![[logo] US EPA](https://webarchive.library.unt.edu/eot2008/20090508050643im_/http://www.epa.gov/epafiles/images/logo_epaseal.gif){kind=logo}
Children’s Environmental Health Center
at the University of Southern California,
and University of California at Los Angeles
Principal Investigator: Frank Gilliland
| Overview | Community Partners |
| Exposures and Outcomes | Selected Results |
| Research Projects | Selected Publications |
The Children's Environmental Health Center (CEHC) at USC and UCLA was established in 1998 to investigate effects of the environment on children's respiratory health, with a focus on asthma and allergic airway disease. The CEHC has made substantial progress in understanding the effects of ambient air pollutants and environmental tobacco smoke (ETS) on children's respiratory health, and researchers have identified characteristics that increase the susceptibility of children. This contributes to a growing consensus that current levels of combustion-related air pollutants are more detrimental to children's airways than previously thought. Furthermore, both exhaust emissions from local traffic and regionally transported secondary pollutants are implicated in asthma pathogenesis, allergic airway disease and reduced lung function growth.
Exposures and Outcomes
Primary Exposures: Air pollutants, including particulate matter (PM), ozone, environmental tobacco smoke, home allergens
Primary Outcomes: Prevalent and incident asthma, allergic airway disease, lung function growth, exhaled nitric oxide
Research Projects
Original Projects: 1998-2003
Project 1: Modulation of Allergic Inflammation by Passive Cigarette Smoke in Children
Project 2 : Childhood Determinants of Respiratory Susceptibility to Air Pollution
Project 3: Community-Based Intervention for Asthma Control
Current Projects: 2003-2008
Project 1: Urban Air Pollution and Persistent Early Life Asthma
Principal Investigator: Rob McConnell, PhD
Community-Based Participatory Research Project
The goal of this project is to evaluate the relationship between early life asthma and traffic-related air pollution. The research questions have been developed from Children's Environmental Health Center research in cooperation with the Long Beach Alliance for Children with Asthma, a coalition of organizations representing children with asthma in Long Beach, and the Center for Community Action and Environmental Justice, a community-based organization in Riverside County, CA. These communities have some of the heaviest traffic in southern California. Preliminary results suggest that exposure to oxidant pollutants near homes may be associated with asthma with onset early in life, but there is considerable uncertainty as to these relationships. Center researchers are examining this question in a case-control study of asthma present in kindergarten and first grade, but with onset earlier in life. Children in the study were lifetime residents in the same home so that estimates of exposure at home will reflect lifetime exposure. The investigators have also hypothesized that susceptibility to ambient air pollution will vary based on genotype for GSTM1, GSTP1, NQO1, HO-1, and TNF-alpha, genes involved in the biologic response to oxidant air pollutants.
The research approach is to assess lifetime exposure by calibrating home measurements to the extensive historical exposure assessment from a monitor in each community operating continuously during the lifetime of participants. Traffic density in close proximity to homes is estimated from traffic counts made by the California Department of Transportation. Community participation in study promotion to participants and in data collection and interpretation will enhance both the quality of Center research and the environmental action plans for families of children with asthma in ongoing projects of the community partners.
The presentation of results in terms of the burden of disease in two areas encompassing almost 1 million people represented by community research partners promises to increase the level of local awareness of the health impact of air pollution. A steering committee representing university and community research partners, and policy makers, is working closely with the Community Outreach and Translation Core to provide the scientific basis necessary for developing policy for the more widespread protection of children from the effects of air pollution.
Abstract | 2004 | 2005 | 2006 | 2007
Project 2: Pollution-Enhanced Allergic Inflammation and Phase II Enzymes
Principal Investigator: David Diaz-Sanchez, PhD
Mechanistic Research Project
In metabolism, Phase I and Phase II enzymes have different roles, but both are used by the body to detoxify compounds such as carcinogens before they can cause damage. However, sometimes these enzyme systems do not work as intended so the Phase I enzymes create a toxic byproduct which is not then converted to a more benign form by the Phase II enzymes. The goal of Project 2 is to determine the role of Phase II enzymes in regulating severity of responses to particulate pollutant-enhanced allergic inflammation in children.
Oxidative stress occurs as a consequence of inflammation in allergic airway diseases such as asthma and rhinitis. Oxidant pollutants such as diesel exhaust particles (DEP) cause an additional oxidative burden in the respiratory tract and thereby mediate their biological effects. A consequence of oxidative stress is the induction of genes that contain the antioxidant response element (ARE) e.g. Phase II enzymes. These enzymes have potent antioxidant effects that potentially may counteract the oxidant effects of the pollutants. The central hypothesis for this project is that generation of these protective enzymes govern the extent of the pro-inflammatory and pro-allergenic effects of oxidant pollutants and are reduced in susceptible sub-populations (such as children and asthmatics).
USC/UCLA Center researchers have developed three aims for studying the role of Phase II enzymes in regulating responses to pollutants in: children's upper airways (Aim #1); the lower airways of healthy and asthmatic individuals (Aim #2) and in mechanistic animal and cellular models of allergic inflammation (Aim #3).
- Aim #1 is testing the hypothesis that Phase II enzyme expression in the upper airways are induced by oxidant pollutants and differ between children and adults. Researchers are determining whether nasal challenge with DEP will induce gene expression of key Phase II enzyme in the upper airways, whether this expression in response to DEP differs between children and adults and whether enhanced cellular responses to DEP in children correlate with Phase II enzyme gene expression.
- Aim #2 is testing the hypothesis that Phase II enzyme expression in the lower airways are induced by oxidant pollutants and differ between asthmatic and non-asthmatic subjects. This is being accomplished by exposing healthy and asthmatic individuals to diesel exhaust and comparing Phase II enzyme gene expression in sputum.
- Aim #3 is determining the role of Phase II enzymes in regulating the adjuvant effects of oxidant pollutants. This is being accomplished by determining whether induction of Phase II enzymes can ameliorate the effects of DEP on allergic inflammation in an in vivo mouse model and by determining whether induction of Phase II enzymes can inhibit DEP-induced mast cell histamine and IL-4 release or cytokine production from epithelial cells.
Allergic airway disease (rhinitis, asthma) is a major health problem in children. The potential benefits to society are an increased understanding of how the body's natural defenses regulate pollution-induced allergic and inflammatory responses. In addition, we will potentially gain important insights into which groups of people may have increased susceptibility to the deleterious effects of pollutants.
Project 3: Air Pollution, Exhaled Breath Markers and Asthma in Susceptible Children
Principal Investigator: Frank Gilliland MD, PhD
Epidemiologic Research Project
Ambient air pollution is well accepted as a cause of asthma exacerbations, but its role in the development of new onset asthma is less clear. Evidence for a role of ambient air pollutants in asthma etiology is emerging from epidemiologic studies, but the ecologic patterns of increasing asthma prevalence concurrent with decreasing levels of some pollutants have raised questions about the validity of these associations. A better understanding of the biological processes that mediate the effects of ambient air pollution on asthma occurrence is likely to contribute to answering these questions.
Chronic oxidative/nitrosative stress and airway inflammation are probably critical processes in asthma etiology and these inter-related processes may mediate the increased asthma risk from air pollution. USC/UCLA researchers are using exhaled nitric oxide (eNO), to study the role of inflammation and oxidative/nitrosative stress in the pathobiology of new onset asthma, with a focus on ambient air pollution and genetic susceptibility. Ambient pollutants were chosen for study based on potential contribution to oxidative/nitrosative stress [ozone; particulates (PM10 and PM2.5 and their chemical constituents), particle counts, gases (NOx,NO and NO2), acid vapors; and fresh tailpipe emissions]. The primary hypotheses are:
- children with high ambient air pollution exposures have chronic airway inflammation as indicated by elevated eNO,
- susceptibility to airway inflammation and oxidative/nitrosative stress from ambient air pollution varies by NOS1, NOS2, NOS3, GSTM1, GSTP1, NQO1, and HO-1 genotypes, and
- children with chronic airway inflammation as indicated by elevated eNO are at increased risk for new onset asthma.
To test these hypotheses, this project builds on the population resource of the Asthma Incidence Risk (AIR) study, an ongoing prospective cohort study of the determinants of new onset asthma in 6000 children in 13 southern California communities, and an extensive program of ambient air pollution exposure characterization in these communities. Researchers are measuring measure eNO using off-line techniques and genotyping 3000 children from the AIR cohort. A number of resources enhance the proposed study, including the Exposure Assessment and Modeling Core of the Children’s Environmental Health Center, the Molecular Biology Core of Southern California Environmental Health Sciences Center, and expertise from the Southern California Particle Center and Supersite.
The findings from this project are likely to contribute to resolving uncertaintiesabout the effects of air pollution on asthma risk, provide new tools for identifyingchildren at highest risk for asthma and aid in asthma prevention efforts.
Abstract | 2004 | 2005 | 2006 | 2007
Long Beach Alliance for Children with Asthma - Long Beach, California 
Center for Community Action and Environmental Justice - Riverside, California
The Community Outreach and Translation Core (COTC) of the USC/UCLA Children's Center serves as a bridge between the Center investigators and members of the local community who are concerned about the impacts of air pollution on children's respiratory health.
The COTC actively participates in the Steering Committee for the Center's CBPR Project. In addition, the COTC plays an important role in disseminating the Center's scientific research findings to the public and to policy makers. With the Center's two key community partners, the COTC director Andrea Hricko and outreach staff, along with Center investigators Rob McConnell and Ed Avol, have also nurtured teams of volunteers who attend training sessions and then conduct community assessments of environmental health problems. The teams, called Neighborhood Assessment or "A" Teams, decided to document the volume of traffic (and resultant air pollution) in certain communities frequented by trucks moving containers to and from the local marine ports. The "A" Team members were trained in advanced traffic counting techniques and in ultrafine particle counting techniques and then assessed identified problem areas in their communities. Some of the neighborhood assessment reports identifying high truck volumes as a percentage of total traffic, coupled with ultrafine particle measurements, have been presented to policy makers. The Neighborhood Assessment Team work is continuing, bolstered by a private foundation grant allowing expansion of the number of trained team members. All "A" Team members are bilingual community residents who receive stipends for their neighborhood assessment activities.
- In utero exposure to maternal smoking increased the risk of asthma especially among children with two phase II enzymes variant genotypes; GSTM1 null and GSTP1 A105G (Gilliland et al., 2002; Gilliland et al., 2003 )
- High levels of exposure to locally emitted fresh vehicle exhaust were associated with increased risk of early life asthma (Gauderman, W. J., E. Avol, F. Lurmann, N. Kuenzli, F. Gilliland, J. Peters and R. McConnell (2005). Childhood asthma and exposure to traffic and nitrogen dioxide. Epidemiology 16(6): 737-743) and (McConnell, R., K. Berhane, L. Yao, M. Jerrett, F. Lurmann, F. Gilliland, N. Kunzli, J. Gauderman, E. Avol, D. Thomas and J. Peters (2006). Traffic, susceptibility, and childhood asthma. Environ Health Perspect 114(5): 766-72.)
- The incidence of newly diagnosed asthma is increased in children playing team sports in high, but not low, O3 communities (McConnell et al., 2002 )
- Clinically significant effects of air pollution of lung function growth were observed in 18 year olds living in Southern California (Gauderman et al., 2004 )
- Improvement in the rate of lung function growth occurred in subjects who moved to areas of lower PM10 compared with those who moved to areas of higher PM10 (Avol et al., 2001 )
- Overweight and obese children are at increased risk for new onset asthma (Gilliland et al., 2003 )
- Deficits in lung function growth occur with increased nitrogen dioxide (NO2) levels (and a cluster of highly correlated pollutants, including nitric acid vapor and particulates) (Gauderman et al., 2000 ). This result has also been replicated in our second cohort of fourth graders enrolled three years later (Gauderman et al., 2002 )
- Diets low in antioxidant vitamins or magnesium are associated with chronic deficits in lung function (Gilliland et al., 2003 )
- A large increase in respiratory-related school absences occurs with daily fluctuations in O3 levels, particularly in low PM10/NO2 communities (Gilliland et al., 2001 )
- An increased risk of respiratory-related school absences is seen in children with and without asthma exposed to second hand smoke (Gilliland et al., 2003 )
- Risk of respiratory-related school absences vary by GSTM1 and GSTP1 genotype (Gilliland et al., 2002 )
- Second hand smoke exposure has adjuvant effects on allergen induced nasal allergic responses that is 10-fold larger in children than adults (Diaz-Sanchez et al., 2002)
- The adjuvant effects of diesel exhaust particles (DEP) on nasal allergic responses strongly depends on GSTM1 and GSTP1 genotype (Gilliland et al., 2004 )
- In utero exposure to maternal smoking increased the risk of asthma in children and grandchildren, even when the mother did not smoke (Li et al., 2005 )
- The antioxidant sulfphoraphane inhibits the pro-allergic effects of diesel exhaust in vitro and in vivo (Ritz et al., 2005)
- The risk of asthma is associated with distance to a major road in children without a family history of asthma (McConnell, et al., 2005 )
- TNFα–308 genotype is associated with early life asthma prevalence, but the effect of the genetic variant is limited to low O3 communities (Li et al., 2006 )
Gauderman WJ, Avol E, Gilliland F, Vora H, Thomas D, Berhane K, McConnell R, Kuenzli N, Lurmann F, Rappaport E, Margolis H, Bates D, Peters J, 2004. The effect of air pollution on lung development from 10 to 18 years of age. New England Journal of Medicine 9;351(11):1057-67.
McConnell R, Berhane K, Yao L, Jerrett M, Lurmann F, Gilliland F, Kunzli N,Gauderman J, Avol E, Thomas D, Peters J, 2006.Traffic, susceptibility, and childhood asthma. Environmental Health Perspectives 114(5):766-72.
Gilliland, F. D., Y.-F. Li, A. Saxon and D. Diaz-Sanchez (2004). Glutathione-S-Transferase M1 and P1 genotypes protect against xenobiotic enhancement of allergic responses. Lancet 363: 119-25.
Gauderman, W. J., E. Avol, F. Lurmann, N. Kuenzli, F. Gilliland, J. Peters and R. McConnell (2005). Childhood asthma and exposure to traffic and nitrogen dioxide. Epidemiology 16(6): 737-743.
Gilliland, F. D., Y.-F. Li, H. Gong and D. Diaz-Sanchez (2006). Glutathione-s-transferase M1 and P1 prevent aggravation of allergic responses by secondhand smoke. American Journal of Respiratory & Critical Care Medicine 2006 Oct 5; [Epub ahead of print] doi:10.1164/rccm.200509-1424OC.
McConnell, R., K. Berhane, F. Gilliland, S. J. London, T. Islam, W. J. Gauderman, E. Avol, H. G. Margolis, and J. M. Peters (2002). Asthma in exercising children exposed to ozone: A cohort study. Lancet 359(9304):386-91.
Wan J, Diaz-Sanchez D (2006). Phase II enzymes induction blocks the enhanced IgE production in B cells by diesel exhaust particles. Journal of Immunology 177(5):3477-83.
Full
List of Publications |
Publications
List from PubMed Database
Centers Funded By: 