Grantee Research Project Results

Endotoxin Exposure and Asthma in Children

EPA Grant Number: R834515C001
Subproject: this is subproject number 001 , 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: Endotoxin Exposure and Asthma in Children
Investigators: Schwartz, David A.
Current Investigators: Schwartz, David A. , Covar, Ronina A , Litonjua, Augusto A. , Liu, Andrew H. , Crooks, James L , Van Dyke, Michael V. , Forssen, Anna , Sordillo, Joanne , Rabinovitch, Nathan , Szefler, Stanley , Fingerlin, Tasha
Institution: Boston University , Harvard University
Current Institution: National Jewish Health , Harvard University , National Jewish Medical and Research Center
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:

Endotoxins are molecules contained in the membrane surrounding the cell wall of certain types of bacteria and become airborne when the bacteria die. Recently, a U.S.-wide survey linked household endotoxin exposure to asthma, making it a U.S. public health concern. However, it is not known whether ambient endotoxin exerts its pathogenic effects on asthma persistence, severity and/or causation. We hypothesize that higher levels of endotoxin exposure cause persistent, problematic asthma and that key environmental (ozone and allergens) and genetic modifiers (variations in the genes coding for endotoxin receptors) contribute to endotoxin susceptibility and pathological asthmatic responses. We propose to study these endotoxin-induced airway conditions in children through three complementary clinical investigations. First, we will capitalize on an ancillary study of a NIH-sponsored multi center cohort of children with asthma (Childhood Asthma Management Program), which has tracked asthma severity for over a decade, to determine if endotoxin exposure, modified by genetics and environment, is associated with greater disease severity and persistence. Second, we propose a panel study of children with asthma to investigate whether endotoxin exposure, modified by environment, is associated with inflamed airways and elevated toll-like receptor (TLR) expression on airway macrophages. TLRs are part of the innate immune system when children are born. Clinically, these inflammatory responses could drive poor asthma control and exacerbations. Finally, we will take advantage of a HUD-sponsored inner-city home intervention study to determine if a home environment intervention will reduce home endotoxin levels and improve asthma.

Expected Results:

This combination of studies will provide an understanding of how endotoxin interacts with other potentially toxic exposures in a susceptible child to cause persistent, problematic asthma. These studies will help us to determine the levels of endotoxin exposure that are likely to be problematic for children with asthma, and to develop environmental educational and intervention programs to improve outcomes.

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 14 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, Health, Scientific Discipline, HUMAN HEALTH, Health Risk Assessment, Physiology, 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

Top of Page

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.