2002 Progress Report: Biomarker Core

EPA Grant Number: R827355C010
Subproject: this is subproject number 010 , established and managed by the Center Director under grant R827355
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Airborne PM - Northwest Research Center for Particulate Air Pollution and Health
Center Director: Koenig, Jane Q.
Title: Biomarker Core
Investigators: Kalman, Dave , Dills, Russell , Katz, Bethany , Paulsen, Michael , Simpson, Chris
Current Investigators: Kalman, Dave , Dills, Russell , Simpson, Chris
Institution: University of Washington
EPA Project Officer: Chung, Serena
Project Period: June 1, 1999 through May 31, 2004 (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

Objective:

The objective of this research project is to develop analytical methods for the determination of organic tracers of woodsmoke, and polycyclic aromatic hydrocarbon (PAH) contribution to particulate matter (PM) in urine and isoprostanes in urine and breath.

Progress Summary:

We completed the development of an assay for the measurement of levoglucosan in PM, and submitted a manuscript describing the method used. We also completed the development of an assay for the measurement of methoxyphenols in PM, and are preparing a manuscript describing the method used.

We validated the use of organic tracers to apportion the woodsmoke contribution to PM. The levoglucosan assay has been applied to approximately 100 IMPROVE filters from Beacon Hill. The analysis of this data set to validate the levoglucosan tracer is underway, and the submission of a manuscript describing this work is expected in June 2003.

Levoglucosan and methoxyphenols have been determined in approximately 700 fixed filters from the Seattle panel study (mainly Year 2 of the project). The interpretation of these data to validate the use of these compounds as woodsmoke tracers is underway, and the submission of a manuscript describing this work is expected in July 2003. One key initial finding is that indoor:outdoor ratios for the woodsmoke tracers are lower than expected based on PM mass. This finding will be further explored in detail.

Validation of a Urinary Biomarker of Exposure to Woodsmoke

To further validate the urinary methoxyphenol biomarker, we recognize the need to analyze samples from subjects with high exposure to biomass smoke. Therefore, we: (1) have designed and obtained human subjects' approval for a managed campfire exposure to woodsmoke; and (2) are developing a sample analysis strategy to be applied to urine and filter samples collected as part of the Pullman agricultural burning to validate the biomarker.

Development of the Dithiothreitol (DTT) Assay as a Measure of the Oxidative Potential of PM Samples

We have begun efforts to implement the DTT assay for measuring the oxidative potential of PM, as described by Art Cho and colleagues at the University of Southern California.

Development of Methods for Measurement of Isoprostanes in Urine and Exhaled Breath Condensate

We have assisted the Center's health core in refining methods for the collection of exhaled breath condensate, and subsequent analysis for F2-isoprostanes by enzyme-linked immunosorbent assay (ELISA). Samples have been collected during the Seattle Panel study (approximately 150 samples) and the New York University panel study (approximately 170 samples). We are involved with the analysis and interpretation of these data. We have completed initial work to implement a high-performance liquid chromatography/mass spectrometry assay for urinary F2-isoprostanes. This assay will be applied to selected urine samples from "responders" and "non-responders" from our various PM Center studies and controlled exposure studies. Henry Gong is collecting urine from concentrated ambient fine particle-exposed asthmatics on our behalf, to be analyzed for F2-isoprostanes.

Future Activities:

Interpretation of Organic Tracer and Biomarker Data. A major effort in the coming year will involve the analysis and interpretation of data from samples already analyzed (primarily Seattle panel study, Years 1 and 2 of the project). This will include the evaluation of the utility of woodsmoke tracer compounds as surrogate measures of the woodsmoke portion of PM in indoor, outdoor, and selected personal samples, and the evaluation of the association of urinary methoxyphenols with woodsmoke and PM exposures.

Biomarker Validation in High-Exposure Settings. Our initial data analysis indicates that woodsmoke levels in Seattle were too low to allow the validation of several aspects of the biomarker, including dose response and pharmacokinetic parameters. Therefore, we will seek to validate the urinary biomarker in higher exposure settings, including: (1), Pullman agricultural burning study; and (2) wildland firefighter cohort.

Continue Validation Efforts Including "Managed Exposure" Studies. We will continue validation efforts, including: (1) managed campfire exposure; and (2) USF smoke chamber study.

Indoor: Outdoor Ratios of Organic Tracers. Initial analysis of woodsmoke tracer ratios indoors versus outdoors suggests a lower than expected indoor:outdoor ratio. This finding will be explored in a more extensive analysis of existing data. If the initial results hold up, we would expand the suite of tracer compounds to include PAHs, and undertake organic chemical analyses on size-fractionated PM samples (either to be collected by ourselves, or obtained from other centers).

Based on Further Discussion With Other PM Investigators, Additional Analysis of Field Study Samples (Atmospheric Tracers, Biomarkers). Analysis of additional personal filters for levoglucosan, and possibly PAHs will be undertaken to fully explore the outdoor > indoor > personal PM > biomarker continuum. Similarly, additional indoor, outdoor, and central-site filters may be analyzed for PAHs to examine the utility of these markers as mobile-source tracers.

Additional filters and urine samples from the Year 3 episodic monitoring study may be extracted and analyzed, if our review of Year 2 sample data indicates that the PM levels experienced in the Year 3 episodes are likely to be sufficiently high to provide useful data. Filter and urine samples associated with specific subjects may be selected for analysis based on health status or responsiveness.

Journal Articles:

No journal articles submitted with this report: View all 19 publications for this subproject

Supplemental Keywords:

air pollution, air pollutants, particulate matter, PM, polycyclic aromatic hydrocarbons, PAHs, isoprostanes in urine, isoprostanes in breath, woodsmoke, organic tracers, methoxyphenols, levoglucosan, Seattle, Washington, WA, indoor exposure, outdoor exposure, biomarker, urinary methoxyphenol biomarker, high biomass smoke, dithiothreitol assay, oxidative potential of PM, ELISA, isoprostanes, health effects, fine particles., RFA, Health, Scientific Discipline, PHYSICAL ASPECTS, Air, ENVIRONMENTAL MANAGEMENT, Geographic Area, particulate matter, Toxicology, air toxics, Environmental Chemistry, Health Risk Assessment, Air Pollutants, Epidemiology, State, Air Pollution Effects, Northwest, Risk Assessments, Susceptibility/Sensitive Population/Genetic Susceptibility, Biochemistry, Physical Processes, genetic susceptability, Atmospheric Sciences, Risk Assessment, biostatistics, health effects, ambient aerosol, particulates, sensitive populations, ambient air quality, morbidity, cardiopulmonary responses, human health effects, exposure and effects, health risks, acute cardiovascular effects, hazardous air pollutants, exposure, epidemelogy, dose-response, air pollution, particle exposure, Human Health Risk Assessment, atmospheric aerosols, ambient particle health effects, mortality studies, cardiopulmonary response, inhalation, human exposure, human susceptibility, mortality, California (CA), biomarker based exposure inference, air quality, particle transport, cardiovascular disease, human health risk, aerosols, atmospheric chemistry, exposure assessment, environmental hazard exposures, toxics

Relevant Websites:

http://depts.washington.edu/pmcenter/ Exit

Progress and Final Reports:

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

  • Main Center Abstract and Reports:

    R827355    Airborne PM - Northwest Research Center for Particulate Air Pollution and Health

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R827355C001 Epidemiologic Study of Particulate Matter and Cardiopulmonary Mortality
    R827355C002 Health Effects
    R827355C003 Personal PM Exposure Assessment
    R827355C004 Characterization of Fine Particulate Matter
    R827355C005 Mechanisms of Toxicity of Particulate Matter Using Transgenic Mouse Strains
    R827355C006 Toxicology Project -- Controlled Exposure Facility
    R827355C007 Health Effects Research Core
    R827355C008 Exposure Core
    R827355C009 Statistics and Data Core
    R827355C010 Biomarker Core
    R827355C011 Oxidation Stress Makers