health effects of air pollution: beyond the “criteria” pollutants philip bromberg md 1 ilona...

Health Effects of Air Pollution:Beyond the “Criteria” Pollutants

Philip Bromberg MD1

Ilona Jaspers PhD1

Ken Sexton PhD1

Harvey Jeffries PhD1

W. Michael Foster PhD2

1 Univ. North Carolina2 Duke University

Air Toxics Workshop IISession 112 June 07Mickey Leland CenterHouston, TX

Introduction

• Ozone (O3)

– Produced in ambient air by photochemistry of NOx and hydrocarbons (primary emissions)

– High reactivity -> ozonized reactive biological products in airways after inhalation

– E.g., 4-OH nonenal, an unsaturated aldehyde with an acrolein motif (-CH=CH-CH=O).

Introduction (cont’d)

• Biologic effects in humans– Irritant (bronchial C fibers and A-delta fibers)– Reversible decrease in lung function– Acute airways inflammation (IL-8, IL-6, PGE2)– Increased epithelial permeability

Introduction (cont’d)

• Ozone as a surrogate– Other toxic species (oxy-organics) in ambient

air– Some oxy-organics are recognized “air toxics”

(e.g., HCHO, acetaldehyde, acrolein)– Others remain to be identified and

characterized– Ozone itself may or may not be directly

involved in their formation– Interaction of poorly volatile oxy-organics with

ambient particulate matter

• Is ozone responsible for all the health effects observed in human populations exposed to photochemical smog?– Yes, and– No!

Respiratory Hospital Admissions by Daily Maximum Ozone Level, Lagged One Day

114

112

110

108

106

104

102

114

112

110

108

106

104

102

Ozone Concentration (ppm)Ozone Concentration (ppm)

Res

pir

ato

ry A

dm

issi

on

sR

esp

irat

ory

Ad

mis

sio

ns

.01 .02 .03 .04 .05 .06 .07 .08 .09 .1.01 .02 .03 .04 .05 .06 .07 .08 .09 .1

D-8a

(Burnett et al, 1994) (Burnett et al, 1994)

In-Vitro Exposure Systems Interfaced to Environmental Irradiation Chambers

• Interfaced in-vitro gaseous exposure systems to these smog chambers, allowing A549 cells, an alveolar type II-like cell line, and primary human bronchial epithelial cells, grown on membranous support, to be exposed in real-time, directly to the gaseous photochemical mixture or ”control” mixture and analyzed for cytotoxicity and cytokine gene expression.

• ?? Attain goal of whole natural gas-phase exposure sample

• All products, both known and unknown, produce exposure; product yields and resulting mixtures are natural (realistic exposure ratios)

Cytotoxicity induced by the photochemical transformation of HAPS

0

1

2

3

4

5

Meth+NO O3 O3+Form Meth+NO+light

LDH

rel

ease

:(f

old

indu

ctio

n ov

er c

ontr

ol)

Methanol

0

1

2

3

4

5

ISO+NO+lightMACR+MVK+O3

O3ISO+NO

LDH

rel

ease

:(f

old

indu

ctio

n ov

er c

ontr

ol) Isoprene (ISO)

LDH

rel

ease

:(f

old

indu

ctio

n ov

er c

ontr

ol)

0

1

2

3

4

5

6

7

BD+NO O3 ACR+O3+ Form

BD+NO+light

$ # *(p=0.06)

$ #

$

1,3-Butadiene (BD)

HC+NOx (no photochemistry)

Ozone

HC primary products

HC+NOx+lightFull product generated

0

1

2

3

4

5

Meth+NO O3 O3+Form Meth+NO+light

LDH

rel

ease

:(f

old

indu

ctio

n ov

er c

ontr

ol)

Methanol

0

1

2

3

4

5

ISO+NO+lightMACR+MVK+O3

O3ISO+NO

LDH

rel

ease

:(f

old

indu

ctio

n ov

er c

ontr

ol) Isoprene (ISO)

LDH

rel

ease

:(f

old

indu

ctio

n ov

er c

ontr

ol)

0

1

2

3

4

5

6

7

BD+NO O3 ACR+O3+ Form

BD+NO+light

$ # *(p=0.06)

$ #

$

1,3-Butadiene (BD)

0

1

2

3

4

5

Meth+NO O3 O3+Form Meth+NO+light

LDH

rel

ease

:(f

old

indu

ctio

n ov

er c

ontr

ol)

Methanol

0

1

2

3

4

5

Meth+NO O3 O3+Form Meth+NO+light

LDH

rel

ease

:(f

old

indu

ctio

n ov

er c

ontr

ol)

Methanol

Meth+NO O3 O3+Form Meth+NO+lightMeth+NO O3 O3+Form Meth+NO+light

LDH

rel

ease

:(f

old

indu

ctio

n ov

er c

ontr

ol)

Methanol

LDH

rel

ease

:(f

old

indu

ctio

n ov

er c

ontr

ol)

Methanol

0

1

2

3

4

5

ISO+NO+lightMACR+MVK+O3

O3ISO+NO

LDH

rel

ease

:(f

old

indu

ctio

n ov

er c

ontr

ol) Isoprene (ISO)

0

1

2

3

4

5

ISO+NO+lightMACR+MVK+O3

O3ISO+NO

LDH

rel

ease

:(f

old

indu

ctio

n ov

er c

ontr

ol) Isoprene (ISO)

ISO+NO+lightMACR+MVK+O3

O3ISO+NO ISO+NO+lightMACR+MVK+O3

O3ISO+NO

LDH

rel

ease

:(f

old

indu

ctio

n ov

er c

ontr

ol) Isoprene (ISO)

LDH

rel

ease

:(f

old

indu

ctio

n ov

er c

ontr

ol) Isoprene (ISO)

LDH

rel

ease

:(f

old

indu

ctio

n ov

er c

ontr

ol)

0

1

2

3

4

5

6

7

BD+NO O3 ACR+O3+ Form

BD+NO+light

$ # *(p=0.06)

$ #

$

1,3-Butadiene (BD)

LDH

rel

ease

:(f

old

indu

ctio

n ov

er c

ontr

ol)

0

1

2

3

4

5

6

7

BD+NO O3 ACR+O3+ Form

BD+NO+light

$ # *(p=0.06)

$ #

$

1,3-Butadiene (BD)

HC+NOx (no photochemistry)

Ozone

HC primary products

HC+NOx+lightFull product generated

HC+NOx (no photochemistry)

Ozone

HC primary products

HC+NOx+lightFull product generated

ISO+NO+light

0

1

2

3

4

5

6

IL-8

pro

duct

ion:

(fol

d in

duct

ion

over

con

trol

)

Meth+NO O3 O3+Form Meth+NO+light

Methanol

IL-8

pro

duct

ion:

(fol

d in

duct

ion

over

con

trol

)

0

1

2

3

4

5

MACR+MVK+O3

O3ISO+NO

Isoprene (ISO)IL

-8 p

rodu

ctio

n:(f

old

indu

ctio

n ov

er c

ontr

ol)

0123456789

1011121314

BD+NO O3 ACR+O3+ Form

BD+NO+light

$ # *

$

$ #

1,3-Butadiene (BD)

HC+NOx (no photochemistry)

Ozone

HC primary products

HC+NOx+lightFull product generated

ISO+NO+light

0

1

2

3

4

5

6

IL-8

pro

duct

ion:

(fol

d in

duct

ion

over

con

trol

)

Meth+NO O3 O3+Form Meth+NO+light

Methanol

IL-8

pro

duct

ion:

(fol

d in

duct

ion

over

con

trol

)

0

1

2

3

4

5

MACR+MVK+O3

O3ISO+NO

Isoprene (ISO)IL

-8 p

rodu

ctio

n:(f

old

indu

ctio

n ov

er c

ontr

ol)

0123456789

1011121314

BD+NO O3 ACR+O3+ Form

BD+NO+light

$ # *

$

$ #

1,3-Butadiene (BD)

HC+NOx (no photochemistry)

Ozone

HC primary products

HC+NOx+lightFull product generated

0

1

2

3

4

5

6

IL-8

pro

duct

ion:

(fol

d in

duct

ion

over

con

trol

)

Meth+NO O3 O3+Form Meth+NO+light

Methanol

0

1

2

3

4

5

6

IL-8

pro

duct

ion:

(fol

d in

duct

ion

over

con

trol

)

Meth+NO O3 O3+Form Meth+NO+light

Methanol

IL-8

pro

duct

ion:

(fol

d in

duct

ion

over

con

trol

)

Meth+NO O3 O3+Form Meth+NO+lightMeth+NO O3 O3+Form Meth+NO+light

Methanol

IL-8

pro

duct

ion:

(fol

d in

duct

ion

over

con

trol

)

0

1

2

3

4

5

MACR+MVK+O3

O3ISO+NO

Isoprene (ISO)

IL-8

pro

duct

ion:

(fol

d in

duct

ion

over

con

trol

)

0

1

2

3

4

5

MACR+MVK+O3

O3ISO+NO

IL-8

pro

duct

ion:

(fol

d in

duct

ion

over

con

trol

)

0

1

2

3

4

5

MACR+MVK+O3

O3ISO+NO MACR+MVK+O3

O3ISO+NO

Isoprene (ISO)IL

-8 p

rodu

ctio

n:(f

old

indu

ctio

n ov

er c

ontr

ol)

0123456789

1011121314

BD+NO O3 ACR+O3+ Form

BD+NO+light

$ # *

$

$ #

1,3-Butadiene (BD)

IL-8

pro

duct

ion:

(fol

d in

duct

ion

over

con

trol

)

0123456789

1011121314

BD+NO O3 ACR+O3+ Form

BD+NO+light

$ # *

$

$ #

1,3-Butadiene (BD)

HC+NOx (no photochemistry)

Ozone

HC primary products

HC+NOx+lightFull product generated

HC+NOx (no photochemistry)

Ozone

HC primary products

HC+NOx+lightFull product generated

Inflammatory gene expression induced by the photochemical transformation of HAPS : Methanol,

Isoprene (ISO), 1,3-Butadiene (BD)

Uncertainties in Estimating Exposure and Risk in Atmospheric Aging Effects

• Many reaction rates and product yields are uncertain

• Many reaction products are detected but not identified

• Many reaction products are unknown or difficult to detect or quantify

• How can we estimate exposure and risk given these uncertainties and unknowns ?

Acrolein

+ HCHO

+ O2

+ CH2OO

+ HCHO

+ CH2OO

+ O2

Glycidaldehyde

+ O(3P)

Acrolein

1,3-Butadiene diepoxide

1,3-Butadienemonoxide

Acrylic AcidHCHO + 2CO+HO2 + OH

OH

O3 OO

O

O

O3

O

O

O O

O

O

O

OO

OOO

O

O O

O

Resuspended DP from Diesel-Urban VOC Mixtures: Effect of

Photochemical Aging• • Create/Obtain DEP in rooftop smog chamber at

UNC • Obtain C57BL/6J mice at Duke• • Day 1- Instill DEPs (6 mice per group)

Dark Fresh 28.8µg/ 50µL• Photochemically Aged 30.5µg/ 50µL • PBS (phosphate buffered saline) 50µL

• Dark Fresh 44.4µg/ 50µL • Dark Aged 39.0µg/ 50µL PBS

(phosphate buffered saline) 50µL • Day 4- Repeat Doses in mice

• Day 7- Repeat Doses in mice• Day 8- Euthanize for lavage/tissue collection

or Perform PFTs

*

*

*

*

* = p<0.05

*

*

* *

Fresh DEP

Aged DEP

PBS Control

Hematoxylin and Eosin (H and E) Staining- stains nucleic acids and intracellular and extracellular proteins

HISTOLOGYHISTOLOGY

Aged DEP instilled mice showed GREATER airway hyperresponsiveness compared to the ozone exposed mice.

*

*

* (p=.079)

Resuspended DP from Diesel-Urban VOC Mixtures: Effect of

Photochemical Aging

Summary/Conclusions

• “Air Toxics” and “Criteria Pollutants” interact. They should not be treated as totally distinct categories.

• Photochemistry transforms many (not all) volatile organic compounds into less volatile oxy-organics that are toxic in their own right and may interact with PM.

Summary/Conclusions (cont’d)

• Photochemical smog clearly causes adverse respiratory health effects, notably in asthmatics. Ozone is toxic on its own, but may also be a surrogate for toxic oxy-organic species.

• Houston is positioned to lead in this area of air pollution research and application.

• A multi-disciplinary team approach is required to obtain the needed information.

Summary/Conclusions (cont’d)

• Such knowledge is essential for– Targeted air quality monitoring– Cost-effective measures to control key

emissions– Reasonable expectation that these measures

will improve public health.

Student Investigators

• Melanie Doyle, PhD (2006)– Currently at Lovelace Resp. Res. Inst.

• Kim deBruijne MS (2006)– Currently a PhD candidate at U.N.C.

• Seth Ebersviller (grad. student)– Currently a PhD candidate at U.N.C.

http://www.oneatmosphere.unc.edu/