Inhaled air pollutants such as ozone are known to exacerbate asthma and may play a potential role in the inception of reactive airway 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 airway 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, airway structure and function. Studies are designed to identify which toll-like receptors (TLRs) are modified following postnatal ozone exposure, to define the changes in airway 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 airway structure and function, following postnatal ozone exposure.

Public Health Relevance

This project has the potential to generate new information that will considerably improve our understanding of the pathogenesis of reactive airway 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 therapeutic measures. The findings will also provide valuable tools for interventions in human.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Program Projects (P01)
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National Jewish Health
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Dutmer, Cullen M; Schiltz, Allison M; Freeman, Kristy L et al. (2018) Observed Home Dampness and Mold Are Associated with Sustained Spikes in Personal Exposure to Particulate Matter Less than 10 ?m in Diameter in Exacerbation-Prone Children with Asthma. Ann Am Thorac Soc 15:S131-S132
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
Yang, Ivana V; Pedersen, Brent S; Liu, Andrew H et al. (2017) The nasal methylome and childhood atopic asthma. J Allergy Clin Immunol 139:1478-1488
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
Dakhama, Azzeddine; Gelfand, Erwin W (2016) In Vivo Assessment of Airway Function in the Mouse Model. Methods Mol Biol 1442:219-30
Keet, Corinne A; McCormack, Meredith C; Pollack, Craig E et al. (2015) Neighborhood poverty, urban residence, race/ethnicity, and asthma: Rethinking the inner-city asthma epidemic. J Allergy Clin Immunol 135:655-62
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

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