Members of the Division of Environmental Health conduct research that focuses primarily on determining the associations between environmental exposure and human disease and on the mechanisms of pathogenesis. In recent years interest has grown in the role of host factors, especially genetic factors, as well as dietary and other factors, in modifying the effects of environmental exposures. The main areas of research in this division involve chronic health effects of booth indoor and outdoor air pollutants including environmental tobacco smoke, childhood determinants of lung susceptibility to air pollution, and community intervention measures for families with asthma.

Ongoing Research Projects

Southern California Environmental Health Sciences Center (“Environmental Exposures, Host Factors, and Human Disease”) (PI: Gilliland) 
The primary purposes of the Southern California Environmental Health Sciences Center are 1) to study the effects of environmental exposures on humans; 2) to determine host factors (genetic and other) influencing response to these exposures; and 3) to inform the public. To accomplish these goals we bring together an interdisciplinary team of investigators from two major Southern California universities: USC and UCLA.  The research of our Center features several interdisciplinary cornerstones: detailed exposure assessment, including toxicokinetics and biomarkers; cutting edge study design, including the most powerful statistical and epidemiologic approaches; and the basic sciences, including physiology, molecular biology, genetics, chemistry and engineering. The foci of the Center cover a wide range of problems and address environmental exposures of public health importance including indoor and outdoor air pollution, pesticides, aflatoxins, radiation and passive smoking.  The Center consists of four Research Cores: Respiratory Effects Research Core, Exposure Assessment Research Core; Cancer Research Core; and Study Design and Statistical Methodology Research Core. There are also three Facility Cores: Molecular Biology, Sample Processing and Storage Facility Core; Exposure Assessment and GIS Facility Core; and Biostatistics Facility Core.  The Center also features an integrative Core for Community Outreach and Education.

Children’s Environmental Health Center (PI: Gilliland)
The objectives of the Children’s Environmental Health Center are: 1) to investigate the role of ambient air pollutants and genetic susceptibility in airway inflammation and in asthma occurrence during childhood; 2) to investigate the mechanism for the modulating effects of ambient air pollutants on allergic inflammation in children; 3) to implement a community-based participatory research program to respond to community concerns about the effects of regional ambient air pollutants and locally emitted fresh vehicle exhaust on early life asthma; 4) to provide a scientific resource for the broader community involved in protecting children’s environmental health. The Children’s Center consists of three scientific projects, an exposure assessment and modeling core, and a community outreach and translation core. Our collaborative multidisciplinary investigative team and strong working relationships with our community research partners, enhance the CEHC’s ability to continue to contribute to understanding the effects of environmental exposures on childhood airway disease and to strengthen public health efforts to protect children.

Genetics, Air Pollution, and Respiratory Effects in Children and Young Adults (PI: Gilliland)           
The program of research in this program project builds on the rich health, exposure and genetic data resources of the Children’s Health Study (CHS), an ongoing cohort study investigating both genetic and environmental factors related to children’s respiratory disease in over 11,000 southern California children. The research hypotheses are based on mounting evidence that oxidant gases, traffic-related exposures and specific combustion-exhaust particle-bound constituents activate oxidative/nitrosative stress and inflammatory pathways and contribute to respiratory morbidity. Our research questions target the following health issues: (1) Are chronic respiratory health effects associated with exposure to near source combustion particles from vehicular exhaust? (2) Do PM mass in specific size fractions (PM0.25, PM0.25-2.5, and PM2.5-10) or specific size-fractionated constituents (e.g., water-soluble or total organic carbon, elemental carbon, or selected transition metals) affect health? (3) Do genetic variants involved in innate or adaptive immune responses or nitrosative/oxidative stress pathways contribute to respiratory disease, deficits in lung development, or differences in susceptibility to the adverse effects of near source combustion products or regional gaseous or particulate pollutants? These questions are being investigated in three inter-related projects with support from three cores (Exposure Assessment, Integrative Health Sciences, and Biostatistics and Data Management). The projects will evaluate the relationship between respiratory health (asthma, lung function growth, exhaled NO) and combustion particulate and gaseous pollutants; examine genetic variation in key pathways that modulate response to air pollution and disease occurrence; and develop new biostatistical methods for GxE studies and integrated analysis across multiple outcomes and exposures. Building upon our large and well-characterized children’s cohorts, rich exposure data, and substantial genetic resources, our collaborative multidisciplinary team applies an integrative approach to efficiently address key gaps in the knowledge base needed for timely and effective disease prevention and treatment.

Factors in Childhood Lung Susceptibility to Pollution (PI: Gilliland)
This study builds on our previous studies of lung function growth, asthma occurrence, and respiratory-related school absenteeism in a large population-based cohort of school-aged children to assess the hypothesis that DNA sequence variations in 38 genes in pathways involved in glutathione synthesis, redox cycling, signaling and metabolism 1) are determinants of children’s respiratory health, 2) modulate susceptibility for slow lung function growth, and 3) increase asthma occurrence and respiratory illnesses from chronic exposure to ozone, nitrogen dioxide, particles and tobacco smoke. Associations of respiratory health outcomes with sequence variants in candidate genes and air pollution are being assessed using haplotypes and functional SNPs. We will test for overall association of a locus with outcomes using functional SNPs and a haplotype-based approach, and gene-gene and gene-environment interaction within and between pathways will also be examined using approaches to minimize multiple comparisons issues.  Confounding by admixture will be addressed using SNP-based genome-wide control methods.  Finally, hierarchical Bayesian models of these complex pathways incorporate a priori knowledge about biological relationships to efficiently examine interactions within and between pathways. The comprehensive approach proposed to assess the role of genetic variation in a large established cohort of children provides a unique opportunity to advance our understanding of children’s respiratory health. 

Air Pollution, Inflammation and New Onset Asthma (PI: Gilliland)
The primary objectives of this study are to assess whether: 1) children with high ambient air pollution exposures have chronic airway inflammation as indicated by elevated eNO, 2) susceptibility to airway inflammation and oxidative/nitrosative stress from ambient air pollution varies by NOS1, NOS2, NOS3, GSTM1, GSTP1, NQO1, and HO-1 haplotypes and functional variants, and 3) children with chronic airway inflammation as indicated by elevated eNO are at increased risk for new onset asthma. This study 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. In this project, are measuring eNO using on- and off-line techniques and are genotyping 3000 children from the AIR cohort. The findings from the proposed research program is likely to contribute to resolving uncertainties about the effects of air pollution on asthma risk, provide new tools for identifying children at highest risk for asthma and aid in asthma prevention efforts.

Air Pollution and Preclinical Atherosclerosis in Elementary School Children  (PI: Avol)
This project pursues the hypothesis that long-term exposure to local and regional air pollutants from outdoor origin promotes atherogenesis in early life, leading to differences in carotid intima media thickness (CIMT) in 10-12 year old children participating in the Children’s Health Study from 13 Southern California communities. Exposure to air pollution will be assessed by outdoor sampling at the homes and schools of the participants. Time spent indoors at home and school, in commuting, and in outdoor activities will be assessed by questionnaire.  The microenvironmental concentrations and time-activity information will provide the input to derive exposure to local and regional pollution for each child. Associations between CIMT and personal lifetime exposure to local and regional outdoor pollution will be analyzed in multilevel spatial regression models.

TROY Study (“Air Pollution, Intima-media Thickness, and Lung Function In College Students”) (PI: Avol)
This project pursues the hypothesis that lifetime cumulative exposure to ambient air pollution is associated with sonographically measured carotid intima-media thickness (CIMT) in college students. CIMT, lifetime residential history, cardio-respiratory covariates, LF, LDL and CRP will be assessed among 800 non-smoking USC College students with lifetime California residencies. Statewide air pollution monitoring information will be assembled to interpolate monthly fine particulate matter (PM2.5), nitrogen-dioxide (NO2) and ozone (O3) concentrations to each residence across lifetime. Concentrations will be weighted by activity levels and time spent indoors and outdoors to individually derive estimates of lifetime exposure. The association between exposure and CIMT and the interaction with LF, CRP and LDL will be investigated with multivariate regressions, tests for interactions, and structural equation modeling.

Prospective Study of Atherosclerosis, Clinical Cardiovascular Disease, and Long-Term Exposure to Ambient Particulate Matter and Other Air Pollutants in a Multi-Ethnic Cohort ("MESA Air ")   (PI: Avol, subcontract)
Our participation in MESA Air is to provide exposure assessment support for the Los Angeles regional study of MESA subjects, one of six regions participating in a national study assign the possible associations between chronic exposure to outdoor air pollution and progression of cardiovascular disease in adults.  Community fixed-site, residential outdoor, residential indoor, and personal particle and gaseous samplers will be deployed to subjects recruited by UCLA clinical collaborators to characterize air pollution exposure in the Los Angeles Region.

The Health, Trade and Cargo Collaborative Project: A Collaboration to Address Health Impacts of Global Trade on Southern California (PI: Hricko)
This project is a collaboration with four community partners and an academic policy institute to study and address the environmental health problems associated with Ports and goods movement in Southern California.

HOPE Partnership (Health Observances and Public Education) (PI: Hricko, subcontract)
Our SCEHSC outreach program is one of 8 university-based community outreach and education programs engaged in a project designed to improve public understanding of biomedical and health-related sciences and the impact of research on human health, while determining the most effective outreach methods to do so. 

Socioeconomic Status, Stress, Air Pollution and Asthma (PI: McConnell)
This project involves (1) assembling a variety of indices of social characteristics of families, communities, schools, and neighborhoods for children participating in the Children’s Health Study; (2) refining and applying new statistical methods for multilevel modeling of social characteristics that may explain the differences between communities in the incidence of wheeze and ultimately of asthma; (3) examining the role of stress as an explanation for any observed relationships between contextual social characteristics and wheeze; (4) assessing through empirical simulations the impact of excluding one or more levels of confounding or effect modification on the association between incident wheeze and air pollution; and (5) assessing confounding and effect modification of the relationship between air pollution and incident wheeze in the ongoing CHS studies.

Spatial Exposure Models for Assessing the Relationship Between Air Pollution and Childhood Asthma at the Intra-Urban Scale (PI: McConnell, pending)
This project tests the following hypotheses: (1) different intra-urban spatial exposure models will produce variations in exposure classification within the Children’s Health Study (CHS) subjects, located in 12 communities across southern California; (2) more refined exposure models will have stronger correlations with household and personal exposure, reducing exposure measurement error; and (3) conditional on hypothesis 2, more refined exposure models will demonstrate larger health effects for incident asthma. These hypotheses translate into the following research objectives: (1) to derive proximity-based, geostatistical, land use regression, and dispersion models of intra-urban exposure as well as an individual exposure model (IEM) for O3, NO2, NO, and fine particles (PM2.5) for the 12 CHS communities; (2) to assess, with empirical and simulation models, which of the ambient exposure models assigned to subjects in the CHS results in the lowest measurement error when compared to household measurements; (3) to use the modeled ambient and personal exposures to assess air pollution-health associations in CHS data sets for determining whether more refined exposure models produce larger health effects; and (4) to apply resulting exposure and health effects estimates to derive the burden of incident asthma attributable to air pollution in the 12 communities.

Ongoing Studies
Technical Report Series