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2006 Progress Report: Cardiopulmonary Effects of Metal-Containing Particulate Exposure

EPA Grant Number: R828678C002
Subproject: this is subproject number 002 , established and managed by the Center Director under grant R824834
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Mickey Leland National Urban Air Toxics Research Center (NUATRC)
Center Director: Beskid, Craig
Title: Cardiopulmonary Effects of Metal-Containing Particulate Exposure
Investigators: Christiani, David , Hauser, Russ , Herrick, Robert , Kim, Jee Young , Magari, Shannon , Smith, Thomas , Wand, Matthew , Williams, Paige L.
Institution: Harvard School of Public Health
EPA Project Officer: Stacey Katz/Gail Robarge,
Project Period: January 1, 1999 through January 31, 2004
Project Period Covered by this Report: January 1, 2005 through January 31, 2006
RFA: Mickey Leland National Urban Air Toxics Research Center (NUATRC) (1997)
Research Category: Air Quality and Air Toxics , Targeted Research

Description:

Objective:

The objective of this study was to investigate the role of exposure to particulates in the development of respiratory and cardiac responses in boilermakers with and without chronic bronchitis. The study employed a detailed continuous responses assessment to particulate matter with an aerodynamic mass median diameter ≤ 2.5 μm (PM2.5) with repeated measures of biologic and physiologic markers of response. The specific aims of the study were to conduct a short-term prospective study of acute airway and cardiovascular responses to combustion particulates. In addition, the relationship between chronic respiratory disease and the cardiac responses to particulates was assessed. The target population was boilermakers exposed to fuel-oil ash particulates. Specific hypotheses tested included:

Hypothesis 1. Exposure to fuel-oil ash particulate induces airway inflammation and airflow obstruction, as reflected in increased expired nitric oxide (NO) and in decreases inforced expiratory volume in one second (FEV1).
Hypothesis 2. Exposure to fuel-oil ash particulates will result in acute changes in cardiovascular function as reflected in changes in heart rate and heart rate variability. Changes in heart rate and heart rate variability will be in a direction believed to reflect increased sympathetic or decreased vagal tone (e.g., decreased heart rate variability).
Hypothesis 3. Chronic bronchitis predisposes particulate-exposed workers to changes in cardiac function, including heart rate and heart rate variability.

The experimental approach was an epidemiologic study employing a prospective, repeat-measurement design assessing several biological parameters in relation to exposure. Continuous personal PM2.5 exposure assessment was performed in conjunction with continuous heart monitoring on subjects during work and at home. Furthermore, integrated total PM2.5 and PM2.5 metal concentrations were determined from gravimetric filter samples. The filters were analyzed for vanadium, chromium, manganese, nickel, copper and lead. The fractional concentration of expired nitric oxide (FENO) was collected pre and post-work shift at the site of an overhaul of an oil-fired boiler. Other predictors of cardiopulmonary function assessed included age, race, body-mass index, smoking, lipid level, blood pressure, history of asthma, chronic obstructive pulmonary disease (COPD), angina, and medication use. Assessment of workload (exertion also was considered a predictor of heart rate, heart-rate regularity and ECG intervals.

Progress Summary:

Occupational exposure to metal-containing PM2.5 was associated with an exposure-dependent decrease in FENO in boilermakers with limited respirator usage. In addition, soluble metal exposures, measured in the air and urine were significantly associated with decreased FENO. Workers experienced altered cardiac autonomic control after exposure to occupational and environmental PM2.5. PM2.5 exposure was associated with decreases in the 5-minute standard deviation of the normal-to-normal index (SDNN), with the largest effect noted using a 3-hour PM2.5 moving average. In contrast, increases in 8-hour average particulate lead and vanadium concentrations were associated with statistically significant mean increases in the SDNN index after adjusting for mean heart rate, age and smoking status. Small changes in mean heart rate were seen with all six metal exposure metrics.

Conclusions:

The initial hypothesis was that exposure to fuel-oil ash particulates would induce airway inflammation, resulting in increased FENO. Further review of the literature suggested that the direction of change in FENO varied depending on the type of exposure. The inverse exposure-response association between metal-containing PM2.5 exposure and FENO indicates that fine particulate exposure and, specifically, soluble transition metals may be partially responsible for the adverse pulmonary responses seen in workers exposed to residual oil fly ash (ROFA). Exposure to fuel-oil ash particulates was hypothesized to be associated with acute changes in cardiovascular function, reflected in increased sympathetic or decreased vagal tone. Analyses of the cardiovascular outcomes suggest that there may be both a long-acting (several hours) and a short-acting (several minutes) component to the mechanism of action following exposure to metal-containing PM2.5. The clinical significance of these effects in a healthy working population is, at present, unclear. These results contribute to the knowledge base of information regarding the relationship between exposure to particulates and human cardiopulmonary responses in both normal and chronic bronchitic populations. Clarification of such exposure-response relationships has important implications for preventive efforts aimed at reducing morbidity and mortality from exposure to respirable particulates and their associated metals.

The NUATRC endorses this research project for its careful design, conduct, and analysis. However, there were a number of contractory results that deserve scrutiny in order to achieve a full and balanced interpretation. For example, this study sought to identify whether fine respirable particulates (PM2.5) and the specific metals in those particles are associated with adverse effects on pulmonary and cardiovascular function. It was conducted among boilermakers and welders, who have unusually high exposure to metal fumes and to PM2.5. Thus, it provides a valuable set of observations on the respiratory and cardiovascular effects of these exposures among a highly exposed population. The study was well designed, conducted and analyzed.

The investigators’ hypothesis that fuel oil ash particulates would induce increased expired nitric oxide was not supported. Their 1999 data indicated that PM2.5 was associated with decreased expired nitric oxide, whereas their 2000 data showed no clear association in either direction. These findings are reasonably compatible with chance. The results provide support for the hypothesis that PM2.5 is associated with decreased airflow (measured as FEV1).

The investigators’ hypothesis that exposure to fuel oil ash particulates would result in decreased heart rate variability was supported by their data showing an association between PM2.5 and decreased heart rate variability. However, their findings regarding specific metals should be interpreted cautiously in light of the inconsistencies in these findings and their dependence on the averaging time used in the analysis. The specific findings that lead and vanadium were associated with increased heart rate variability are in the direction opposite to their hypothesis. FENO was analyzed in relation to each of the six metals measured in urine in ten different time-lagged models. The authors reported eight of these 60 models, all of which showed statically significant relationships. Given that not all of the time-lagged models were reported, the biological relevance of the relationship between urinary metals excretion and FENO is unclear. The p-values and confidence limits they provide are post-hoc and their interpretation was not moderated in light of the number of analyses done. It is also possible that the findings reflect a direct effect of the particles apart from their metals content, or that there is some unmeasured covariate such as an unmeasured exposure that is associated with welding. It will be important for additional studies to both replicate these findings and to further explore the characteristics of the particles that are most clearly associated with the effects found.


Journal Articles on this Report: 6 Displayed | Download in RIS Format

Other subproject views: All 11 publications 6 publications in selected types All 6 journal articles
Other center views: All 122 publications 54 publications in selected types All 46 journal articles

Type Citation Sub Project Document Sources
Journal Article Kim JY, Wand MP, Hauser R, Mukherjee S, Herrick RF, Christiani DC. Association of expired nitric oxide with occupational particulate exposure. Environmental Health Perspectives 2003;111(5):676-680. R828678C002 (2002)
R828678C002 (2003)
R828678C002 (2004)
R828678C002 (2005)
R828678C002 (2006)
  • Abstract from PubMed
  • Full-text: Environmental Health Perspectives Full Text
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  • Other: Environmental Health Perspectives PDF
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  • Journal Article Kim JY, Hauser R, Wand MP, Herrick RF, Houk RS, Aeschliman DB, Woodin MA, Christiani DC. Association of expired nitric oxide with urinary metal concentrations in boilermakers exposed to residual oil fly ash. American Journal of Industrial Medicine 2003;44(5):458-466. R828678C002 (2005)
    R828678C002 (2006)
  • Abstract from PubMed
  • Journal Article Kim JY, Hauser R, Wand MP, Herrick RF, Amarasiriwardena CJ, Christiani DC. The association of expired nitric oxide with occupational particulate metal exposure. Environmental Research 2003;93(2):158-166. R828678C002 (2004)
    R828678C002 (2005)
    R828678C002 (2006)
  • Abstract from PubMed
  • Full-text: Science Direct Full Text
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  • Other: Science Direct PDF
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  • Journal Article Magari SR, Hauser R, Schwartz J, Williams PL, Smith TJ, Christiani DC. Association of heart rate variability with occupational and environmental exposure to particulate air pollution. Circulation 2001;104(9):986-991. R828678C002 (2001)
    R828678C002 (2003)
    R828678C002 (2004)
    R828678C002 (2005)
    R828678C002 (2006)
    R827353 (Final)
  • Abstract from PubMed
  • Full-text: AHA Full Text
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  • Other: AHA PDF
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  • Journal Article Magari SR, Schwartz J, Williams PL, Hauser R, Smith TJ, Christiani DC. The association between personal measurements of environmental exposure to particulates and heart rate variability. Epidemiology 2002;13(3):305-310. R828678C002 (2002)
    R828678C002 (2003)
    R828678C002 (2004)
    R828678C002 (2005)
    R828678C002 (2006)
  • Abstract from PubMed
  • Journal Article Magari SR, Schwartz J, Williams PL, Hauser R, Smith TJ, Christiani DC. The association of particulate air metal concentrations with heart rate variability. Environmental Health Perspectives 2002;110(9):875-880. R828678C002 (2002)
    R828678C002 (2003)
    R828678C002 (2004)
    R828678C002 (2005)
    R828678C002 (2006)
  • Abstract from PubMed
  • Full-text: Environmental Health Perspectives Full Text
    Exit EPA Disclaimer
  • Other: Environmental Health Perspectives PDF
    Exit EPA Disclaimer
  • Supplemental Keywords:

    , HUMAN HEALTH, Air, Scientific Discipline, Health, RFA, Susceptibility/Sensitive Population/Genetic Susceptibility, Biology, Risk Assessments, genetic susceptability, Health Risk Assessment, air toxics, Atmospheric Sciences, particulate matter, Environmental Chemistry, Exposure, cardiopulmonary, chemical mixtures, environmental hazard exposures, airborne urban contaminants, acute exposure, Acute health effects, cardiovascular disease, mortality, air contaminant exposure, co-pollutants, cardiac arrest, air quality, cardiopulmonary response, cardiotoxicity, fine particles, cardiopulmonary responses, human health risk, lung inflammation, toxics, acute cardiovascular effects, chronic health effects, PM 2.5, sensitive populations, acute lung injury, air pollution, inhaled, atmospheric particulate matter, National Cohort Studies, copollutant exposures, susceptible subpopulations, long term exposure, human susceptibility, time series analysis, human exposure, morbidity, particulate exposure
    Relevant Websites:

    http://www.sph.uth.tmc.edu/mleland/ exit EPA

    Progress and Final Reports:
    2001 Progress Report
    2002 Progress Report
    2003 Progress Report
    2004 Progress Report
    2005 Progress Report
    Original Abstract


    Main Center Abstract and Reports:
    R824834    Mickey Leland National Urban Air Toxics Research Center (NUATRC)

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R824834C001 Air Toxics Exposures Among Teenagers in New York City and Los Angeles - A Columbia-Harvard Study (TEACH)
    R824834C002 Cardiopulmonary Response to Particulate Exposure
    R824834C003 VOC Exposure in an Industry Impacted Community
    R824834C004 A Study of Personal Exposure to Air Toxics Among a Subset of the Residential U.S. Population (VOC Project)
    R824834C005 Methods Development Project for a Study of Personal Exposures to Toxic Air Pollutants
    R824834C006 Relationship Between Indoor, Outdoor and Personal Air (RIOPA)
    R824834C007 Development of the "Leland Legacy" Air Sampling Pump
    R824834C008 Source Apportionment of Indoor Polycyclic Aromatic Hydrocarbons (PAHs) in Urban Residences
    R824834C009 Development of a Personal Cascade Impactor Sampler (PCIS)
    R824834C010 Testing the Metals Hypothesis in Spokane
    R828678C001 Air Toxics Exposures Among Teenagers in New York City and Los Angeles—A Columbia-Harvard Study (TEACH)
    R828678C002 Cardiopulmonary Effects of Metal-Containing Particulate Exposure
    R828678C003 VOC Exposure in an Industry Impacted Community
    R828678C004 A Study of Personal Exposure to Air Toxics Among a Subset of the Residential U.S. Population (VOC Project)
    R828678C005 Oxygenated Urban Air Toxics and Asthma Variability in Middle School Children: A Panel Study (ATAC–Air Toxics and Asthma in Children)
    R828678C006 Relationship between Indoor, Outdoor and Personal Air (RIOPA). Part II: Analyses of Concentrations of Particulate Matter Species
    R828678C007 Development of the “Leland Legacy” Air Sampling Pump
    R828678C008 Source Apportionment of Indoor PAHs in Urban Residences 98-03B
    R828678C009 Development of a Personal Cascade Impactor Sampler (PCIS)
    R828678C010 Testing the Metals Hypothesis in Spokane
    R828678C011 A Pilot Geospatial Analysis of Exposure to Air Pollutants (with Special Attention to Air Toxics) and Hospital Admissions in Harris County, Texas
    R828678C012 Impact of Exposure to Urban Air Toxics on Asthma Utilization for the Pediatric Medicaid Population in Dearborn, Michigan
    R828678C013 Field Validation of the Sioutas Sampler and Leland Legacy Pump – Joint Project with EPA’s Environmental Technology Validation Program (ETV)
    R828678C014 Performance Evaluation of the 3M Charcoal Vapor Monitor for Monitor Low Ambient Concentrations of VOCs
    R828678C015 RIOPA Database Development
    R828678C016 Contributions of Outdoor PM Sources to Indoor and Personal Exposures: Analysis of PM Species Concentrations” Focused on the PM Speciation and Apportioning of Sources
    R828678C017 The Short and Long-Term Respiratory Effects of Exposure to PAHs from Traffic in a Cohort of Asthmatic Children

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    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.


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