ozone and the lung: biological effects during development laura van winkle phd dabt university of...
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Ozone and the Lung: Biological Effects during Development
Laura Van Winkle PhD DABT University of California, Davis
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
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
Number of Airway Branches to First Alveolus
Copyright ©2003 American Physiological Society
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
Copyright ©2003 American Physiological Society
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
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
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