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Research Priorities for Airborne Particulate Matter: III. Early Research Progress (2001)

Chapter: 3. Review of Research Progress and Status

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Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

3

Review of Research Progress and Status

INTRODUCTION

In this chapter, the committee reviews the progress made in implementing the particulate-matter (PM) research portfolio over the period from 1998 (the year in which the portfolio was first recommended by the committee) to the middle of 2000. Because that period represents the initial stage of the PM research program, the committee's assessment necessarily focused more on continuing and planned research projects than on published results.

For each of the 10 topics in the research portfolio, the committee first characterizes the status of relevant research and progress, including the approximate numbers of studies in progress on various subtopics (the committee did not attempt to list all relevant research projects but did attempt to capture the major studies across the spectrum of the research in progress), then considers the adequacy of the current research in addressing specific needs as identified in its first two reports, and finally applies the first three evaluation criteria discussed in Chapter 2: scientific value, decisionmaking value, and feasibility and timing. The remaining three criteria—largely cross-cutting—are considered in more general terms in Chapter 4. The committee's next report, due near the end 2002, will consider research in relation to these criteria in more detail.

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

RESEARCH TOPIC 1. OUTDOOR MEASURES VERSUS ACTUAL HUMAN EXPOSURES

What are the quantitative relationships between concentrations of particulate matter and gaseous copollutants measured at stationary outdoor air-monitoring sites and the contributions of these concentrations to actual personal exposures, especially for subpopulations and individuals?

In its first report (NRC 1998), the committee recommended that information be obtained on relationships between total personal exposures and outdoor concentrations of PM. Specifically, the committee recommended longitudinal panel studies, in which groups of 10-40 persons would be studied at successive times to examine the relationship between their exposures to PM and the corresponding outdoor concentrations. The studies were intended to focus not only on the general population, but also on subpopulations that could be susceptible1 to the effects of PM exposures, such as the elderly, children, and persons with respiratory or cardiovascular disease. It was recommended that some of the exposure studies include measurements of PM with an aerodynamic diameter of 2.5 µm or less (PM2.5), PM with an aerodynamic diameter of 10 µm or less (PM10), and gaseous copollutants. It was expected that the investigations would quantify the contribution of outdoor sources to personal and indoor exposures. The design and execution of studies were to take about 3 years, and the suggestion was made to conduct the studies at various geographical locations in different seasons.

Research Progress and Status

Substantial research is in progress, and some studies, started before the committee's first report, have been completed. Results of

1  

The committee is aware that there are several definitions of “susceptibility” (Parkin and Balbus 2000). in using the term in this report, the committee refers to an increased risk at a particular exposure that is greater for susceptible people than for healthy people.

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

recent panel studies of personal exposure conducted in Wageningen, Netherlands (Janssen et al. 1999), Boston, MA (Rojas-Bracho et al. 2000), Baltimore, MD (Sarnat 2000; Williams et al. 2000), and other places suggest that 12-15 measurements per person are sufficient to examine relationships between personal exposures and outdoor PM concentrations. These longitudinal panel studies have increased the understanding of the relationships between personal exposures and outdoor concentrations more than did earlier cross-sectional exposure studies. Several additional longitudinal panel studies are going on in other U.S. cities, including New York, NY; Atlanta, GA; Los Angeles, CA; Research Triangle Park, NC; and Seattle, WA. A number of research and funding organizations—including academic institutions, the U.S. Environmental Protection Agency (EPA), the Health Effects Institute (HEI), the Electric Power Research Institute (EPRI), and the American Petroleum Institute (API)—already have been engaged in this effort. Collectively, the studies should provide an understanding of the relationships between personal exposures and outdoor pollutant concentrations in a large number of geographic areas in the United States.

Several insights have been gained from the results of completed studies (Janssen et al. 1999, 2000; Ebelt et al. 2000; Rojas-Bracho et al. 2000; Sarnat et al. 2000; Williams et al. 2000). These studies have observed significant differences among study participants in the relationship between personal exposures and outdoor concentrations. When such relationships were analyzed for each person, substantial variability was found. Because outdoor concentrations exhibited little spatial variability, the heterogeneity was attributed to differences in indoor concentrations. Indeed, indoor concentrations were found to be an excellent predictor of personal exposures for most study participants, independently of city (Baltimore or Boston), season (winter or summer), and panel (elderly; chronic obstructive pulmonary disease, or COPD; or children). The finding that indoor concentration is an excellent predictor of personal exposure is not surprising, in that people spend more than 80% of their time indoors (EPA 1996a). Apart from exposures to tobacco smoke and emissions from cooking, which produce long-term increases in PM exposures of around 30 µg/m3 (Spengler et al. 1981) and 15-20 µg/m3 (Ozkaynak 1996), respectively,

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

home activities that were expected to produce particles, such as vacuum-cleaning and dusting (EPA 1996; Ozkaynak 1996), were found to explain very little of the total variability in personal exposures (Rojas-Bracho et al. 2000). In general, indoor sources tend to operate intermittently and, when measured by continuous monitors, can produce indoor concentrations as high as several hundred micrograms per cubic meter (Abt et al. 2000). The impact of these indoor (or other microenvironmental) peak concentrations can be captured only by real-time or semicontinuous personal monitors (Howard-Reed et al. 2000). However, when such short-term increases in concentration are averaged, their contributions to the average 24-hr indoor concentrations or personal exposures are estimated to be small.

Analyses of data from the study of elderly people in Baltimore (Sarnat et al. 2000) and the study of COPD patients in Boston (Rojas-Bracho et al. 2000) have demonstrated that ventilation (rate of exchange of indoor with outdoor air) is the measure that most strongly influences the relationship of personal-exposure to outdoor concentration. Personal exposure data were classified into three groups based on reported home ventilation status, a surrogate for the rate of exchange of indoor with outdoor air. Homes were classified as “well,” “moderately,” or “poorly” ventilated, as defined by the distribution of the fraction of time that windows were open while a person was in an indoor environment. When the PM datasets were stratified into these ventilation groups and analyzed cross-sectionally, strong relationships between personal exposures and outdoor concentrations were observed for well-ventilated homes and, to a lesser extent, for moderately ventilated homes. However, a low correlation coefficient was found for the poorly ventilated homes. Those findings suggest that for homes with no smokers and little cooking activity most of the variability in indoor concentrations, as well as in personal exposures of occupants, is due to the varied impact of outdoor sources on the indoor environment. That effect is underscored by the influence of air-exchange rates on the relationship between indoor and outdoor concentrations when no activities are occurring in the homes. For instance, for well-ventilated homes, indoor-to-outdoor particle ratios are close to 1.0, whereas for homes with low rates of exchange and

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

no activities, indoor-to-outdoor ratios can be substantially lower (about 0.4-0.6) (Abt et al. 2000; Long et al. 2000).

Home ventilation rates are expected to vary with season, geographical location, and home characteristics; that implies that the relationship of human exposures to outdoor PM concentrations will also vary with these factors. Therefore, PM risk relationships estimated from epidemiological studies might differ by city, season, and overall home characteristics. However, the additional influence of personal activity patterns on the overall relationship between human exposure and outdoor PM concentrations is also relevant to interpretation of the results of observational studies. The pattern of reported findings is still based on a small number of studies, and replication of the results will be needed from current or recently completed studies in other cities before firm conclusions can be drawn.

Adequacy of Current Research in Addressing Research Needs

Considerable effort is going into examining the relationship between ambient particle concentrations and personal exposures. Several longitudinal panel studies are being conducted in various geographic locations, including New York, NY; Atlanta, GA; Los Angeles and Fresno, CA; and Seattle, WA (see Table 3.1). Collectively, these studies are assessing exposures of healthy subjects and susceptible subpopulations (such as those with COPD; myocardial infarction, or MI; or asthma) to PM and some gaseous copollutants (such as ozone, sulfur dioxide, and nitrogen dioxide). The studies are expected to greatly expand the database on personal exposures, indoor and outdoor concentrations, human activities, and home characteristics. They are also expected to improve understanding of factors that influence the relationship between ambient concentrations and personal exposures. Therefore, as new information from the panel studies accumulates, it appears that, in spite of the time needed to initiate them, many of the elements of research topic 1 are being addressed. Most of the studies have not been completed; their findings are expected to appear in the peer-reviewed literature in the next several years.

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

TABLE 3.1 Current Studies Relevant to ResearchTopic 1

Funding Agencya

Research Groupb

Location

Proposed Cohortc

EPA

New York University

New York, NY

Anaheim, CA

Seattle, WA

16 asthmatic, 16 COPD

16 asthmatic, 16 COPD

16 asthmatic, 16 COPD

EPRI and API

Harvard University

Nashville, TN

Boston, MA

10 COPD

18 COPD

EPA

University of Washington

Seattle, WAd

48 COPD and elderly

48 COPD and elderly

48 MI

48 MI

24 COPD and elderly, 24 MI

25 COPD and elderly, 24 MI

EPRI and API

Harvard University

Baltimore, MDd

15 elderly

HEI and Mickey Leland

EOHSI, UMDNJ, and Rutgers University

Elizabeth, NJ

Houston, TX

Los Angeles, CA

50 healthy adults

50 healthy adults

50 healthy adults

HEI

Harvard University

Baltimore, MDd

Baltimore, MDd

Boston, MAd

15 children

15 COPD, 15 children

15 children, 15 elderly

EPA and EPRI,e

Harvard University

Boston, MAd

15 MI, 15 MI spouses

15 healthy adults

CARBf

Emory University

Rutgers University and UMDNJ

Atlanta, GAd

Los Angeles, CAd

15 COPD

15 COPD

EPA

EPA and RTI

Baltimore, MD

Fresno, CA

Fresno, CA

15 elderly

5 elderly

60 elderly

EPAg

EPA and RTI

Research Triangle Park, NC

15 MI, 15 low-SES healthy adults

CARB

University of California, Berkeley

Fresno, CAh

25 asthmatic children

CARB and EPA (planned)

Harvard University, Rutgers University, and IES

Los Angeles, CAd

16 healthy adults (nonsmoking)

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

HEI

Wagenigen University

Helsinki, Finland and Amsterdam, Netherlands

50 healthy adults

DOE,

OCDO,

EPRI,

API, and EPA

Harvard University and CONSOL Energy Inc.

Steubenville, OH d

25 elderly

15 children

EPRI and EPA

Harvard University and Washington University

St. Louis, MO

Not determined

a  

API = American Petroleum Institute

CARB = California Air Resources Board

DOE = U.S. Department of Energy

EPA = U.S. Environmental Protection Agency

EPRI = Electric Power Research Institute

HEI = Health Effects Institute

Mickey Leland = Mickey Leland National Urban Air Toxics Research Center

OCDO = Ohio Coal Development Office

b  

EOHSI = Environmental and Occupational Health Sciences Institute

IES = Integrated Environmental Sciences

UMDNJ = University of Medicine and Dentistry-New Jersey

RTI = Research Triangle Institute

c   COPD = chronic obstructive pulmonary disease

MI = myocardial infarction

SES = socioeconomic status

d   Copollutants (NO2, O3) also measured

e   Funding for Atlanta panel study to be provided by EPRI

f   Cofunding for Los Angeles panel provided by CARB

g   Information is preliminary

h   Copollutants (CO, O3, SO2, NO2) also measured

Many of the recently completed and current studies examine the relationship between ambient concentrations of gaseous pollutants and personal exposures. Understanding that relationship will provide profiles of multipollutant exposures that can inform understanding of research topic 7 (combined effects of PM and gaseous pollutants). In

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

addition, understanding of differences between personal exposure and ambient concentrations for a suite of gaseous pollutants and PM will provide input into analyses of measurement error in a multi-pollutant context (see research topic 10, analysis and measurement).

Application of Evaluation Criteria
Scientific Value

The current panel exposure studies are straightforward and have expanded on findings from previous investigations. They have used well-established research tools for conducting personal and micro-environmental measurements. They have also relied on field protocols developed as part of previous exposure studies, (such as the Particle Total Exposure Assessment Methodology (PTEAM) study (Pellizzari et al. 1993). The studies are generally designed to assess the range of exposures including those that occur in the home, in the workplace, and while traveling. To a large extent, the scientific value of these investigations will be judged by the appropriateness of their design. It appears that the study designs, (such as repeated measurements of a small number of people) can adequately address the scientific questions in research topic 1.

Completed studies have indicated key factors that influence outdoor-personal relationships. Preliminary results suggest that for homes with no smokers and little cooking activity, home ventilation rate (or air-exchange rate) is the most important modifier of personal exposure. To a great extent, ventilation rate controls the impact of both outdoor and indoor sources on the indoor environment, where people spend most of their time. If correct, this observation implies that such entities as home characteristics, season, and location could be more important determinants of personal exposure than activities and type of susceptible subpopulation studied.

The panel studies will also produce a large set of data on human activities and home characteristics. These data will substantially enrich the existing information and will be available to other researchers

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

involved in human-exposure assessment investigations (such as EPA 's National Human Exposure Assessment Survey).

Decisionmaking Value

Exposure assessment is of paramount importance for understanding the effects of ambient particles and for developing cost-effective exposure-control strategies. The current studies should allow the scientific community and decisionmakers to understand the factors that affect the relationship between personal exposure and outdoor concentrations. That will be accomplished through the continued development of personal-exposure monitoring tools that allow a better understanding of the sources of exposure, physical and chemical properties of PM, and sampling durations that could be relevant to the subpopulations being studied. Although the panel studies are based on small numbers of participants (10-50 per panel), they are addressing factors that influence relationships between outdoor air and personal exposures. This is the first step in attempts to develop a comprehensive exposure model, which is a key research tool in the source-exposure-dose-response paradigm.

Feasibility and Timing

Sampling and analytical procedures, time-activity questionnaires, and other related methods necessary for conducting the panel studies have been adequately tested. They have been implemented successfully in various geographical locations by various research groups (such as Janssen et al. 1999, 2000; Ebelt et al. 2000; Rojas-Bracho et al. 2000; Sarnat et al. 2000; Williams et al. 2000). Therefore, it is expected that the current longitudinal panel studies will be completed without great difficulty. Although there was some delay in initiating some of the studies, abundant personal and microenvironmental measurements have been collected. Reporting of results from research related to this topic began during the summer of 2000, and the re-

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

maining studies should be reported.within about 2 years, a year later than originally planned.

RESEARCH TOPIC 2. EXPOSURES OF SUSCEPTIBLE SUBPOPULATIONS TO TOXIC PARTICULATE-MATTER COMPONENTS

What are the exposures to biologically important constituents and specific characteristics of particulate matter that cause responses in potentially susceptible subpopulations and the general population?

The committee recommended that after obtaining and interpreting results of studies from research topic 1 human exposure-assessment studies examine exposures to specific chemical constituents of PM considered relevant to health effects. To make research topic 2 investigations more practicable, it will be necessary to characterize susceptible subpopulations more fully, identify toxicologically important chemical constituents or particle-size fractions, develop and field-test exposure-measurement techniques for relevant properties of PM, and design comprehensive studies to determine population exposures.

Methods of measuring personal exposures to particles of various physical properties (such as particle number and size) or chemical properties (such as sulfate, nitrate, carbon, and other elements) are available and are being field-tested. Methods of measuring personal exposures to some gaseous copollutants—such as ozone, nitrogen dioxide, and sulfur dioxide—are also used. As interest in personal-exposure measurements increases, new sampling and analytical techniques will probably emerge.

The results of the longitudinal panel studies discussed under research topic 1 should facilitate the design of cost-effective protocols for future exposure studies that focus on PM components considered in determining toxicity. These studies will be based on toxicity and epidemiological studies that are successful in identifying particle properties of interest over the next few years; because they will prob-

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

ably not get under way for several years, the committee is planning to evaluate their progress in its next report.

RESEARCH TOPIC 3. CHARACTERIZATION OF EMISSION SOURCES

What are the size distribution, chemical composition, and mass-emission rates of particulate matter emitted from the collection of primary-particle sources in the United States, and what are the emissions of reactive gases that lead to secondary particle formation through atmospheric chemical reactions?

In its second report, the committee created a separate set of research recommendations that address measurement of the size distribution and chemical composition of PM emissions from sources. Characterization of the emission rates of reactive gases that can form particles on reaction in the atmosphere was also emphasized, including the need to maintain emission data on sulfur oxides, nitrogen oxides, ammonia, and volatile organic compounds (VOCs) (specifically those components that lead to particle formation).

The committee noted that traditional emission inventories have focused on representing PM mass emissions summed over all particles smaller than a given size, without detailed accounting of the particle-size distribution or chemical composition. Health-effects research recommended by the committee emphasized identification of the specific chemical components or size characteristics of the particles that are most directly related to the biological mechanisms that lead to the health effects of airborne particles. Detailed information on the size and composition of particle emissions from sources is important for this process of hazard identification and effective regulation. In the near term, toxicologists and epidemiologists need to know the size and composition of particles emitted from key emission sources to form hypotheses about the importance of particle characteristics and to give priority to their evaluation in laboratory- and field-based health-effects studies. In the longer term, detailed information on

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

particle size and composition will be needed for the design of effective air-quality control programs if those programs become more precisely targeted at the most biologically active components of the atmospheric particle mixture.

Detailed data on the particle size distribution and chemical composition of emissions from sources are also needed to support the application and evaluation of air-quality models that relate source emissions to ambient-air pollutant concentrations and chemical composition. These models are central to the process of evaluating emission-control strategies in advance of their adoption. Source-oriented models for particle transport and new particle formation can require detailed data on particle size and composition for use in condensation-evaporation calculations. Chemical mass-balance (CMB) receptor-oriented air-quality models determine source contributions to ambient particle concentrations by computing the best-fit linear combination of source chemical-composition profiles needed to reconstruct the chemical composition of atmospheric samples. These CMB models inherently require the use of accurate data on the chemical composition of particle emissions at their source. Finally, emissions data on particle chemical composition and size will be needed in the future to support detailed studies of air-quality model performance. Even when the regulated pollutant is fine-particle mass, assurances are needed that air-quality models are getting the right answers for the right reasons. Model-evaluation studies conducted in a way that tests a model's ability to account for ambient particle size and chemical composition can be used to confirm that the model has arrived at agreement between the predicted and observed mass-concentration values for the correct reasons.

In light of those needs for data on the size and chemical composition of particle emissions from sources, the committee's second report outlined the following set of research needs: establish standard source-test methods for measurement of particle size and chemical composition, characterize primary particle size and composition of emissions from the most important sources, develop new measurement methods and use of data to characterize sources of gas-phase ammonia and semivolatile organic vapors, and translate new source-

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

test procedures and source-test data into comprehensive national emission inventories.

Research Progress and Status
Establish Standard Source-Test Methods for Measurement of Particle Size and Chemical Composition

Research into the establishment of new source-test methods for measurement of fine- particle chemical composition is under way at EPA. A dilution source sampler for measurement of emissions from stationary sources has been built and tested. It permits measurement of particle size distributions and elemental carbon, organic carbon, speciated organic compounds, inorganic ions, and trace elements. The inorganic ions typically would include sulfates, nitrates, ammonium, and chlorides. Catalytic trace metals are included among the more than 30 trace elements that will be measured. These measurements are aligned with many of the potentially hazardous characteristics of the particles that have been identified by the committee and include determination of size-fractionated PM mass, PM surface area, PM number concentration, transition metals, soot, polycyclic aromatic hydrocarbons (PAHs), sulfates, nitrates, and some copollutants. It is not clear whether plans are being made to measure strong acids, bioaerosols, peroxides, or free radicals, which constitute other categories of concern to the health-effects community in determining the toxicity of particles. The methods being developed can be used to collect data on volatile and semivolatile organic vapor emissions and could be adapted to measure ammonia emissions. Methods for dilution source sampling of diesel exhaust particles are also under development.

EPA has conducted field tests of these advanced emission-measurement methods for open biomass burning, residential wood stoves, heavy-duty diesel trucks, and small oil-fired boilers. Construction dust emissions have also been measured. Plans for the near future include measurement of PM emissions from diesel trucks, wood-

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

fired boilers, large residual oil-fired boilers, jet aircraft engines, and coal-fired boilers. In addition, dilution source sampling to determine particle size and composition by comparable methods is being supported by EPA through the Science to Achieve Results (STAR) grants program (biomass smoke), American Petroleum Institute (API) (petroleum-refinery processes), the Coordinating Research Council or CRC (diesel trucks), the California Air Resources Board, the National Park Service (NPS), the Department of Defense (motor vehicles, boilers, and so on), and the Department of Energy.

Those dilution source-sampling methods have been developed for research purposes and are being used to gather data to prepare accurate emission inventories. However, the new methods have not yet replaced earlier methods for testing to establish and enforce emission limits. EPA 's Office of Air and Radiation (OAR) is evaluating a dilution-based source-testing procedure for PM2.5 compliance source-testing that might be proposed in the 2002 Federal Register.

Characterize Primary Particle Size and Composition of Emissions

In its second report, the committee advised EPA that development of new source-test methods would probably require substantial attention during FY 2000 and 2001. It was suggested that the new methods be used to characterize a larger number of sources over a 5-year period, beginning in FY 2002, because this information will be needed to revise the nation's emission inventories. EPA's method-development effort is well under way as recommended, but it is too early to expect large-scale application of the new methods.

In the course of development and testing of the new source-measurement methods, emissions from about six important source types have been characterized by EPA according to their particle size distributions and chemical composition, and another six will be characterized in the near future. Beyond those advances, EPA OAR reports that current resources will not support plans to conduct measurements of PM emissions from other stationary sources with either newly developed or more traditional source-test methods. Historically, few states

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

have devoted substantial resources to source testing for the purposes of emission-inventory development. Some source testing has been supported by government agencies other than EPA (such as CARB, the state of Colorado, NPS, and DOE) and by industry (for example, CRC, EPRI, and API). The committee located more than 150 projects related to source testing either under way or recently completed, with studies generally distributed as shown in Table 3.2. However, few of these studies use methods, such as the dilution source-sampling system being developed by EPA, that fully characterize particle size and chemical composition.

The small number of sources scheduled for full characterization falls far short of a well-designed comprehensive testing program that would lead to more-accurate emission inventories. EPA has noted its reply to the committee's questions about the range of sources to be tested that “ORD can only test a limited number of source categories annually with currently available staff and funding. In addition, the ORD method development effort is unable to test sources within any one category under the full range of operating conditions typically encountered in the field. As previously stated, the number and diversity of sources means that, at any foreseeable resource level, many years would be needed to test a representative sample of all distinctive types of sources” (EPA response to questions from the committee

TABLE 3.2 PM Emissions-Related Research

Category

EPA-Funded Projects

Projects Funded by Other Organizations

Mobile sources

11

50

Fugitive sources

9

23

Stationary-source fuel combustion

3

10

Industrial processes

2

6

Other (such as mixtures of sources)

1

8

Inventory simulation

3

13

Ammonia

1

12

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

dated June 2000). In its second report, the committee recommended that EPA plan to systematically achieve nearly complete characterization of emissions by particle size and composition for sources that contribute about 80% of the primary particle emissions nationally. The committee notes that now is the time to begin planning the selection of sources to be tested during the 5-year cycle beginning in FY 2002 to achieve that objective.

In its second report, the committee specifically recommended an expanded source-testing program at the level of an additional $5 million per year, beginning in FY 2002. That recommendation, if followed, will remove the program's current financial constraints. Therefore, it is appropriate to begin planning for a comprehensive source-testing program that will systematically measure the particle size distribution, particle chemical composition, and gaseous particle precursor emissions characteristics of a reasonably complete set of the relevant sources over a 5-year period. Consultations should be held with researchers in health effects, exposure, source-oriented air-quality modeling, and receptor-oriented air-quality modeling to solicit recommendations on sources to be tested and any additional chemical and physical dimensions that should be measured during the national source-testing program.

Develop New Measurement Methods and Use of Data to Characterize Sources of Gas-Phase Ammonia and Semivolatile Organic Vapors.

Methods for measurement of ammonia from nonpoint sources, such as hog-feeding facilities and highway operation of motor vehicles, have been tested by EPA ORD during the last year. Additional measurements of ammonia emissions from animal husbandry are planned for next year. Semivolatile organic compound emissions are among the dimensions listed as measurable by the research-grade dilution source-sampling procedures developed by ORD. As in the previous discussion of fine-particle emission characterization, there appears to be no program in place that will characterize more than a

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

handful of the relevant emission source types within the foreseeable future. Before FY 2002, a plan should be put into place for a comprehensive source-testing program that will lead to the creation of a national ammonia emission inventory based on credible and recent experimental data.

Translate New Source-Test Procedures and Source-Test Data into Comprehensive National Emission Inventories

EPA maintains a national regulatory emission inventory for PM2.5, PM10, and gases that act as particle precursors. The PM emission inventory is primarily a mass-emission inventory that does not extend to particle size distributions and particle chemical composition. EPA maintains a file of source chemical-composition profiles that can be used to estimate particle chemical-composition in many cases. These source chemical-composition profiles need to be brought up to date through a continuing program of literature review and additional source testing.

Funds appear to be available to incorporate data from new emission measurements into the national emission inventory. Although the new data are incorporated into the inventory continuously as they are collected, there is no specific date for completion of a truly new inventory. This process might appear to be one of continuous improvement, but that is not necessarily the case. Technologies used in various types of emission sources change over time. As a result, older emission data can become obsolete faster than the program of continuous improvement can keep up with the changes, especially if the emission inventory program does not have a systematic schedule for review and replacement of existing data. Highway diesel engines, for example, could be scheduled for new source-characterization experiments, but it is possible that many other diesel-engine types used in heavy-duty off-highway applications —such as construction equipment, railroad locomotives, and ships—are represented by obsolete source-test data as these technologies change over time.

The committee has recommended the compilation, beginning in

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

FY 2006, of a thoroughly revised national emission inventory for PM as a function of particle size and composition, and for gaseous particle precursors based on the new source-test data generated in accordance with the above recommendations. The infrastructure exists to support this work, and the committee has recommended new funds of $1 million per year to finance the effort over several years, beginning in FY 2006.

Application of Evaluation Criteria Scientific Value
Scientific Value

There is great scientific value to the research under way to develop new source-test methods and demonstrate their capabilities to measure particle size, particle chemical composition, and rates of emission of ammonia and semivolatile organic compounds. This information is needed to guide exposure-assessment studies and help toxicologists and epidemiologists form potential hypotheses about components of PM that could be hazardous to human health. The emission data are also needed to support tests of advanced air-quality models that seek to relate pollutant emissions to ambient-air quality. Emission data that describe particle size and chemical composition are needed to permit the calculation of gas-to-particle conversion rates and support calculations of heterogeneous chemical reactions that occur clouds in clouds, haze, and fog. Furthermore, when emission data on particle size and composition are available, air-quality models that account for particle size and composition can be put to very demanding tests that ensure that they are producing the right answers for the right reasons.

Decisionmaking Value

Decisions about alternative emission-control policies have to be based on an accurate understanding of the relative strength and possible toxicity of emissions from various sources. Accurate emission

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
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inventories are absolutely fundamental to the decisionmaking process. Although there is scientific merit in the work that is under way to develop new source-test methods, the potentially important benefits to the decisionmaking process of more-complete and accurate knowledge of particle emissions evaluated according to size and composition can be realized only if EPA proceeds to expand its present source-testing program substantially by FY 2002, in accordance with the committee 's recommendations. EPA should now develop a comprehensive plan for systematically translating the new source-test methods into a completed comprehensive national emissions inventory based on contemporary source tests of comparable quality. There is still ample opportunity to plan that future source-test program. The first step would involve the systematic creation of a master list of sources that most need to be tested over a specific period. The timeline for this testing must allow for the incorporation of revised and updated data into an overall emission inventory of predetermined quality and completeness by the time the next round of PM implementation plans must be drafted.

Feasibility and Timing

In the committee's second report, it was estimated that five to 15 source-testing campaigns would need to be directed at different source types each year for a 5-year period beginning in FY 2002 to bring new source-test methods to bear in creation of a reasonably complete emission inventory for particle size and composition based on contemporary data of high quality. EPA ORD is conducting about six such testing campaigns per year, at a cost of about $2.3 million per year while it is in the method-development phase that precedes the work of source testing for an emission inventory. That is reasonably consistent with the committee's recommendation that about $2.5 million per year should be spent during FY 2000 and 2001 on method-development research. On the basis of the observation that EPA ORD alone has been able to conduct about six source-test campaigns per year with an annual budget of $2.3 million, it seems reasonable that funds of $5-$7.5 million per year, as recommended by the committee

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
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for FY 2002-2006, will be sufficient to support the proposed testing needed for a thorough upgrade of the emission inventory. With the FY 2002-2006 timeline, EPA has at least a year in which to draft a plan that identifies the sources to be tested in the future to ensure reasonably complete representation (a goal of about 80% coverage on a mass basis) of the national fine- particle emission inventory. Although some of the remarks by EPA in reply to committee questions appear to assume that a reasonably complete reworking of the emission inventory is beyond the planning horizon of the agency, the goal of a high-quality inventory for particle size and chemical composition is not out of reach. Drafting of a comprehensive plan that preselects sources to be tested and sets priorities for the work to be done over about a 5-year period will help to ensure the success of the research effort.

RESEARCH TOPIC 4. AIR-QUALITY MODEL DEVELOPMENT AND TESTING

What are the linkages between emission sources and ambient concentra tions of the biologically important components of particulate matter?

The focus of this research topic is development and testing of source-oriented and receptor-oriented models that represent the linkages between emission sources and ambient concentrations of the most biologically important components of PM. Comprehensive source-oriented models for PM are still under development; before they are ready for regulatory applications, they require more-certain emission inventories (see research topic 3) and an improved understanding of the chemical and physical processes that determine the size distribution and chemical composition of ambient particles. Receptor-oriented models have been used to apportion particle mass measurements to primary emission sources through a mathematical comparison of chemical profiles of ambient PM samples with the profiles of emission-source types. However, better mathematical tools and chemical tracers are needed to resolve additional sources and to handle secondary species. Before the models can be used with suffi-

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
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cient confidence, both the receptor-oriented and source-oriented approaches need to be tested with observations from intensive field programs and then compared with each other.

Air-Quality Model Development
Source-Oriented Models

EPA has developed its major new modeling platform, MODELS 3, over the last decade. MODELS 3 is just beginning to be deployed and has not yet been extensively tested. It has been developed in a specific configuration, Community Model for Air Quality (CMAQ), primarily for modeling ozone. Scientific reviews of MODELS 3 have focused primarily on its ability to provide adequate representations of chemical processes to estimate ozone. Only recently has there been active consideration of incorporating PM formation and transport into the model.

The atmospheric-science community had limited interaction with EPA during the development of MODELS 3. In EPA's response to the committee 's questions, the agency suggested that there was limited interaction because EPA faces relatively few major uncertainties about atmospheric processes and it is simply a matter of time before all the science that is needed to produce adequate estimates will be incorporated into the model. The committee did not get an indication as to whether MODELS 3 had been sufficiently tested with regard to PM formation and transport.

Table 3.3 presents a summary of the current studies identified by EPA and others as sources of information on atmospheric processes. These studies demonstrate the efforts under way to understand the processes governing atmospheric phenomena. However, the committee does not believe that current or planned efforts are sufficiently organized to effectively assess and use the information obtained through these studies.

EPA has developed a second model, the Regulatory Modeling System for Aerosols and Deposition (REMSAD), that is designed to simu-

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
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TABLE 3.3 Summary of Current Studies Identified by EPA as Sources of Information on Atmospheric Processes

Study Topic

No. EPA-Funded Projects

No. Projects Funded by Other Agencies

Meteorology

1

1

Ultraviolet photometry

0

1

Fog

0

0

Semivolatile compounds

6

8

Acid precipitation

2

3

VOC-oxidant

2

2

Plume chemistry

1

0

Dry and wet deposition

1

2

Source characterization, soil

0

4

Source characterization, smoke

1

4

late the concentrations and chemical composition of primary and secondary PM2.5 concentrations, PM10 concentrations, and depositions of acids, nutrients, and toxic chemicals. To reduce computational time and costs, REMSAD uses simpler chemistry and physics modules than MODELS 3. REMSAD has been applied to model concentrations of total PM2.5 and PM2.5 species (sulfate, nitrate, organic carbon, elemental carbon, and other directly emitted PM2.5) over the conterminous United States for every hour of every day in 1990. Annual, seasonal, and daily averages from the 1990 base case have been compared with data from the Interagency Monitoring of Protected Visual Environments (IMPROVE) network and the Clean Air Status and Trends Network (CASTNET). Sensitivity analyses have also been conducted for changes in SOx, NOx, ammonia, and directly emitted PM2.5. Because of the lack or sparseness of available data on many areas of the United States (for example, IMPROVE provided only two 24-hour-average concentrations per week for a few dozen sites in 1990), there has not been an effective national evaluation of the model for PM. It is not clear whether REMSAD's simplified representations of chemistry

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
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adequately capture the complex atmospheric processes that govern observed particle concentrations.

A number of other source-oriented PM models are being developed by individual investigators at universities or consulting companies. Seigneur et al. (1998, 1999) reviewed 10 Eulerian grid models: seven for episodic applications and three for long-term applications. The episodic models are the California Institute of Technology (CIT) model, the Denver Air Quality Model (DAQM), the Gas, Aerosol, Transport, and Radiation (GATOR) model, the Regional Particulate Model (RPM), the SARMAP Air Quality Model with Aerosols (SAQM-AERO), the Urban Airshed Model Version IV with Aerosols (UAM-AERO), and the Urban Airshed Model Version IV with an aerosol module based on the Aerosol Inorganic Model (UAM-AIM). The long-term models are the REMSAD, the Urban Airshed Model Version IV with Linearized Chemistry (UAM-LC), and the Visibility and Haze in the Western Atmosphere (VISHWA) model. In addition, several university groups are developing additional PM models that are primarily extensions of the CIT model to other areas of the country.

It appears that none of the models reviewed by Seigneur et al. (1998, 1999) is suitable for simulating PM ambient concentrations under a wide range of conditions. The following limitations were identified in both episodic and long-term models:

  • Most models need improvement, albeit to various extents, in their treatment of sulfate and nitrate formation in the presence of fog, haze, and/or clouds.

  • All models need improvement, albeit to various extents, in their treatment of secondary organic particle formation.

  • The urban-scale models will require modifications if they are to be applied to regional scales.

  • All models but one lack subgrid-scale treatment of point-source plumes.

In addition to the limitations identified above, the reliability of the simplified treatments of chemistry used for estimating the effect of emission changes on PM concentrations in the long-term models has

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
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not been sufficiently tested. An alternative approach for predicting annual average PM concentrations has also not been adequately tested. This approach—to be used by EPA in applications of MODELS 3/CMAQ—is to approximate a full year by combining several typical meteorological scenarios with appropriate weighting factors and applying an episodic model separately to each scenario. The validity of the approach depends on, among other things, the meteorological representativeness of the selected scenarios. The approach has not yet been the subject of a comprehensive evaluation, so its validity is unknown.

In addition to the limitations indicated above regarding the formulations of PM source models, it must be noted that the application of PM source models requires input data for emission, meteorology, and ambient concentrations of PM and gases. For example, it might be possible to improve the models by incorporating more information on atmospheric processes, but any apparent improvements will need to be tested for their success in reproducing observations during specific meteorological situations. Substantial uncertainties are still associated with PM emission inventories, as described under research topic 3. Ammonia and VOC emission inventories involve large gaps that will affect the predictions of secondary PM, and uncertainties in natural and anthropogenic emissions of mineral dust will affect the predictions of primary PM. Moreover, the most comprehensive modeling input databases are for California regions, and there are insufficient data on other states.

Emission and process data related to specific components of PM are notably lacking. A long-term research goal is to identify specific physical or chemical components in PM that are primarily responsible for the adverse health effects. EPA models focus on total mass concentrations and major PM constituents, such as sulfate and nitrate. However, future models could expand their focus to size distributions and other chemical constituents.

Efforts are under way at academic and other research institutions (such as EPRI) to improve air-quality models. Efforts are also under way to link and integrate air-quality models with exposure and dose

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
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models. However, it appears that there is no coordinated effort to compare the various models with one another or to use improvements developed for one or another model to improve the others, particularly those earmarked for regulatory applications. It is not clear that the appropriate commitment is being made to have the best models available at the local air-quality management levels for use in PM planning efforts.

Receptor-Oriented Models

There has been very little support for the development and testing of new receptor-oriented models. Such models are used to identify and quantitatively appropriate an ambient PM sample from a given location (receptor) to its sources. The CMB model has been rewritten to run under the Windows operating system, and EPA has supported factor-analysis model development under a single STAR grant. Both products are now in the process of external review, with probable release at the end of 2000. A new version of the EPA source-profile library will run under modern PC operating systems. However, only 16 profiles have been added to the library since its revision in 1992—an indication of the lack of incorporation of recently published source profiles. Seigneur et al. (1998, 1999) reviewed existing receptor models, including back-trajectory-based analyses to locate candidate source areas, alternative factor-analysis models based on least-squares fitting, and alternative solution methods for the CMB. However, further development and testing are required before they can be widely distributed for air-quality management purposes.

There is a particular need for data-analysis tools to handle newly emerging monitoring technologies, such as aerosol mass spectroscopy. A number of approaches have been presented in the literature, but they are typically applied to only a single location or region. There has not been an extensive effort to test the effectiveness of these alternative methods or to review their potential use in future development of air-quality management strategies.

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
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Air-Quality Model Testing

To test the predictive capability of models, it is necessary to have both the model input data and appropriately detailed sets of air-quality observations to compare with the model outputs. Earlier field campaigns —such as the Southern Oxidants Study (SOS; www2.ncsu.edu/ncsu/CIL/southern_oxidants/index.html), the Northern Front Range Air Quality Study (NFRAQS; www.nfraqs.colostate.edu/index2.html), the Southern California Air Quality Study (SCAQS; Lawson 1990), and the San Joaquin Valley Air Quality Study (SJVAQS; Lagarias and Sylte 1991; Chow et al. 1998)—provide the necessary data for model testing. (SOS, until recently, and SJVAQS have limited utility for PM models because they focused primarily on ozone.) Although those earlier efforts provided insights into basic atmospheric processes, only some of the supersite monitoring stations can possibly have sufficient data to validate regional-scale air-quality models. It is clear that more field campaigns are needed to provide data to test the predictive capability of state-of-the-science PM models.

A number of large studies are just starting, such as the supersite efforts, and continuing studies, such as SOS. However, there do not appear to be plans to use these databases fully for testing air-quality models. ORD personnel have suggested that EPA will use the data to test MODELS 3/CMAQ, but it is not clear to the committee that there will be effective internal and external review. The committee is aware of no defined plans to compare MODELS 3/CMAQ with any of the other similar-scale models. Such comparisons are needed, and a plan for evaluation and revision of the EPA model should be developed as part of EPA's PM research program.

This lack of effort to use available data effectively highlights the need for EPA to be active in defining the nature of the data needed to test Models 3/CMAQ fully and compare it with other independently developed models. There is now an agreement among the Baltimore, New York City, and Pittsburgh supersites and the NARSTO NE-OPS (Northeast Oxidant and Particle study) program in Philadelphia to operate in an intensive mode during July 2001. There will be only sparse upper-air measurements using LIDAR in Baltimore and Philadel-

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
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phia. Although it might be too late to organize extensive additional upper-air measurements for those particular studies, this is one example of the kind of opportunity that EPA should be actively seeking, particularly in the eastern and southeastern United States, where such large-scale, detailed data are lacking.

It might be possible to build on the speciation network, once it is in place, to develop appropriate field campaigns. By operating these systems more intensively (more frequently than daily) and supplementing the speciation network monitors with particle-size measurement devices, it would be possible to provide a suitable database for regional-scale model testing.

The testing of receptor models is similarly incomplete. It appears that there has been no clear plan for development, testing, and deployment of additional receptor-modeling tools. CRC recently supported an effort to evaluate receptor models for VOCs, using grid models to produce test data. EPA has had a small effort to compare factor-analysis models, but a more extensive program will be needed to provide the full range of tools necessary for a comprehensive analysis, particularly for PM2.5.

Application of Evaluation Criteria
Scientific Value

There is substantial support of current studies that are expected to make substantial contributions to the understanding of atmospheric processes. The development of source-oriented models represents the codification of a portion of new knowledge into an organized framework for application. The testing of individual models and the comparison of the results of multiple models can help to identify the effects of different approaches to incorporation of the knowledge into prediction based upon models. Such comparisons will help to refine the available knowledge. The development of better algorithms for source- and receptor-oriented models will also be substantial scientific advances.

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
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Decisionmaking Value

Air-quality models are essential for making regulatory decisions. They provide the critical information required to develop the effective and efficient air-quality management strategies that are needed for state implementation plans (SIPs), which are developed when areas are found to be in nonattainment of the PM National Ambient Air Quality Standards (NAAQS). Regional-scale models are needed for reducing visibility impairment, acid precipitation, and other adverse environmental effects. Improved models would also provide critical exposure-related data that could be used in health studies to examine the relationships between ambient PM concentrations and health. There is insufficient effort to test the models developed by EPA and others or to use extensive comparison with other models to ascertain the differences and similarities in the results. Such efforts would provide further improvements in the models and greater confidence in the decisions based on the model results. In addition, it is important to link air-quality models with exposure models. EPA is collaborating with other organizations to develop a population exposure model for PM to provide such a linkage.

Feasibility and Timing

The development and testing of models is highly feasible. The increase in computational power permits the incorporation of greater numbers of observations and understanding of atmospheric processes into source-oriented models. The same computational power permits much more sophisticated methods for data analysis to be used in receptor-oriented models.

The new PM monitoring program provides a base from which data can be obtained for testing of the models. If research topic 3 is appropriately implemented, the necessary source data and source-oriented models will be readily available. The source profiles developed under research topic 3 will also provide data to introduce into recep-

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

tor-oriented models. Thus, the plan for testing models presented in the committee's second report can be used to provide the necessary tests and improvements for models. However, the planning process should be started immediately to allow time for important regional-scale field studies. It should be noted that the data needed for model testing and evaluation are not necessarily the same as data needed for developing exposure metrics, which is discussed later in this chapter.

There is also time to develop, test, and deploy advanced receptor models more fully before requirements arise from the SIP process. However, there must be a more concerted effort to recognize the need for improved models and improved data for existing models.

Integration and Planning

There appears to be insufficient effort in organizing and carrying out the field studies that would provide the data for thorough evaluation of existing models; only a small effort to leverage the investment is being made in the PM monitoring program to provide these data. There is a large body of historical data that would be of great value in model testing if they could be processed in a standard way into a central repository from which they can be easily accessed. It appears that EPA does not yet recognize the need for full model testing, so it has not mobilized the needed resources.

It appears that there has been no comprehensive planning for the development and deployment of receptor-oriented models. The current ad hoc approach to receptor-model development will not provide the additional tools essential to develop future state implementation plans. With the development of several new factor-analysis models, there has been some effort to compare them, but there is still no evidence of a plan for developing and implementing improved models in the context and timeframe of what will be needed for the PM2.5 SIP process.

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
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RESEARCH TOPIC 5. ASSESSMENT OF HAZARDOUS PARTICULATE-MATTER COMPONENTS

What is the role of physicochemical characteristics of particulate matter in eliciting adverse health effects?

The initial research portfolio (NRC 1998) outlined a research agenda designed to improve the understanding of the roles of specific characteristics of ambient PM (such as particle size distribution, particle shape, and chemical constituents) in determining the toxicity for underlying adverse health outcomes associated with PM exposure. The research plan indicated not only studies aimed at determining the relevance of those characteristics, but also work designed to evaluate the dose metrics that have been used to relate PM exposure to health effects in epidemiological and toxicological evaluations. Research was needed to develop PM surrogates, that is, material with specified characteristics for use in toxicity studies. In its second report, the committee (NRC 1999) reconfirmed the importance of this kind of investigation.

The nature of the chemical or physical characteristics of ambient PM that might account for its biological activity remains a critically important component of the PM research portfolio. In addition to providing mechanistic plausibility for epidemiological findings related to PM, an understanding of the relationship between mechanisms of biological action and specific PM characteristics will be a key element in selecting future control strategies. The following list of particle characteristics potentially relevant to health risk is large and possibly variable across health effects:

Size-fractionated PM mass concentration

PM surface area

PM number concentration

Transition metals

Acids

Soot and organic chemicals

Bioaerosols

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
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Sulfate and nitrate

Peroxides and other free radicals

Those particle characteristics may be associated with cardiovascular disease, acute respiratory infection, chronic obstructive pulmonary disease, asthma, and morbidity. Inspection of this list, which could be expanded, makes clear the challenge that is faced by the investigative community and by research managers who need to focus resources toward the key relationships between particle characteristics and health effects.

In addressing this research topic, both toxicological and epidemiological approaches are needed. Hypotheses advanced from data in one domain need to be tested in the other, complementary domain. Greater certainty will be achieved as evidence from the laboratory and the population converges and as integrative research models merge the population and laboratory data into a common framework. For example, particles obtained from filters in the Utah Valley, the site of epidemiological studies of health risks posed by particles from a steel mill, have been assessed for toxicity in laboratory systems (Frampton et al. 1999; Soukup et al. 2000; Dye et al. in press). The availability of particle concentrators could also facilitate the implementation of integrative research models, in that animals and people can be exposed to a comparable mixture of real-world particles.

The general methodological issues arising in connection with this research topic are akin to the problem of assessing the toxicity of a mixture and determining the specific characteristics that are responsible for its toxicity. Particles, in fact, constitute a mixture: urban atmospheres are contaminated by diverse sources, and the characteristics of particles can change and vary among regions. The difficulties of studying mixtures have been addressed by numerous panels, including committees of the National Research Council (NRC 1988). Accepted and informative research models have not yet been developed, and even attempting to characterize several toxicity-determining characteristics of mixtures has proved challenging.

One objective of research related to this topic was to assess relevant dose metrics for PM to explain adverse health outcomes. EPA

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
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routinely measures size-specific mass concentration, previously PM 10 and now PM2.5 as well. The selection of these concentrations and the timeframe over which they are measured (24 hours) reflect technological feasibility to a greater extent than fit with time-exposure-response relationships of PM with health risk. Routine regulatory monitoring provides only 24-hour averaged mass concentrations, but special monitoring programs —including those instituted in support of epidemiological studies, the speciation sites, and the supersites program—offer the opportunity to explore alternative dose (exposure) metrics. Newer techniques to monitor PM2.5 over shorter periods, and even continuously, are being developed and tested.

Another objective, to evaluate the role of particle size in toxicological responses to PM and that related to epidemiological outcomes, focuses on the size of particles that are relevant to the health effects observed in the epidemiological studies. To date, the associations of PM with both illness and death have been demonstrated in studies using indexes that incorporate particles with a large range of sizes (such as total suspended particles, or TSP, and PM10). These studies have drawn on the available data. PM10, of course, includes particles in all smaller size categories and thus includes PM2.5 and ultrafine particles (those smaller than 0.1 µm in diameter). Ultrafine particles probably make up a very small fraction of PM10 mass, but pathophysiological considerations and some initial toxicological findings have focused attention on the hypothesis that such smaller particles may be responsible for some toxicological responses that lead to the epidemiological findings.

Research Progress and Status
Toxicology

New work directed at this research topic has been based largely on toxicological approaches. Forty-eight toxicology projects described in the HEI database were identified as potentially related to the topic.

Ambient PM is a complex mixture that contains various chemical components in various size fractions. Evaluation of whether biologi-

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
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cal responses to PM are nonspecific—that is, are due merely to inhalation of any particle—or depend on specific PM properties is a critical focus of current research. Regarding the latter possibility, research performed in the recent past has indicated some specific potential characteristics that appear to be involved in PM-induced health effects. A compilation of these (Mauderly et al. 1998) is as follows: size-fractionated particle mass concentration; particle surface area; particle number concentration, which is generally related to the ultrafine component of PM; transition metals (especially the fraction soluble in vivo); acids; organic compounds (especially PAHs); bioaerosols; sulfates and nitrates, typically existing in ambient air as ammonium or sodium compounds; peroxides and free radicals that can accompany, and help to form, particles; soot (elemental carbon, black carbon, or light-absorbing carbon); and correlated cofactors (such as the presence of gaseous pollutants and variations in meteorology). The current toxicological research portfolio as reported in the HEI database was examined with regard to each of those specific chemical or physical characteristics.

  • Size-Fractionated Particle Mass Concentration. The mass concentration—the mass (weight) of collected PM per unit volume of sampled air, generally within some selected particle-size range or below some upper size cutoff—was the exposure metric most commonly evaluated in relation to health effects in the studies in the HEI database. More-recent epidemiological studies of ambient particles have generally focused on the 0.1- to 2.5-µm size range, although there have been a few studies of coarse particles. In a number of cases, the particle-size cutoffs used in toxicity studies differed from those commonly used to define size fractions obtained with ambient monitoring networks, namely PM2.5, coarse PM (PM10 minus PM2.5), and PM10, and TSP. For example, some toxicity studies have used mass in sizes termed PM1.7 and PM3.7-20, whereas others have included particles of up to 4 µm in the definition of “fine” particles. Definitions of specific size fractions, such as “fine” and “coarse,” used in toxicological research should be consistent with those used in ambient monitoring studies and in epidemiological studies.

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
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  • PM Surface Area. A few studies in the HEI database address particle surface area in the context of particle size, specifically in terms of its relation to health effects. Surface area is also relevant to the absorption of gases onto particle surfaces.

  • PM Number Concentration. A few studies address the issue of particle number concentration, which is generally used to describe exposures to the ultrafine particles in ambient PM. These include in vivo and in vitro studies, the former including clinical-exposure studies and involving particles ranging from 0.01 to 0.1 µm.

  • Transition Metals. The transition metals include titanium (Ti), vanadium (V), chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), cadmium (Cd), and mercury (Hg). Some—Cr, Mn, Co, Ni, Cd, and Hg—are both transition metals and listed as EPA hazardous air pollutants. Although a number of studies address the issue of toxic metals, many use material containing a mix of various metals, and few specify single metals for evaluation. For example, residual-oil fly ash particles containing nickel and vanadium are commonly used in toxicity studies related to PM; such studies have involved both animal in vivo and in vitro study designs. Other studies have examined pulmonary inflammation related to Fe, V, Zn, and Ni; DNA damage related to Cr(VI); and oxidative stress after exposure to Fe. In general, however, exposure doses in these studies have been high and not relevant to ambient exposure. Metal concentrations found in ambient and source samples should serve as broad exposure guidelines for these experiments. Because in vitro studies often involve material extracted from ambient-air filters, methods of filter extraction (for example, water extraction vs. acid digestion) and analysis need to be standardized.

  • Acids. Health effects of exposure to acid aerosols have been extensively studied and are specifically addressed in the current controlled-exposure research portfolio in only a few studies reported in the HEI database. However, ambient acidity is generally not analyzed in filters obtained from studies that use ambient-particle concentrators. Such data would be valuable for comparison with pub-

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

lished epidemiological data on health effects. Furthermore, little information on specific types of acids is given in the project descriptions in the HEI database.

  • Soot, Organic Compounds, and Associated PAHs. The effects of PAHs are specifically addressed in only one in vivo study described in the HEI database. Characteristics of combustion-related organic chemicals will be explored further by the EPA-sponsored PM centers. Studies of diesel exhaust, diesel soot, and black carbon focus mainly on elemental carbon. More research with emphasis on organic speciation is needed to evaluate potential health effects. Because there are so many organic compounds in ambient PM, a subset specifically related to pollution sources needs to be defined for in vivo and in vitro studies.

  • Bioaerosols. One of the subjects clearly in need of evaluation is the role of biological agents in adverse health effects related to ambient PM exposure. Biological agents that might be involved in PM-induced response are diverse, and few are being evaluated. One class, endotoxins, has been identified as having the ability to induce or potentiate adverse health effects induced by PM, and some studies are addressing this issue. Another antigen being evaluated for its role in PM-related health effects is that derived from dust mites. Although exposure to dust mites largely occurs indoors, it may offer an informative example.

  • Sulfates and Nitrates. Sulfate has been examined in several studies, but nitrate and other nitrogen species have been largely ignored except as components of complex particle mixtures.

  • Peroxides and Other Free Radicals. One in vivo study addresses the role of peroxide in PM toxicity. This is a subject on which further research is needed.

  • Copollutants. There is an increasing effort in the research portfolio to evaluate the potential for interaction between PM and gaseous copollutants. The gases of potential concern include O3, NO2,

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

SO2, CO, and irritant hydrocarbons. Data on precursor gases (especially HNO3, NH3, and SO2) are important to relate ambient secondary particles to health effects. This subject is discussed further with regard to research topic 7.

The committee is unable to identify any studies reported in the HEI database that address the issue of experimental PM surrogates that can mimic daily, seasonal, and regional particle characteristics. Specific in vivo and in vitro tests provide snapshots of adverse effect. Understanding of the role of PM characteristics in eliciting biological responses, measurements of PM components or analyses of aerosol filters should include extensive chemical speciation, consistent with the national PM2.5 chemical-speciation network, in which mass, elements (40 elements from sodium to uranium), ions (nitrate, sulfate, ammonium, and water-soluble sodium and potassium), and carbon (organic and elemental) are determined. Furthermore, there needs to be a reconciliation of ambient concentrations with the exposures used in controlled studies. Concentrations of specific chemical compounds in PM vary widely. For example, V and Ni are often found at less than 0.01 µg/m3 in ambient samples, although most other metals are typically found at 0.01-0.5 µg/m3. But crust-related materials (such as aluminum (Al), silicon (Si), calcium (Ca), Fe, and Mn) are often present at 0.5-10 µg/m3, and many toxicity studies use concentrations as high as about 100-5,000 µg/m3. The relevance of such high-exposure studies for materials present at much lower concentrations in ambient air must be considered in controlled-exposure studies. Furthermore, the ratio of specific chemical species in ambient air to those occurring in experimental atmospheres must be considered in experimental-study designs.

Epidemiology

Epidemiologists have approached the problem of mixtures or, in this instance, the toxicity-determining characteristics of particles, by evaluating risk in relation to heterogeneity in exposure, whether over time or across geographical regions. For example, time-series studies identified particles in urban air as a key determinant of morbidity and

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
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mortality by evaluating risk for events on a day-by-day basis in relation to changing daily concentrations of particles and other pollutants. Statistical models, such as Poisson regression, are used to “separate” the effects of one pollutant from those of another. Comparisons have also been made across regions that have different pollution characteristics. Panel studies can also be used for this purpose.

In applying the epidemiological approach in investigating particle characteristics, there is a need to have measurements of particles in general and of the specific characteristics of interest over the period of the study. Because monitoring for particle characteristics of specific interest has been limited, opportunities for testing hypotheses related to those characteristics have also been somewhat limited, and few studies that incorporate substantial monitoring of both particle concentration and other specific characteristics have been carried out. One example is afforded by the work carried out in Erfurt, Germany, where particle mass, concentration, and numbers have been carefully tracked for a decade. The resulting data have been used to support several epidemiological studies of health effects in that community (Peters et al. 1997). EPA's supersite program will also offer a platform for carrying out observational studies on particle characteristics related to health risk.

Epidemiological data, if sufficiently abundant, can be used for testing alternative dose metrics. Statistical modeling approaches can be used to test which exposure metrics are most consistent with the data; with this general approach, the fit of the statistical model to the data is compared across exposure metrics, and the metric that best fits the data is given preference, assuming that its biological plausibility is at least equivalent to that of alternatives. For example, 2-day running averages might be compared with 24-hour averages, or peak values obtained with continuous monitoring might be contrasted with averages over longer periods. If a strong preference for one metric over alternatives is to be gained, the data requirements of this approach are substantial. Epidemiological studies relevant to this research topic need to be large and require data on the exposure metrics to be compared.

Table 3.4 shows that the number of potentially informative epidemiological studies is small. Studies in Erfurt, Germany, and in Atlanta

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
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TABLE 3.4 Number of Epidemiological Studies Relating Health Outcomes to Target Pollutants a

Health Outcome

PM b

PM, Copollutants c

PM Metals

PM, Ultrafines d

PM, Ultrafines, Copollutants c

PM, Ultafines, d Metals

Asthma onset

1

1

Asthma, exacerbation of symptoms

4

4

1

1

Respiratory outcomes, children under 10 years old

3

2

1

Respiratory outcomes, children 10-19 years old

7

3

1

Pulmonary function, children 10-19 years old

2

5

1

Respiratory outcomes, normals

3

Minority groups

1

Respiratory outcomes, people over 65 years old

7

1

Pulmonary function, people over 65 years old

3

Morbidity and mortality, respiratory elderly

1

7

2

Morbidity and mortality, cardiac elderly

5

11

2

2

Total mortality

4

8

1

2

Total

37

44

3

5

5

3

a   Some studies consider more than one health outcome. The quality of a study and its ability to address the research priorities are not considered here.

b   Denotes various size fractions of PM, including PM2.5, PM10, TSP, and unspecified size fractions.

c   Copollutants include SO2, O3, NO2, and CO.

d   ines refers to PM with a diameter equal to or less than 0.1 µm.

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

capture mass concentrations, particle counts, and acidity; other studies are addressing ultrafine particles and risk of myocardial infarction in Augsburg, Germany, and in Atlanta. Several time-series studies include measurements of sulfate and acid aerosols, and a number of panel studies also incorporate measurements of a variety of particle characteristics. PM components are being considered in a small number of existing or planned studies. More data will probably be needed, particularly to obtain evidence related to the general issue of exposure metrics as applied to population risk. A number of current studies should provide information on the risks posed by ultrafine particles; these risks are the focus of one of the PM centers. Panel studies conducted by EPA will also contribute useful information.

Adequacy of Current Research in Addressing Research Needs

There is considerable effort in evaluating physiochemical properties of PM in relation to biological effects. However, it has generally been concerned with only a few chemical characteristics; the largest body of work involves metals. Other potentially important PM characteristics as illustrated in Table 3.4, have received less attention. Current work is beginning to address the issue of exposure or dose metrics other than mass concentration, although most studies continue to evaluate health effects in terms of total mass concentration during exposure. The relevance of high doses used in many controlled exposure studies to the low exposures to some components of ambient PM remains a subject that must be more adequately considered in study design than it is now.

In its second report, the committee noted that although most of the research activities recommended in its first report were being addressed or planned by EPA or other organizations, studies in one cross-cutting research topic of critical importance did not yet appear to be adequately under way or planned: studies of the effects of long-term exposure to PM and other major air pollutants. The committee recommended that efforts be undertaken to conduct epidemiological studies of the effects of long-term exposures to particle constituents, including ultrafine particles. There does not yet appear to be a sys-

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

tematic, sustained plan for implementing studies of human chronic exposure, including examining ultrafine particles.

Application of Evaluation Criteria
Scientific Value

This research topic is a key scientific question in the understanding of PM and health: Are effects of PM nonspecific—that is, determined only by the mass dose delivered to target sites—or do they depend on the specific physical and/or chemical characteristics of the particles? Data relevant to this question would be informative as to cardiopulmonary and/or systemic effects and therefore would guide mechanistic research. Thus, the scientific value of this research topic remains high. Identification of characteristics that produce adverse responses in controlled studies will allow comparison with PM properties obtained from epidemiological evaluations and will thus provide important confirmation of the role of specific properties in adverse health outcomes. There should be coordination between toxicological and epidemiological studies, including use of a consistent terminology for such PM characteristics as specific size fractions, so that study comparisons are possible not only between the two disciplines, but also among different controlled-exposure studies.

Integration across exposure assessment, toxicology, and epidemiology will be critical for obtaining a comprehensive body of evidence on this research topic that can guide decisionmakers from health effects back to responsible emission sources. Epidemiological studies need to include sufficient exposure assessment to guide toxicity studies of PM characteristics. Opportunities should be sought to apply hybrid research models that combine toxicological and epidemiological research.

Decisionmaking Value

Evidence on the particle characteristics that determine risk could have a profound influence on decisionmaking. At present, an ap-

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

proach of regulating particle mass in general is followed, in the recognition that particles vary substantially in size, makeup, and chemical properties. There are multiple sources of PM, and decisionmakers need guidance on whether some sources are producing more hazardous particles or whether all sources produce particles of equivalent toxicity.

Epidemiological research alone will not provide sufficiently certain evidence on this research topic; joint toxicological and epidemiological study is required. However, epidemiological data will be critical for decisionmakers, in that such data will confirm laboratory- based findings and hypotheses.

Feasibility and Timing

This is one of the most challenging research topics in the committee 's research portfolio. In the laboratory setting, characteristics of particles can be controlled through experimental design, so carefully measured studies of particles that have specific characteristics can be assessed. In the population setting, in contrast, participants in epidemiological studies inhale PM that has multiple sources and that changes in characteristics as participants move from location to location over the day and possibly even in one location at different times. Data on substantial numbers of persons will be needed to test hypotheses related to particle characteristics. Nonetheless, epidemiological studies can be carried out for this purpose; one of the most effective approaches is likely to be the panel study, with specific, tailored monitoring for particle characteristics of interest. Such studies are feasible, as shown, for example, by the studies in Erfurt (Peters et al. 1997).

RESEARCH TOPIC 6. DOSIMETRY: DEPOSITION AND FATE OF PARTICLES IN THE RESPIRATORY TRACT

What are the deposition patterns and fate of particles in the respiratory tract of individuals belonging to presumed susceptible subpopulations?

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

The committee's recommended research portfolio (NRC 1998) outlined research needed to improve understanding of the deposition of particles in the respiratory tract, their translocation, and their clearance. The recommendations encompassed the development of new data and predictive models and the validation of the models for respiratory-tract structure; respiratory variables; total, regional, and local deposition; and particle clearance. Also included were the micro-dosimetry of particles and particle-derived hazardous chemical species and metabolites in intrapulmonary and extrapulmonary tissues.

Information on dosimetry is important for decisionmaking because it is critical to understanding of the exposure-dose-response relationship that is key to setting the NAAQS. It is also important for understanding of how exposure-dose-response relationships differ between normal and especially susceptible subpopulations, if the standard is to be adjusted to protect sensitive people. Knowledge of interspecies differences is important for extrapolating results from animals to humans.

The committee's recommendations focused on dosimetry in people potentially more susceptible to particles because of respiratory abnormalities or age (children and the elderly). A large portion of the population is in one or more of the categories of concern. Most people spend at least one-fourth of their lives in stages during which lungs are developing or senescent. In 1997, an estimated 44.3 million adults were former smokers and 48 million were current smokers (ALA 2000a); many smokers develop some degree of airway abnormality. Asthma afflicts over 17 million Americans, including 5 million children whose lungs are still developing (ALA 2000b). COPD afflicts about 16.4 million people (ALA 2000c). All respiratory diseases together kill one of seven Americans (ALA 2000d). The focus of past dosimetry research —almost entirely on normal young adult humans and animals—leaves us with little ability to estimate exposure-dose-response relationships in the above subpopulations.

In its second report (NRC 1999), the committee confirmed its initial recommendations, added a recommendation for research to bolster interspecies dosimetry extrapolation models, and re-emphasized the need for dosimetric research in animals to focus on models of human susceptibility factors.

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

Several sources of information were examined to assess current research and recent research progress on the dosimetry of PM. The review of current research centered on the HEI-EPA database on PM research. The database was examined as of August 2000 for research projects and programs, including dosimetric research in the abstracts. Numerous additional past or current projects were evident from published reports, but because of uncertainty as to whether these projects were continuing, only those listed in the HEI database were included in Table 3.5. In all, 22 project descriptions were identified as apparently responsive to the dosimetry research needs.

New information since the 1996 criteria document was assessed by examining published papers and abstracts from meetings. A search of the recent published literature was conducted by using numerous

TABLE 3.5 Summary of Dosimetry Projects and Reports

Topic

No. of Projects a

No. of Reports a

Deposition:

Influence of susceptibility conditions on deposition

15

26

Quantitative data on structure and respiration

7

8

Effects of particle size and hygroscopicity, and respiratory variables

1

23

Development and validation of mathematical models

5

13

Interspecies differences, especially for ultrafines

3

5

Translocation and clearance:

Translocation, clearance, and bioavailability

5

24

Disposition of ultrafine particles after deposition

1

2

Interspecies differences

0

5

Total

37

106

Projects (from HEI database) and reports (abstracts of papers and presentations) might be listed in more than one category if they address multiple issues. For example, the 37 "projects" were derived from a total of 22 individual project descriptions.

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

key words pertaining to the research recommendations. The first external review draft of the new criteria document for PM (EPA 1999) was examined for its portrayal of new information since the last criteria document, published in 1996. References added to the revised dosimetry chapter as of September 2000 were also reviewed. Published abstracts from 1999 and 2000 meetings of the American Thoracic Society (ATS 1999, 2000), HEI (HEI 1999, 2000), and the Society of Toxicology (SOT 1999, 2000) were examined for relevant research, as were the abstracts from the 1999 meeting of the International Society for Aerosols in Medicine (ISAM 1999). The abstracts and papers from the Third Colloquium on Particulate Air Pollution and Human Health in June 1999 (Phalen and Bell 1999) and from the “PM2000” conference in January 2000 (AWMA 2000) were also examined for relevant completed research. The evaluation of reports was limited to reviewing of abstracts. Published papers were not reviewed in detail, and authors were not queried.

In all, 62 papers and 59 presentation abstracts were identified as potentially relevant to the dosimetry research needs as set forth by the committee. On review of abstracts, some proved to fall outside the scope of the recommended research portfolio, and many more related to the recommendations only indirectly. A total of 96 reports were considered relevant to the dosimetry research needs. Although this review undoubtedly missed some potentially relevant reports, it was considered sufficient to provide a reasonable evaluation of the extent to which the recommendations are being addressed. The results of the review are summarized below, by categories according to the committee 's research recommendations (in italics). A numerical summary of the projects and reports is presented in Table 3.5.

Deposition
  1. Conduct research on deposition of particles in the respiratory tracts of individuals having respiratory abnormalities presumed to increase susceptibility to particles, and on the differences in deposition between these susceptible subpopulations and normals.

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×
  1. Obtain quantitative data on lung morphology and respiration for individuals of different ages and having respiratory abnormalities.

    Research using advanced imaging and reconstruction techniques is producing new information on the effects of age, sex, and several types of abnormalities on airway dimensions. This information can serve as the foundation of mathematical models of deposition in abnormal airways. Some researchers are using stereolithography to construct physical models of airways from stereo images and computer-controlled etching of solid media. Other researchers are using magnetic resonance imaging to create airway images and develop digital data from which structures can be modeled or physical replicas can be machined. These techniques show promise for obtaining new morphological data useful for modeling deposition in a broad range of airway abnormalities. It is likely that, in some cases, these approaches will allow acquisition of data for more varied subjects and at a greater rate than is practical with traditional postmortem airway casting.

    A modest amount of work is continuing with the more traditional methods of evaluating solid casts made from cadaver lungs and airways and measurements of airway dimensions with light microscopy of lung sections.

    Information on the effect of age and respiratory abnormalities on breathing patterns and dosimetry in humans has been expanded substantially in the last 2 years. The EPA intramural program is the strongest contributor in this field. Laboratories working in this field are addressing the variables of age, sex, asthma, COPD, and cystic fibrosis. Inclusion of a broader range of susceptibility factors and particle types is needed. For example, there is little emphasis on people who have respiratory infections or edema related to cardiopulmonary failure. Most studies have measured only total particle uptake; information on regional and local dosimetry is also needed.

  2. Determine the effects on deposition of particle size, hygroscopicity, and respiratory variables in individuals with respiratory abnormalities.

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

New information has been obtained on the influence of sex on regional (pulmonary vs. tracheobronchial and extrathoracic) fractional deposition and on differences between children and adults, and these data are being extended by current projects. Work on the effects of respiratory abnormalities on regional or local deposition has been limited largely to modeling or work with airway replicas. There has been little validation of the models with measurements of living subjects. An important advance has been the finding that total fractional deposition is greater in people who have asthma and COPD and in smokers than in people who have normal lungs. Total fractional deposition has been found to be similar in normal elderly people and young adults. More emphasis is needed on regional and local deposition in lungs and airways of susceptible subjects.

The influences of particle size and hygroscopicity on deposition have been addressed by some studies, but only a small portion of this work has included subjects or airway replicas that have abnormalities or different ages. There appears to be little emphasis on the influence of particle and respiratory variables on deposition in susceptible people or on the development of predictive models that incorporate these variables. In addition, only a few particle types and only a few of the many common combinations of ambient particle sizes and compositions have been studied.

As in the past, there continues to be only modest effort aimed at identifying the type and location of particles retained in lungs at autopsy. Although the locations are sometimes characterized as reflecting sites of particle deposition, the results typically reflect sites of retention of only the most biopersistent classes of deposited particles and might not reflect accurately the sites of deposition or the dose of the full spectrum of inhaled particles. When coupled with evaluations of accompanying tissue changes, this approach provides useful information on the relationship between long-term particle retention and disease.

  1. Develop mathematical models for predicting particle deposition in susceptible individuals and validate the models by measurements in individuals having those conditions.

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

Several recently completed or current efforts have led, and will continue to lead, to the development and refinement of models for predicting deposition in abnormal lungs. Most efforts have focused on the effect of flow limitation in conducting airways and on the heterogeneity of local particle deposition.

Very few efforts have included validation of models by measurements in living subjects. Only two of the reports in this category involved validation experiments—one for deposition in asthmatics and one for the effect of particle size on deposition in rats. More emphasis is needed on model validation and on modeling a greater range of susceptibility factors.

  1. Develop information on interspecies differences and similarities in the deposition of ultrafine particles in abnormal vs. normal respiratory tracts.

    Although this recommendation focused on ultrafine particles, there is a dearth of information on deposition of particles of any size in animals that have respiratory abnormalities. As noted in the toxicology sections that follow, continued effort is needed to develop, refine, and validate animal models of human respiratory abnormalities. Progress has been made, but it has been accompanied by little effort to examine particle dosimetry in the models. Although a few laboratories are attempting to develop and refine mathematical models for interspecies adjustments in particle deposition, there is still little attempt to validate the models by comparing deposition in animals and humans directly, and only one group is generating comparative data on the deposition of ultrafine particles.

    Several projects have developed models to predict comparative deposition in normal rats and humans, and most can be adapted for ultrafine particles. Other animal species have been largely ignored. The committee 's first report recommended increased development and use of animal models of human susceptibility factors, as described in other sections. Because differences in deposited dose can contribute substantially to differences in the models' response, there is a need for more work on particle deposition in animal models of respiratory abnormalities.

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×
Translocation, Clearance, and Bioavailability
  1. Conduct research on the translocation and clearance of particles and the bioavailability of particle-borne compounds in the respiratory tracts of individuals having respiratory abnormalities presumed to confer increased susceptibility. Determine differences in the disposition of particles between these susceptible subpopulations and normals.

New information is beginning to accumulate that shows that respiratory abnormalities can have variable effects on short-term clearance of inhaled particles deposited on conducting airways. As is the case for deposition, information on clearance is being developed in both the pharmaceutical and environmental fields. There are data on short-term airway clearance in adult humans who have asthma, chronic bronchitis, and COPD, including comparisons with normal subjects.

Although the available information is still sketchy, it reveals both the potential importance and the complexity of the issue. For example, Svartengren et al. (1996) did not find that clearance from small ciliated airways of unprovoked asthmatics differed from that of normal people, but later (Svartengren et al. 1999) found that more particles were retained in airways of asthmatics than of normal subjects when the allergic asthmatics were challenged with allergen before deposition of the particles. There is little information on the influence of respiratory abnormalities on longer-term clearance from the pulmonary region and little information on age-related differences. Some data suggest that there is little influence of age or sex on particle clearance in normal humans.

Several recent studies have demonstrated the importance of the bioavailability (solubility) of particleborne metals in eliciting adverse responses. A modest amount of work is being done on the bioavailability of particleborne organic compounds. Little if any effort is being expended to determine differences in bioavailability or the importance of bioavailability between normal and abnormal respiratory tracts.

It appears that differences in particle clearance are not yet being incorporated into models for predicting differences between normal

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

and susceptible people in the dosimetry of particles or particle-associated compounds.

  1. Determine the disposition of ultrafine particles after deposition in the respiratory tract, and whether respiratory abnormalities alter the disposition pathways or rates.

Despite the current interest in potential differences between the disposition of fine and ultrafine particles after deposition in the respiratory tract, little progress has been made, and little work appears to be under way. The technical difficulty of measuring small amounts of ultrafine particles in various intrapulmonary and extrapulmonary locations continues to be a deterrent to progress. The recent development of 13C-labeled ultrafine carbon particles is likely to advance this field, and tracer technologies need to be developed and applied for use with other types of ultrafines.

Sufficient work has been done to confirm that solid ultrafine particles can penetrate into the circulatory system and reach other organs, but quantitative data are still lacking. There has been no apparent effort to study the dosimetry of nonsolid ultrafine condensates. Moreover, there has been no work on the disposition of ultrafines in either humans or animals that have respiratory abnormalities. As investigative techniques are developed, it is important that they be applied to both normal and abnormal subjects.

  1. Develop information on interspecies differences and similarities in the translocation, bioavailability, and clearance of particles in abnormal vs. normal respiratory tracts.

Little research appears to have been completed recently or to be under way addressing interspecies differences in particle clearance, translocation, or bioavailability in either normal or abnormal respiratory tracts. Recent work demonstrated marked differences in the sites of retention of fine particles in lungs of normal rats and nonhuman primates, but at lung loadings much higher than would result from environmental exposures. There are some new data and reviews on

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

particle clearance in different species, but the committee is unable to identify any direct intercomparisons among species or comparisons in the presence of respiratory abnormalities.

Adequacy of Current Research in Addressing Information Needs

Although the volume of dosimetric work shown in Table 3.5 reflects a level of effort commensurate with the committee's recommendations, there is not yet an adequate focus on the specific information needs described by the committee. Only a portion of the work has addressed characteristics other than age and sex; there has been insufficient work on the impact of respiratory abnormalities. The committee called for development and validation of mathematical models for predicting deposition and clearance in abnormal lungs. There has been only modest advancement in the modeling of dosimetry in susceptible people and little effort to validate the models. Efforts to improve interspecies extrapolation models continue in a few laboratories but, again, little effort to validate the models. There has been little effort to assess dosimetry of any type in animal models of human respiratory abnormalities. Many potentially important aspects of respiratory abnormalities—such as microdosimetry in tissues and cells, bioavailability of particleborne compounds, translocation and clearance, and handling of diverse particle types—have been addressed little or not at all. Although the level of effort might appear adequate, the degree of focus is not yet adequate.

Among the many programs, studies, and recent reports contributing new information on the dosimetry of particles, only a portion are focused specifically on dosimetric issues. Much of the information was produced as a byproduct of research focused on health responses to inhaled particles, rather than on particle dosimetry. That is appropriate, but effort is needed to make investigators broadly aware of the need for dosimetric information to encourage them to develop and publish the data as a specific, albeit opportunistic, product of their research. In a related vein, our review demonstrated that relevant information is being produced as a byproduct of pharmaceutical re-

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

search. That suggests the importance of looking beyond the traditional environmental research community when searching for and summarizing information relevant to environmental dosimetric issues.

The information on particle deposition in potentially susceptible subgroups has grown since the 1996 PM criteria document; results have demonstrated important differences in total fractional deposition in some disease states. The findings support the importance of the committee's recommendations. Work is needed on a wider range of susceptibility conditions, and more emphasis is needed on regional and local deposition (deposition “hot spots”) in susceptible people.

Much less information has been, or is apparently being, produced on differences in the clearance and translocation of deposited particles and in bioavailability of and cellular response to particleborne compounds due to age or respiratory abnormalities. Although many adverse responses might be most strongly moderated by deposition, some might be more strongly influenced by the amount and location of retained dose. Translocation and bioavailability issues remain important for an understanding of response mechanisms.

The research recommendations noted ultrafine particles as a specific class on which more dosimetric information is needed. The effort focused on ultrafines is modest and addresses a narrow range of ultrafine-particle types. Like coarse and fine particles, ultrafines include diverse physiochemical classes that can be expected to behave differently when deposited.

There is not yet an adequate effort to determine the dosimetry of particles of any type in animals that are used to study characteristics of human susceptibility. If the animal models of susceptibility are to be useful, differences in particle deposition and disposition, as well as differences in response, must be considered. Not only might differences in dosimetry help to explain differences in response on a total or regional dose basis, but the models might also be useful for predicting the influences of abnormalities on local deposition in susceptible people on whom such data might never be obtained directly. Research sponsors need to explicitly encourage investigators to evaluate dosimetry as an integral component of the characterization of the responses of animal models.

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×
Application of Evaluation Criteria
Scientific Value

The scientific value of this research is generally high. Nearly all the work noted above builds on previous knowledge in a logical way that will lead to a more integrated understanding of PM-related health effects. Most of the dosimetric data collected in response to PM research needs will also have high value for other purposes, such as understanding and predicting the dosimetry of inhaled pharmaceuticals in normal vs. abnormal respiratory tracts and in animal models vs. humans. Findings pointing toward differences in respiratory control, anatomy, and defenses are raising issues likely to lead to more studies that will provide a more complete understanding of respiratory-tract structure and function.

Although insufficient effort is being expended to evaluate dosimetry in animal models of respiratory abnormalities, the resulting data will have high scientific value for determining the extent to which differences in health responses between normal and susceptible people are due to differences in dose and differences in responsiveness. This information is important for the selection and interpretation of the animal models.

Considering the previous lack of data on dosimetry in people who have respiratory abnormalities or animal models of these conditions, almost any such data would have scientific value. As results accumulate, it will be important to focus on more-specific and more-detailed issues, for example, on local and regional deposition rather than total deposition.

Decisionmaking Value

The results of this research will have a direct bearing on the setting of air-quality standards in two principal ways: providing the dose component of dose-response information required to set the standard, and providing information on the dose component of susceptibility as input into the adjustment of the standard for protection of sensitive subpopulations.

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

Knowledge of differences between the deposited doses received by normal people and those who have respiratory abnormalities will play a direct role in the estimating of safe and hazardous PM exposures. In this role, dosimetry is an equal partner in the exposure-dose-response paradigm that is integral to risk assessment. In addition, knowledge of dosimetry in animal models of susceptibility will play an indirect role in decisionmaking by influencing the selection of appropriate models, the interpretation of results of the use of the models, and the understanding of the role of dose variables in the susceptibility of humans.

Feasibility and Timing

Lack of feasibility is not impeding the progress of dosimetric research. As noted in the committee's first report ( NRC 1998), there are few technical limitations on obtaining the needed data. An exception might be current technical limitations on detecting ultrafine particles in tissues and fluids.

The research gaps identified above result from inadequate coverage of topics, not from inadequate research tools or personnel. It remains true, as stated in the first report, that with the combination of modest funding and its direction toward key information gaps, most dosimetric issues could be resolved soon. It is clear that not all important topics are being covered, although most of the time originally projected for this work has been spent. Without greater attention to targeting particular gaps, key issues might not be adequately resolved.

RESEARCH TOPIC 7. COMBINED EFFECTS OF PARTICULATE MATTER AND GASEOUS POLLUTANTS

How can the effects of particulate matter be disentangled from the effects of other pollutants? How can the effects of long-term exposure to particulate matter and other pollutants be better understood?

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×
Research Progress and Status
Toxicology

PM exists in outdoor air in a pollutant mixture that also contains gases. Thus, biological effects attributed to PM alone in an observational study might also include those of other pollutants that arise independently or through interactions with PM. There might be chemical interactions between gases and PM, or gases can be adsorbed onto particles and thus carried into the lung. Interactions can also occur in the process of deposition on lung airway surfaces and later through lung injury. Research relevant to this topic includes toxicological and clinical studies that examine the effects of gaseous copollutants on the health impacts of PM.

The committee's first two reports (NRC 1998, 1999) indicated that it is important to consider the effects of combined exposures to particles and copollutants when characterizing health risks associated with PM exposure. This research topic remains of critical importance because epidemiological studies might not be able to characterize fully the specific contributions of PM and gases in causing health outcomes. Thus, mechanistic studies are needed to determine the relative roles that various components of ambient pollution play in observed health effects of exposure to atmospheric mixtures.

The HEI database was examined to determine the research status of this topic. A number of current studies involve pre-exposure to high levels of ambient gases (such as ozone and sulfur dioxide) to induce pulmonary pathology in animals so that effects of PM in a compromised host model can be assessed. However, those types of studies are not considered to fit this research theme. A number of studies are using concentrated ambient PM (CAP), and such exposure atmospheres might include ambient gases unless they are specifically scrubbed out before entering the exposure system. However, it was often not possible from a study description in the database to determine whether the effects of these gases on response to PM were being examined. One group of researchers is exposing animals specifically to highly complex emission atmospheres to determine the rela-

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
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tive contributions of PM and gaseous copollutants to various health effects.

Studies of interactions of gaseous copollutants with PM are being conducted with both animal and controlled human-exposure studies. Fewer studies are examining such effects in vitro. Endpoints span the array of effects observed in populations but focus largely on cardiovascular effects, inflammatory response, and mediators. Some animal studies and some human studies also involve the use of compromised hosts to compare effects with those occurring in normal animals and humans. As with all animal toxicity studies, it is important to be able to relate responses to human responses. That is specifically addressed as a goal in only one study program being performed at one of the EPA-sponsored PM centers.

One of the gaseous copollutants of major concern with regard to interaction with PM is ozone, and this copollutant is the subject of the greatest research effort. That is evident in Table 3.6, which shows the list of gaseous pollutants being studied and the number of research projects addressing them. However, some attention is also being given to other gases of potential concern, such as sulfur dioxide and nitrogen dioxide. Other suggested modulators of PM-induced effects are receiving little attention. The role of ambient gases should receive more attention in studies with CAP because these types of expo sures are the most realistic and do not require the generation of “sur-

TABLE 3.6 Gaseous-Copollutant Studies

Gaseous Copollutant

No. of Animal Toxicity Studies

No. of Human-Exposure Studies

O3

12

7

SO2

4

0

NO2

3

1

NH3

1

0

CO

1

0

Unspecified

5

1

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

rogate” atmospheres. Opportunities should be sought to augment CAP with concentrated gaseous pollutants or to scrub out specific residual gasses.

Epidemiology

PM in outdoor air is one component of a complex mixture that varies over time and also geographically on both small and large spatial scales. PM is one of the six pollutants in outdoor air regulated as “criteria pollutants.” In part, driven by the needs of evidence-based regulation, epidemiologists and other researchers have attempted to separate the effects of PM from those of other pollutants, even though they are often components of the same mixtures and their concentrations are often correlated, reflecting their shared sources. The effects of the individual components of the mixture can be assessed in time-series approaches with multivariate statistical methods or in designs that incorporate contrasts in exposures to mixtures by drawing participants from locations that have different pollutant mixtures (for example, with higher and lower ozone concentrations).

In addressing the “combined effects” of PM and other pollutants, one of the scientific questions of interest is whether the risks to health associated with PM exposure vary with the concentrations of other pollutants. For example, are risks posed by PM to children who have asthma higher in communities that typically have higher background concentrations of ozone than in other communities? Epidemiologists refer to this phenomenon as “effect modification, ” and its presence is generally assessed with statistical methods that test for interaction in multivariable models. Effect modification that is positive, or synergistic, results in greater risks than would be predicted on the basis of estimates of risk posed by PM itself. Studies of effect modification need substantial sample sizes if statistical power is to be sufficient.

Studies on combined effects need to include information on PM and the copollutants of interest. Epidemiological studies of diverse design are potentially relevant to this topic. As for studies of mixtures

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

generally, a precise characterization of combined effects requires a substantial body of data.

Examination of the HEI research inventory shows that many studies in progress should provide relevant information on modification of PM risks by other pollutants. The range of PM indicators across the studies is broad, but most studies include monitoring results for the principal gaseous pollutants of concern. Samples range from too small and consequently uninformative to large enough to provide insights into combined effects.

Adequacy of Current Research in Addressing Research Needs

Although attention to the issue of effects of gaseous copollutants on the toxicity of PM is increasing, the current controlled-exposure research portfolio aimed at assessing the role of gaseous pollutants in health effects of PM is not adequate. The use of CAP can provide valuable information on effects of exposure to complex mixtures. Furthermore, the research effort in evaluating the role of gases in influencing particle effects seems to be lagging behind the effort in studying of specific components of PM in the absence of gaseous copollutants. The epidemiological research portfolio on this topic is relatively substantial; as most epidemiological studies of PM include data on gaseous copollutants. There does not yet appear to be a systematic, sustained plan for implementing studies of chronic exposure.

Application of Evaluation Criteria
Scientific Value

The criteria pollutants have long been addressed as though their effects on health were independent, with recognition that they exist as components of complex mixtures in the air. Rather than seeking to characterize mixture toxicity overall, researchers have sought to determine, experimentally or in observational data, whether the pres-

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

ence of one pollutant changes the effect of another (a phenomenon referred to in epidemiology as “effect modification”). Findings on effect modification inform estimates of risk posed by mixtures and suggest hypotheses for followup laboratory investigation.

Decisionmaking Value

Present regulations are based on the tenet that effects of individual pollutants are independent and that public-health goals can be met by keeping individual pollutants at or below mandated concentrations. Epidemiological demonstration of effect modification for PM effects by other pollutants, such as ozone, would indicate that the regulatory structure does not fully reflect the actual risks to the population.

Feasibility and Timing

Epidemiological and controlled-exposure studies of effect modification or interaction can be carried out; in fact, most contemporary studies include the requisite data on other pollutants. Thus, studies could be readily carried out now to explore whether other prevalent pollutants affect risks posed by PM. Methods for experiments involving mixed atmospheres are available. Analytical information derived from evaluation of atmospheres in epidemiological studies can help to determine specific components of mixed atmospheres to be used in controlled-exposure protocols.

RESEARCH TOPIC 8. SUSCEPTIBLE SUBPOPULATIONS

What subpopulations are at increased risk of adverse health outcomes from particulate matter?

A number of subgroups within the population at large are postulated to be susceptible to the effects of inhaled PM. They include

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

people who have COPD, asthma, or coronary heart disease; the elderly; and infants. Also, fetuses are possibly susceptible. Those groups have long been assumed to be susceptible to the effects of air pollution, in general, and therefore assumed to be at risk from PM. Epidemiological data support that assumption, as does understanding of the compromised organ systems of people with chronic heart and lung diseases and of the physiologic and immunologic vulnerability of infants and the elderly. A number of epidemiological and controlled-exposure investigations are now directed at characterizing health effects of PM in those subpopulations. Other populations might also be at excess risk from PM, and the committee considers that this research topic includes both subpopulations already considered susceptible and others yet to be identified.

In susceptible subpopulations, there is likely to be a range of vulnerability reflecting the severity of underlying disease. For example, in persons with asthma, there is a broad distribution of level of lung function and of increased nonspecific airway responsiveness, a hallmark of the disease. The degree of susceptibility can also depend on the temporal exposure pattern. However, data to support such biologically based speculations are still notably lacking. For example, whether all children are equally at risk or only children who are exercising or who have specific predisposing factors, such as a history of atopy or asthma or other respiratory disease history, is unknown. In adults, the interplay among factors that determine susceptibility, such as the presence of both COPD and coronary heart disease, is not yet understood. Findings of both acute and chronic morbidity and mortality studies suggest that those with prior respiratory disease are more susceptible to acute changes in ambient PM concentrations.

Although from the early days of air-pollution research hypotheses have been proposed related to increased susceptibility of selected fractions of the population, much of that work has been directed at identifying acute morbid events during acute exposures. For example, research in London in the 1950s followed up on the observation that many of the excess deaths noted in the December 1952 fog were of persons who were already quite sick, many with heart or lung disease. Panels of people with chronic bronchitis were followed during the 1950s and 1960s with monitoring of pulmonary function and symp-

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

toms. Those studies followed a design now referred to as a panel study, which involves following a susceptible subpopulation with relatively detailed tracking of their status. This model is particularly useful for assessing acute effects of exposure and can provide evidence relevant from both the clinical and the public-health perspectives. More recently, work has been directed toward testing whether exposure to particles can contribute to initiation of disease, as well as exacerbating existing conditions. To date, the collective evidence indicates that there are susceptible subpopulations, particularly of people who have chronic heart or lung diseases.

Research Progress and Status
Controlled-Exposure Studies

The committee identified 53 animal and human studies in the HEI database that specifically addressed the issue of subpopulations susceptible to PM-induced diseases (Table 3.7). In several cases, a study identified more than one susceptible subpopulation; for these, each population group was entered into the table.

Almost all the studies concern with diseases of the respiratory and cardiac systems; only one concerns increased susceptibility to cancer induction. Twelve studies concern age as a risk factor. The disease states of concern include pulmonary allergies, asthma, bronchitis, emphysema, COPD, and cardiac disease. Twenty-four of the studies involve human subjects, and 29 use animal models intended to mimic human disease.

The particulate atmospheres most frequently being used for toxicity studies are those with CAPs, carbon black, and residual-oil fly ash delivered via inhalation or intratracheal instillation. The duration of the exposures is variable but typically only hours or a few days; this contrasts with epidemiological studies that involve chronically exposed populations.

A strength of the studies is their focus on the major human diseases that have been identified by epidemiological studies as placing

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

TABLE 3.7 Controlled-Exposure Studies on Effects of PM on Susceptible Subpopulations

Susceptibility Factor

Humans

Laboratory Animals

Disease

Allergies

1

1

Asthma

9

1

Bronchitis

7

Emphysema

3

Cardiac

1

8

Chronic obstructive pulmonary disease

8

1

Cancer

1

Age

Infants

1

2

Children

3

Elderly

1

5

people at risk from exposure to PM. An additional strength is that epidemiological studies in which exposures cannot be controlled are complemented with controlled-exposure studies of humans and laboratory animals.

There are difficulties in investigating susceptible populations. The effect of PM exposure is not large enough to be readily and precisely detected without carrying out fairly large studies. Identifying study participants can be difficult, particularly if emphasis is placed on the most susceptible persons. Frail elderly persons and persons with advanced heart and lung disease, for example, might be reluctant to participate if study protocols are demanding. In contrast, experimental studies involve very small populations and typically short observation periods. In laboratory-animal studies, investigators typically attempt to circumvent this issue of population size by increasing the level of exposure or dose. It is common for all the treated animals to manifest disease or some other response. However, a critical ques-

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

tion is whether the disease states observed and the underlying mechanisms of pathogenesis with short-term high exposures (doses) studied over periods of days, and occasionally weeks, are relevant to assessing the risks posed by exposure over long periods, even at high ambient doses.

Beyond the extrapolation issue, the adequacy of the design of each toxicity study must be addressed. For example, in most cases, the investigators are typically studying relatively young animals, usually in the first fourth of their normal life span, whereas in humans a substantial portion of the disease of concern occurs in the last fourth of the normal life span. Many of the human diseases of concern are chronic, with periods of acute exacerbation. It is crucial that additional effort be directed at evaluating the animal models to assess the degree to which they mimic human disease.

Rationales for selection of the exposure atmospheres, exposure concentrations, and exposure durations were not always readily apparent from the project descriptions. There is also a special need to articulate the relevance of using intratracheal instillation, which delivers a large dose of particles at once, in contrast with the chronic exposures of concern for human populations.

Epidemiology

A general concern for the health effects of air pollution, including particles, on susceptible persons has permeated epidemiological research on air pollution. This concern has become increasingly focused as the body of evidence has expanded and led to hypothesis-driven studies of susceptible subpopulations. In addition, with the recognition that much of the morbidity and mortality associated with PM exposure appears to have been from cardiovascular diseases, the efforts to understand susceptibility have expanded greatly beyond considerations of chronic respiratory conditions, particularly asthma and COPD, to include persons with underlying heart disease.

About 70 funded studies using epidemiological databases were reviewed to identify those directed to understanding the impact of

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

particulate pollution on susceptible subjects, patients, or populations. In general, the studies can be divided into those related to people who have an underlying chronic condition (such as asthma, COPD, or pre-existing coronary arterial disease), those related to persons free of disease but considered to be at increased risk because of a relatively high pollution dose resulting from exertion or exercise, and those related to persons generally at risk for increased morbidity or mortality (such as the elderly). Across the studies, a wide variety of measures of exposure are used, and insights can be gained on some aspects of particle characteristics and toxicity. However, only a few of the strata of the matrix defined by subpopulation and particle characteristics are being addressed.

Taken together, the efforts under way indicate that a rigorous evaluation of risks posed by PM exposure of susceptible subpopulations with established diseases—such as asthma, COPD, coronary arterial disease, heart failure, and hypertension—can be expected. The evidence will be primarily in relation to PM mass as the exposure metric. The groups that have been or are being studied, as summarized in the examined HEI database, include subjects potentially at risk and patients. Few studies are identified specifically as targeted to ethnic minority populations.

Efforts are also under way to explore pathogenesis and intermediate markers of risk, including changes in blood concentrations of inflammatory markers and clotting factors; additional predictors of cardiac risk, including changes in heart-rate variability; and other risk factors for sudden death.

Several studies directed toward an understanding of mechanisms of putative cardiac effects in humans are being carried out in the EPA, at several of the EPA-sponsored PM centers, and through other funding agencies. These include panel studies and clinical studies of healthy persons and potentially high-risk persons exposed to ambient PM and to CAP. These studies are being conducted by multidisciplinary teams that include expertise in exposure assessment, epidemiology, and clinical toxicology. Investigating the role of PM in initiating disease is more challenging, and less progress can be expected in understanding how susceptibility plays a role in initiation of chronic

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

diseases, simply because the susceptible groups have been less well defined.

In all the studies mentioned above, most of the efforts are directed to explaining acute effects of relatively short-term modeled or directly measured exposures to ambient particles. In a few instances, copollutants or other gases are also being considered. In only a very few cases are effects of chronic exposure being considered; in those cases, long-term exposure is being modeled for relatively recently measured exposures and historical extrapolations of known industrial or ambient particles. Better modeling of past exposure is needed, to develop new efforts directed toward the understanding of chronic effects in potentially susceptible groups. Such data would also be useful in conjunction with studies of factors that determine the development of susceptibility.

Adequacy of Current Research in Addressing Research Needs

There is increasing use of animal models and humans with chronic heart or lung disease in studies to evaluate effects of PM exposure. However, the animal studies need to mimic the human disease state of interest properly. Better modeling of past exposure is needed to develop new efforts to understand chronic effects in potentially susceptible subpopulations. Collection of such data in conjunction with studies of factors that determine the development of susceptibility would be useful.

Application of Evaluation Criteria
Scientific Value

The hypothesis that particular groups in the population have increased susceptibility has been long advanced and supported by substantial epidemiological evidence. In fact, a general acceptance of the hypothesis has led to focusing of effort in a large number of projects

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

on the assessment of acute air-pollution effects on morbidity and mortality in selected groups of potentially susceptible persons. The results have been relatively consistent in demonstrating modest effects of particles as measured by mass. The same susceptible subpopulations will need to be reinvestigated, and previously unrecognized subpopulations will need to be considered as hypotheses concerning toxicity-determining characteristics of particles are increasingly refined.

Decisionmaking Value

Data on susceptible populations are critical to decisionmakers because the Clean Air Act requires that protection against risks posed by air pollution be extended to almost all persons. Standards are, in fact, intended to provide protection with “an adequate margin of safety.” Sufficient studies are under way to identify and reduce uncertainty related to susceptible groups with respect to acute effects of particle mass. However, for each individual study and for the studies as a group, it is important to anticipate how the results will influence decisions in establishing a NAAQS for PM—that is, will the information obtained provide an improved scientific basis for a decision on appropriate standards for ambient PM? It appears that few of the investigators have adequately considered this matter in a critical manner, especially for the controlled-exposure studies.

Feasibility and Timing

The only practical way to increase the number of investigations with regard to either acute or chronic exposures is to undertake studies in conjunction with current supersite or speciation-site data collections or with the use of additional exposure-data sources in the future. There is continuing development of animal models that mimic various aspects of potentially susceptible human conditions. Thus, this field continues to evolve.

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

RESEARCH TOPIC 9. MECHANISMS OF INJURY

What are the underlying mechanisms (local pulmonary and systemic) that can explain the epidemiologicalal findings of mortality/morbidity associated with exposure to ambient particulate matter?

Epidemiological studies have associated various health outcomes with exposure to ambient PM. Controlled-exposure studies are attempting to provide plausible underlying biological mechanisms for these health effects. The results have indicated a number of potential biological responses by which PM could underly possible pulmonary or systemic responses to PM exposures, many of which have been related to specific particulate characteristics, such as chemical or particle size. The major potential biological responses which have been suggested as underlying the reported human health effects from ambient PM exposures include oxidative stress, pulmonary inflammation, airway hyperreactivity, and alterations in the cardiovascular system, such as changes in blood viscosity, rate and pattern of heartbeat, and heart-rate variability. The issue of mechanistic plausibility has been addressed with animal models, in vitro systems, and clinical models. Of the studies described in the HEI database, about 50% involve animal toxicology, and the other 50% are roughly evenly divided between in vitro and clinical and studies. The relative apportionment of research effort for specific mechanisms of PM-induced responses and the allocation of these efforts among the three research approaches are indicated in Table 3.8.

Research Topic 9a. Animal Models

What are the appropriate animal models to use in studies of particulate matter toxicity?

As previously noted, epidemiological studies suggest that exposure to low concentrations of PM is associated with morbidity or mortality in susceptible people and not in normal healthy people.

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

TABLE 3.8 Mechanistic Studies

 

Experimental Approacha

Mechanism Examined

Animal Toxicology

In Vitro

Human Clinical

Pulmonary

Inflammation

20

9

14

Airway reactivity

5

3

Oxidative stress

4

4

Pulmonary function

1

4

Infection, immunology (includes asthma)

11

1

5

Otherb

12

3

4

Cardiovascular

Heart-rate pattern, variability

3

2

Blood coagulation

3

1

Other

16

7

a   Number of studies from HEI database. Some studies might be examining more than one endpoint.

b   In many cases, the specific mechanism examined was not indicated in the description in the database.

Experimental data show that healthy animals exposed to similar low concentrations of PM also show little to no effect. Animal models are needed to mimic susceptible human subpopulations, because, without supporting data from animal studies, it is difficult to identify individual toxic materials in ambient PM and the mechanisms by which they induce damage to human and pulmonary and cardiovascular systerms. The occurrence of some pathological conditions in an exposed population can establish the probability that some of or all the pollutants produce damages but, in any reasonable time frame, it cannot always differentiate the effects, if any, of specific pollutants or the mechanisms of their action. That will ultimately require controlled exposures of animals to individual pollutants and relevant mixtures and then

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

measurements of response. In the initial stages of investigating the toxicity of PM and copollutants, it was sufficient to determine a correlation between their presence in inspired air and disease. Now, however, animal models are clearly needed to establish causality, help to unravel cellular mechanisms, and help to elucidate specific PM components that produce responses.

Research Progress and Status

In assessing progress toward the development of animal models, the committee found projects to be distinguished by their heterogeneity. Of the 47 relevant studies identified, most used young normal animals, which were not models for susceptible disease. Fewer studies used older animals as models to evaluate the effects of age, and others used animal models of disease, such as asthma and hypersensitivity, chronic lung diseases, and cardiac dysfunction. Normal or mutant animals were used in some studies.

There are a number of difficulties in developing animal models of human diseases. Deposition of particles in animal lungs differs in both rate and location from that in human lungs, and there is a need for detailed knowledge of the distribution of deposition in animal lungs so that it can be related to deposition in human lungs (see research topic 6). Advanced scaling and modeling of the lung airways in animals should be encouraged. The cellular mechanisms by which the pertinent lung and cardiovascular diseases are produced in humans and by which particles exacerbate or initiate these conditions are not understood so it is difficult to produce analogous pathological conditions in animals. The lung contains more types of cells than most other organs and thus provides the opportunity for numerous types of interactions between cells exposed to PM atmospheres and increases the complexity of particle-tissue interaction.

It has been possible to mimic some aspects of specific human diseases in animals. Therefore, it might be necessary to be satisfied with modeling and studying only part of a disease constellation at a time. For example, “asthma-like” allergic conditions have been mod-

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

eled by sensitizing animals to various foreign proteins. That might produce marked contraction of airway smooth muscle on appropriate challenge but not involve other aspects of human asthma, such as inflammation and mucus gland hypertrophy.

Adequacy of Current Research in Addressing Research Needs

It is encouraging that numerous animal models are being used to measure the effects of exposure to PM. However, a substantial number of studies exposed healthy normal animals to particles, and this is not necessarily a useful model of exposure of susceptible humans. Even though animal models of cardiac and lung disease are being used to investigate the effect of particles, relevance to the human situation must be considered. Research to develop models that more closely mimic the natural history of human diseases caused by air pollution should be emphasized. Models need to be well characterized and validated before use.

Application of Evaluation Criteria
Scientific Value

The use of animal models that mimic susceptible human populations is important for the study of effects of ambient or surrogate PM. However, all models must be validated for their relevance to the human condition. Validated models will provide important insights into the mechanisms of action of ambient PM and associated pollutants.

Decisionmaking Value

Studies that use validated animal models will assist in the evaluation of particle characteristics that underlie human health effects of exposure to ambient PM. They will provide input into the standards-

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

setting process by contributing information needed to determine margins of safety for exposure.

Feasibility and Timing

Continued development and use of appropriate animal models are required. The necessary tools for such development are readily available.

Research Topic 9b. In Vitro Studies

What are the appropriate in vitro models to use in studies of particulate-matter toxicity?

In vitro studies are important in helping to determine underlying toxicological mechanisms. They remain a necessary complement to animal and clinical evaluations.

Research Progress and Status

The HEI database and the proceedings of the PM 2000 meeting list 34 studies related to this research topic. However, three of the studies do not deal with in vitro methods, and four are not relevant to the PM issue, but rather address issues of occupational and fibrogenic particle exposure. Most in vitro studies with PM are still conducted without considering the important issue of relevant doses to be used or, at a minimum, the use of a study design incorporating dose-response assessments. Many studies also focus on only one particle type collected from different ambient sources without including any control particles; in general, this type of study design should be avoided.

Several in vitro studies reported in the database are based on findings of animal studies that use very high doses of a specific particle type. Although state-of-the-art methods of cellular and molecular

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

toxicology are applied, the lack of an adequate justification for doses, the lack of control particles, and the presence of insufficient discussion of these important issues make the interpretation of results difficult. The results, contrary to what investigators of those studies conclude, will not be directly applicable to an understanding of pathophysiological mechanisms of PM action, nor will they be useful for the validation of high-dose animal studies as models of human respiratory-tract responses to much lower doses. Conclusions that are based on high doses do not provide arguments for the biological plausibility of effects of ambient PM. At best, the studies could contribute mechanistic information on PM effects in occupationally exposed workers whose lungs are generally exposed to a particulate compound at several milligrams per cubic meter.

On the positive side, several studies that are under way do use appropriate dose-response designs. Recognizing the need to use lower doses, these studies compare the toxicity of different particle types and responses in animal vs. human cells; this facilitates extrapolation of in vivo responses in animals to humans. Although high doses are also delivered, the studies are valuable with respect to a toxicological evaluation of potentially reactive components, but will require followup studies with more realistic doses. Another well-designed study includes a comparison of responses in airway biopsy cells from normals and asthmatics for an in vitro determination of relative sensitivities to ambient PM. One study in this category of comparative in vitro studies evaluated the response of human bronchial epithelial cells to PM collected before and after a steel mill closure; the goal was to identify the importance of differing PM composition—in this case related to transition metals—for inducing adverse health effects.

Several other studies use methods of in vitro priming—for example, with lipopolysaccharides—of specific respiratory-tract cells, including alveolar macrophages and epithelial cells, to compare responses of oxidative stress induction by PM in sensitized cells and normal cells. These studies are aimed at assessing mechanistic concepts of PM toxicity and contribute to the establishment of a good basis for designing further in vivo studies.

Two planned in vitro studies are designed to investigate age differences by using cells from young and old animals and applying a variety

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

of doses down to very low ones. Plans of one group of investigators include delivery of particles in the airborne state to in vitro cell cultures so that the dosing will be similar to in vivo conditions. The importance of coculture of different cell types is realized in one study in which an in vitro lung-slice technology is used to compare responses to a variety of PM of different sources and to surrogate control particles. One in vitro study is aimed at evaluating mutagenic effects of airborne PM and associated organic compounds, addressing long-term effects. However, administered doses and the use of a dose-response design are not indicated, and it is necessary to consider these issues in studies addressing potential long-term effects.

Adequacy of Current Research in Addressing Research Needs

The current and planned in vitro studies are designed to investigate several components of PM by using a number of end points, such as changes in the levels of inflammatory cytokines, and chemokines, release of oxidants, and oxidative stress responses. The issues of age-dependent responses and modulation of responses in cells from susceptible subjects are also being investigated. However, many current in vitro studies do not use or consider appropriate doses but, instead, are using unrealistic high doses; a dose-response design is still the exception in these types of studies. Despite those shortcomings, which need to be rectified, comparative in vitro toxicity studies to establish concepts and elucidate mechanistic events of PM toxicity are valuable additions to the database.

Application of Evaluation Criteria
Scientific Value

Specific mechanistic hypotheses related mainly to PM-induced effects are being tested at several laboratories. Although in vitro models are used for investigating mechanisms of PM-induced toxicity, the relevance of identified mechanistic pathways is highly question-

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
×

able when they are based on high doses, as is the case in most of the current studies. A major gap is a lack of testing of the validity of conclusions for specific mechanisms by using relevant low doses; this is due in large part to the lack of a demonstrated causal relationship between relatively low PM exposures and adverse effects in controlled in vivo studies. Thus, in vitro studies have their greatest scientific value when they are designed on the basis of results of controlled whole-animal or clinical studies, involve relatively realistic exposures, and test specific mechanistic hypotheses.

Decisionmaking Value

Mechanistic information at the cellular and molecular levels obtained from well-designed in vitro studies can contribute to the weight of evidence regarding a causal relationship between PM exposure and health effects. That will reduce uncertainties related to the plausibility of observed adverse PM effects. Knowledge gained about mechanisms of PM toxicity will contribute greatly to the scientific justification of the PM standards.

Feasibility and Timing

In vitro studies clearly are feasible in many laboratories. It is important for special attention to be directed toward the use of relevant doses. Moreover, the development of appropriate new methods for in vitro studies should be encouraged, including airborne-particle exposures of cell cultures, use of cells from compromised lungs, and use of genetically modified cells. Because the developmental phase of these models is potentially long, useful results might not become available very soon.

Research Topic 9c. Clinical Models

What are the appropriate clinical models to use in studies of particulate matter toxicity?

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
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Clinical studies are controlled exposures of humans. In the case of PM, such studies are designed to use laboratory-generated surrogate particles or concentrated ambient-air particles. The use of human subjects avoids the need to extrapolate results from other species. Both normal and susceptible subpopulations can be studied, and physiologic, cellular, immunologic, electrocardiographic and vascular end points, as well as symptoms, can be assessed. Elucidation of responses in humans is key to understanding the importance of ambient pollution and determining the nature of adverse health effects of PM exposure.

Research Progress and Status

Review of the HEI database and proceedings of the PM 2000 meeting identified about 10 active human-exposure studies. All are using particles of concern, which include CAP, ultrafine carbon, ultrafine acidic sulfates, diluted diesel exhaust, and smoke from burning of vegetable matter. Studies are under way in healthy volunteers, asthmatics, and atopic people. Studies in people who have COPD or cardiac disease are planned. The clinical studies focus on evaluation of pulmonary and systemic responses, such as pulmonary inflammation and injury to epithelial cells; cardiac rhythm, rate, and variability; initiation of the coagulation cascade; and symptoms.

Few laboratories are equipped to perform clinical studies of PM. However, the similarities in their protocols enhance the likelihood of obtaining useful data. For example, studies with CAP and ultrafine particles have incorporated prolonged electrocardiographic monitoring after exposure. All studies include physiologic assessments of lung function, and indicators of airway inflammation in nasal or bronchoalveolar lavage fluid, induced sputum, or exhaled air (such as nitric oxide). In addition, coagulation indexes in blood are examined in some of the studies. In selected cases, efforts have been made to centralize analytical studies in a core laboratory for standardization of techniques.

There are a number of difficulties in establishing clinical models to study PM. Although the particle concentrators allow exposure to

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
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relevant atmospheres, the mixtures vary from day to day and, typically, minimal chemical analyses of the particles are performed. If responses to CAP are variable, it is not possible to determine whether the variability resulted from differences in human susceptibility or in particle chemistry. In contrast, studies with surrogate particles result in reproducible exposures but mimic only selected aspects of ambient particulate pollution. Furthermore, the epidemiological data suggest that the most severely ill are at risk of pollutant effects; these subgroups cannot be used in controlled clinical studies. Because clinical studies by design are limited to short-term exposures, they will rarely be able to contribute to an understanding of development of chronic disease secondary to exposure to particles.

The particle-exposure systems used in clinical studies include environmental chambers, facemasks, and mouthpieces. Each design offers specific advantages, but the mouthpiece studies with ultrafine particles have incorporated measurements of total particle deposition. One clinical study will investigate the interaction of particles with ozone, another plans to incorporate metals into the particles, and virtually all include some level of exercise to enhance minute ventilation, thus increasing the inhaled dose of pollutants.

Adequacy of Current Research in Addressing Research Needs

The current and planned clinical studies are designed to investigate CAP and several specific components of PM (such as size, acids, metals, and diesel exhaust) with a number of pulmonary and systemic end points. Studies are under way in susceptible subpopulations and are planned in other subgroups with pre-existing disease. Despite the limited facilities available for clinical research, the array of studies under way should provide valuable information on PM toxicity.

Application of Evaluation Criteria
Scientific Value

Clinical studies present an opportunity to examine responses to

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
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PM in both healthy and susceptible subpopulations. Carefully designed controlled exposures provide information on symptomatic, physiologic, and cellular responses in both healthy and at-risk groups. They also provide important insights into mechanisms of action of PM. Such studies can provide needed information on PM deposition and retention in healthy and susceptible subpopulations (see research topic 6).

Decisionmaking Value

Clinical studies often provide important information for regulatory decisions. Assessing acute responses in groups that have chronic diseases will establish important insights into plausible mechanistic pathways. In addition, they provide crucial data on relative differences in responsiveness between healthy and potentially at-risk populations.

Feasibility and Timing

Studies are under way in several laboratories. They should provide highly relevant information for the next review of PM for regulatory decisions.

RESEARCH TOPIC 10. ANALYSIS AND MEASUREMENT

To what extent does the choice of statistical methods in the analysis of data from epidemiological studies influence estimates of health risks from exposures to particulate matter? Can existing methods be improved? What is the effect of measurement error and misclassification on estimates of the association between air pollution and health?

The first report of this committee (NRC 1998) outlined several methodological issues that needed further study. These included the

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
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choice of statistical methods for analyzing data obtained from other studies, especially epidemiologic studies. Because more than one method can be used to analyze data, it will be important to understand the extent to which alternative approaches can influence analytical results. In addition, new study designs will require new approaches to analyze the data. These include development of analytical methods to examine several constituents and fractions of PM in an effort to understand their associations with health end points and design of models and approaches to incorporate new biological insights. Specific attention was given to measurement error, an issue inherent in most epidemiological studies that use ambient-air data to characterize subjects' exposure. The committee's second report (NRC 1999) reiterated those needs and noted the existence of relevant research and papers nearing completion.

Review of scientific literature, meeting abstracts, and the HEI database identified extensive progress on several methodological subjects. The review was intended to evaluate the extent to which the research needs previously identified by the committee are being addressed and to stimulate further targeted research.

General Methodological Issues
Model Development and Evaluation

Over the last several years, there has been considerable development of time-series data-analysis methods, which have provided much of the evidence on the association between PM exposures and health effects. The methods assess the variation in day-to-day mortality or morbidity counts with variation in PM concentrations on the same or previous day. Although systematic and comprehensive comparisons of alternative methods have not been reported, limited comparisons have suggested that results are relatively robust to the statistical approach used. However, the choices of input variables and data have been shown occasionally to influence results (Lipfert et al. 2000). That is particularly true with respect to the choice of pollution variables in

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
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the statistical models. The presence of other variables in the models can influence the association between health measures and particulate air pollution.

The application of the time-series studies has been facilitated by recent advances in hardware and software and by the development of statistical approaches that can appropriately account for the data structure of the daily time series. Time-series analyses were initially conducted on a single location that had been selected primarily on the basis of data availability, rather than representing selection from a defined sampling frame. Meta-analysis was then used to summarize the data and to gain a more precise estimate of the effect of PM on mortality or morbidity. Recently, studies of more-formal, multicity designs have been conducted. These approaches have a priori plans for selecting locations and have standardized statistical methods across locations. The European Air Pollution and Health: A European Approach (APHEA) project (Katsouyanni et al. 1995) is a pioneering effort that initially analyzed routinely collected data from 15 European cities in 10 countries with a common statistical protocol, examining mortality and emergency hospitalizations in some cities. In the United States, the HEI has funded the National Morbidity, Mortality and Air Pollution Study (NMMAPS) (Samet et al. 2000, 2001). The NMMAPS includes analyses of mortality and morbidity separately; a joint analysis of morbidity and mortality is planned. For the mortality analysis, the NMMAPS investigators used a sampling frame defined by U.S. counties. The 90 largest urban areas (by population) were selected, and the daily mortality data for 1987-1994 were analyzed to assess associations with PM and other pollutants.

The methods used in the APHEA project and the NMMAPS show the potential power of multicity approaches. The potential selection bias of only a single or a few locations is avoided. Combining information across locations, increases power and heterogeneity. In addition, health effects can be compared between regions that have similar air-pollution levels.

Other research efforts involving model development are the exploration of distributed-lag models (Schwartz 2000a; Zanobetti et al. 2000), efforts to understand the dose-response relationship between PM exposure and health effects (Schwartz 2000b; Smith et al. 2000;

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
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Schwartz and Zanobetti 2000), and examination of alternative ways of analyzing the relationship between air-quality data and health end points (Beer and Ricci 1999; Sunyer at al. 2000; Tu and Piegorsch 2000; Zhang et al. 2000). Other research efforts have also aimed at combining results from several studies, including those by Stroup et al. (2000) and Sutton et al. (2000).

Measurement Error

The difference between actual exposures and measured ambient-air concentrations is termed measurement error. Measurement error can occur when measures of ambient air pollution are used as an index of personal exposure. For PM, the three sources of measurement error are instrument error (the accuracy and precision of the monitoring instrument), error resulting from the nonrepresentativeness of a monitoring site (reflected by the spatial variability of the pollutant measured), and differences between the average personal exposure to a pollutant and the monitored concentration (influenced by microenvironmental exposures).

With regard to assessing the impact of outdoor exposures, the most important source of measurement error is related to the representativeness of the placement of monitors. In acute studies, other sources of error will not vary substantially from day to day. But in chronic studies, the most important errors are those associated with microenvironmental exposures. The presence of indoor sources of PM and the influence of home characteristics on penetration of outdoor particles into the indoor environment can be a source of substantial exposure error. The influence of home characteristics is important because it varies with geographical location, climate, socioeconomic factors, and season. Because those factors could introduce systematic errors, they must be considered in the analysis and interpretation of results of chronic epidemiological studies. They are often taken into account by using not direct measures of exposure, but surrogate measures that would influence the exposures, such as smoking in the household, the presence of gas stoves, and air conditioning.

Measurement error is of particular concern in studies intended to

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
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isolate the effects of particles from those of gases or to distinguish the effects of individual particle species or size fractions from each other. When several population variables are included in the same analyses and the different variables have different magnitudes and types of measurement error, the issue of estimating the associations between health responses and specific variables is even more complicated. A well-measured but benign substance might serve as the best empirical predictor of community health effects, rather than a poorly measured but toxic substance that is similarly distributed in the atmosphere. The problem is that most pollutants tend to be similarly distributed, so collocated time series of pollutant measurements tend to covary because all pollutants are modulated by synoptic meteorological conditions. Long-term averages of pollutant concentrations tend to covary across cities because the rates of many categories of emissions tend to increase roughly with population. Various methods are available to adjust statistical analyses for the effects of differential measurement error (Fuller 1987; Carroll et al. 1995).

Several statistical issues must be considered in addressing measurement error. A full discussion of these issues is found in Fuller (1987) and Carroll et al. (1995). The most important is the type of model in which the measurement error is imbedded. Generally, in linear models, measurement error can be understood if it is assumed that errors are independent of each other and of other variables in the model and that they follow the same statistical distribution. However, it is common for measurement-error distribution and properties not to be readily apparent, for example in ambient-air quality data, because “true” measurements of personal exposure have not been available. Recent studies have generated data that will provide a better understanding of the properties of measurement error. Until its specific properties are understood, its consequences will be unclear. For instance, Stefanski (1997) cites examples from a linear model in which the regression coefficient could be biased in either direction or unbiased, depending on the characteristics of the measurement error. The issues are increasingly complex as one moves to multiple-regression models (Carroll and Galindo, 1998) and then to nonlinear models.

Development of a framework or method will be useful in consider-

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
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ing the effects of measurement error on population-mortality relative risks (Zeger et al. 2000). The framework demonstrates that for a wide range of circumstances the impacts of measurement error will either lead to underestimates of association or have a negligible effect. Combined with some of the data now being generated, the framework promises considerable progress toward an understanding of measurement error.

Harvesting

Harvesting is an issue raised by time-series mortality studies. The term “harvesting” refers to the question of whether deaths from air pollution occur in people who are highly susceptible and near death (and die a few days earlier because of air pollution than they otherwise would have) or the air pollution leads to the death of people who are not otherwise near death.

Many studies have identified associations between daily mortality and air-quality variables measured at the same time or a few days before deaths, but none of them has been able to address fully the issue of harvesting, although several recent analyses (Zeger et al. 1999, Schwartz 2000c) suggest that the findings of daily time-series studies do not reflect mortality displacement alone. Several analytical approaches have been proposed to address harvesting, and they need to be tried on additional data sets and refined to quantify better the degree of life-shortening associated with PM and other pollutants. Four recent papers examine this issue from different perspectives (Smith et al. 1999; Zeger at al. 1999; Murray and Nelson 2000; Schwartz 2000c).

Spatial Analytical Methods

An important issue in the analysis of data from studies that examine the association between city-specific mortality and long-term average pollutant concentrations, is whether observations of individual subjects are independent or correlated. Spatial correlation in

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
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mortality can result from common social and physical environments among residents of the same city. Air pollution can be spatially autocorrelated as a result of broad regional patterns stemming from source and dispersion patterns.

In a recent reanalysis of data from the study by Pope et al. (1995), which examined associations between mortality in 154 cities throughout the United States and fine-particle and sulfate concentrations, Krewski et al. (2000) developed and applied new methods to allow for the presence of spatial autocorrelation in the data. The methods included two-stage random-effects regression methods, which were used to account for spatial patterns in mortality data and between-and within-city specific-particle air pollution levels, and application of spatial filtering to remove regional patterns in the data. Taking spatial autocorrelation into account in this manner increased the estimate of the mortality ratios associated with exposure to PM and led to wider confidence limits than in the original analysis; it was assumed that all individuals in the study represented independent observations.

The initial work on the development of analytical methods for the analysis of community-level data that exhibit clear spatial patterns warrants further investigation. Failure to take such spatial patterns into account can lead to bias in the estimates of mortality associated with long-term exposure to fine particles and to inaccurate indications of statistical significance.

Adequacy of Current Research in Addressing Information Needs

The recent research appears to address the research gaps and needs addressed by the committee. That is especially true for the measurement-error and harvesting issues. Because this research is new, it needs to be digested and applied to several data sets to increase our understanding. Data that are available or being collected allow further testing of the applications and methods. However, several subjects for further research are: elucidation of the statistical properties of the new spatial approaches discussed, consideration of

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
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alternative ways of addressing spatial autocorrelation in the data, and application of such spatial analytical methods to additional data sets.

Application of Evaluation Criteria
Scientific Value

The research has been well conducted with strong statistical tools. In addition, it has taken advantage of the existing literature and statistical tools while applying them to new subjects. However, the statistical tools have been applied to few data sets. The value of the research will increase as it is applied to more data sets and as approaches and results from the various studies are compared, synthesized, and reconciled.

Decisionmaking Value

The research can contribute substantially to decisionmaking. Understanding of potential influence of model approaches on results is key to adequate use of the research findings. Because measurement error can affect the results, insights into the influence of measurement error will assist in the interpretation of the results and ultimately increase their influence in decisionmaking. Understanding of harvesting will help to place estimates of effects on mortality in a public-health perspective.

Feasibility and Timing

Feasibility is not a deterrent to the research in this field. It appears that extensive results will be available within the timeframe laid out by this committee.

Suggested Citation:"3. Review of Research Progress and Status." National Research Council. 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: The National Academies Press. doi: 10.17226/10065.
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Next: 4. Overall Findings and Recommendations »
Research Priorities for Airborne Particulate Matter: III. Early Research Progress Get This Book
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Regulatory standards are already on the books at the the U.S. Environmental Protection Agency (EPA) to address health risks posed by inhaling tiny particles from smoke, vehicle exhaust, and other sources.

At the same time, Congress and EPA have initiated a multimillion dollar research effort to better understand the sources of these airborne particles, the levels of exposure to people, and the ways that these particles cause damage.

To provide independent guidance to the EPA, Congress asked the National Research Council to study the relevant issues. The result is a series of four reports on the particulate-matter research program. The first two books offered a conceptual framework for a national research program, identified the 10 most critical research needs, and described the recommended timing and estimated costs of such research.

This, the third volume, begins the task of assessing the progress made in implementing the research program. The National Research Council ultimately concludes that the ongoing program is appropriately addressing many of the key uncertainties. However, it also identifies a number of critical specific subjects that should be given greater attention. Research Priorities for Airborne Particulate Matter focuses on the most current and planned research projects with an eye toward the fourth and final report, which will contain an updated assessment.

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