1. Traffic Source Exposures and Health: Studies from the Harvard EPA Particle Center. John J. Godleski, MD Department of Environmental Health Deputy Director, Harvard EPA Particle Center Society for Risk Analysis New England Chapter

2. Novel Exposure Scenarios to Define the Health Effects of Particle Sources Petros Koutrakis, PI: Center Director John Godleski, Deputy Director Harvard University University of Toronto University of Michigan Brigham & Women’s Hospital Veteran’s Administration Harvard/EPA PM Center

3. Center Strategy A multi-faceted exposure approach encompassing ambient, Concentrated Ambient Particles (CAPs), and specific- source exposures Assessing a large array of biological responses, in humans and animals, focusing on pulmonary and cardiovascular outcomes

4. Center Projects and Cores P1: Normative Aging Study (Yrs 1-5) P2: Human CAPs Study (Yrs 1-5) P3: Animal CAPs Study (Yrs 1-2.5) P4: TERESA Study (Yrs 2.5-5) C1: Administrative Core (Yrs 1-5) C2: Particle Technology Core (Yrs 1-5) C3: Biostatistical Core (Yrs 1-5)

5. Project 1 Cardiovascular Responses in the Normative Aging Study: Exploring the Pathways of Particle Toxicity PI: Joel Schwartz Project 2 Cardiovascular Toxicity of Concentrated Ambient Fine, Ultrafine and Coarse Particles in Controlled Human Exposures PI: Frances Silverman Project 3 Assessing Toxicity of Local and Transported Particles Using Animal Models Exposed to CAPs PI: John Godleski Project 4 Toxicological Evaluation of Realistic Emission Source Aerosol (TERESA): Investigation of Vehicular Emissions PIs: Petros Koutrakis and John Godleski

6. Study Design Project 4 A mixture of primary particles and gases from a vehicular traffic source will be studied. These emissions will also undergo photochemical oxidation to form secondary PM derived from traffic emissions. A large tunnel in the Northeast will be used as the source of primary emissions Exposure scenarios will be assessed vs filtered air controls: –Primary gas and particle emissions –Primary plus secondary particles –Secondary particles formed in the absence of primary particles

7. Figure 1. The TERESA Source-Specific Emission Exposure System (SEES)

8. The TERESA Photochemical Reaction Simulation System

9. Parallel Plate Diffusion Denuder Ruiz et al, Environmental Science & Technology 2006: 40(16): 5058-5063.

10. Biological Outcomes Sprague Dawley Rats will be studied. Biological measurements will include: –pulmonary, systemic, and cardiovascular effects –continuous measurements of blood pressure and pulmonary function Selected scenarios will be further investigated using animal models of disease to assess susceptibility

11. Many necessary preliminary studies have been completed in preparation for these tunnel studies. On site inspection of our mobile laboratory by the Harvard Medical Area Standing Committee on Animals was just completed in the past two weeks. Animal exposures to these atmospheres are just beginning. Status of Project 4 Experiments

12. Integration of Center Projects 1-3 in Relationship to Blood Pressure Mechanisms and Outcomes The studies in the literature on blood pressure changes as an outcome in relationship to ambient air pollution have been inconsistent.

13. From Project 1 Environmental Health Perspectives 2009: 117:1767–1772.

14. Black Carbon was significantly associated with increases in systolic and diastolic blood pressure, but PM 2.5 was not. There was no associated effect modification by gene variants related to oxidative stress. Mordukhovich et al Environmental Health Perspectives 2009: 117:1767–1772

15. From Project 2 Hypertension 2009: 54: 659-667

16. Harvard Ambient Fine Particle Concentrator

17. University of Toronto location is an urban setting along a heavily traveled street – Concentrator inlet is about 25’ from the street Brook et al Hypertension 2009: 54: 659-667

18. Brook et al Hypertension 2009: 54: 659-667

19. CAPs + Ozone CAPs Alone Brook et al Hypertension 2009: 54: 659-667

20. From Project 3 Environmental Health Perspectives 2009: 117(3): 361-366.

21. CAPs: PM 2.5 Concentration is ~30x ambient Composition is same as ambient Harvard Ambient Particle Concentrator Godleski et al HEI Report 91,2000 Inlet about 75 meters from Huntington Ave.

22. Systolic and Diastolic Blood Pressure increased Significantly with CAPs exposure over 6 hours Bartoli et al. Environmental Health Perspectives 2009: 117(3): 361-366.

24. Caps Filter Air Rat studies of Blood pressure over 5 hours of exposure

25. Hours of Exposure

26. Barorecptor Reflex Sensitivity (BRS) – A potential mechanism Baroreceptors (or baroceptors) in the body detect the pressure of blood flowing through them, and send messages to the central nervous system to increase or decrease total peripheral resistance and cardiac output.bodycentral nervous systemtotal peripheral resistancecardiac output Baroreceptor reflex is one of the body's homeostatic mechanisms for maintaining blood pressure. It provides a negative feedback loop in which an elevated blood pressure reflexively causes blood pressure to decrease; similarly, decreased blood pressure depresses the baroreflex, causing blood pressure to rise homeostaticblood pressurenegative feedback loop

27. BRS Studies We evaluated pre- and post-exposure BRS following intravenous injection of phenylepherine (10µg/kg), Heart rate and BP after the injection of agonist are plotted to determine whether the BRS set point has changed.

28. Bartoli et al. Environmental Health Perspectives 2009: 117(3): 361-366.

29. BRS Interpretation The findings suggest a compensatory response takes place during the exposure.

30. Alpha Adrenergic Blockers Prevent CAPs Effect on Blood Pressure Bartoli et al. Environmental Health Perspectives 2009: 117(3): 361-366.

31. Summary In all studies of our Center, blood pressure increased significantly, and associations were strongest with markers of urban traffic. The timing of measuring blood pressure in relationship to exposure is important in assessing the magnitude of change. Homeostatic mechanisms control increases in blood pressure and limit the amount of change during longer exposures. The sympathetic nervous system plays a role in the change in blood pressure with exposure.