Health Effects of Air Pollution: Beyond the “Criteria” Pollutants Philip Bromberg MD 1 Ilona Jaspers PhD 1 Ken Sexton PhD 1 Harvey Jeffries PhD 1 W. Michael Foster PhD 2 1 Univ. North Carolina 2 Duke University Air Toxics Workshop II Session 1 12 June 07 Mickey Leland Center Houston, TX

Introduction Ozone (O 3 ) –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 Ozone Concentration (ppm) Respiratory Admissions D-8a (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

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 ?

Resuspended DP from Diesel-Urban VOC Mixtures: Effect of Photochemical Aging Create/Obtain DEP in rooftop smog chamberat 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 HISTOLOGY

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.