Grantee Research Project Results
2004 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
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, 2003 through May 31, 2004
RFA: Airborne Particulate Matter (PM) Centers (1999) RFA Text | Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air
Objective:
The basic hypotheses of this project are that:
- ambient particles are responsible for short-term cardiopulmonary pulmonary health effects observed epidemiologically in Los Angeles and other urban areas on “highpollution” days;
- specific effects depend on particle size, composition, dosing characteristics, and preexisting health risk factors; and
- these effects can be demonstrated clearly by controlled exposures of volunteers representing “high-risk” segments of the exposed population.
We have used ambient particle concentrators interfaced to exposure chambers to investigate these effects in human volunteers. We have documented effects of fine (PM2.5) and coarse (PM10-2.5) particles, and are currently investigating ultrafine particles (PM0.1) (UFP) in the primary-pollution (coastal) region of Los Angeles.
Volunteer subjects for the current investigation are younger adults, both healthy and with asthma. Older adults, both healthy and with chronic obstructive pulmonary disease (COPD), also have been studied in exposures to PM2.5 exposures, with and without added nitrogen dioxide. No clearly adverse health responses have been observed in any of these exposure studies. However, there have been small changes possibly relevant to epidemiologically-observed morbidity, including altered heart rate variability, decreased arterial blood oxygenation (measured by pulse oximetry), decreases in sputum columnar epithelial cell counts, and changes in blood biochemistry possibly related to coagulopathy and systemic inflammation.
Progress Summary:
New Findings
The target sample size for UFP exposure studies is 32 subjects. Originally it was planned to study 8 healthy and 24 asthmatic volunteers, because asthmatics were expected to be more susceptible but also more variable in their responses. However, initial observations indicated equal or greater response in healthy subjects, so the plan was changed to call for 16 healthy and 16 asthmatic subjects. In Year 6, complete studies have been performed on 9 healthy and 7 asthmatic volunteers. Two additional asthmatic volunteers completed studies begun in Year 5. One additional asthmatic was enrolled but withdrew before completion. To date, a total of 28 subjects (14 healthy, 14 asthmatic) have completed exposure studies with concentrated UFP, as well as sham-control studies with filtered air.
Initial exposures exhibited inconsistent (frequently low) particle counts relative to mass concentration. This was eventually found attributable to a combination of intermittently low output of ultrafine particles from some concentrator modules and leakage of ambient air (containing larger particles) into the exposure chamber. To alleviate these problems, exposures via facemask were adopted in place of whole-body exposures. In an interim analysis including the first 20 completed subjects (6 healthy + 14 asthmatic), the overall mean particle count in UFP exposures was about 140,000/ml and the overall mean mass concentration was about 110 μg/m3. Preliminary analysis of all completed subjects (17 healthy and 14 asthmatic), indicates a small significant (P < 0.01) decline in arterial oxygen saturation as estimated by pulse oximetry (SpO2) was observed (see Figure 1), along with equivocal disturbances of heart rate variability and decreases in forced vital capacity. There was no suggestion of changes in blood pressure, sputum total and differential cell counts related to UFP exposures, but there were small significant changes in forced expired volume in one second (FEV1) and exhaled nitric oxide, of uncertain health implications. Blood samples for biochemical analysis are being stored until completion of the study; they will then be shipped to Dr. Robert Devlin's laboratory at USEPA for analysis.
Figure 1. Graph Illustrates Net Change in Arterial Oxygen Saturation Measured by Pulse Oximetry (SpO2) After Ultrafine Particle (UFP) Exposure Relative to Filtered Air (FA), for all 17 Healthy + 14 Asthmatic Subjects. Overall net loss is significant, P < .01. No significant variation by time of measurement or asthma status.
Future Activities:
Project Plan for Year 6 (Extension)
The current plan is to study 2 additional healthy and 2 additional asthmatic subjects, thus completing the planned experiment, by December 2005. Plans for extending the study to another location (freeway, inland) and/or to other “high-risk” subject groups (e.g., cardiovascular patients) are on hold, as no funds are available for this task in the renewal project. The tentative plan is to apply for funding from the National Institutes of Health to support this proposed work.
At the conclusion of Year 6 exposure studies, our pooled exposure and response data set will include 60 or more individuals with 2-6 studies each, 3 different risk factors (advanced age, asthma, COPD), and 3 different particle size ranges (ultrafine, fine, coarse). Analysis of this pooled data set can potentially identify relationships between health endpoints and exposure factors that are not obvious within data from individual experiments. This will be pursued in collaboration with the SCPCS statistician (Daniel Stram, Ph.D).
Journal Articles:
No journal articles submitted with this report: View all 9 publications for this subprojectSupplemental Keywords:
RFA, Scientific Discipline, Health, 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.