Novel Immunological Approaches to Link Ambient Air Pollution Exposure to Health OutcomesEPA Grant Number: R834786
Title: Novel Immunological Approaches to Link Ambient Air Pollution Exposure to Health Outcomes
Investigators: Nadeau, Kari
Institution: Stanford University
EPA Project Officer: Nolt-Helms, Cynthia
Project Period: January 1, 2011 through December 31, 2013
Project Amount: $250,000
RFA: Exploring Linkages Between Health Outcomes and Environmental Hazards, Exposures, and Interventions for Public Health Tracking and Risk Management (2009) RFA Text | Recipients Lists
Research Category: Air Quality and Air Toxics , Health
The overall goal of this research is to further understand the link between indicators of exposure and outcomes on human health by studying immune system changes in subjects exposed to elevated levels of ambient air pollution.
We hypothesize that immunological indicators linked to environmental exposure and health outcomes will elucidate the role and mechanism of air pollution in asthma, a link which is theoretically understood, circumstantially clear, but not yet proven. The objectives of the research are (1) to examine the link between specific immune indicators and ambient air pollution exposure (level of exposure, chronicity of exposure, and type of exposure: ozone, NO/NO2, CO, PM2.5, PM10, sulfate, elemental carbon, polyaromatic hydrocarbons, daily naphthalene, endotoxin, fungal spores, and/or pollens) through a database collected in a large population in Fresno, CA. and (2) to characterize the relationship between immune indicators and health outcomes of asthma.
Our approach will be to examine asthma outcomes via a comprehensive collection of environmental exposure data through an established 8 year cohort study, the Fresno Asthmatic Children's Environmental Study (FACES) (n=116 total). Health outcome data, individual estimate exposure levels, and blood sample results collected longitudinally from each subject will be compared. The proposed research addresses the need to research the linkage between immune indicators, environmental exposure, and health outcomes. To do this, we have developed a comprehensive novel indicator of hazard exposure that can be performed on one drop of blood. We will correlate cellular, serological, and epigenetic biomarker changes in peripheral blood which can be broadly applied to an individual health outcome.Expected Results:
Overall, we expect that our study could lead to important mechanistic explanations of environmental exposures on human health. The results of the proposed research could also provide indicators for long-term tracking and surveillance of environmental public health.
Results expected during the project (output). We expect that our data will demonstrate:
- that DNA methylation of the Foxp3 gene results in decreased FoxP3 protein levels in Treg and that the levels of FoxP3 decrease are associated with increases in levels of exposure to polyaromatic hydrocarbons (9).
- that downregulation of chemokine receptor/cognate ligand pairs (CCR8/CCL1) is worsened by exposure to elemental carbon given preliminary data from FACES (1,2),
- that decreases in Treg-associated (TGF- and IL-10) and increases in Th2-associated plasma markers (IL-4 and IL-13) correlate with increased levels of exposure to ambient air pollution,
- that higher degrees of Treg impairment correlate with severity of asthma, and
- that lower levels of Treg immune indicators can be detected in non-asthmatic children exposed to elevated levels of ambient air pollution and that if the Treg immune indicators increase over the 4 time points of the study (TE, TE+ 6mo, 12 mo and 18 mo), then these children might be at risk for developing asthma. Definitive analysis for the positive predictive value of a Treg immune indicator is outside the scope of this study but we plan to collect evidence in this proposed research to further test predictive value in the future.
The potential benefits of the results (outcomes). We expect our results to
- provide sufficient evidence to help understand the link between the environmental hazard, exposure (individual estimate exposures), and the health outcomes (asthma) through the database collected in a large population in the Fresno, CA,
- characterize the relationship between ambient air pollution exposure and biomarkers that can be used to indicate the health outcomes of asthma,
- be applicable and generalizable to other environmental circumstances (hazard exposure in different media at a diverse range of geographical locations in all ages sampled) since Treg as immunological indicators are associated with other diseases (cancer, autoimmunity, prematurity), since they are present at all stages of human development, and since they can be easily detected in blood samples,
- be used in the future for long-term monitoring since the long-term effects of exposure to increased levels of ambient pollutants has become a major focus for population risk assessment and management in the setting of air quality standards. The immune indicator focus of this study could contribute in a major way to the lack of data in this area since it is not only important in longitudinal studies but also cross-generational studies (ie. epigenetic studies of Foxp3 gene methylation patterns).
The proposal is aimed to innovatively examine whether chronic ambient air exposures, the health outcomes of individual children, and changes in the immune system are correlated. The results will be essential for understanding immune mechanisms that could be related to exposure and health outcomes. Overall, the results would help in decreasing and preventing the burden of asthma and allergy and reducing exposure to air pollution.