Grantee Research Project Results
2001 Progress Report: Controlled Human Exposure Studies with Concentrated PM
EPA Grant Number: R827352C012Subproject: this is subproject number 012 , established and managed by the Center Director under grant R827352
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Southern California Children's Environmental Health Center
Center Director: McConnell, Rob Scot
Title: Controlled Human Exposure Studies with Concentrated PM
Investigators: Gong, Henry , Linn, William S. , Sioutas, Constantinos
Current Investigators: Gong, Henry
Institution: Rancho Los Amigos Medical Center , University of Southern California
Current Institution: Rancho Los Amigos Medical Center
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, 2000 through May 31, 2001
RFA: Airborne Particulate Matter (PM) Centers (1999) RFA Text | Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air
Objective:
The objective of this research project is to focus on the central hypothesis of the Southern California Particle Center and Supersite (SCPCS), which is that organic constituents associated with particulate matter (PM)—including quinones, other organic compounds (polycyclic aromatic hydrocarbons [PAHs], nitro-PAHs, and aldehydes/ketones), and metals—are capable of generating reactive oxygen species and acting as electrophilic agents. They have a central role in allergic airway disease such as asthma and cardiovascular effects through their ability to generate oxidative stress, inflammation, and immunomodulating effects in the lungs and airways.
The specific objective of this research project is to utilize three different types of ambient particle concentrators to evaluate cardiopulmonary responses of human volunteers exposed to concentrated ambient particles (CAPs) in the South Coast Air Basin of California.
The hypothesis for this study is that exposure to CAPs will affect cardiopulmonary health in normal persons and individuals with asthma and chronic obstructive pulmonary disease (COPD).
Progress Summary:
Within the context of the hypothesis for this study, acute cardiopulmonary responses to fine, ultrafine, and coarse CAPs in healthy human volunteers, and patients with COPD and asthma are being studied in a site on the western side of the Los Angeles Basin (LAB) in reasonable proximity to multiple arteries but not within 500 meters of a freeway. This site is considered a “source” site as a result of a lack of photochemical processes. Later, similar studies will be conducted in a receptor site to gauge the effects of atmospheric chemistry on cardiopulmonary responses in human volunteers.
This research makes use of the newly constructed concentrators to study the cardiopulmonary effects from exposure to CAPs. We have established a critical mass of technical and clinical experience, laboratory facilities, and personnel to conduct controlled human exposure studies with CAPs and co-pollutants using Center and other support. We have completed exposure studies of healthy, asthmatic, and COPD volunteers exposed to concentrated LA source-area ambient fine PM at worst-case concentrations. We have initiated exposure studies with concentrated fine PM and co-pollutant (NO2) in healthy elderly and COPD volunteers with separate U.S. Environmental Protection Agency (EPA) funding. We have developed technology to extend the above studies to coarse and ultrafine particles. Multiple biochemical and heart-rate-variability endpoints are being analyzed.
Results are now available for healthy and asthmatic subjects exposed to concentrated fine particles (2 hours at approximately 200 μg/m3). No pulmonary dysfunction was found, although there was a shift in airway cell populations recoverable by sputum induction (not obviously of an inflammatory nature). Slight changes in heart rate variability were found, suggesting decreased sympathetic relative to parasympathetic influence on the heart. In addition, very slight but statistically significant increases in cardiovascular symptoms were found during/after exposure, but both heart rate and minute ventilation rate declined during concentrated particle exposure, relative to the filtered-air control condition. Finally, some blood biochemical indices changed in a manner to suggest increased coagulability after concentrated particle exposure. The major collaboration with the EPA in the evaluation and comparison of human biomarkers of PM exposure and effects (e.g., in cardiac electrophysiology, blood, and sputum assays) will be continued and include intensive statistical analysis of pooled volunteer groups exposed to source-area fine PM with and without co-pollutants, test concentration-response relationships, implementation of new noninvasive measurements of lower respiratory inflammatory response to particle exposure by expired gas analysis, and extension of human exposure studies to fine and ultrafine particles.
Future Activities:
We will conduct human clinical studies at receptor sites, using subject group(s) and size range(s) most likely to show effects. We will relate clinical responses of human volunteers to PM exposures and their genotypic profiles (with gene arrays) to characterize gene-environment interactions.
Through collaboration with other PM Centers, we intend to conduct a meta-analysis of human PM exposure findings here and elsewhere, to increase the power to detect subtle effects. We shall conduct small-panel studies of individuals in source and receptor areas identified as “high risk” by earlier animal and human studies, using any noninvasive measures of response found to be sensitive in earlier controlled exposure studies.
SCPCS will apply the research conducted during Years 3-5 on gene array techniques to relate clinical responses of human volunteers to PM exposures and their genotypic profiles to characterize gene-environment interactions.
Journal Articles:
No journal articles submitted with this report: View all 9 publications for this subprojectSupplemental Keywords:
airborne particulate matter, aerosol, size distribution, particle concentrator, NRC priorities, mechanism, quinones, allergens, bioaerosols, dosimetry, children’s study, indoor exposure, exposure assessment, ultrafine, fine and coarse particles, regional human exposure model, REHEX, asthma, polycyclic aromatic hydrocarbons, PAHs, clinical human exposures, source-receptor, measurement error, study design, susceptible populations, geo-code, toxicology, epidemiology, regional modeling, source/receptor analysis, Southern California, Los Angeles Basin, LAB, photochemistry, meteorology, trajectory modeling, peroxides, Southern California Particle Center and Supersite, SCPCS, air, geographic area, scientific discipline, health, RFA, susceptibility/sensitive population/genetic susceptibility, biology, risk assessments, genetic susceptibility, health risk assessment, atmospheric sciences, biochemistry, particulate matter, mobile sources, state, aerosols, automotive exhaust, epidemiology, exposure assessment, California (CA), environmentally caused disease, engine exhaust, environmental hazard exposures, allergen, indoor air, indoor air quality, allergens, particle concentrator, air quality, diesel exhaust, particulate emissions, toxics, human health effects, particulates, sensitive populations, toxicology, diesel exhaust particles, environmental triggers, air pollution, airway disease, atmospheric chemistry, children, trajectory modeling, automotive emissions, dosimetry, exposure, inhaled particles, motor vehicle emissions, asthma triggers, PM characteristics, ambient aerosol, asthma, human exposure, particle transport,, RFA, Health, Scientific Discipline, Air, Geographic Area, particulate matter, Environmental Chemistry, Health Risk Assessment, State, Risk Assessments, ambient aerosol, asthma, particulates, epidemiology, human health effects, toxicology, airway disease, allergic airway disease, exposure, air pollution, children, PAH, human exposure, particulate exposure, trajectory modeling, California (CA), allergens, indoor air quality, aerosols, atmospheric chemistry, dosimetry, particle transport, particle concentrator, airborne urban contaminants, cardiovascular diseaseRelevant Websites:
http://www.scpcs.ucla.edu Exit
Progress and Final Reports:
Original AbstractMain Center Abstract and Reports:
R827352 Southern California Children's Environmental Health Center Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R827352C001 The Chemical Toxicology of Particulate Matter
R827352C002 Pro-inflammatory and the Pro-oxidative Effects of Diesel Exhaust Particulate in Vivo and in Vitro
R827352C003 Measurement of the “Effective” Surface Area of Ultrafine and Accumulation Mode PM (Pilot Project)
R827352C004 Effect of Exposure to Freeways with Heavy Diesel Traffic and Gasoline Traffic on Asthma Mouse Model
R827352C005 Effects of Exposure to Fine and Ultrafine Concentrated Ambient Particles near a Heavily Trafficked Freeway in Geriatric Rats (Pilot Project)
R827352C006 Relationship Between Ultrafine Particle Size Distribution and Distance From Highways
R827352C007 Exposure to Vehicular Pollutants and Respiratory Health
R827352C008 Traffic Density and Human Reproductive Health
R827352C009 The Role of Quinones, Aldehydes, Polycyclic Aromatic Hydrocarbons, and other Atmospheric Transformation Products on Chronic Health Effects in Children
R827352C010 Novel Method for Measurement of Acrolein in Aerosols
R827352C011 Off-Line Sampling of Exhaled Nitric Oxide in Respiratory Health Surveys
R827352C012 Controlled Human Exposure Studies with Concentrated PM
R827352C013 Particle Size Distributions of Polycyclic Aromatic Hydrocarbons in the LAB
R827352C014 Physical and Chemical Characteristics of PM in the LAB (Source Receptor Study)
R827352C015 Exposure Assessment and Airshed Modeling Applications in Support of SCPC and CHS Projects
R827352C016 Particle Dosimetry
R827352C017 Conduct Research and Monitoring That Contributes to a Better Understanding of the Measurement, Sources, Size Distribution, Chemical Composition, Physical State, Spatial and Temporal Variability, and Health Effects of Suspended PM in the Los Angeles Basin (LAB)
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 Progress Report
- 2003 Progress Report
- 2002 Progress Report
- 2000
- 1999
- Original Abstract
9 journal articles for this subproject
Main Center: R827352
150 publications for this center
149 journal articles for this center