Final Report: Controlled Human Exposure Studies with Concentrated PM

EPA Grant Number: R827352C012
Subproject: 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 Particle Center and Supersite
Center Director: Froines, John R.
Title: Controlled Human Exposure Studies with Concentrated PM
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)
RFA: Airborne Particulate Matter (PM) Centers (1999) RFA Text |  Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air

Objective:

Topic C: Studies of the Effects of Varying Spatial and Temporal Patterns of Ambient Particulate Matter (PM) and Co-pollutants and Resulting Health Effects with Emphasis on the Role of Atmospheric Chemistry

Ambient particle concentrators were used to expose human volunteers to fine particles (F), coarse particles (C), and ultrafine particles (UF) to simulate severe particulate pollution episodes in a metropolitan area of Los Angeles. Volunteer subjects were exposed for two hour periods with intermittent exercise. Similar exposures to filtered air on separate occasions served as controls. Acute health responses were assessed by measuring multiple indices of cardiac electrophysiology, pulmonary mechanics, airway and systemic inflammation, and blood coagulation properties. For any given study, most of these endpoints showed little significant change attributable to exposure to particulate pollution. In each study, a few endpoints did show statistically significant changes consistent with unfavorable effects (predominantly in the cardiovascular system). Given the short duration of exposure, exposure levels within ambient range, and practical limitations on the number of study subjects, it is of note that we were able to detect changes consistent with cardiovascular effects of PM.

The initial study, funded primarily from the Health Effects Institute, included healthy and asthmatic adult volunteers (age 50 or below) exposed to concentrated F. The mean exposure concentration was close to the target concentration of 200 μg/m3. Slight or equivocal responses were observed, including alteration of epithelial cell counts in induced sputum in exposed subjects. Individual exposure to particle sulfate was associated with decreasing respiratory rate and minute volume during exposure, and decreased forced expiratory function post-exposure, although the overall difference in respiratory function between exposed and control subjects at the group level was non-significant. Heart rate variability data suggested a slight increase in parasympathetic influence on the heart during or after PM exposure, while sympathetic influence was unchanged or slightly decreased.

During the next stage, funded primarily by the Southern California Particle Center and Supersite (SCPCS), we evaluated short term health responses in elderly adult volunteers with and without chronic obstructive pulmonary disease (COPD). Exposure conditions were similar to the previous study. No significant effects on lung function, symptom reports, or airway inflammation were observed, but some acute cardiopulmonary responses to PM were noted. Unexpectedly, alterations were more pronounced in healthy individuals than those with COPD. A significant negative effect of exposure on arterial oxygenation measured by pulse oximetry occurred immediately post exposure in healthy subjects. Heart rate variability was lower after exposure in healthy but not COPD subjects, a finding that would have implications for cardiovascular morbidity and mortality if confirmed in a larger population. In a parallel U.S. Environmental Protection Agency (EPA) Science To Achieve Results (STAR) project, exposures to 0.4 ppm NO2 and to NO2 plus PM2.5 were added. Addition of NO2 did not increase the responses, and again, the slight statistically significant responses were more apparent in healthy subjects.

In the subsequent study, healthy and asthmatic adult volunteers were exposed to concentrated C. The target concentration of C was 200 μg/m3 and the actual mean exposure concentration was 157 μg/m3. Slight, but statistically significant increases in heart rate and decreases in heart rate variability were associated with these exposures. No excess cardiac ectopy, lung function disturbances, or indications of airway inflammation were found.

Finally, healthy and asthmatic adult volunteers were exposed to concentrated UF. The target exposure level was 200,000 particles/ml; the actual mean particle count was 145,000 particles/ml. These exposures were associated with a small significant decrease in arterial oxygen saturation, a slight decline in forced expiratory function measured 24 hr later, and a transient decrease in low-frequency (sympathetic) heart rate variability during rest.

Summary/Accomplishments (Outputs/Outcomes):

This series of exposure studies with different size fractions of ambient particulate pollution in Los Angeles has demonstrated that such controlled human exposures are feasible, safe, and can yield helpful information about the pathophysiology and mechanisms of PM-related health effects. The various changes in cardiovascular status, especially heart rate variability, that were statistically significant in these small groups of subjects are consistent with epidemiologic findings that associate urban particulate pollution with morbidity and mortality. On the other hand, minimal respiratory effects were detected. Limitations that might explain the difficulty in detection of positive findings include the brief experimental exposures, small self-selected groups of subjects, secondary stresses associated with particle concentrator and exposure chamber operation, and inability to control subjects’ ambient exposures outside of the experimental observation period.

Technical Report:

Full Final Technical Report (PDF, 6pp., 33.7KB, about PDF)


Journal Articles on this Report : 9 Displayed | Download in RIS Format

Other subproject views: All 9 publications 9 publications in selected types All 9 journal articles
Other center views: All 150 publications 149 publications in selected types All 149 journal articles
Type Citation Sub Project Document Sources
Journal Article Gong Jr. H, Sioutas C, Linn WS, Clark KW, Terrell SL, Terrell LL, Anderson KR, Kim S, Chang M-C. Controlled human exposures to concentrated ambient fine particles in metropolitan Los Angeles:methodology and preliminary health-effect findings. Inhalation Toxicology 2000;12(Suppl 1):107-119. R827352 (2004)
R827352 (Final)
R827352C012 (Final)
R827352C014 (Final)
R826708 (2000)
R826708 (2001)
R826708 (2002)
R826708 (Final)
  • Abstract: Taylor and Francis-Abstract
    Exit
  • Journal Article Gong Jr. H, Linn WS, Sioutas C, Terrell SL, Clark KW, Anderson KR, Terrell LL. Controlled exposures of healthy and asthmatic volunteers to concentrated ambient fine particles in Los Angeles. Inhalation Toxicology 2003;15(4):305-325. R827352 (2004)
    R827352 (Final)
    R827352C012 (Final)
    R827352C014 (Final)
    R831861 (2005)
  • Abstract from PubMed
  • Abstract: Taylor and Francis-Abstract
    Exit
  • Journal Article Gong Jr. H, Linn WS, Terrell SL, Clark KW, Geller MD, Anderson KR, Cascio WE, Sioutas C. Altered heart-rate variability in asthmatic and healthy volunteers exposed to concentrated ambient coarse particles. Inhalation Toxicology 2004;16(6-7):335-343. R827352 (2004)
    R827352 (Final)
    R827352C012 (Final)
    R827352C014 (Final)
    R834797 (2016)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Abstract: Taylor and Francis-Abstract
    Exit
  • Journal Article Gong Jr. H, Linn WS, Terrell SL, Anderson KR, Clark KW, Sioutas C, Cascio WE, Alexis N, Devlin RB. Exposures of elderly volunteers with and without chronic obstructive pulmonary disease (COPD) to concentrated ambient fine particulate pollution. Inhalation Toxicology 2004;16(11-12):731-744. R827352 (2004)
    R827352 (Final)
    R827352C012 (Final)
    R827352C014 (Final)
    R827999 (Final)
    R831861 (2005)
  • Abstract from PubMed
  • Abstract: Taylor and Francis-Abstract
    Exit
  • Journal Article Gong Jr. H, Linn WS, Clark KW, Anderson KR, Geller MD, Sioutas C. Respiratory responses to exposures with fine particulates and nitrogen dioxide in the elderly with and without COPD. Inhalation Toxicology 2005;17(3):123-132. R827352 (Final)
    R827352C012 (Final)
    R827352C014 (Final)
    R826708 (Final)
    R827999 (Final)
    R831861 (2005)
  • Abstract from PubMed
  • Full-text: University of Southern California-Full Text PDF
    Exit
  • Abstract: Taylor and Francis-Abstract
    Exit
  • Journal Article Kim S, Sioutas C, Chang M-C, Gong Jr. H. Factors affecting the stability of the performance of ambient fine-particle concentrators. Inhalation Toxicology 2000;12(Suppl 4):281-298. R827352 (2004)
    R827352 (Final)
    R827352C012 (Final)
    R827352C014 (Final)
    R825513C024 (Final)
    R826708 (2000)
    R826708 (2001)
    R826708 (2002)
    R826708 (Final)
    R828598 (Final)
    R828598C700 (Final)
  • Abstract from PubMed
  • Abstract: Taylor and Francis-Abstract
    Exit
  • Journal Article Linn WS, Szlachcic Y, Gong Jr. H, Kinney PL, Berhane KT. Air pollution and daily hospital admissions in metropolitan Los Angeles. Environmental Health Perspectives 2000;108(5):427-434. R827352 (2004)
    R827352 (Final)
    R827352C012 (Final)
    R826708 (2000)
    R826708 (2001)
    R826708 (2002)
    R826708 (Final)
    R826708C001 (2000)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Journal Article Linn WS, Avila M, Gong H Jr. Exhaled nitric oxide: sources of error in offline measurement. Archives of Environmental Health 2004;59(8):385-391. R827352 (Final)
    R827352C011 (Final)
    R827352C012 (Final)
    R831861 (2005)
    R831861 (Final)
    R831861C001 (Final)
    R831861C002 (Final)
    R831861C003 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Abstract: AEH-Abstract
    Exit
  • Journal Article Sioutas C, Kim S, Chang M, Terrell LL, Gong Jr. H. Field evaluation of a modified DataRAM MIE scattering monitor for real-time PM2.5 mass concentration measurements. Atmospheric Environment 2000;34(28):4829-4838. R827352 (Final)
    R827352C012 (Final)
    R827352C014 (Final)
    R826708 (2000)
    R826708 (2001)
    R826708 (2002)
    R826708 (Final)
  • Full-text: ScienceDirect-Full Text HTML
    Exit
  • Abstract: ScienceDirect-Abstract
    Exit
  • Other: ScienceDirect-Full Text PDF
    Exit
  • Supplemental Keywords:

    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 disease

    Relevant Websites:

    Full Final Technical Report (PDF, 6pp., 33.7KB, about PDF)
    http://www.scpcs.ucla.edu Exit

    Progress and Final Reports:

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

  • Main Center Abstract and Reports:

    R827352    Southern California Particle Center and Supersite

    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)