SOT’s 52nd Annual Meeting San Antonio, Texas March 10–14 2013

ENHANCING PM EPIDEMIOLOGICAL CONCENTRATION-RESPONSE FUNCTIONS BY INCORPORATING LUNG

DEPOSITION AND OXIDATIVE POTENTIAL

Dimosthenis A. Sarigiannis1,2, Spyros P. Karakitsios1, Vasilis Kalaitzis1, Marianthi Kermenidou1

1Aristotle University of Thessaloniki, Department of Chemical Engineering, Environmental Engineering Laboratory, Thessaloniki, 54124, Greece; 2Centre for Research and Technology Hellas (CE.R.T.H.), Thessaloniki, 57001,Greece

SOT’s 52nd Annual Meeting San Antonio, Texas March 10–14 2013

Rationale

Measurements/chemical analysis• Ambient air PM10/2.5/1 at the sites of interest • Ambient air UFPs PNC measurements (from 10.9 to 359 nm, with 1 s time resolution) at the sites of

interest• ROS analysis to all the above particles using the DDT assay

Modelling• PM and UFPs exposure modelling using INTERA model• PM and UFPs respiratory tract deposition using the Multiple-Path Particle Dosimetry model

Aim of the study• Deriving a more informative exposure metric to be used on PM exposure/health associations

How?• Assessment of a wide range of PM (10, 2.5, 1, UFPs) exposure near a traffic site and an urban

background site, in order to understand spatial and temporal differences• Assessment of PM human respiratory tract deposition under realistic exposure scenarios• Assessment of oxidative potential

SOT’s 52nd Annual Meeting San Antonio, Texas March 10–14 2013

INTERA model

Indoor processes Outdoor penetration Dispersion Sorption Deposition Chemical reactions Resuspension Dilution/ventilation

Inhalation exposure

Source conditions: e.g. Emission strength Time pattern Chemical/physical

properties of compounds

Housing conditions: e.g. Dimensions and layout Ventilation

characteristics Sources location

Individual conditions: e.g.• Time activity patterns • Inhalation intensity based on activity• Age, gender

0 a

dCV Q C C C E kCV

dt

2

1

2

2, exp

2

y y

z yy y

q yC x y dy

u

Outdoor Indoor

HRT model

T n n nn

E f C inh loc loc actn

E = f C inh

SOT’s 52nd Annual Meeting San Antonio, Texas March 10–14 2013

Multiple-Path Particle Dosimetry model

• Airway morphometry parametersLung geometry modelLung expansionVolumetric parameters

• Particle propertiesParticle densityParticle diameter (Median diameters)Geometric standard deviation

• Exposure conditionsAerosol concentrationBreathing conditions

• Clearance parametersClearance ratesExposure duration

Model Inputs

Model Overview• Aerosol deposition and clearance in the respiratory tract.• Monodisperse or lognormally distributed polydisperse aerosols.• Particles range from ultrafine (0.01 microns) to coarse (20 microns)

sizes.• Deposition by diffusion, sedimentation and impaction within the

airway or airway bifurcation.• Mucociliary particle clearance in the conducting airways.• Three-compartment clearance model (ICRP 1994) in the alveolar

region for humans.

Model Outputs• Deposition distribution per acinus or lobe• Regional deposition• Deposition vs diameter • Deposition vs time• Clearance & retention in tracheobronchial and alveolar regions

SOT’s 52nd Annual Meeting San Antonio, Texas March 10–14 2013

UFPs PM1 PM2.5 PM10 UFPs PM1 PM2.5 PM10Traffic Urban background

0

30

60

90

120 PM concentrations Q1MedianMean

PM c

once

ntra

tion

(μg/

m3)

Results

SOT’s 52nd Annual Meeting San Antonio, Texas March 10–14 2013

0 50 100 150 200 250 300 350 400

050100150200250300350

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

0

20000

40000

60000

80000

100000

120000

140000

Urban backgroundTraffic

Particle diameter (nm)

# Pa

rtic

les

Particle diameter (nm)

# Pa

rtic

les

Results

SOT’s 52nd Annual Meeting San Antonio, Texas March 10–14 2013

• Dilution

• Nucleation of semivolatile organic compounds

(SVOCs) to yield new particles

• SVOC condensation

• Deposition mainly determined by Brownian

diffusion

• Hygroscopic growth

SOT’s 52nd Annual Meeting San Antonio, Texas March 10–14 2013

Na-

soph

a-ry

ngea

l

Tra-

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-br

onch

ial

Pulm

onar

y br

onch

iole

s

Na-

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a-ry

ngea

l

Tra-

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-br

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ial

Pulm

onar

y br

onch

iole

sTraffic Urban background

0

50

100

150

200

250

300

350 HRT deposition

Q1

Median

Mean

PM

mas

s (μ

g)Results

SOT’s 52nd Annual Meeting San Antonio, Texas March 10–14 2013

UFPs PM1 PM2.5 PM10 UFPs PM1 PM2.5 PM10Traffic Urban background

0.00

0.07

0.14

0.21 ROS (DDT activity)

Q1MedianMean

RO

S (p

mol

/min

/μg)

Results

SOT’s 52nd Annual Meeting San Antonio, Texas March 10–14 2013

Results

Na-

soph

a-ry

ngea

l

Tra-

cheo

-br

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ial

Pulm

onar

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iole

s

Na-

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-br

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ial

Pulm

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Traffic Urban background

0

5

10

15

20

25 Region specific oxidative potential index

Q1MedianMean

Inde

x

SOT’s 52nd Annual Meeting San Antonio, Texas March 10–14 2013

0

1

2

3

4

5

Exposure/dose/toxicity differences

SOT’s 52nd Annual Meeting San Antonio, Texas March 10–14 2013

Adopted from Sturm, R. (2011), Radioactivity and lung cancer-mathematical models of radionuclide deposition in the human lungs, Journal of Thoracic Disease, 3, 231-243.

Adopted from Brook, R.D., et al (2010), Particulate matter air pollution and cardiovascular disease: An update to the scientific statement from the American heart association, Circulation, 121, 2331-2378..

Nasopharyngeal Trachiobroncial Pulmonary bronchioles0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

115 μm

10 μm

5 μm

1 μm

0.1 μm

0.05 μm

Dep

ositi

on fr

actio

n

“an elevation of UFP count by 9748/cm3 has been associated with an increase in cardiovascular mortality of approximately 3% within 4 days in Erfurt, Germany”“Stolzel, M., S. Breitner, J. Cyrys, M. Pitz, G. Wolke, W. Kreyling, J. Heinrich, H.E. Wichmann and A. Peters (2006), Daily mortality and particulate matter in different size classes in Erfurt, Germany, J Expos Sci Environ Epidemiol, 17, 458-467.”

Implications forenvironment-health associations

SOT’s 52nd Annual Meeting San Antonio, Texas March 10–14 2013

Conclusions

The region specific oxidative stress index proposed in this work could serve as a starting point for re-evaluating environmental information (PM measurements and ROS analysis), beyond existing concentration response functions that associate PM to mortality and morbidity

The proposed methodology facilitates the joint exploitation of exposure and toxicity related differences reflecting:i) differences in PM size distributions across the sampling sites and how these are

translated into HRT deposition valuesii) differences in the oxidative potential of different size PM are linked to specific regions of

HRT

Region specific oxidative stress values can be associated to specific health endpoints:• respiratory hospital admissions including influenza linked to upper HRT regions; • cardiovascular diseases linked to lower HRT This approach will lead to improved associations to molecular (e.g exposure and markers of systemic inflammation such as glutathione (GSH), or to urinary 8-hydroxy-20-deoxyguanosine, a biomarker of oxidative stress) and spatial epidemiology

SOT’s 52nd Annual Meeting San Antonio, Texas March 10–14 2013

Thank you for your kind attention

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