health effects of air pollution: beyond the “criteria” pollutants philip bromberg md 1 ilona...
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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
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108
106
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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/