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Denver Children’s Environmental Health Center - Environmental Determinants of Airway Disease in Children - National Jewish Health

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National Jewish Health Center

Center Director: David A Schwartz

Project 1: Endotoxin Exposure and Asthma in Children
Could high environmental levels of bacterial endotoxin be a cause of persistent asthma in children? Could exposure to ozone and allergens in addition to endotoxin along with genetic differences make a child more susceptible to get asthma?

Project 2: Environmental Determinants of Early Host Response to RSV
Does ozone exposure in young infants alter lung development and change immune system response to early life viral infection and allergen exposure, contributing to the development of airway disease?

Project 3: Environmental Determinants of Host Defense
Can we confirm that activation of toll-like receptors (TLRs) in the lungs is influenced by ozone and/or endotoxin and genetic factors, and that activation of TLRs leads to lung infections and allergic airway disease?


This Center is looking into possible causes of asthma and other respiratory diseases which are the most common chronic childhood illnesses. Symptoms can include coughing and difficulty breathing which can dramatically affect a child’s quality of life. Environmental exposures may impair the lung’s ability to respond to irritants and increase a child’s risk of developing respiratory disease. Researchers are focusing on ozone and bacterial endotoxin, which are common environmental exposures and can be inhaled. Ozone is an air pollutant and a component of smog while endotoxins are part of the cell wall of some bacteria, released into the air when the bacteria die. Researchers believe that such exposures could change the response of the developing immune system, leading to lung inflammation and impaired lung function, making a child more susceptible to getting asthma or other lung diseases.

Environmental Exposures and Health Outcomes

Primary Environmental Exposures: Air pollutants (ozone), ambient bacterial endotoxin
Primary Health Outcomes: Asthma, immune system function

Research Projects

Overview of the scientific program of the Denver CEHC Project 1: Endotoxin Exposure and Asthma in Children
For this project, the center is building on a multi-center cohort of children with asthma, the Childhood Asthma Management Program (CAMP), to determine if exposure to endotoxin, modified by genetics and the presence of allergens and/or ozone in the air, is associated with greater asthma severity and persistence. Ambient endotoxin is known to affect the immune system but it is not clear whether it can cause asthma or can make it worse. It is not known whether endotoxin exerts its effects on asthma persistence, severity and/or causation. This project will provide an understanding of how endotoxin interacts with other potentially toxic exposures in combination with genetic differences in a susceptible child to cause persistent asthma. These studies will help to determine the levels of endotoxin exposure that are likely to be problematic for children, and to develop environmental educational and intervention programs to improve outcomes.

Project Leader: Andrew H. Liu, M.D., National Jewish Health

Project 2: Environmental Determinants of Early Host Response to RSV
Inhaled air pollutants such as ozone are known to exacerbate asthma and may play a potential role in development of airway disease in early life. Researchers are investigating whether exposure to ozone in the first weeks after birth alters lung development and modifies a child’s immune response to early life infection with respiratory syncytial virus (RSV) and to allergens, contributing to the development of reactive airway disease. This project is looking at how ozone influences lung development and host immune response in infancy. Scientists are studying how ozone affects young children’s response to RSV and to dust mites in house dust.

Project Leaders: Azzeddine Dakhama, Ph.D. and Carl W. White, M.D., National Jewish Health

Project 3: Environmental Determinants of Host Defense
The overall goal of this project is to understand how and why air pollution alters the immune system response in the lungs using mice and cells in the laboratory. Researchers are investigating whether the activation of toll-like receptors (TLRs) in the lungs, related to lung infection and allergies, is influenced by environmental (ozone and/or pathogen-associated molecular patterns, or PAMPs) and genetic factors. Investigators are collaborating with a federally sponsored inner-city home environment intervention study to determine how to reduce bacterial endotoxin levels in the home and potentially improve asthma outcomes. The findings from this Center are expected to enhance the understanding of airway disease in children and to inform the design of programs to identify, treat and ultimately prevent respiratory diseases in children, combined with education and intervention programs to improve children’s health.

Project Leaders: David A. Schwartz, M.D. and Ivana V. Yang, Ph.D., National Jewish Health

Community Partners

Centers Funded By:
Centers Funded by Epa and NIEHS

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