2001 Progress Report: Human Health Effects of Exposure to Ultrafine Particles

EPA Grant Number: R826781
Title: Human Health Effects of Exposure to Ultrafine Particles
Investigators: Frampton, Mark W. , Marder, Victor J. , Oberd√∂rster, G√ľnter , Utell, Mark J. , Zareba, Wojciech
Institution: University of Rochester
EPA Project Officer: Chung, Serena
Project Period: October 1, 1998 through September 30, 2001 (Extended to September 30, 2002)
Project Period Covered by this Report: October 1, 2000 through September 30, 2001
Project Amount: $736,260
RFA: Health Effects of Particulate Matter and Associated Air Pollutants (1998) RFA Text |  Recipients Lists
Research Category: Air , Health Effects , Particulate Matter , Air Quality and Air Toxics

Objective:

The objective of this research project is to utilize controlled human exposures to examine, in healthy and potentially susceptible subjects, the deposition and fate of inhaled ultrafine carbon particles (UFP), and the role of UFP in inducing health effects.

Progress Summary:

UFP Exposure in Subjects With Asthma. Subjects with asthma may represent a group with increased susceptibility to the health effects of ultrafine particles, both because of the possibility of increased airways deposition of particles, and because of underlying airway inflammation. We have completed a clinical exposure study (co-funded by the Health Effects Institute) of subjects with mild asthma. Sixteen subjects (8 male, 8 female) were exposed to air and to 10 µg/m3 carbon UFP for 2 hours with intermittent exercise. We measured effects on pulmonary function, symptoms, airway inflammation (exhaled nitric oxide [NO] and induced sputum), blood leukocyte activation, and cardiac electrophysiologic function. Because these studies were performed using mouthpiece exposures, we were able to measure ultrafine particle deposition during exposure and compare the findings with our previous studies in healthy subjects.

Ultrafine Particle Deposition. In the asthmatic subjects, we found that total respiratory fractional deposition by particle number was high at rest (0.77±0.05) and increased during exercise (0.86±0.04). Rest deposition was increased significantly compared with our previous study in healthy subjects at rest (0.63±0.03). We conclude that ultrafine particle deposition is increased in mild asthmatic subjects compared with healthy subjects (see Figure 1).

Figure 1.

Symptoms and Lung Function. There were no significant changes in respiratory symptoms or pulmonary function in response to these exposures. Subjects did not report an increase in medication use following exposures.

Blood studies revealed a particle-related increase in the total white blood cell count, with an increase in blood PMN and decreases in blood lymphocytes and eosinophils. There was a reduction in expression of several adhesion molecules on circulating blood leukocytes, including ICAM-1 (CD54) and L-selectin (CD62L) (see Figure 2). These data are similar to the effects on blood cells seen in our earlier studies of healthy subjects, but appear to be present at a lower exposure concentration in asthmatic subjects, suggesting asthmatics may have heightened sensitivity for these effects. These findings are consistent with a change in vascular retention of leukocyte subsets in the hours following UFP exposure.

Figure 2.

Effects of UFP Exposure on Endothelial Function. For the last six subjects studied in this project, we examined effects of UFP exposure on endothelial function by performing flow mediated dilatation of the forearm circulation before exposure and 24 and 48 hours after exposure. Figure 3 shows the change from preexposure in post-ischemic total forearm flow compared with the baseline measurement. After air exposure, flow-mediated dilation increased compared with preexposure baseline, an expected response to the exercise during the previous day’s exposure. However, this response was blunted following UFP exposure. At 48 hours, there appeared to be a rebound, with the change in total flow greater after UFP than after air.

Figure 3. Change in flow-mediated dilation and blood nitrates.

Flow-mediated dilation is mediated by endothelial NO, so we measured the plasma NO products nitrite and nitrate before and after exposure in all 16 subjects in this study. As shown in the inset in Figure 3, we found a significant increase in blood nitrates 48 hours after exposure. This finding is consistent with a rebound increase in NO production, which likely mediates the rebound seen in flow mediated dilation. These data support the hypothesis that exposure to very low concentrations of UFP alters systemic endothelial function. This is a novel finding, and we have now begun a study to determine if exposures in healthy subjects have similar effects on vascular function, and to determine the time course of the response.

In summary, our study indicates that asthmatics have increased airway deposition of ultrafine particles, and that exposure to even low mass concentrations of ultrafine particles alters circulating leukocyte subsets. These data are most consistent with an alteration in leukocyte retention in the pulmonary circulation. In addition, our preliminary results suggest there also are effects on systemic endothelial function.

Future Activities:

Future activities include the continued testing of healthy and potentially susceptible subjects to further investigate the role of UFP in relation to human health. We plan to test the hypothesis that exposure to carbon UFP alters systemic endothelial function. We are initiating a new study in healthy subjects using an exposure concentration of 50 µg/m3. Subjects will be monitored for a total of 48 hours after exposure and we will examine the time course of effects on endothelial function using the forearm flow mediated dilation test. We also will measure plasma levels of the vasoactive mediators NO and endothelins. The common blood endpoints that we have developed with Core 2 also will be measured in this study.


Journal Articles on this Report : 8 Displayed | Download in RIS Format

Other project views: All 28 publications 16 publications in selected types All 13 journal articles
Type Citation Project Document Sources
Journal Article Azadniv M, Torres A, Boscia J, Speers DM, Frasier LM, Utell MJ, Frampton MW. Neutrophils in lung inflammation: which reactive oxygen species are being measured? Inhalation Toxicology 2001;13(6):485-495. R826781 (2001)
R826781 (Final)
R827354 (2004)
R827354 (Final)
R827354C003 (2001)
R827354C003 (2002)
R827354C003 (Final)
R832415 (2010)
R832415 (2011)
R832415 (Final)
R832415C003 (2011)
  • Abstract from PubMed
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  • 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. R826781 (2001)
    R826781 (Final)
    R827354 (2004)
    R827354 (Final)
    R827354C003 (1999)
    R827354C003 (2000)
    R827354C003 (2001)
    R827354C003 (2002)
    R827354C003 (2003)
    R827354C003 (2004)
    R827354C003 (Final)
    R827354C004 (Final)
    R832415 (2010)
    R832415 (2011)
    R832415 (Final)
    R832415C003 (2011)
    R832415C004 (2011)
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  • Abstract: Taylor and Francis-Abstract
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  • Journal Article Frampton MW. Systemic and cardiovascular effects of airway injury and inflammation: ultrafine particle exposure in humans. Environmental Health Perspectives 2001;109(Suppl 4):529-532. R826781 (2001)
    R826781 (Final)
    R827354 (Final)
    R827354C003 (2001)
    R827354C003 (2002)
    R827354C003 (Final)
    R832415 (2010)
    R832415 (2011)
    R832415 (Final)
    R832415C003 (2011)
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  • Journal Article Geigel EJ, Hyde RW, Perillo IB, Torres A, Perkins PT, Pietropaoli AP, Frasier LM, Frampton MW, Utell MJ. Rate of nitric oxide production by lower alveolar airways of human lungs. Journal of Applied Physiology 1999;86(1):211-221. R826781 (2001)
    R826781 (Final)
  • Abstract from PubMed
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  • Journal Article Perillo IB, Hyde RW, Olszowka AJ, Pietropaoli AP, Frasier LM, Torres A, Perkins PT, Forster II RE, Utell MJ, Frampton MW. Chemiluminescent measurements of nitric oxide pulmonary diffusing capacity and alveolar production in humans. Journal of Applied Physiology 2001;91(5):1931-1940. R826781 (2001)
    R826781 (Final)
  • Abstract from PubMed
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  • Journal Article Pietropaoli AP, Perillo IB, Torres A, Perkins PT, Frasier LM, Utell MJ, Frampton MW, Hyde RW. Simultaneous measurement of nitric oxide production by conducting and alveolar airways of humans. Journal of Applied Physiology 1999;87(4):1532-1542. R826781 (2001)
    R826781 (Final)
  • Abstract from PubMed
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  • Abstract: JAP-Abstract
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  • Journal Article Riesenfeld E, Chalupa D, Gibb FR, Oberdo G, Gelein R, Morrow PE, Utell MJ, Frampton MW. Ultrafine particle concentrations in a hospital. Inhalation Toxicology 2000;12(Suppl 2):83-94. R826781 (2000)
    R826781 (2001)
    R826781 (Final)
    R827354 (Final)
    R827354C003 (2000)
    R827354C003 (2001)
    R827354C003 (2002)
    R827354C003 (Final)
    R827354C004 (2000)
    R827354C004 (Final)
    R832415 (2010)
    R832415 (2011)
    R832415 (Final)
    R832415C003 (2011)
    R832415C004 (2011)
  • Abstract from PubMed
  • Abstract: Taylor and Francis-Abstract
    Exit
  • Journal Article Utell MJ, Frampton MW, Zareba W, Devlin RB, Cascio WE. Cardiovascular effects associated with air pollution:potential mechanisms and methods of testing. Inhalation Toxicology 2002;14(12):1231-1247. R826781 (2001)
    R826781 (Final)
    R827354 (Final)
    R827354C003 (2001)
    R827354C003 (2002)
    R827354C003 (Final)
    R832415 (2010)
    R832415 (2011)
    R832415 (Final)
    R832415C003 (2011)
  • Abstract from PubMed
  • Abstract: Taylor and Francis-Abstract
    Exit
  • Supplemental Keywords:

    ambient air, atmosphere, sensitive populations, susceptibility, particulates, metals, dosimetry., RFA, Health, Scientific Discipline, Air, particulate matter, Health Risk Assessment, Chemistry, Risk Assessments, Susceptibility/Sensitive Population/Genetic Susceptibility, Allergens/Asthma, genetic susceptability, Atmospheric Sciences, ambient air quality, asthma, particle size, particulates, cardiopulmonary responses, human health effects, ultrafine iron oxide, airway disease, cardiovascular vulnerability, exposure, Lymphocytes, airway inflammation, human exposure, inhalation, environmental chemistry, clinical studies, analytical chemistry, Acute health effects, air quality, metals, ultrafine particles, ultrafine carbon

    Progress and Final Reports:

    Original Abstract
  • 1999 Progress Report
  • 2000 Progress Report
  • Final Report