CENTER FOR AMBIENT PARTICLE HEALTH EFFECTS:
EXPOSURE, SUSCEPTIBILITY, AND BIOLOGICAL MECHANISMS/DOSIMETRY


Proposal by:

Petros Koutrakis, Ph.D. (Center Director), John Godleski, M.D. (Center Co-Director), Joel Schwartz, Ph.D. (Center Co-Director), Douglas W. Dockery, Sc.D., Frank E. Speizer, M.D., Helen H. Suh, Sc.D., Diane R. Gold, M.D., Richard L. Verrier, Ph.D., Akira Tsuda, Ph.D., James Ware, Ph. D., Paul Catalano, Sc.D., John S. Evans, Sc.D., James P. Butler, Ph.D., Lester Kobzik, M.D., Peter Stone, M.D., Jack D. Spengler, Ph.D., Harriet A. Burge, Ph.D, Joseph D. Brain, Ph.D., David Christiani, M.D., Karl Kelsey, M.D., John Graham, Ph.D., and James Hammitt, Ph.D.

Harvard University
School of Public Health


For

United States Environmental Protection Agency
Science to Achieve Results Program
Sorting Code: 98-NCERQA-U1
October 28, 1998 .A. STANDARD FORM 424


ABSTRACT

1. Sorting Code: 98-NCERQA-U1

2. Title: Ambient Particle Health Effects: Exposure, Susceptibility, and Biological Mechanisms/Dosimetry.

3. Investigators: Harvard University: Petros Koutrakis, Ph.D. (Center Director), John J. Godleski, M.D. (Center Co-Director), Joel Schwartz, Ph.D. (Center Co-Director), Douglas W. Dockery, Sc.D., Frank E. Speizer, M.D. , Helen H. Suh, Sc.D., Diane R. Gold, M.D., Richard L. Verrier, Ph.D., James Ware, Ph.D., Paul Catalano, Sc.D. , John S. Evans, Sc.D., James P. Butler, Ph.D., Akira Tsuda, Ph.D., Lester Kobzik, M.D., Peter Stone, M.D., John D. Spengler, Ph.D., Harriet A. Burge, Ph.D., Joseph D. Brain, Ph.D., David Christiani, M.D., John Graham, Ph.D., James Hammitt, Ph.D., and Karl Kelsey, M.D.

4. Project Summary: (a) Objectives: The objective of the Harvard Center is to address key scientific issues regarding the health effects of ambient particles using our rich foundation of ongoing research and expertise.

(b) Approach: The specific aims of the Center reflect the National Research Council's research priorities for ambient particle research (NRC, 1998). To address these aims, our Center will focus upon three research themes: (I) Exposure, (II) Susceptibility, and (III) Biological Mechanisms/Dosimetry. Each theme will encompass a series of highly integrated and interdisciplinary research projects. The proposed research will be performed by a group of scientists which has worked together for many years and has expertise in a variety of fields, including particle chemistry, exposure and risk assessment, environmental epidemiology, cardiac and pulmonary health, toxicology, physiology, biostatistics, dosimetry, public policy, indoor air pollution and air microbiology.

Theme I will investigate human exposures to particles and gaseous co-pollutants in order to differentiate the health effects of particles from outdoor and indoor sources. This theme also will quantify the effect of exposure error for fine particles and their co-pollutants on risk estimates from epidemiological studies. Theme II will identify individuals who are sensitive to the effects of air pollution and will measure the effect of chronic exposure on the development of chronic diseases. Theme III will identify the particulate characteristics and gaseous air pollutants that trigger adverse health effects and will define the biological mechanisms that may lead to fatal outcomes.

Theme I includes three projects that are based on data from our previous and ongoing exposure studies conducted in a variety of U.S. cities (Boston, Atlanta, Baltimore, and Los Angeles). Project Ia is intended to characterize the particulate and gaseous exposures of healthy and susceptible cohorts as a function of climate, cohort, home characteristics, and activity patterns. It will also identify factors affecting the relationship between personal exposures and outdoor concentrations. Project Ib will quantify the effect of measurement error for fine particles and their co-pollutants (coarse mass and the criteria gases) on risk estimates from epidemiological studies. Project Ic will differentiate the health effects of particles from indoor and outdoor sources.

Theme II includes four projects which will be based on data and methods from our ongoing epidemiological studies. Project IIa is a prospective cohort study that uses the Medicare database and the National Death Index to identify populations which are susceptible to particulate and gaseous air pollutants. The cities included in the initial phase of this study are: Boston, New Haven, Chicago, Utah County, Salt Lake, Minneapolis-St. Paul, and Spokane. Project IIb will use innovative analytical methods to examine whether particles advance mortality by a few days (harvesting) or have a more profound impact on public health. Project IIc will assess the chronic effects of air pollution exposure by extending follow up of adults in the Six Cities Study up to twenty-four years. Project IId will assess the chemical characteristics of particles associated with respiratory illness and lower lung function in children in 29 North American Cities.

Theme III includes three projects which aim to identify the particulate and gaseous air pollutants responsible for increased cardiac vulnerability as an adverse health effect and to define the biological mechanisms that lead to this outcome. Using our dog model of coronary occlusion with exposures to concentrated ambient particles, Project IIIa will explore the role of particle size (coarse, fine, and ultrafine), particle composition (metals, ions, and carbon), and criteria gases (O3, NO2, CO, and SO2) on cardiac and respiratory health (Project IIIa). Project IIIa will also use pharmacological intervention to explore biological mechanisms by which particles accelerate and increase sensitivity to the ischemic response, examining both autonomic nervous system and inflammatory mechanisms (Project IIIa). Project IIIb will determine in situ particle doses during the inhalation studies using online measurements of particle number and size in the inhaled and exhaled air. This will enable us to provide a better interpretation of the observed outcomes and to examine the role of particle composition, gaseous co-pollutants, and susceptibility on particle deposition. Project IIIc, a human panel study, will be performed concurrent with these animal inhalation projects. It will investigate the effects of particle mass, composition, and gaseous co- pollutants on blood viscosity, other clotting parameters, and cardiac health of individuals living in the Boston Metropolitan area. Results from this project will be integrated with results from laboratory studies to better our understanding of the role of particle composition and gaseous co-pollutants and biological mechanisms.

Collectively, our proposed projects will address eight out of the ten research priorities included in the NRC report. Our research agenda may be redirected to respond to future research needs by refocusing existing or developing new projects. This will be accomplished by using a multi-step process described in the Research Coordination and Integration Core. Finally, we have included a Technology Core that focuses on the development and transfer of technologies, such as particle generation systems for inhalation studies, personal exposure monitors, statistical tools to analyze data from particle epidemiological studies, and software to process cardiac function data. One of the objectives of our Center is to coordinate research activities and to exchange methods and technologies with the other particle Centers.

(c,d) Expected Results/Public Policy: Existing data and resources will be utilized in order to obtain the most relevant and essential scientific information. Since each of the Center's projects will leverage existing research conducted by Center investigators, the projects will be comprehensive, cost-effective, and innovative. The inter-disciplinary nature of the Center will enable us to integrate findings from a variety of studies as they emerge and, combined with structured methods to evaluate research needs and priorities, will allow the Center to remain flexible and at the forefront of the health effects research on particles. Findings from the Center will have important ramifications to environmental policy and control. Our findings will improve our ability to set appropriate and effective air quality standards for particulate matter. It will help us determine the relevant particle parameter and the appropriate level to regulate. These gains will, in turn, allow effective particle control strategies to be determined and will ensure the protection of public health from particle exposures.

5. Key Words: ambient particles, exposure, health effects, susceptibility, metals, public policy, biology, engineering, epidemiology, toxicology, environmental chemistry, monitoring.