The theme of this proposed Center is to investigate the etiology and pathogenesis of airway disease in children. We chose this theme for our program for the following reasons: 1) asthma and other forms of ainway disease are the most common chronic illnesses in children;2) the environment results in unique combinations of exposures to children that affect lung immunity and consequently alters the risk of developing airway disease;3) environmental models of airway disease provide an ideal opportunity to investigate basic mechanisms involved in the development of childhood airway disease;and 4) this theme builds on existing scientific expertise and relationships with community stakeholders and members to ensure a highly interactive program. Since ozone and endotoxin are common environmental exposures, and both of these agents have been demonstrated to have immune modulating affects, we have decided to use these relevant environmental exposures to further focus the projects in our proposed program. The end result is a highly integrated and focused Center that has the potential to make a number of novel, related observations. In aggregate, the coupled scientific findings from the proposed program will substantially enhance our understanding of ainway disease in children that can be immediately translated to communities in Colorado. The overarching hypothesis that unifies this research program is that lung host defense and lung immunity are dynamic biologically, are affected by ozone and endotoxin, and that this dynamic biology can alter susceptibility to agents known to cause airway disease in children. We believe that understanding the basic and translational aspects of this hypothesis will provide the scientific rationale to develop primary, secondary, and tertiary prevention programs that reduce the morbidity and mortality of childhood ain/vay disease/illnesses. Our PPG proposal includes three interactive projects (1 clinical and 2 basic), a Community Outreach and Translational Core, an Inhalation Toxicology Core, and an Administrative Core.

Public Health Relevance

Respiratory conditions in children are a serious public health concern throughout the world. Asthma is the most common chronic childhood disease, affecting 9 million children in the U.S. This disease is increasing in prevalence, incidence, and severity, particularly in developed countries. Air pollution accounts for substantial morbidity and mortality in children. The objective of our proposed program is to understand the etiology and pathogenesis of ainway disease in children.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZES1-LKB-G (P1))
Program Officer
Gray, Kimberly A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
National Jewish Health
United States
Zip Code
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