Skip to main content

Currently Skimming:

3. Review of Research Progress and Status
Pages 47-129

The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.


From page 47...
... in its first two reports, and finally applies the first three evaluation criteria ciiscussed 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.
From page 48...
... In its first report (NRC 1998) , the committee recommended that information be obtained on relationships between total personal exposures and outdoor concentrations of PM.
From page 49...
... These longitudinal pane! studies have increased the understanding of the relationships between personal exposures and outdoor concentrations more than did earlier cross-sectional exposure studies.
From page 50...
... Homes were classified as "well," "moderately," or "poorly" ventilated, as defined bythe distribution of the fraction oftime 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.
From page 51...
... . The studies are expected to greatly expand the database on personal exposures, indoor and outdoor concentrations, human activities, and home characteristics.
From page 52...
... 52 Research Priorities for Airborne Particulate Matter TABLE 3.1 Current Studies Relevant to Research Topic 1 Funding Research Agencya Groupb Location Proposed Cohorts EPA New York University New York, NY 16 asthmatic, 16 COPD Anaheim, CA 16 asthmatic, 16 COPD Seattle, WA 16 asthmatic, 16 COPD EPRI and Harvard University Nashville, TN 10 COPD API Boston, MA 18 COPD EPA University of Seattle, WAN 48 COPD and elderly Washington 48 COPD and elderly 48 Ml 48 Ml 24 COPD and elderly, 24 Ml 25 COPD and elderly, 24 Ml EPRI and Harvard University Baltimore, MD 15 elderly API HEI and EOHSI, UMDNJ, and Elizabeth, NJ 50 healthy adults Mickey Rutgers University Houston,TX 50 healthy adults Leland Los Angeles, CA 50 healthy adults HEI Harvard University Baltimore, MD 15 children Baltimore, MA 15 COPD, 15 children Boston, MAN 15 children, 15 elderly EPA and Harvard University Boston, MAN 15 Ml, 15 Ml spouses EPRI,e 15 healthy adults CARBf Emory University Atlanta, GAS 15 COPD Rutgers University and Los Angeles, CAN 15 COPD UMDNJ EPA EPA and RTI Baltimore, MD 15 elderly Fresno, CA 5 elderly Fresno, CA 60 elderly EPA9 EPA and RTI Research 15 Ml, 15 low-SES Triangle Park, healthy adults NC CARB UniversityofCalifornia, Fresno, CAh Berkeley CARB Harvard University, and EPA Rutgers University, (planned) and IES 25 asthmatic children Los Angeles, CAN 16 healthy adults (nonsmoking)
From page 53...
... also measured 50 healthy adults 25 elderly 15 children Not determined Many of the recently completed ant! current studies examine the relationship between ambient concentrations of gaseous pollutants and personal exposures.
From page 54...
... 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 anti type of susceptible subpopulation studied.
From page 55...
... Exposure assessment is of paramount importance for understandng 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.
From page 56...
... To make research topic ~ investigations more practicable, it will be necessary to characterize susceptible subpopulations more fully, identifytoxicologically important chemical constituents or particle-size fractions, develop and fieldtest 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)
From page 57...
... RESEARCH TOPIC 3. CHARACTERIZATION OF EMISSION SOURCES What are the size distribution, chemical composition, and mass-emission rates of particulate matter emittedirom 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?
From page 58...
... 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 mode} has arrived at agreement between the predicted and observed mass-concentration values for the correct reasons. In light ofthose 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
From page 59...
... 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.
From page 60...
... EPA's methori-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 ofthe 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, ant} another six will be characterized in the near future.
From page 61...
... However, few of these studies use methods, such as the dilution source-sampling system being clevelopeci 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-designeci comprehensive testing program that would lead to more-accurate emission inventories.
From page 62...
... 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 airqualitymodeling, and receptor-oriented air-qualitymodelingto solicit recommendations on sources to be tested and any additional chemical and physical dimensions that should be measured during the national source-testing program.
From page 63...
... Translate New Source-Test Procedures and Source-Test Data into Comprehensive National Emission Inventories EPA maintains a national regulatory emission inventory for PM25, Pow, 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.
From page 64...
... 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 anti semivolatile organic compounds.
From page 65...
... Feasibility and Timing In the committee's second report, it was estimated that five to ~ 5 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.
From page 66...
... ofthe national fine- particle emission inventory. Though 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 ofthe agency, the goal of a highquality inventory for particle size and chemical composition is not out of reach.
From page 67...
... 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.
From page 68...
... Projects Funded Study Topic Projects 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 chemists 1 0 Dry and wet deposition 1 2 Source characterization, soil 0 Source characterization, smoke 1 4 4 late the concentrations and chemical composition of primary and secondary PM2 5 concentrations, PM~o concentrations, and depositions of acids, nutrients, and toxic chemicals. To reduce computational time and costs, REM SAD uses simpler chemistry and physics modules than MODELS 3.
From page 69...
... , 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)
From page 70...
... 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.
From page 71...
... Review of Research Progress and Status 71 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 mode} to improve the others, particularly those earmarked for regulatory applications.
From page 72...
... 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.
From page 73...
... 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.
From page 74...
... 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.
From page 75...
... 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.
From page 76...
... -A r The initial research portfolio (NRC ~ 998) outlined a research agencIa designed to improve the understancling of the roles of specific characteristics of ambient PM (such as particle size ciistribution, particle shape, and chemical constituents)
From page 77...
... Greater certaintywill 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.
From page 78...
... 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 PM~o)
From page 79...
... 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.
From page 80...
... 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 viva and in vitro studies, the former inducing clinical-exposure studies and involving particles ranging from 0.01 to 0.]
From page 81...
... 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,
From page 82...
... 0 ,ug/m3, and many toxicity studies use concentrations as high as about ~ 00-5,000 ~g/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.
From page 83...
... 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.
From page 84...
... 84 CO in 3 a)
From page 85...
... The committee recommencled that efforts be undertaken to conduct epidemiological studies ofthe effects of long-term exposures to particle constituents, including ultrafine particles. There does not yet appear to be a sys
From page 86...
... 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.
From page 87...
... 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.
From page 88...
... 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)
From page 89...
... of No. of Projectsa Repodsa Translocation and clearance: Translocation, clearance, and bioavailability 5 Disposition of ultrafine particles after deposition 1 o Interspecies differences Total 15 26 8 23 13 5 24 2 5 106 aProjects (from HEI database)
From page 90...
... Deposition ~ . Conduct research on deposition ofparticles in the respiratory tracts of individuals having respiratory abnormalitiespresumed to increase susceptibility to particles, anc'on the differences in deposition between these susceptible subpopulations and normals.
From page 91...
... b. Determine the effects on deposition of particle size, hygroscopicity, and respiratory variables in individuals with respiratory abnormalities.
From page 92...
... The influences of particle size and hygroscopicity on deposition have been addressed by some studies, but only a small portion ofthis 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 respiratoryvariables on deposition in susceptible people or on the development of predictive models that incorporate these variables.
From page 93...
... 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.
From page 94...
... 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.
From page 95...
... 2. Determine the disposition of ultrafineparticles after deposition in the respiratory tract, and whether respiratory abnormalities alter the disposition pathways or rates.
From page 96...
... There has been little effort to assess dosimetry of anytype 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, transIocation and clearance, and handling of ciiverse particle types have been addressed little or not at all.
From page 97...
... 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 predictingthe 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 ofthe characterization ofthe responses of animal models.
From page 98...
... Although insufficient effort is being expended to evaluate dosimetr~r in animal models of respirator 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.
From page 99...
... 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.
From page 100...
... 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.
From page 101...
... 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.
From page 102...
... Epidemiological studies of diverse design are potentially relevant to this topic. As for studies of mixtures
From page 103...
... 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.
From page 104...
... RESEARCH TOPIC 8. SUSCEPTIBLE SUBPOPULATIONS What subpopulations are at increased risk of adverse health outcomes from particulate matter?
From page 105...
... 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.
From page 106...
... 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-oi!
From page 107...
... 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.
From page 108...
... 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 ciegree to which they mimic human disease.
From page 109...
... However, only a few ofthe strata ofthe matrix defined by subpopulation and particle characteristics are being aciciressed. 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, anti hypertension can be expected.
From page 110...
... 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.
From page 111...
... There is continuing development of animal models that mimic various aspects of potentially susceptible human conditions. Thus, this field continues to evolve.
From page 112...
... 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.
From page 113...
... 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 identitr individual toxic materials in ambient PM and the mechanisms by which they induce damage to human and pulmonary and cardiovascular systerms.
From page 114...
... Of the 47 relevant studies identified, most used young normal animals, which were not mociels 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.
From page 115...
... 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.
From page 116...
... Several in vitro studies reported in the database are based on findings of animal studies that use very high closes of a specific particle type. Although state-of-the-art methods of cellular and molecular
From page 117...
... 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 icientify the importance of differing PM composition in this case related to transition metals—for inducing adverse health effects.
From page 118...
... 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.
From page 119...
... 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.
From page 120...
... Review ofthe HEI database and proceedings ofthe PM 2000 meet~ng 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.
From page 121...
... 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 oftotal particle deposition.
From page 122...
... 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 prom exposures to particulate matter?
From page 123...
... 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.
From page 124...
... 124 Research Priorities for Airborne Particulate Matter the statistical models. The presence of other variables in the models can influence the association between health measures and particulate air pollution.
From page 125...
... Measurement error can occur when measures of ambient air pollution are user! as an index of personal exposure.
From page 126...
... 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 mode} 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.
From page 127...
... 20001. 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.
From page 128...
... The methods included two-stage random-effects regression methods, which were used to account for spatial patterns in mortality data and betweenand 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.
From page 129...
... 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.


This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More information on Chapter Skim is available.