Grantee Research Project Results

2004 Progress Report: Clinical Studies of Ultrafine Particle Exposure in Susceptible Human Subjects

EPA Grant Number: R827354C003
Subproject: 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: Rochester PM Center
Center Director: Oberdörster, Günter
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: Chung, Serena
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) RFA Text | Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air

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

Publications Views
Other subproject views:	All 27 publications	26 publications in selected types	All 24 journal articles
Other center views:	All 106 publications	99 publications in selected types	All 91 journal articles

Publications
Type	Citation	Sub Project	Document Sources
Journal Article	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) R832415 (2010) R832415 (2011) R832415 (Final) R832415C003 (2011) R832415C004 (2011)	Abstract from PubMed Abstract: Taylor and Francis-Abstract Exit

Supplemental Keywords:

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,, RFA, Scientific Discipline, Health, Air, particulate matter, Environmental Chemistry, Health Risk Assessment, air toxics, Risk Assessments, Biochemistry, Atmospheric Sciences, Molecular Biology/Genetics, ambient air quality, cytokine production, particle size, particulates, sensitive populations, health effects, risk assessment, cardiopulmonary responses, fine particles, human health effects, morbidity, ambient air monitoring, lung, cardiovascular vulnerability, pulmonary disease, susceptible populations, animal model, carbon particles, environmental health effects, particle exposure, ambient monitoring, human exposure, particulate exposure, lung inflamation, pulmonary, coronary artery disease, inhalation toxicology, urban air pollution, mortality, urban environment, aerosol, cardiopulmonary, human health, aerosols, cardiovascular disease, ultrafine particles, pathophysiological mechanisms

Relevant Websites:

http://www2.envmed.rochester.edu/envmed/PMC/ Exit

Progress and Final Reports:

Original Abstract

Main Center Abstract and Reports:

R827354 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

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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.