successfully) pressure tested for uniformity in water. Additionally, the entire surface of the drum was remachined to reduce the pore size and increase the uniformity of the pressure drop along the axis of the fritted metal drum.
The newly rolled/machined drum was reassembled with the centrifugal concentrator shell and tested with indoor ambient particles. It was first tested with a high efficiency particulate air (HEPA) filter connected to the inlet blower to ensure that the centrifugal concentrator did not generate particles. Nephelometer readings indicated negligible particles in the output stream with the HEPA filter connected. Next, the HEPA filter was removed, and indoor air (5 to 8 μg/m3) was introduced into the concentrator. The centrifugal concentrator met our anticipated criteria with a 15 to 20X concentrating factor at 10,000 rpm and 8 to 10 L/minute flow to the exposure port. Because of the need to use a new fritted drum with smaller, more evenly distributed pores, further validation of the centrifugal concentrator was postponed until a new rotating drum was manufactured, machined, pores reactivated, and balanced. This newly refurbished concentrator has been delivered, and initial tests are underway. Very preliminary results suggest that indoor air particles are concentrated five- to eightfold, and that 0.3 μm sodium chloride particles are concentrated threefold. These findings are similar to the concentrating efficiency obtained with the old Gerber centrifugal concentrator and must be optimized to deliver a greater concentration factor for ambient particles of tenfold for 0.5 to 2.5 μm particles at a 151/minute output flow rate.
Normal subjects underwent bronchoscopy, and their airways were brushed to retrieve human bronchial epithelial cells. The cells were grown in culture to test the hypotheses that: (1) ambient PM upregulates granulocyte macrophage-colony stimulating factor (GM-CSF) production in human bronchial epithelial cells (HBECs) in a size-dependent manner; and (2) stimulation of GM-CSF results from activation of mitogen-activated protein kinase (MAPK) pathways. Size-fractionated ambient PM was collected from New York City air on inert filters (Nucleopore or Teflon) with a cascade impactor (microorifice uniform deposit impactor) over 10-14 days. PM was extracted into medium (ultrasonification, 20 minutes), and GM-CSF secretion by primary human bronchial epithelial cells (third passage) was determined using a commercial enzyme-linked immunosorbent assay (ELISA) kit after 18 hours of treatment. We determined that components of size-fractionated ambient PM upregulate GM-CSF expression in cultured bronchial epithelial cells. On a mass basis, ultrafine (UF) PM was the most potent size-fractionated stimulus for GM-CSF production. Because treatment of cells with lipopolysaccharide (LPS), similar size carbon particles, and Mount St. Helen dust did not stimulate GM-CSF production, GM-CSF upregulation by UF did not appear to be a result of a general-particle effect or LPS contamination of ambient particles. In addition, inhibitor studies demonstrated that UF particles activated the MAPKerk1/2 pathway in HBECs, and that activation of the MAPKerkl/2, MAPKp38, and PKC pathways are necessary for UF particle-induced GM-CSF production. These findings demonstrate a pathway by which ambient PM can upregulate cytokine pathways involved in allergic airway responses.
Future Activities:
We will examine the 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 will examine the potential for airway epithelial cells (primary culture) to modulate the immune system. Size-fractionated ambient PM will be collected with a multi-orifice uniform diameter impacter (MOUDI) for 2-week intervals throughout the year and used to treat human bronchial epithelial cells obtained from normal human volunteers. We also will conduct experiments with inhibitors to determine whether MAPK pathways are involved in the ambient particle effects on GM-CSF secretion by epithelial cells.
Journal Articles:
No journal articles submitted with this report: View all 3 publications for this subprojectSupplemental Keywords:
thoracic particles, particulate matter, PM, PM10, fine particles, PM2.5, ultrafine particles, PM0.1, lung dosimetry models, human exposure models, pulmonary responses, cardiovascular responses, immunological responses, criteria air pollutants, concentrated ambient aerosols, air, health, waste, biochemistry, biology, chemical engineering, chemistry, children’s health, civil engineering, environmental engineering, environmental chemistry, physics, analytical chemistry, epidemiology, health risk assessment, immunology, incineration, combustion, combustion contaminants, combustion emissions, air toxics, tropospheric ozone, aerosol, air pollutants, air pollution, airborne pollutants, airway disease, airway inflammation, airway variability, allergen, ambient air, ambient air quality, assessment of exposure, asthma, asthma morbidity, atmospheric monitoring, biological markers, childhood respiratory disease, children, compliance monitoring, dosimetry, exposure, exposure and effects, health effects, heart rate variability, human exposure, human health, human health effects, lead, lung, mercury, morbidity, pulmonary, pulmonary disease, respiratory, cardiovascular, epithelial cell, sulfur dioxide, acute cardiovascular effects, aerosol composition, airborne particulate matter, ambient air monitoring, atmospheric aerosol particles, atmospheric particles, atmospheric particulate matter, chemical characteristics, environmental risks, exposure assessment, human health risk, ozone, ozone monitoring, particulates, ultrafine, UF, high efficiency particulate air, HEPA, human bronchial epithelial cells, HBECs,, 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 assessmentRelevant Websites:
http://www.med.nyu.edu/environmental/centers/epa/ Exit
Progress and Final Reports:
Original AbstractMain Center Abstract and Reports:
R827351 Health Effects Institute (2000 — 2005) 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
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.
Project Research Results
- Final Report
- 2004
- 2003
- 2002 Progress Report
- 2001 Progress Report
- 2000 Progress Report
- Original Abstract
3 journal articles for this subproject
Main Center: R827351
112 publications for this center
89 journal articles for this center