2012 Progress Report: Novel Immunological Approaches to Link Ambient Air Pollution Exposure to Health Outcomes

EPA 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 Period Covered by this Report: January 1, 2012 through December 31,2012
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. 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.

The objectives of the research are to: (1) 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) characterize the relationship between immune indicators and health outcomes of asthma.

Progress Summary:

The work on the project aims has proceeded smoothly and at the pace anticipated. All has progressed according to timelines and all subjects have been recruited and are enrolled in the study. We are in the process of performing all cellular and molecular analyses on the blood samples obtained from the subjects. Some preliminary results and publications have occurred and these are detailed below. The aims of the project are unchanged.

As described in the preliminary results section below, significant immunotoxic effects were observed using in vivo and ex vivo studies.

Overall Impact: The research 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 are 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.

Results expected during the project (output). Our preliminary data 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 polycyclic aromatic hydrocarbons.
  • Downregulation of chemokine receptor/cognate ligand pairs (CCR8/CCL1) is worsened by exposure to polycyclic aromatic hydrocarbons.
  • Decreases in Treg-associated (TGF-b 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.
  • Higher degrees of Treg impairment correlate with severity of asthma.
  • 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 (baseline, 6 mo, 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 research to further test predictive value in the future.

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 Fresno,CA; and
  • characterize the relationship between ambient air pollution exposure and biomarkers that can be used to indicate the health outcomes of asthma.

Future Activities:

During the next reporting period we plan to:

  • Complete all collection of samples and clinical outcome measures every 6 months.
  • Complete our analysis of repeat immune measures (i.e., Treg function, Foxp3 expression, DNA methylation of Foxp3 locus) and repeat clinical outcomes (pulmonary function tests and health questionnaires) on each subject.
  • If data represent interesting findings, we will continue to submit manuscripts on the EPA-funded cohorts.

Journal Articles on this Report : 2 Displayed | Download in RIS Format

Other project views: All 9 publications 4 publications in selected types All 4 journal articles
Type Citation Project Document Sources
Journal Article Kohli A, Garcia MA, Miller RL, Maher C, Humblet O, Hammond SK, Nadeau K. Secondhand smoke in combination with ambient air pollution exposure is associated with increased CpG methylation and decreased expression of IFN-γ in T effector cells and Foxp3 in T regulatory cells in children. Clinical Epigenetics 2012;4(1):17 (16 pp.). R834786 (2012)
R834596 (2011)
R834596 (2012)
R834596 (Final)
R834596C003 (2011)
R834596C003 (2012)
R834596C003 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: BioMed Central-Full Text HTML
  • Abstract: BioMed Central-Abstract
  • Other: BioMed Central-Full Text PDF
  • Journal Article Liu J, Zhang L, Winterroth LC, Garcia M, Weiman S, Wong JW, Sunwoo JB, Nadeau KC. Epigenetically mediated pathogenic effects of phenanthrene on regulatory T cells. Journal of Toxicology 2013;2013:967029 (13 pp.). R834786 (2012)
    R834596 (2012)
    R834596 (Final)
    R834596C003 (2012)
    R834596C003 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: Hindawi Publishing-Full Text HTML
  • Abstract: Hindawi Publishing-Abstract
  • Other: Hindawi Publishing-Full Text PDF
  • Supplemental Keywords:

    biology, genetics, epidemiology, analytical, California, CA, Region 9, transportation, air pollution, asthma, children, allergy, immune system, RFA, Health, Scientific Discipline, Air, HUMAN HEALTH, particulate matter, Health Risk Assessment, Allergens/Asthma, Biochemistry, Health Effects, Biology, Immunology, asthma, ambient air quality, PM10, biomarkers, human health effects, PM 2.5, airborne particulate matter, bioavailability, airborne pollutants, allergic response

    Progress and Final Reports:

    Original Abstract
  • 2011 Progress Report
  • Final Report