Ultrafine Particles: Characterization, Health Effects and Pathophysiological Mechanisms

EPA Grant Number: R827354
Center: Airborne PM - Rochester PM Center
Center Director: Oberdörster, Günter
Title: Ultrafine Particles: Characterization, Health Effects and Pathophysiological Mechanisms
Investigators: Oberdörster, Günter , Beckett, William , Cass, Glen , Cox, Christopher , Ensor, David , Finkelstein, Jacob N. , Frampton, Mark W. , Heyder, Joachim , Looney, John , Marder, Victor J. , Morrow, P. E. , OReilly, Michael , Peters, Annette , Phipps, Richard , Prather, Kimberly A. , Schwarz, Edward , Sharp, Zachary , Stripp, Barry , Utell, Mark J. , Wichmann, Heinz-Erich , Yu, C. P. , Zareba, Wojciech
Current Investigators: Oberdörster, Günter , Beckett, William , Cass, Glen , Cox, Christopher , Ensor, David , Finkelstein, Jacob N. , Frampton, Mark W. , Heyder, Joachim , Looney, John , Marder, Victor J. , Morrow, P. E. , O'Reilly, Michael , Peters, Annette , Phipps, Richard , Prather, Kimberly A. , Schwarz, Edward , Sharp, Zachary , Stripp, Barry , Utell, Mark J. , Wichmann, Heinz-Erich , Yu, C. P. , Zareba, Wojciech
Institution: University of Rochester
Current Institution: University of Rochester , GSF- Institute for Epidemiologie , Georgia Institute of Technology , Research Triangle Institute , University of California - Los Angeles , University of California - San Diego
EPA Project Officer: Chung, Serena
Project Period: June 1, 1999 through May 31, 2005 (Extended to May 31, 2006)
Project Amount: $8,302,447
RFA: Airborne Particulate Matter (PM) Centers (1999) RFA Text |  Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air

Objective:

The Rochester PM Center brings together a multi-disciplinary team of experienced investigators to test the hypothesis that ultrafine particles occurring in the urban atmosphere cause adverse health effects. Epidemiological studies have consistently found an association between small increases in urban particulates and health effects, including increased morbidity and mortality in people with respiratory and cardiac disease. The observed effects are associated with the fine rather than the coarse particles in the atmosphere. Moreover, animal studies have shown that ultrafine particles have a significantly greater pulmonary inflammatory potency than larger submicronic particles. A recent epidemiological study found that particle number - reflecting ambient ultrafine particles - correlated better than fine particle mass with increased symptoms in asthmatics. These results form the basis for the ultrafine particle hypothesis. The proposed studies are designed to rigorously test the ultrafine particle hypothesis by comparing ultrafine (~10-50 nm) with accumulation mode particles (~100-500 nm) in all phases of this research. Thus, the following objectives will be addressed by 5 interactive research cores in the Rochester PM Center over a 5-year study period: (a) to determine the number, mass concentration, and composition of urban ultrafine and accumulation mode particles of an eastern and western U.S. city; (b) evaluate the association between ambient particle number/mass concentrations and respiratory as well as cardiovascular effects in a susceptible cohort; (c) compare exposure-dose-response relationships for respiratory and cardiovascular endpoints between ultrafine and accumulation mode particles in controlled clinical and animal studies; (d) assess the significance of factors enhancing ultrafine particle effects: age, disease, co-pollutants, pre-exposure history, exercise; (e) measure total and regional deposition of ultrafine particles in the lower respiratory tract of rodents and total deposition in humans for purposes of extrapolation modeling between species and for in vitro dosing; (f) perform mechanistic studies at a cellular and molecular level to test the hypothesis that ultrafine particle effects are due to oxidative stress induced events; (g) support the development of an ambient ultrafine particle concentrator and test the feasibility for its use in controlled in-vitro, animal, and clinical studies; (h) coordinate research efforts and dissemination of results with other centers.

Approach:

The multi-disciplinary team of the Rochester PM Center consists of atmospheric scientists, aerosol physicists, biostatisticians, epidemiologists, physicians specializing in pulmonary, cardiac and vascular medicine, inhalation toxicologists and cell/molecular biologists. These investigators work in close collaboration with each other in 5 research cores dedicated to areas of urban PM characterization, field studies of PM effects, controlled clinical studies, toxicological animal studies and mechanistic in vitro studies. These research cores are supported by 5 facility cores which provide specific expertise for particle generation and characterization, biostatistical input for study design, evaluation, and extrapolation modeling for immunologic analyses, assessment of vascular and coagulation effects, and measurement of subclinical cardiac effects. The activities of the facility and research cores are closely integrated with each other. Interim results from individual research cores will be integrated into the study design of other cores so that there is continuous feedback between the cores to further advance our knowledge of ultrafine PM induced effects.

Core 1, Ambient Particle Characterization (Cass), research on the characterization of urban ultrafine and accumulation mode particles will allow compositional analysis in real time of single particles. The objective of the research proposed here is to greatly expand the understanding of the chemical composition of ultrafine particles, both in the atmosphere and in source emissions. New instrumentation will be assembled that is capable of determining ultrafine particle chemical composition both in bulk samples of ultrafine particles collected by cascade impaction and by a novel ultrafine particle aerosol time of flight mass spectrometer designed to determine the chemical composition of ultrafine particles at the single particle level. This instrumentation will be field tested and then used to characterize ultrafine particles in the atmosphere of one western city and one eastern city during each season of the year. In addition, archived data on ultrafine particle chemical composition measured previously during source tests by the Caltech group will be reprocessed to display the chemical composition of the smallest particles emitted. Comparisons will then be drawn between atmospheric samples and source samples to determine the extent to which the two data sets do or do not resemble each other, which will shed light on the extent to which atmospheric ultrafine particles may be affected by atmospheric chemical transformations or new particle formation. These results will serve to adjust the composition of the laboratory generated PM for the controlled clinical, animal and in vitro studies.

Core 2, Field Studies (Wichmann), studies will be conducted in Germany by a group with an established program for epidemiologic analyses of ultrafine particle effects on subjects with COPD and angina. The inclusion of this group in a consortia arrangement allows access to a large-scale ongoing European study evaluating ultrafine particle effects. As part of the epidemiological project the effects of PM-oxidant (e.g., ozone) mixtures will be assessed. The objective of the study is to characterize the association between ambient particle exposures and changes in biomarkers of inflammation in the airways and the blood of patients with stable coronary artery disease as well as of patients with COPD. Monitoring of the autonomic function of the heart will investigate how these changes in the inflammatory state relate to alterations in autonomic control. The following hypotheses will be tested in patients with chronic diseases of the lung and the heart: (1) Concentration of ambient accumulation mode (AP) and ultrafine particles (UP) is associated with inflammation of the airways, as well as increases in plasma viscosity, fibrinogen and other acute phase proteins in the blood, (2) increases in the coagulability of the blood are associated with changes in the autonomic control of the heart, and (3) exposure to UP is more closely related to the health effects than exposure to AP mass. The result of this Core will be a valuable input for the clinical, animal and in vitro studies with respect to planned mixed PM-oxidant exposures.

Core 3, Clinical Studies (Frampton, Utell), will make use of results from the field studies, starting initially with controlled exposures in healthy subjects and asthmatics, and then of elderly subjects with COPD and coronary artery disease, similar to the field study cohorts. These studies will utilize controlled human exposures to examine, in healthy and potentially susceptible subjects, the deposition and fate of inhaled ultrafine carbon particles (UP), and the role of UP and ultrafine carbon particles containing trace metals (UM) in inducing health effects. The proposed pathophysiology for pollutant-induced lung inflammation involves the following sequence of events: (i) Injury to epithelial cells by reactive oxygen species, possibly enhanced in the presence of metals via Haber-Weiss and Fenton chemistry, accompanied by activation of nuclear regulatory factors, leading to elaboration of proinflammatory cytokines, including interleukins-8 (IL-8) and -6 (IL-6), and increased expression of nitric oxide synthase (NOS), with increased nitric oxide (NO) in exhaled air. (ii) Activation of vascular endothelium and circulating leukocytes. Emigration of inflammatory cells from blood to tissue sites involves up-regulation of adhesion molecules and other markers on vascular endothelium and on circulating leukocytes. The events in the process of leukocyte-endothelial binding include a) increased expression of adhesion molecules followed by shedding of adhesion molecules as cells "tether and roll", b) leukocyte activation, c) stable adhesion, and d) transmigration through the epithelium. Platelets become activated and adhere to endothelium and leukocytes. Endothelial activation may further contribute to the increase in exhaled NO concentrations seen with airway inflammation. (iii) Increased release of IL-6 and tissue factor by activated blood mononuclear cells. Interleukin-6 initiates hepatic synthesis of acute phase proteins, including serum amyloid A (SAA), fibrinogen, and plasminogen activator inhibitor-1 (PAI-1). Monocyte tissue factor and endothelial cell activation initiate the coagulation cascade, as reflected by the presence of D-dimer, soluble fibrin, and prothrombin1+2. (iv) Possible adverse cardiac events in patients with critical coronary lesions, as a consequence of increased blood coagulability, platelet activation, and endothelial dysfunction.

Core 4, Animal Studies (Oberdorster), will extend the clinical studies by using rat models of human conditions including hypertension, sensitization and old age as well as transgenic mice to evaluate mechanistic hypothesis of PM induced pulmonary oxidative stress and its ramifications for cardiac and vascular events. The animal studies are designed to be complementary to the field and controlled clinical studies and to form a link to the mechanistic in vitro studies. We will analyze pulmonary and systemic responses to inhaled environmentally-relevant ultrafine (UP) and accumulation mode (AP) particles in rodent models of human disease to test our central hypothesis that the increased morbidity of susceptible people in association with small increases in urban particles is caused by UP. Thus, the overall objective of the animal studies is to identify factors which are causally associated with adverse pulmonary and cardiovascular health effects after low-level exposures to environmentally-relevant particles. These factors are related to particle characteristics (UP vs. AP; transition metals); dosimetric aspects (lung deposition and disposition); host susceptibility (advanced age; cardiovascular disorders; respiratory tract sensitization); cellular mechanisms (role of Clara cells); and pollutant co-exposure (ozone). Our mechanistic hypothesis is that inhaled ultrafine particles activate resident inflammatory cells leading to oxidative stress and production of cytokines, and that this primary response is further amplified through inflammatory cell recruitment and elaboration of both inflammatory and epithelial cell-derived cytokines. Based upon our preliminary data we further hypothesize that the primary response is greater to UP than AP, and which is further enhanced by endotoxin exposure. Amplification of the pulmonary response leads to a parallel amplification of the systemic acute phase response with associated changes in blood coagulability and cardiac events.

Core 5, In vitro Mechanisms (Finkelstein), studies will further expand the testing of oxidative stress hypotheses to a cellular/molecular level, making use of a novel in vitro exposure system which allows for realistic airborne exposures of pulmonary target cells. The in vitro and ex vivo experiments proposed within this project are designed to address specific mechanistic hypotheses regarding the interactions between inhaled ultrafine particles and specific pulmonary cell populations. We will use cell lines and primary cells derived from rats and humans to test the overall PM Center hypothesis that increased morbidity and mortality in susceptible populations is due to the unique characteristics of ultrafine particles in comparison to accumulation mode particles of similar composition. The proposed experiments are intended to provide a link between the whole animal and controlled clinical (human) exposures, described in the other programs of this PM Center, by defining mechanisms that follow particle cell contact and to test the specific hypothesis that many of the subsequent physiologic effects are the consequences of cellular oxidative stress. We further plan to examine host and environmental factors, including age, the influence of co-exposure to gaseous oxidants or prior priming or activation by pre-exposure to other inflammatory stimuli. A key component of the proposed studies is our plan to examine these particle cell interactions in individual cell populations to begin to assess the role of epithelial, inflammatory and interstitial cells in the systemic response to UP. We suggest that production of both inflammatory and fibrotic mediators following particle interaction is not limited to classic inflammatory cells, and that pulmonary parenchymal elements including epithelial cells (type II, Clara cells) and fibroblasts may also contribute to the milieu.

The Facilities Cores consist of Particle Generation (Morrow), Biostatistics (Cox), Immunology (Looney), Vascular (Marder), and Cardiac (Zareba) facilities which serve to link the projects. A number of the same endpoints related to pulmonary inflammatory responses and cardiac events as well as measurements related to the blood coagulation cascade will be measured by the respective facility cores in samples received from the epidemiological field studies, the controlled clinical studies and the toxicological animal studies. The controlled clinical, animal and in vitro studies will use the same freshly generated carbon particles of ultrafine (~25 nm) and accumulation mode (~250 nm) size at concentrations down to 10 µg/m3. Subsequently, the impact of controlled additions of transition metals to the carbon particles ? as determined from ambient PM measurements by the Exposure Research Core ? on respiratory and systemic endpoints will be assessed. This coordinated approach ? from particles ? target cells ? animals ? humans ? allows the extrapolation of results and mechanisms from in vitro studies to the human target, supported further by extensive dosimetric measurements in the animal and clinical studies.

As a Pilot Project an ultrafine particle concentrator will be developed, which allows exposures with concentrated urban ultrafine particles. The objective of this study is to build a prototype particle concentrator that will be capable of concentrating urban ultrafine particles (UP, <0.1 µm) for use in toxicological studies at ambient pressure.

Currently available urban particle concentrators are based on the principle of virtual impaction and are effective for particle sizes down to about 0.2 µm. They operate at lower than ambient pressure. An ultrafine particle concentrator would allow controlled exposures of test animals, cell systems in vitro and eventually human subjects to real world urban UP in addition to using surrogate UP. The heads of the five Research Cores constitute the Executive Committee that monitors progress and recommends utilization of resources and coordination and integration of the Center's research to the Center director and co-director. They will also be in contact with members of the external Scientific Advisory Committee (SAC) to request advice in specific areas of expertise. The two directors will provide overall oversight, coordination and integration of the Center's activities and coordinate contact with other PM Centers. They are assisted by the Administrative Core which is responsible for the day-to-day logistical needs including communication with the consortia. New projects in the form of pilot studies to pursue specific questions in one of the Research Cores are reviewed annually by the SAC members who provide recommendations for funding to the Center Director. The development of an ultrafine particle concentrator for use in in-vitro and animal/clinical studies is the first in this series of pilot projects. Additional Enrichment Programs will further enhance the activities of the Rochester PM Center, including a dedicated seminar series, educational programs and visiting scientists.

Expected Results:

The integrated multi-disciplinary approach of the Rochester PM Center will answer the key question of causality of ultrafine particle involvement for effects observed in previous epidemiological studies. The expectation is that the controlled laboratory studies will reveal that ultrafine particles, but not larger accumulation mode particles, at environmentally relevant concentrations will show pulmonary inflammatory and secondary cardio-vascular effects in the compromised organism; and that the field studies will show that ultrafine particles are better correlated with health effects than larger particles.

Improvements in Risk Assessment or Risk Management: In support of Improvements in Risk Assessment or Risk Management, it is expected that the Center will uncover specific cellular and molecular mechanisms which can explain the progression of UP-induced pulmonary responses to vascular and cardiac events. Confirmation of the ultrafine particle hypotheses will have significant consequences for public health and regulatory PM standards and lead to important improvements in risk assessment and risk management. Not only will the new PM2.5 standard have to be re-evaluated, but an additional standard defined by particle number needs to be considered. Furthermore, sources of ultrafine particles - e.g. combustion engines, residential natural gas heating - may require further regulation.


Journal Articles: 90 Displayed | Download in RIS Format

Other center views: All 104 publications 98 publications in selected types All 90 journal articles
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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. R827354 (2004)
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  • Journal Article Beckett WS, Chalupa DF, Pauly-Brown A, Speers DM, Stewart JC, Frampton MW, Utell MJ, Huang L-S, Cox C, Zareba W, Oberdorster G. Comparing inhaled ultrafine versus fine zinc oxide particles in healthy adults:a human inhalation study. American Journal of Respiratory and Critical Care Medicine 2005;171(10):1129-1135. R827354 (2004)
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  • Journal Article Begum BA, Kim E, Jeong C-H, Lee D-W, Hopke PK. Evaluation of the potential source contribution function using the 2002 Quebec forest fire episode. Atmospheric Environment 2005;39(20):3719-3724. R827354 (Final)
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  • Journal Article Berger A, Zareba W, Schneider A, Ruckerl R, Ibald-Mulli A, Cyrys J, Wichmann HE, Peters A. Runs of ventricular and supraventricular tachycardia triggered by air pollution in patients with coronary heart disease. Journal of Occupational and Environmental Medicine 2006;48(11):1149-1158. R827354 (Final)
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  • Journal Article Berglind N, Bellander T, Forastiere F, von Klot S, Aalto P, Elosua R, Kulmala M, Lanki T, Lowel H, Peters A, Picciotto S, Salomaa V, Stafoggia M, Sunyer J, Nyberg F, HEAPSS Study Group. Ambient air pollution and daily mortality among survivors of myocardial infarction. Epidemiology 2009;20(1):110-118. R827354 (Final)
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  • Journal Article Bruske I, Hampel R, Socher MM, Ruckerl R, Schneider A, Heinrich J, Oberdorster G, Wichmann H-E, Peters A. Impact of ambient air pollution on the differential white blood cell count in patients with chronic pulmonary disease. Inhalation Toxicology 2010;22(3):245-252. R827354 (Final)
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  • Journal Article Cass GR, Hughes LA, Bhave P, Kleeman MJ, Allen JO, Salmon LG. The chemical composition of atmospheric ultrafine particles. Philosophical Transactions of the Royal Society of London Series A-Mathematical Physical & Engineering Sciences 2000;358(1775):2581-2592. R827354 (2004)
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  • Journal Article Chalupa DC, Morrow PE, Oberdorster G, Utell MJ, Frampton MW. Ultrafine particle deposition in subjects with asthma. Environmental Health Perspectives 2004;112(8):879-882. R827354 (2004)
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  • Journal Article Cyrys J, Heinrich J, Peters A, Kreyling W, Wichmann HE. Emission, immission und messung feiner und ultrafeiner partikel (Emission, immission and measurement of fine and ultrafine particles). Umweltmedizin Forschung Und Praxis 2002;7(2):67-77. R827354 (2004)
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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. R827354 (2004)
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  • Journal Article Dillner AM, Schauer JJ, Christensen WF, Cass GR. A quantitative method for clustering size distributions of elements. Atmospheric Environment 2005;39(8):1525-1537. R827354 (2004)
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  • Journal Article Elder ACP, Gelein R, Azadniv M, Frampton M, Finkelstein J, Oberdorster G. Systemic interactions between inhaled ultrafine particles and endotoxin. Annals of Occupational Hygiene 2002;46(Suppl 1):231-234. R827354 (Final)
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  • Journal Article Elder ACP, Gelein R, Azadniv M, Frampton M, Finkelstein J, Oberdorster G. Systemic effects of inhaled ultrafine particles in two compromised, aged rat strains. Inhalation Toxicology 2004;16(6-7):461-471. R827354 (Final)
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  • Journal Article Elder ACP, Gelein R, Oberdorster G, Finkelstein J, Notter R, Wang Z. Efficient depletion of alveolar macrophages using intratracheally inhaled aerosols of liposome-encapsulated clodronate. Experimental Lung Research 2004;30(2):105-120. R827354 (Final)
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  • Journal Article Elder A, Gelein R, Finkelstein J, Phipps R, Frampton M, Utell M, Kittelson DB, Watts WF, Hopke P, Jeong C-H, Kim E, Liu W, Zhao W, Zhuo L, Vincent R, Kumarathasan P, Oberdorster G. On-road exposure to highway aerosols. 2. Exposures of aged, compromised rats. Inhalation Toxicology 2004;16(Suppl 1):41-53. R827354 (Final)
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  • Journal Article Elder A, Johnston C, Gelein R, Finkelstein J, Wang Z, Notter R, Oberdorster G. Lung inflammation induced by endotoxin is enhanced in rats depleted of alveolar macrophages with aerosolized clodronate. Experimental Lung Research 2005;31(6):527-546. R827354 (Final)
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  • Journal Article Elder A, Gelein R, Silva V, Feikert T, Opanashuk L, Carter J, Potter R, Maynard A, Ito Y, Finkelstein J, Oberdorster G. Translocation of inhaled ultrafine manganese oxide particles to the central nervous system. Environmental Health Perspectives 2006;114(8):1172-1178. R827354 (Final)
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  • Journal Article Elder A, Couderc J-P, Gelein R, Eberly S, Cox C, Xia X, Zareba W, Hopke P, Watts W, Kittelson D, Frampton M, Utell M, Oberdorster G. Effects of on-road highway aerosol exposures on autonomic responses in aged, spontaneously hypertensive rats. Inhalation Toxicology 2007;19(1):1-12. R827354 (Final)
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  • Journal Article Fanning EW, Froines JR, Utell MJ, Lippmann M, Oberdorster G, Frampton M, Godleski J, Larson TV. Particulate Matter (PM) Research Centers (1999-2005) and the role of interdisciplinary center-based research. Environmental Health Perspectives 2009;117(2):167-174. R827354 (Final)
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  • Journal Article Fazal F, Bijli KM, Minhajuddin M, Rein T, Finkelstein JN, Rahman A. Essential role of cofilin-1 in regulating thrombin-induced RelA/p65 nuclear translocation and intercellular adhesion molecule 1 (ICAM-1) expression in endothelial cells. Journal of Biological Chemistry 2009;284(31):21047-21056. R827354 (Final)
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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. R827354 (Final)
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  • Journal Article Frampton MW, Stewart JC, Oberdorster G, Morrow PE, Chalupa D, Pietropaoli AP, Frasier LM, Speers DM, Cox C, Huang L-S, Utell MJ. Inhalation of ultrafine particles alters blood leukocyte expression of adhesion molecules in humans. Environmental Health Perspectives 2006;114(1):51-58. R827354 (Final)
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  • Journal Article Frampton MW. Does inhalation of ultrafine particles cause pulmonary vascular effects in humans? Inhalation Toxicology 2007;19(Suppl 1):75-79. R827354 (Final)
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  • Journal Article Hampel R, Schneider A, Bruske I, Zareba W, Cyrys J, Ruckerl R, Breitner S, Korb H, Sunyer J, Wichmann HE, Peters A. Altered cardiac repolarization in association with air pollution and air temperature among myocardial infarction survivors. Environmental Health Perspectives 2010;118(12):1755-1761. R827354 (Final)
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  • Journal Article Henneberger A, Zareba W, Ibald-Mulli A, Ruckerl R, Cyrys J, Couderc J-P, Mykins B, Woelke G, Wichmann H-E, Peters A. Repolarization changes induced by air pollution in ischemic heart disease patients. Environmental Health Perspectives 2005;113(4):440-446. R827354 (Final)
    R827354C002 (2003)
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  • Journal Article Hopke PK, Ito K, Mar T, Christiansen WF, Eatough DJ, Henry RC, Kim E, Laden F, Lall R, Larson TV, Liu H, Neas L, Pinto J, Stolzel M, Suh H, Paatero P, Thurston GD. PM source apportionment and health effects:1. Intercomparison of source apportionment results. Journal of Exposure Science & Environmental Epidemiology 2006;16(3):275-286. R827354 (Final)
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    R832415 (2010)
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  • Journal Article Huang YC, Schmitt M, Yang Z, Que LG, Stewart JC, Frampton MW, Devlin RB. Gene expression profile in circulating mononuclear cells after exposure to ultrafine carbon particles. Inhalation Toxicology 2010;22(10):835-846. R827354 (Final)
    R826781 (Final)
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  • Journal Article Ibald-Mulli A, Wichmann HE, Kreyling W, Peters A. Epidemiological evidence on health effects of ultrafine particles. Journal of Aerosol Medicine 2002;15(2):189-201. R827354 (Final)
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  • Journal Article Ito K, Christensen WF, Eatough DJ, Henry RC, Kim E, Laden F, Lall R, Larson TV, Neas L, Hopke PK, Thurston GD. PM source apportionment and health effects: 2. An investigation of intermethod variability in associations between source-apportioned fine particle mass and daily mortality in Washington, DC. Journal of Exposure Science & Environmental Epidemiology 2006;16(4):300-310. R827354 (Final)
    R827354C001 (Final)
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    R832415 (2010)
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  • Full-text: JESEE-Full Text HTML
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  • Journal Article Jeong C-H, Hopke PK, Chalupa D, Utell M. Characteristics of nucleation and growth events of ultrafine particles measured in Rochester, NY. Environmental Science & Technology 2004;38(7):1933-1940. R827354 (Final)
    R827354C001 (2003)
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  • Journal Article Jeong C-H, Lee D-W, Kim E, Hopke PK. Measurement of real-time PM2.5 mass, sulfate, and carbonaceous aerosols at the multiple monitoring sites. Atmospheric Environment 2004;38(31):5247-5256. R827354 (Final)
    R827354C001 (2003)
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  • Journal Article Jeong C-H, Hopke PK, Kim E, Lee D-W. The comparison between thermal-optical transmittance elemental carbon and Aethalometer black carbon measured at multiple monitoring sites. Atmospheric Environment 2004;38(31):5193-5204. R827354 (Final)
    R827354C001 (2003)
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  • Full-text: ScienceDirect-Full Text HTML
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  • Journal Article Jeong C-H, Evans GJ, Hopke PK, Chalupa D, Utell MJ. Influence of atmospheric dispersion and new particle formation events on ambient particle number concentration in Rochester, United States, and Toronto, Canada. Journal of the Air & Waste Management Association 2006;56(4):431-443. R827354 (Final)
    R827354C001 (Final)
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    R832415C003 (2011)
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  • Full-text: Taylor & Francis Online - Full Text PDF
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  • Journal Article Kim E, Larson TV, Hopke PK, Slaughter C, Sheppard LE, Claiborn C. Source identification of PM2.5 in an arid Northwest U.S. city by positive matrix factorization. Atmospheric Research 2003;66(4):291-305. R827354 (Final)
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  • Journal Article Kim E, Hopke PK, Larson TV, Maykut NN, Lewtas J. Factor analysis of Seattle fine particles. Aerosol Science and Technology 2004;38(7):724-738. R827354 (Final)
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  • Full-text: Taylor&Francis-Full Text HTML
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  • Journal Article Kim E, Hopke PK, Larson TV, Covert DS. Analysis of ambient particle size distributions using Unmix and positive matrix factorization. Environmental Science & Technology 2004;38(1):202-209. R827354 (Final)
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  • Journal Article Kittelson DB, Watts WF, Johnson JP, Remerowki ML, Ische EE, Oberdorster G, Gelein RM, Elder A, Hopke PK, Kim E, Zhao W, Zhou L, Jeong C-H. On-road exposure to highway aerosols. 1. Aerosol and gas measurements. Inhalation Toxicology 2004;16(Suppl 1):31-39. R827354 (Final)
    R827354C001 (Final)
    R827354C004 (2003)
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  • Journal Article Kreyling WG, Semmler M, Erbe F, Mayer P, Takenaka S, Schulz H, Oberdorster G, Ziesenis A. Translocation of ultrafine insoluble iridium particles from lung epithelium to extrapulmonary organs is size dependent but very low. Journal of Toxicology and Environmental Health-Part A 2002;65(20):1513-1530. R827354 (Final)
    R827354C004 (2001)
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  • Journal Article Lanki T, Pekkanen J, Aalto P, Elosua R, Berglind N, D'Ippoliti D, Kulmala M, Nyberg F, Peters A, Picciotto S, Salomaa V, Sunyer J, Tiittanen P, von Klot S, Forastiere F. Associations of traffic related air pollutants with hospitalisation for first acute myocardial infarction:the HEAPSS study. Occupational and Environmental Medicine 2006;63(12):844-851. R827354 (Final)
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  • Journal Article Lippmann M, Frampton M, Schwartz J, Dockery D, Schlesinger R, Koutrakis P, Froines J, Nel A, Finkelstein J, Godleski J, Kaufman J, Koenig J, Larson T, Luchtel D, Liu L-JS, Oberdorster G, Peters A, Sarnat J, Sioutas C, Suh H, Sullivan J, Utell M, Wichmann E, Zelikoff J. The U.S. Environmental Protection Agency Particulate Matter Health Effects Research Centers Program: a midcourse report of status, progress, and plans. Environmental Health Perspectives 2003;111(8):1074-1092. R827354 (Final)
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  • Journal Article Mar TF, Ito K, Koenig JQ, Larson TV, Eatough DJ, Henry RC, Kim E, Laden F, Lall R, Neas L, Stolzel M, Paatero P, Hopke PK, Thurston GD. PM source apportionment and health effects. 3. Investigation of inter-method variations in associations between estimated source contributions of PM2.5 and daily mortality in Phoenix, AZ. Journal of Exposure Science & Environmental Epidemiology 2006;16(4):311-320. R827354 (Final)
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  • Journal Article Moffet RC, Shields LG, Berntsen J, Devlin RB, Prather KA. Characterization of an ambient coarse particle concentrator used for human exposure studies: aerosol size distributions, chemical composition, and concentration enrichment. Aerosol Science and Technology 2004;38(11):1123-1137. R827354 (Final)
    R827354C001 (2003)
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  • Journal Article Oberdorster G. Pulmonary effects of inhaled ultrafine particles. International Archives of Occupational and Environmental Health 2001;74(1):1-8. R827354 (Final)
    R827354C004 (2000)
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  • Journal Article Oberdorster G, Utell MJ. Ultrafine particles in the urban air:to the respiratory tract—and beyond? Environmental Health Perspectives 2002;110(8):A440-A441. R827354 (Final)
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  • Journal Article Oberdorster G, Sharp Z, Atudorei V, Elder A, Gelein R, Lunts A, Kreyling W, Cox C. Extrapulmonary translocation of ultrafine carbon particles following whole-body inhalation exposure of rats. Journal of Toxicology and Environmental Health, Part A: Current Issues 2002;65(20):1531-1543. R827354 (Final)
    R827354C004 (2001)
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  • Journal Article Oberdorster G, Sharp Z, Atudorei V, Elder A, Gelein R, Kreyling W, Cox C. Translocation of inhaled ultrafine particles to the brain. Inhalation Toxicology 2004;16(6-7):437-445. R827354 (Final)
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  • Journal Article Oberdorster G, Oberdorster E, Oberdorster J. Nanotoxicology:an emerging discipline evolving from studies of ultrafine particles. Environmental Health Perspectives 2005;113(7):823-839. R827354 (Final)
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  • Journal Article Ogulei D, Hopke PK, Chalupa DC, Utell MJ. Modeling source contributions to submicron particle number concentrations measured in Rochester, New York. Aerosol Science and Technology 2007;41(2):179-201. R827354 (Final)
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  • Journal Article Pekkanen J, Peters A, Hoek G, Tiittanen P, Brunekreef B, de Hartog J, Heinrich J, Ibald-Mulli A, Kreyling WG, Lanki T, Timonen KL, Vanninen E. Particulate air pollution and risk of ST-segment depression during repeated submaximal exercise tests among subjects with coronary heart disease:the Exposure and Risk Assessment for Fine and Ultrafine Particles in Ambient Air (ULTRA) study. Circulation 2002;106(8):933-938. R827354 (Final)
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  • Full-text: Circulation - Full Text HTML
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  • Journal Article Peters A, Heinrich J, Wichmann H-E. Gesundheitliche Wirkungen von Feinstaub: Epidemiologie der Kurzzeiteffekte (Health impact of exposure to fine particles: epidemiology of short-term effects). Umweltmedizin in Forschung und Praxis 2002;7(2):101-115. R827354 (Final)
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  • Journal Article Peters A, von Klot S, Heier M, Trentinaglia I, Hormann A, Wichmann HE, Lowel H, Cooperative Health Research in the Region of Augsburg Study Group. Exposure to traffic and the onset of myocardial infarction. New England Journal of Medicine 2004;351(17):1721-1730. R827354 (Final)
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  • Journal Article Peters A. Particulate matter and heart disease:evidence from epidemiological studies. Toxicology and Applied Pharmacology 2005;207(2-Suppl):477-482. R827354 (Final)
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  • Journal Article Pietropaoli AP, Frampton MW, Hyde RW, Morrow PE, Oberdorster G, Cox C, Speers DM, Frasier LM, Chalupa DC, Huang L-S, Utell MJ. Pulmonary function, diffusing capacity, and inflammation in healthy and asthmatic subjects exposed to ultrafine particles. Inhalation Toxicology 2004;16(Suppl 1):59-72. R827354 (Final)
    R827354C003 (2003)
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  • Journal Article Pietropaoli AP, Perillo IB, Perkins PT, Frasier LM, Speers DM, Frampton MW, Utell MJ, Hyde RW. Smokers have reduced nitric oxide production by conducting airways but normal levels in the alveoli. Inhalation Toxicology 2007;19(6-7):533-541. R827354 (Final)
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  • Journal Article Reemtsma T, These A, Venkatachari P, Xia X, Hopke PK, Springer A, Linscheid M. Identification of fulvic acids and sulfated and nitrated analogues in atmospheric aerosol by electrospray ionization fourier transform ion cyclotron resonance mass spectrometry. Analytical Chemistry 2006;78(24):8299-8304. R827354 (Final)
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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. R827354 (Final)
    R827354C003 (2000)
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  • Journal Article Ruckerl R, Ibald-Mulli A, Koenig W, Schneider A, Woelke G, Cyrys J, Heinrich J, Marder V, Frampton M, Wichmann HE, Peters A. Air pollution and markers of inflammation and coagulation in patients with coronary heart disease. American Journal of Respiratory and Critical Care Medicine 2006;173(4):432-441. R827354 (Final)
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  • Journal Article Ruckerl R, Phipps RP, Schneider A, Frampton M, Cyrys J, Oberdorster G, Wichmann HE, Peters A. Ultrafine particles and platelet activation in patients with coronary heart disease – results from a prospective panel study. Particle and Fibre Toxicology 2007;4:1. R827354 (Final)
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  • Journal Article Silva VM, Corson N, Elder A, Oberdorster G. The rat ear vein model for investigating in vivo thrombogenicity of ultrafine particles (UFP). Toxicological Sciences 2005;85(2):983-989. R827354 (Final)
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  • Journal Article Singal M, Finkelstein JN. Use of indicator cell lines for determining inflammatory gene changes and screening the inflammatory potential of particulate and non-particulate stimuli. Inhalation Toxicology 2005;17(9):415-425. R827354 (Final)
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  • Journal Article Singal M, Finkelstein JN. Amorphous silica particles promote inflammatory gene expression through the redox sensitive transcription factor, AP-1, in alveolar epithelial cells. Experimental Lung Research 2005;31(6):581-597. R827354 (Final)
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  • Journal Article Spencer MT, Prather KA. Using ATOFMS to determine OC/EC mass fractions in particles. Aerosol Science and Technology 2006;40(8):585-594. R827354 (Final)
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  • Journal Article Spencer MT, Shields LG, Sodeman DA, Toner SM, Prather KA. Comparison of oil and fuel particle chemical signatures with particle emissions from heavy and light duty vehicles. Atmospheric Environment 2006;40(27):5224-5235. R827354 (Final)
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  • Journal Article Spencer MT, Shields LG, Prather KA. Simultaneous measurement of the effective density and chemical composition of ambient aerosol particles. Environmental Science & Technology 2007;41(4):1303-1309. R827354 (Final)
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  • Journal Article Stolzel M, Breitner S, Cyrys J, Pitz M, Wolke G, Kreyling W, Heinrich J, Wichmann H-E, Peters A. Daily mortality and particulate matter in different size classes in Erfurt, Germany. Journal of Exposure Science & Environmental Epidemiology 2007;17(5):458-467. R827354 (Final)
    R827354C002 (Final)
    R832415 (2010)
    R832415 (Final)
    R832415C002 (2011)
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  • Full-text: Nature Publishing - Full Text HTML
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  • Journal Article Su Y, Sipin MF, Furutani H, Prather KA. Development and characterization of an aerosol time-of-flight mass spectrometer with increased detection efficiency. Analytical Chemistry 2004;76(3):712-719. R827354 (Final)
    R827354C001 (2003)
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  • Journal Article Su Y, Sipin MF, Prather KA, Gelein RM, Lunts A, Oberdorster G. ATOFMS characterization of individual model aerosol particles used for exposure studies. Aerosol Science and Technology 2005;39(5):400-407. R827354 (Final)
    R827354C001 (2003)
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    R832415 (2010)
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    R832415C004 (2011)
  • Full-text: Taylor & Francis-Full Text PDF
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  • Journal Article Su Y, Sipin MF, Spencer MT, Qin X, Moffet RC, Shields LG, Prather KA, Venkatachari P, Jeong C-H, Kim E, Hopke PK, Gelein RM, Utell MJ, Oberdorster G, Berntsen J, Devlin RB, Chen LC. Real-time characterization of the composition of individual particles emitted from ultrafine particle concentrators. Aerosol Science and Technology 2006;40(6):437-455. R827354 (Final)
    R827354C001 (Final)
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    R832415C003 (2011)
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  • Full-text: Taylor & Francis - Full Text HTML
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  • Journal Article Thurston GD, Ito K, Mar T, Christensen WF, Eatough DJ, Henry RC, Kim E, Laden F, Lall R, Larson TV, Liu H, Neas L, Pinto J, Stolzel M, Suh H, Hopke PK. Workgroup report: Workshop on source apportionment of particulate matter health effects—intercomparison of results and implications. Environmental Health Perspectives 2005;113(12):1768-1774. R827354 (Final)
    R827354C001 (Final)
    R827351 (Final)
    R827351C001 (Final)
    R827353 (Final)
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    R827355C008 (Final)
    R832415 (2010)
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    R832415 (Final)
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  • Journal Article Toner SM, Shields LG, Sodeman DA, Prather KA. Using mass spectral source signatures to apportion exhaust particles from gasoline and diesel powered vehicles in a freeway study using UF-ATOFMS. Atmospheric Environment 2008;42(3):568-581. R827354 (Final)
    R827354C001 (Final)
    R832415 (2010)
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    R832415C001 (2011)
  • Full-text: ScienceDirect-Full Text HTML
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  • Journal Article Utell MJ, Frampton MW. Toxicologic methods: controlled human exposures. Environmental Health Perspectives 2000;108(Suppl 4):605-613. R827354 (Final)
    R826781 (Final)
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    R832415C003 (2011)
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  • Journal Article Utell MJ, Frampton MW. Acute health effects of ambient air pollution: the ultrafine particle hypothesis. Journal of Aerosol Medicine 2000;13(4):355-359. R827354 (Final)
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    R832415C003 (2011)
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  • Abstract: MaryAnnLiebert-Abstract
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  • 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. R827354 (Final)
    R827354C003 (2001)
    R827354C003 (2002)
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    R826781 (2001)
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  • Journal Article Venkatachari P, Hopke PK, Grover BD, Eatough DJ. Measurement of particle-bound reactive oxygen species in rubidoux aerosols. Journal of Atmospheric Chemistry 2005;50(1):49-58. R827354 (Final)
    R827354C001 (2003)
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    R832415 (2010)
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  • Abstract: SpringerLink-Abstract
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  • Other: Environmental Expert-Full Text PDF
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  • Journal Article Venkatachari P, Zhou L, Hopke PK, Felton D, Rattigan OV, Schwab JJ, Demerjian KL. Spatial and temporal variability of black carbon in New York City. Journal of Geophysical Research 2006;111(D10):D10S05 (9 pp.). R827354 (Final)
    R827354C001 (Final)
    R832415 (2011)
    R832415 (Final)
  • Full-text: Wiley Online-Full Text
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  • Abstract: Wiley Online-Abstract
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  • Journal Article Venkatachari P, Zhou L, Hopke PK, Schwab JJ, Demerjian KL, Weimer S, Hogrefe O, Felton D, Rattigan O. An intercomparison of measurement methods for carbonaceous aerosol in the ambient air in New York City. Aerosol Science and Technology 2006;40(10):788-795. R827354 (Final)
    R827354C001 (Final)
    R832415 (2010)
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  • Full-text: Taylor & Francis-Full Text HTML
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  • Journal Article Venkatachari P, Hopke PK, Brune WH, Ren X, Lesher R, Mao J, Mitchell M. Characterization of wintertime reactive oxygen species concentrations in Flushing, New York. Aerosol Science and Technology 2007;41(2):97-111. R827354 (Final)
    R832415 (2010)
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    R832415 (Final)
    R832415C001 (2011)
  • Full-text: Taylor & Francis-Full Text HTML
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  • Journal Article Venkatachari P, Hopke PK. Characterization of products formed in the reaction of ozone with α-pinene: case for organic peroxides. Journal of Environmental Monitoring 2008;10(8):966-974. R827354 (Final)
    R832415 (2010)
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    R832415C001 (2011)
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  • Abstract: RSC-Abstract
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  • Journal Article Venkatachari P, Hopke PK. Development and evaluation of a particle-bound reactive oxygen species generator. Journal of Aerosol Science 2008;39(2):168-174. R827354 (Final)
    R832415 (2010)
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    R832415C001 (2011)
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  • Journal Article Veranth JM, Gelein R, Oberdorster G. Vaporization – condensation generation of ultrafine hydrocarbon particulate matter for inhalation toxicology studies. Aerosol Science and Technology 2003;37(7):603-609. R827354 (Final)
    R832415 (2010)
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    R832415C004 (2011)
  • Full-text: Taylor & Francis-Full Text PDF
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  • Journal Article Veranth JM, Gelein R, Oberdorster G. Vaporization–condensation generation of ultrafine hydrocarbon particulate matter for inhalation toxicology studies. Aerosol Science and Technology 2003;37(7):603-609. R827354C004 (2001)
    R827354C004 (Final)
  • Full-text: Tandfonline-Full Text
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  • Abstract: Informaworld
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  • Journal Article von Klot S, Peters A, Aalto P, Bellander T, Berglind N, D'Ippoliti D, Elosua R, Hormann A, Kulmala M, Lanki T, Lowel H, Pekkanen J, Picciotto S, Sunyer J, Forastiere F. Ambient air pollution is associated with increased risk of hospital cardiac readmissions of myocardial infarction survivors in five European cities. Circulation 2005;112(20):3073-3079. R827354 (Final)
    R827354C002 (Final)
    R832415 (2010)
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  • Abstract from PubMed
  • Full-text: Circulation - Full Text HTML
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  • Abstract: Circulation - Abstract
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  • Journal Article Yue W, Schneider A, Stolzel M, Ruckerl R, Cyrys J, Pan X, Zareba W, Koenig W, Wichmann H-E, Peters A. Ambient source-specific particles are associated with prolonged repolarization and increased levels of inflammation in male coronary artery disease patients. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 2007;621(1-2):50-60. R827354 (Final)
    R832415 (2010)
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    R832415C003 (2011)
    R832415C004 (2011)
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  • Journal Article Yue W, Schneider A, Ruckerl R, Koenig W, Marder V, Wang S, Wichmann H-E, Peters A, Zareba W. Relationship between electrocardiographic and biochemical variables in coronary artery disease. International Journal of Cardiology 2007;119(2):185-191. R827354 (Final)
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    R832415C003 (2011)
    R832415C004 (2011)
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  • Abstract: Elsevier-Abstract
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  • Journal Article Yue W, Stolzel M, Cyrys J, Pitz M, Heinrich J, Kreyling WG, Wichmann H-E, Peters A, Wang S, Hopke PK. Source apportionment of ambient fine particle size distribution using positive matrix factorization in Erfurt, Germany. Science of the Total Environment 2008;398(1-3):133-144. R827354 (Final)
    R832415 (2007)
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    R832415C001 (2008)
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    R832415C002 (2006)
    R832415C002 (2008)
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    R832415C002 (2011)
    R834797 (2016)
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  • Journal Article Zareba W, Nomura A, Couderc JP. Cardiovascular effects of air pollution:what to measure in ECG? Environmental Health Perspectives 2001;109(Suppl 4):533-538. R827354 (Final)
    R827354C003 (Final)
    R827354C004 (Final)
    R832415 (2010)
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  • Journal Article Zareba W, Couderc JP, Oberdorster G, Chalupa D, Cox C, Huang L-S, Peters A, Utell MJ, Frampton MW. ECG parameters and exposure to carbon ultrafine particles in young healthy subjects. Inhalation Toxicology 2009;21(3):223-233. R827354 (Final)
    R832415 (2008)
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    R832415C002 (2010)
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    R832415C004 (2009)
    R832415C004 (2010)
    R832415C004 (2011)
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  • Journal Article Zhao W, Hopke PK, Qin X, Prather KA. Predicting bulk ambient aerosol compositions from ATOFMS data with ART-2a and multivariate analysis. Analytica Chimica Acta 2005;549(1-2):179-187. R827354 (Final)
    R827354C001 (Final)
    R831083 (Final)
    R832415 (2010)
    R832415 (2011)
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  • Journal Article Zhou L, Kim E, Hopke PK, Stanier C, Pandis SN. Mining airborne particulate size distribution data by positive matrix factorization. Journal of Geophysical Research 2005;110(D7):D07S19 (15 pp.). R827354 (Final)
    R827354C001 (Final)
    R832415 (2010)
    R832415 (2011)
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  • Full-text: Wiley Online-Full Text HTML
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  • Abstract: Wiley Online-Abstract
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  • Other: University of Iowa-Full Text PDF
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  • Journal Article Zhou L, Hopke PK, Venkatachari P. Cluster analysis of single particle mass spectra at Flushing, NY. Analytica Chimica Acta 2006;555(1):47-56. R827354 (Final)
    R827354C001 (Final)
    R832415 (2010)
    R832415 (2011)
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  • Supplemental Keywords:

    pollution prevention, atmosphere, particulates, metals, sensitive population., RFA, Health, Scientific Discipline, Air, Waste, particulate matter, air toxics, Environmental Chemistry, Health Risk Assessment, Risk Assessments, Biochemistry, Children's Health, tropospheric ozone, Molecular Biology/Genetics, Incineration/Combustion, ambient air quality, cytokine production, particle size, particulates, sensitive populations, health effects, risk assessment, cardiopulmonary responses, epidemiology, fine particles, human health effects, morbidity, ambient air monitoring, lung, stratospheric ozone, PM 2.5, cardiovascular vulnerability, pulmonary disease, susceptible populations, animal model, epidemelogy, ambient air, lead, environmental health effects, particle exposure, ambient monitoring, human exposure, particulate exposure, lung inflamation, pulmonary, coronary artery disease, inhalation toxicology, combustion engines, PM2.5, urban air pollution, mortality, urban environment, aerosol, cardiopulmonary, human health, aerosols, cardiovascular disease, ultrafine particles, pathophysiological mechanisms, metals

    Progress and Final Reports:

  • 1999
  • 2000
  • 2001
  • 2002
  • 2003
  • 2004 Progress Report
  • Final Report
  • 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