Inhaled air pollutants such as ozone are known to exacerbate asthma and may play a potential role in the inception of reactive ain/vay disease in early life. While ozone can cause significant respiratory health problems in the majority of exposed individuals, young children are particularly at greater risk for developing serious adverse health effects from ozone exposure. This is because their lungs are still developing rapidly, and exposures during this critical window of susceptibility may alter lung development, resulting in permanent respiratory health problems. Air pollutants may also influence the developing immune system in young children, increasing susceptibility to infection and promoting ainway sensitization to common aeroallergens. The overall objective of this project is to define how ozone influences lung development and host immune response in early postnatal life. Our general hypothesis is that ozone exposure in the early postnatal phase alters lung development and modifies the host immune response to early life viral infection and allergen exposure, thereby contributing to the development of reactive airway disease. To test this hypothesis, we will pursue the following aims: 1. To define the influence of ozone on innate immune response, ain/vay structure and function. Studies are designed to identify which toll-like receptors (TLRs) are modified following postnatal ozone exposure, to define the changes in ainway structure and function, and to determine the role of TLR-4 in these responses. 2. To define the influence of ozone on the early host response to respiratory syncytial virus (RSV) infection and house dust mite (HDM) allergen exposure. The proposed studies will determine how ozone modifies the host response to RSV and HDM during the postnatal phase and will define the associated changes in airway structure and function and the role of TLR-4 in these responses. 3. To determine how lipopolysaccharide (LPS), an air contaminant that interacts with TLR-4, modifies the host response to RSV and HDM following postnatal ozone exposure. We will determine how LPS modifies the early host response to RSV and HDM, and associated changes in ainway structure and function, following postnatal ozone exposure.

Public Health Relevance

This project has the potenfial to generate new informafion that will considerably improve our understanding of the pathogenesis of reactive ainway disease in children. The proposed studies are expected to identify novel pathways and define mechanisms that may help in the development of effective preventative and therapeufic measures. The findings will also provide valuable tools for intervenfions in human.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Program Projects (P01)
Project #
5P01ES018181-04
Application #
8382739
Study Section
Special Emphasis Panel (ZES1-LKB-G)
Project Start
Project End
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
4
Fiscal Year
2012
Total Cost
$271,013
Indirect Cost
$126,794
Name
National Jewish Health
Department
Type
DUNS #
076443019
City
Denver
State
CO
Country
United States
Zip Code
80206
Yang, Ivana V; Richards, Adam; Davidson, Elizabeth J et al. (2017) The Nasal Methylome: A Key to Understanding Allergic Asthma. Am J Respir Crit Care Med 195:829-831
Breton, Carrie V; Marsit, Carmen J; Faustman, Elaine et al. (2017) Small-Magnitude Effect Sizes in Epigenetic End Points are Important in Children's Environmental Health Studies: The Children's Environmental Health and Disease Prevention Research Center's Epigenetics Working Group. Environ Health Perspect 125:511-526
Alper, Scott; Warg, Laura A; De Arras, Lesly et al. (2016) Novel Innate Immune Genes Regulating the Macrophage Response to Gram Positive Bacteria. Genetics 204:327-36
Szefler, Stanley J (2015) Advances in pediatric asthma in 2014: Moving toward a population health perspective. J Allergy Clin Immunol 135:644-52
Davis, Meghan F; Peng, Roger D; McCormack, Meredith C et al. (2015) Staphylococcus aureus colonization is associated with wheeze and asthma among US children and young adults. J Allergy Clin Immunol 135:811-3.e5
Julian, Colleen G; Pedersen, Brent S; Salmon, Carlos Salinas et al. (2015) Unique DNA Methylation Patterns in Offspring of Hypertensive Pregnancy. Clin Transl Sci 8:740-5
Liang, Liming; Willis-Owen, Saffron A G; Laprise, Catherine et al. (2015) An epigenome-wide association study of total serum immunoglobulin E concentration. Nature 520:670-674
Szefler, Stanley J (2015) Monitoring and adherence in asthma management. Lancet Respir Med 3:175-6
Yang, Ivana V; Pedersen, Brent S; Liu, Andrew et al. (2015) DNA methylation and childhood asthma in the inner city. J Allergy Clin Immunol 136:69-80
Lai, Peggy S; Liang, Liming; Cibas, Edmund S et al. (2015) Alternate methods of nasal epithelial cell sampling for airway genomic studies. J Allergy Clin Immunol 136:1120-3.e4

Showing the most recent 10 out of 30 publications