Ozone and the Lung: Biological Effects during Development Laura Van Winkle PhD DABT University of California, Davis [email protected].

Ozone and the Lung: Biological Effects during Development

Laura Van Winkle PhD DABT University of California, Davis

[email protected]

Oxidant Air Pollution

Ozone (03):- created by a chemical reaction between oxides of nitrogen and volatile organic compounds; facilitated by sunlight- the primary constituent of smog, tends to form in hot, stagnant air ; a “summertime” pollutant- The new primary and secondary standards, announced Mar 12 2008 by EPA, are identical: an 8 hr standard of 0.075 parts per million (ppm) which replaces the standard set in 1997 of 0.08.

Air Pollution and Children: Reasons for Concern

The lung is still developing and growing in the postnatal period; damage during “critical windows of susceptibility” can permanently diminish lung function

Children are more likely to exercise vigorously outdoors when ozone concentrations are high and are less cognizant of ozone effects on their health

High respiratory rate with a small body size

More time to develop environmentally-induced diseases

Lung Structure, Development and Ozone Effects

The lung is not fully formed at birth and during the postnatal period many cells are still differentiating while the lung is also growing.

Maturation of airway epithelium occurs in a proximal to distal direction

Epithelial-Mesenchymal Trophic Unit Epithelial-Mesenchymal Trophic Unit of the Conducting Airwaysof the Conducting Airways

Evans, Van Winkle et al AJRCMB 1999 21 (6):655-7

Ozone Effects in the Lung

High levels cause cellular damage affecting primarily ciliated epithelium

Lower levels cause oxidant stress

Injury is dose, timing and species dependent with episodic exposures having larger effects on airway remodeling than chronic exposures or single acute exposures.

Ozone effects during lung development

Ozone exposure during lung development causes airway, immune system and parenchymal remodeling

Copyright ©2006 American Physiological Society

Fanucchi, M. V. et al. Am J Physiol Lung Cell Mol Physiol 291: L644-L650 2006;doi:10.1152/ajplung.00027.2006

Position of First Airway OutpocketingChanges following episodic ozone exposures in

the postnatal period



Number of Airway Branches to First Alveolus


Evans, M. J. et al. Am J Physiol Lung Cell Mol Physiol 285: L931-L939 2003;doi:10.1152/ajplung.00175.2003

Fibroblast growth factor-2 (FGF-2) immunoreactivity

Remodeling of the basement membrane

FA Control Postnatal Ozone


Evans, M. J. et al. Am J Physiol Lung Cell Mol Physiol 285: L931-L939 2003;doi:10.1152/ajplung.00175.2003

Syndecan-4 and FGFR-1 immunoreactivity in basal cells

PGP 9.5 positive neuroendocrine cells

Larson, Schelegle et al Toxicol Appl Pharmacol 2004 194 (3): 211-20



Effect of postnatal ozone exposure on smooth muscle bundle orientation ({theta}) in bronchioles

Ozone effects during lung developmentThe following alterations were found after exposure to ozone:

reduced airway number hyperplasia of bronchial epithelium increased mucous cells shifts in distal airway smooth muscle bundle orientation and

abundance to favor hyperreactivity interrupted postnatal basement membrane zone

differentiation modified epithelial nerve fiber distribution reorganization of the airway vascular and immune system

Ozone exposure during lung development can cause airway, immune system, neural and parenchymal remodeling

The net effect of this, especially when combined with allergic sensitization, is increased airways reactivity and bronchoconstriction as well as potential for obstruction in airways in response to provocation.

Program Investigators in UCD Pulmonary Group• Mark Avdalovic, M.D. Pulmonary Medicine – Med & CNPRC

•Nicole Baumgarth, DVM, Ph.D. Pathology, Microbiology & Immunology - Vet Med & Center for Comp Med

•Chuck Bevins, M.D., Ph.D. Med Micro & Immunology – Med

•Alan Buckpitt, Ph.D. Molecular Biosciences - Vet Med

•Carrol Cross, M.D. Pulmonary Medicine – Med

•Jason Eiserich, Ph.D. Nephrology - Med

•Michael Evans, Ph.D. Anatomy, Physiology & Cell Biology - Vet Med & CNPRC

•Laurel Gershwin, DVM, Ph.D. Pathology, Microbiology & Immunology - Vet Med

•Richart Harper,M.D. Pulmonary Medicine – Med

• Dallas Hyde, Ph.D. Anatomy, Physiology & Cell Biology - Vet Med & CNPRC

• Jesse Joad, M.D. Pediatrics - Med

• Nick Kenyon, M.D. Pulmonary Medicine – Med

•Jerry Last, Ph.D. Pulmonary Medicine – Med

•Ruth McDonald, M.D. Pediatrics - Med

• Lisa Miller, Ph.D. Anatomy, Physiology & Cell Biology - Vet Med & CNPRC

•Karen Oslund, DVM, Ph.D. Pathology, Microbiology & Immunology - Vet Med

• Kent Pinkerton, Ph.D. Anatomy, Physiology & Cell Biology - Vet Med & CNPRC

• Charles Plopper, Ph.D. Anatomy, Physiology & Cell Biology - Vet Med & CNPRC

• Edward Schelegle, Ph.D. Anatomy, Physiology & Cell Biology - Vet Med & CNPRC

•Scott Simon, PhD Biomed Eng – Engineering

•Charles Stephensen, Ph.D. Nutrition – Ag & Environ Sciences

•Jonathan Widdicombe, Ph.D. Physiology & Membrane Biology - Med

• Laura Van Winkle, Ph.D. Anatomy, Physiology & Cell Biology - Vet Med

•Dennis Wilson, DVM, Ph.D. Pathology, Microbiology & Immunology - Vet Med

• Reen Wu, Ph.D. Anatomy, Physiology & Cell Biology - Vet Med & Pul Med – Med

5P01ES000628-34 Pulmonary Effects of Environmental Oxidant Pollutants

Ozone and the Lung: Biological Effects during Development Laura Van Winkle PhD DABT University of California, Davis [email protected].

Documents

lung structure

alveolus slide

postnatal period slide

lung high levels

lung development causes

cognizant of ozone effects

ozone concentrations

parenchymal remodeling