Traffic Source Exposures and Health: Studies from the Harvard EPA Particle Center.

John J. Godleski, MDDepartment of Environmental Health

Deputy Director, Harvard EPA Particle Center

Society for Risk AnalysisNew England Chapter

Novel Exposure Scenarios to Define the Health Effects of

Particle Sources

Petros Koutrakis, PI: Center DirectorJohn Godleski, Deputy Director

Harvard UniversityUniversity of Toronto

University of Michigan Brigham & Women’s Hospital

Veteran’s Administration

Harvard/EPA PM Center

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

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)

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

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

SAMPLINGSYSTEM

MOBILEREACTION

LABORATORY

MOBILEEXPOSURE

LABORATORY

VENTILATIONSHAFT

SECONDARY AEROSOL

VENT.SHAFT

EXHAUST

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

The TERESA Photochemical Reaction Simulation System

Chamber 1 Chamber 2 DiffusionDenuder

Dilution

AnimalExposure

UV 340 Lights

UV 340 Lights

Room Fluorescent

Lights

Room Fluorescent

Lights

Chamber 1 Chamber 2 DiffusionDenuder

Dilution

AnimalExposure

UV 340 Lights

UV 340 Lights

Room Fluorescent

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Room Fluorescent

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AIR OUT

CLEAN AIR IN

FROMREACTION CHAMBER

AIR OUTCLEAN AIR IN

TO SAMPLING MANIFOLD AND

EXPOSURE CHAMBERS

MICRO-POROUS TEFLON (GAS DIFFUSION) MEMBRANES

GASES

ONLY

PARTICLES AND GASES

GASES

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Parallel Plate Diffusion Denuder

Ruiz et al, Environmental Science & Technology 2006: 40(16): 5058-5063.

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

•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

Integration of Center Projects 1-3in 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.

From Project 1

Environmental Health Perspectives 2009: 117:1767–1772.

Black Carbon was significantly associated with increases in systolic and diastolic blood pressure, but PM2.5 was not.

There was no associated effect modification by genevariants related to oxidative stress. Mordukhovich et al Environmental Health Perspectives 2009: 117:1767–1772

From Project 2

Hypertension 2009: 54: 659-667

Harvard Ambient Fine Particle Concentrator

University of Toronto location is an urban setting alonga heavily traveled street – Concentrator inlet is about 25’ from the street

Brook et al Hypertension 2009: 54: 659-667

Brook et al Hypertension 2009: 54: 659-667

CAPs + Ozone

CAPs Alone

Brook et al Hypertension 2009: 54: 659-667

From Project 3

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

CAPs:• PM2.5

• Concentration is ~30x ambient

• Composition issame as ambient

Harvard Ambient Particle Concentrator

Godleski et al HEI Report 91,2000Inlet about 75 meters from Huntington Ave.

Systolic and Diastolic Blood Pressure increased Significantly with CAPs exposure over 6 hours

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

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

Caps

Filter Air

Rat studies of Blood pressure over 5 hours of exposure

Dias tolic P res s ure C omparis on B etween B as eline, S ham, and C AP s E xpos ures

40

50

60

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0 1 2 3 4 5

mm

Hg

2/11/2005-B aseline

2/14/2005-S HAM

3/8/2005-C AP s

Hours of Exposure

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.

• 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

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.

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

BRS Interpretation

• The findings suggest a compensatory response takes place during the exposure.

Alpha Adrenergic Blockers Prevent CAPs Effect on Blood Pressure

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

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.