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2004 Progress Report: Clinical Studies of Ultrafine Particle Exposure in Susceptible Human Subjects
EPA Grant Number: R827354C003Subproject: this is subproject number 003 , established and managed by the Center Director under grant R827354
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Airborne PM - Rochester PM Center
Center Director: Oberdorster, Gunter
Title: Clinical Studies of Ultrafine Particle Exposure in Susceptible Human Subjects
Investigators: Frampton, Mark W. , Utell, Mark J.
Institution: University of Rochester
EPA Project Officer: Stacey Katz/Gail Robarge,
Project Period: June 1, 1999 through May 31, 2005 (Extended to May 31, 2006)
Project Period Covered by this Report: June 1, 2004 through May 31, 2005
RFA: Airborne Particulate Matter (PM) Centers (1999)
Research Category: Particulate Matter
Description:
Objective:The overall objective of this research project is to utilize controlled human exposures to examine, in healthy and potentially susceptible subjects, the role of ultrafine particles (UFP) in inducing respiratory and cardiovascular health effects. The specific objectives for Year 6 of this study were to: (1) perform a clinical study to compare the effects of ultrafine and fine carbon particles on the diffusing capacity for carbon monoxide; and (2) measure mediators of vascular function in plasma samples.
Progress Summary:We now have completed a study to test the hypothesis that the effects on pulmonary diffusing capacity are a consequence of the high surface area of UFP, with their potential to deliver reactive oxygen species to the endothelium. In this study, 12 healthy never-smoking adults underwent three separate exposures, separated by at least 2 weeks: (1) air; (2) 50 µg/m3 UFP (count median diameter ~30 nm, particle number ~1 x 107/cm3, surface area ~750 m2/g); and (3) 100 µg/m3 fine particles (FP) (count median diameter ~300 nm, particle number ~1 x 103/cm3, surface area ~7 m2/g). The higher mass concentration used for FP relative to UFP was designed to provide an equivalent mass deposition in the lung, in view of the lower predicted deposition efficiency for FP. Exposures were by mouthpiece for 2 hours with intermittent exercise, randomized and double-blinded. Effects on oxygen saturation, DLCO, and diffusing capacity for nitric oxide (DLNO) were assessed before and at intervals after exposure. Blood plasma was analyzed for nitric oxide metabolites and nitration products.
Our preliminary findings confirm that exposure to carbon UFP decreases the DLCO relative to air exposure. When the changes in DLCO following UFP exposure in this study were combined with data from our previous study in healthy subjects, the DLCO decreased from 30.15 ± 1.28 to 28.23 ± 1.16 mL/min/mm Hg 24 hours after UFP exposure (p = 0.002 vs. air exposure). The DLCO also decreased after exposure to fine carbon particles, but the difference was not significant. We also found an increase in the DLNO/DLCO ratio, suggesting a decrease in pulmonary capillary blood volume, with both UFP and FP exposure. However, this ratio was not significantly changed when the two studies were combined. There were no significant exposure effects on NO products, including nitrate, nitrite, S-nitrosohemoglobin, and iron-nitrosyl hemoglobin. Additional analyses are in progress.
This study provides important confirmation of the effects of inhaled UFP on the pulmonary diffusing capacity for carbon monoxide. To our knowledge, no previous human clinical study has demonstrated pulmonary effects following exposures to such low mass concentrations of particulate matter. The data support the hypothesis that UFP inhalation alters endothelial function in the pulmonary vasculature of healthy nonsmokers.
Future Activities:Work during the extension period will include additional analyses of blood markers of vascular function and inflammation in the above study, formal statistical analysis of the data in collaboration with our biostatistical colleagues, and preparation of publications.
Journal Articles on this Report: 1 Displayed | Download in RIS Format
| Other subproject views: | All 29 publications | 29 publications in selected types | All 26 journal articles |
| Other center views: | All 87 publications | 85 publications in selected types | All 78 journal articles |
| Type | Citation | ||
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Daigle CC, Chalupa DC, Gibb FR, Morrow PE, Oberdorster G, Utell MJ, Frampton MW. Ultrafine particle deposition in humans during rest and exercise. Inhalation Toxicology 2003;15(6):539-552. |
R827354 (2004) R827354 (Final) R827354C003 (1999) R827354C003 (2000) R827354C003 (2001) R827354C003 (2002) R827354C003 (2003) R827354C003 (2004) R827354C003 (Final) R827354C004 (Final) R826781 (2001) R826781 (Final) |
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pollution prevention, urban air pollution, atmosphere, metals, air, health, waste, atmospheric sciences, biochemistry, children’s health, environmental chemistry, epidemiology, genetics, virology, molecular biology, health risk assessment, risk assessments, incineration, combustion, combustion engines, air toxics, tropospheric ozone, PM2.5, particulates, ultrafine particles, particulate matter, particle exposure, particle size, aerosol, aerosols, ambient air, ambient air monitoring, ambient air quality, animal model, atmospheric, cardiopulmonary, cardiopulmonary responses, cardiovascular disease, cardiovascular vulnerability, coronary artery disease, cytokine production, fine particles, human exposure, human health, human health effects, environmental health effects, inhalation toxicology, lead, lung, lung inflammation, metals, morbidity, mortality, pathophysiological mechanisms, pulmonary, pulmonary disease, stratospheric ozone, sensitive populations, susceptible populations,
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Air, Scientific Discipline, Health, RFA, Molecular Biology/Genetics, Risk Assessments, Health Risk Assessment, air toxics, Atmospheric Sciences, Biochemistry, particulate matter, Environmental Chemistry, aerosols, cardiopulmonary, risk assessment, susceptible populations, ultrafine particles, urban environment, aerosol, ambient air quality, cardiovascular disease, cardiovascular vulnerability, coronary artery disease, health effects, mortality, lung inflamation, carbon particles, inhalation toxicology, fine particles, environmental health effects, cardiopulmonary responses, cytokine production, particle exposure, human health effects, particulates, sensitive populations, ambient monitoring, lung, metals, ambient air monitoring, pathophysiological mechanisms, pulmonary, urban air pollution, human health, human exposure, morbidity, particle size, pulmonary disease, animal model
Relevant Websites:
http://www2.envmed.rochester.edu/envmed/PMC/ 
Progress and Final Reports:
1999 Progress Report
2000 Progress Report
2001 Progress Report
2002 Progress Report
2003 Progress Report
Original Abstract
Final Report
Main Center Abstract and Reports:
R827354 Airborne PM - Rochester PM Center
Subprojects under this Center:
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R827354C001 Characterization of the Chemical Composition of Atmospheric Ultrafine Particles
R827354C002 Inflammatory Responses and Cardiovascular Risk Factors in Susceptible Populations
R827354C003 Clinical Studies of Ultrafine Particle Exposure in Susceptible Human Subjects
R827354C004 Animal Models: Dosimetry, and Pulmonary and Cardiovascular Events
R827354C005 Ultrafine Particle Cell Interactions: Molecular Mechanisms Leading to Altered Gene Expression
R827354C006 Development of an Electrodynamic Quadrupole Aerosol Concentrator
R827354C007 Kinetics of Clearance and Relocation of Insoluble Ultrafine Iridium Particles From the Rat Lung Epithelium to Extrapulmonary Organs and Tissues (Pilot Project)
R827354C008 Ultrafine Oil Aerosol Generation for Inhalation Studies