Grantee Research Project Results

Environmental Determinants of Early Host Response to RSV

EPA Grant Number: R834515C002
Subproject: this is subproject number 002 , established and managed by the Center Director under grant R834515
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Denver Childrens Environmental Health Center - Environmental Determinants of Airway Disease in Children
Center Director: Guo, Yanbing
Title: Environmental Determinants of Early Host Response to RSV
Investigators: Schwartz, David A.
Current Investigators: Schwartz, David A. , White, Carl W. , Dakhama, Azzeddine , Yang, Jing , Loader, Joan , Correll, Kelly , Gabehart, Kelsa
Institution: Boston University , Harvard University
Current Institution: National Jewish Health , National Jewish Medical and Research Center , University of Colorado at Denver , University of North Carolina at Charlotte
EPA Project Officer: Hahn, Intaek
Project Period: June 22, 2010 through June 21, 2015 (Extended to June 21, 2017)
RFA: Children's Environmental Health and Disease Prevention Research Centers (with NIEHS) (2009) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health

Objective:

Inhaled air pollutants such as ozone are known to exacerbate asthma and may play a potential role in the development of reactive airway disease such as asthma in early life. While ozone can cause significant respiratory health problems in the majority of exposed individuals, young children are particularly at risk for developing serious adverse health effects from ozone exposure. This is because their lungs are still rapidly developing, and exposures during this critical time period 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 airborne allergens. The overall objective of this project is to define how ozone influences children’s lung development and immune system response early in life. Our general hypothesis is that ozone exposure in the early period after birth alters lung development and modifies the child’s immune response to early life viral infection and allergen exposure, thereby contributing to the development of reactive airway disease such as asthma.

Approach:

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 response to respiratory syncytial virus (RSV) infection and house dust mite (HDM) allergen exposure.

Expected Results:

The proposed studies will determine how ozone modifies the host response to RSV and HDM just after birth 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 from bacterial endotoxin 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.

Publications and Presentations:

Publications have been submitted on this subproject: View all 23 publications for this subproject | View all 51 publications for this center

Journal Articles:

Journal Articles have been submitted on this subproject: View all 13 journal articles for this subproject | View all 30 journal articles for this center

Supplemental Keywords:

Endotoxin, exposure, children, asthma, risk, health effects, susceptibility, sensitive populations, genetic pre-disposition, genetic polymorphism, indoor air, dose-response, ozone, remediation, human health, Scientific Discipline, Health, Health Effects, Biology, Health Risk Assessment, Allergens/Asthma, asthma indices, intervention, endotoxin, sensitive populations, children, asthma triggers, allergic response, asthma, airway inflammation, Health, Scientific Discipline, HUMAN HEALTH, Health Risk Assessment, Allergens/Asthma, Health Effects, Biology, asthma, asthma triggers, sensitive populations, endotoxin, asthma indices, airway inflammation, children, allergic response

Progress and Final Reports:

Main Center Abstract and Reports:

R834515 Denver Childrens Environmental Health Center - Environmental Determinants of Airway Disease in Children

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R834515C001 Endotoxin Exposure and Asthma in Children
R834515C002 Environmental Determinants of Early Host Response to RSV
R834515C003 Environmental Determinants of Host Defense

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The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.