Grantee Research Project Results
2010 Progress Report: Berkeley/Stanford Children’s Environmental Health Center
EPA Grant Number: R834596Center: UC Berkeley/Stanford Children’s Environment Health Center
Center Director: Tager, Ira
Title: Berkeley/Stanford Children’s Environmental Health Center
Investigators: Hammond, S. Katharine , Tager, Ira , Shaw, Gary M. , Balmes, John R. , Mann, Jennifer , Nadeau, Kari
Current Investigators: Hammond, S. Katharine , Tager, Ira , Gale, Sara L , Shaw, Gary M. , Balmes, John R. , Padula, Amy , Eisen, Ellen , Mann, Jennifer , Nadeau, Kari
Institution: University of California - Berkeley , University of California - San Francisco , Stanford University
Current Institution: University of California - Berkeley , Stanford University
EPA Project Officer: Callan, Richard
Project Period: May 7, 2010 through May 6, 2013 (Extended to May 6, 2014)
Project Period Covered by this Report: May 7, 2010 through May 6,2011
Project Amount: $1,091,783
RFA: Children's Environmental Health and Disease Prevention Research Centers: Formative Centers (with NIEHS) (2009) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health
Objective:
Project 1: Effect of Multi-level Environmental Exposure on Birth Outcomes
Hypothesis—The associations between adverse pregnancy outcomes (low birth weight [LBW], pre-term and small for gestation age) and exposure to ambient air pollutants and endotoxin are increased in women who reside in impoverished neighborhoods and are socially disadvantaged at the individual level.
Project 2: Exposure to Air Pollutants and Risk of Birth Defects
Hypothesis—Exposure to specific air pollutants and mixtures of air pollutants during critical periods of fetal organogenesis are associated with structural birth defects (so-call “congenital” anomalies or birth defects).
Project 3: Ambient Pollutants/Bioaerosol Effects on Treg Function
Hypothesis—The reported associations between ambient air pollution and endotoxin and asthma onset and exacerbation are mediated through pollutant/endotoxin alterations of regulatory T-cells (Treg) and these effects on Treg are related to exposure in the year prior to specimen collection and exposure during the late 1st and early 2nd trimesters when T-cell differentiation and function begin to develop.
Community Outreach and Translation Core (COTC): To engage community-based stakeholders in the ongoing conduct of studies of the effects of air pollution in children in the San Joaquin Valley by Center investigators and to facilitate translation of results of these studies into useful information for such stakeholders.
Exposure Core: The purpose of the Exposure Core is to supply exposure data for the three projects, which involves acquisition and processing of routinely measured ambient air pollutants, and collection of new PAH and endotoxin data in the San Joaquin Valley (SJV).
Progress Summary:
Project 1: Effect of Multi-level Environmental Exposure on Birth Outcomes
One unique feature of this project is to use methods to assign neighborhoods to individual subjects (Gale S, et al. Crime, neighborhood deprivation, and asthma: a GIS approach to define and assess neighborhoods. Spatial and Spatio-temporal Epidemiology, under review). The analysis for the P20 will be limited to Fresno County, but we are collecting data for four counties in the Central Valley that would be included in a P01 application. To this end, we have collected or are in the progress of ordering the following data: 1) updated road networks and traffic (done); 2) alcohol sales outlets (done); 3) cigarette point of sales (on order); 4) perimeters of wildfires in CA (done); 5) point locations of Superfund sites (done); 6) point locations of all grocery stores and farmers markets (ordered); 7) crime statistics (in progress with Fresno County sheriff); 8) block group census data (done); 9) schools (done); 10) daycare sites (done); 11) hospitals (done); and 12) water district data (done). All of these data will be used to develop a deprivation index. The method to develop the index will be under the guidance of Professor A. Hubbard, who is head of the Center’s Biostat Core.
Project 2: Exposure to Air Pollutants and Risk of Birth Defects
In this project we are using data from the largest case-control study conducted to date in the United States on birth defects—the National Birth Defects Prevention Study. We limit our inquiries to the California study site, which is being conducted in the San Joaquin Valley—an area with demonstrated poor air quality. This study includes information on 30 birth defect phenotypes.
In this first year, project activities have focused on preparing the data for exposure assessment and for epidemiologic analyses. Addresses were geocoded using the Centrus Software (http://www.qmsoft.com/), which combines reference street networks from Tele Atlas (http://www.teleatlas.com/OurProducts/MapData/Dynamap/index.htm) and United States Postal Service data. Geocodes were available for 95% of cases and 93% of controls—approximately 3,500 cases and controls. Ambient air pollution measurements and traffic metrics were assigned to each of the geocoded residences reported by the study subjects during the first and second month of pregnancy. Exposure assignments were made if the geocodes were within the San Joaquin Valley and accounted for at least 75% of the first and second month of pregnancy. The pollutants included: ozone (O3), nitrogen dioxide (NO2), nitrogen oxide (NO), carbon monoxide (CO), particulate matter less than 10 μg/m3 (PM10), and PM less than 2.5 μg/m3 (PM2.5). Daily 24-hour averages for all of the pollutants as well as a daily daytime 8-hour maximum for ozone then were averaged over the first 2 months of pregnancy.
Project 3: Ambient Pollutants/Bioaerosol Effects on Treg Function
We are recruiting subjects from the following three sources to reach our target of 200 non-asthmatic and 200 asthmatic children: 1) middle schools (fliers); 2) siblings of subjects in our previous studies; and 3) friends of participants in our previous studies. Recruitment as of November 11 is provided in Table 1. Data to stratify by race/ethnicity will be available when all data are entered in the database. The spatial distribution of the subjects is balanced in relation to the overall population distribution of the study area. Clearly, we are on target to reach our goal of 400 subjects within 18 months. All but 2 subjects have provided blood specimens for immunological and epigenetic analyses discussed in the application. We already have demonstrated that we can carry out the analyses in the preliminary results section of our application. We have supplemented those data, and the results have been published (Nadeau K, et al. Air pollution impairs regulatory T-cell function in asthma. J Allergy Clin Immunol 2010;126:845-852). On this basis, we are confident that our hypothesis will be supported with larger sample. With funds from an EPA STAR grant, we plan to extend these analyses to other genes relevant to methyl group metabolism and to alteration of histones.
Community Outreach and Translation Core (COTC)
In June, 2010, John Balmes, Jennifer Mann, and Kathie Hammond, presented at a conference sponsored by the San Joaquin Valley Air Pollution Control District (SJVAPCD), Particulate Pollution in the San Joaquin Valley. Dr. Mann presented results from the Fresno Asthmatic Children’s Environment Study on the relationship of air pollution and wheeze in subgroups of asthmatic children. Dr. Balmes discussed California Air Resources Board and U.S. EPA regulatory efforts to improve air quality. Dr. Hammond presented PAH exposure models that were developed as part of FACES and are being used in CHAPS-SJV.
Several members of the CHAPS research team have been doing work in Fresno, continuously, since 2000. From May to December 2011, Dr. Balmes and Dr. Mann traveled to Fresno on several occasions to meet with environmental and asthma advocates as well as past local research collaborators.
Drs. Balmes and Mann wrote an article for the FACES/CHAPS newsletter, which described the results of recent FACES analyses that showed effects of Fresno pollution on a) T-regulatory cells and b) wheezing in children with asthma. This newsletter was sent to all FACES and all CHAPS participants, and posted on our website.
Exposure Core
The main task for year 1 of Project 2 is to set up a monitoring network in Bakersfield. Originally, it was planned to obtain 2-week integrated samples of speciated PAH data in two size ranges (d<0.2 µm and d<2.5 µm). To verify that this would give accurate results, a pilot study was conducted. Sampling was carried out in diesel bus facility on the UC Berkeley campus. Simultaneous daily, weekly and 2-week samples were collected. The results showed that the weekly samples were less than the sum of the simultaneous samples. Therefore, 2-week integrated sampling is not possible. A second round of experiments determined that 4-day samples can be integrated without loss of accuracy for the majority of the PAHs.
The monitoring focused on wintertime PAHs. We have established contacts with the:
- Kern County School Board, which has given us access to all high school sites in Bakersfield;
- Selected local school boards, which administer elementary and middle schools; and
- Residents who are willing to have monitors placed at their homes.
The figure below shows the sampling sites for the PAH monitoring campaign.
Four 4-day samples were collected at 14 locations and analyzed to improve our understanding of the spatial variations within urban areas in the SJV. These data are being used to evaluate the similarities in parameters (traffic, population density, agricultural burning) that explain spatial PAH variations in Bakersfield and Fresno. The chemical analyses of these samples collected in year 1 currently are underway and will continue into year 2.
Future Activities:
Project 1
Our plans are to next combine the initial work performed on the creation of the neighborhood deprivation index and the analysis of air pollution and birth outcomes and determine whether the associations differ by levels of neighborhood deprivation.
Project 2
Our plans and goal have essentially not changed. Many analyses are planned in the coming year.
Project 3
- 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.
- Obtain short-term and long-term individual estimate exposures to ambient air PAHs, PM2.5, black carbon and ozone, and then test whether there is an association of the extent of exposure in each subject to immune outcome measures in the same subject.
- If data represent interesting findings, we will submit a manuscript on the EPA-funded cohorts.
COTC
We plan to continue quarterly CAB meetings to facilitate planning for the P01 submission.
Exposure Core
We plan to continue efforts as outlined in the original proposal. Our future plans are to continue the chemical analysis of the PAH samples. Endotxin samples will be collected in Bakersfield and analyzed. Routinely collected air pollution data will be acquired and quality assured. The exposures of subjects in Projects 1, 2 and 3 to PAHs and other air pollutants will be assessed.
Journal Articles: 15 Displayed | Download in RIS Format
| Other center views: | All 50 publications | 15 publications in selected types | All 15 journal articles |
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Balmes JR. How does diesel exhaust impact asthma? Thorax 2011;66(1):4-6. |
R834596 (2010) R834596 (2011) R834596 (2012) R834596 (Final) R834596C003 (2012) |
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Gale SL, Noth EM , Mann J, Balmes J, Hammond SK, Tager IB. Polycyclic aromatic hydrocarbon exposure and wheeze in a cohort of children with asthma in Fresno, CA. Journal of Exposure Science & Environmental Epidemiology 2012;22(4):386-392. |
R834596 (2010) R834596 (2011) R834596 (2012) R834596 (Final) R834596C003 (2012) |
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Hew KM, Walker AI, Kohli A, Garcia M, Syed A, McDonald-Hyman C, Noth EM, Mann JK, Pratt B, Balmes J, Hammond SK, Eisen EA, Nadeau KC. Childhood exposure to ambient polycyclic aromatic hydrocarbons is linked to epigenetic modifications and impaired systemic immunity in T cells. Clinical & Experimental Allergy 2015;45(1):238-248. |
R834596 (2012) R834596 (Final) R834596C003 (Final) R834786 (Final) R835435 (2014) R835435 (2015) R835435 (2016) R835435 (Final) |
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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.). |
R834596 (2011) R834596 (2012) R834596 (Final) R834596C003 (2011) R834596C003 (2012) R834596C003 (Final) R834786 (2012) R835435 (Final) |
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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. |
R834596 (2012) R834596 (Final) R834596C003 (2012) R834596C003 (Final) R834786 (2012) R835435 (Final) |
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Mann JK, Balmes JR, Bruckner TA, Mortimer KM, Margolis HG, Pratt B, Hammond SK, Lurmann FW, Tager IB. Short-term effects of air pollution on wheeze in asthmatic children in Fresno, California. Environmental Health Perspectives 2010;118(10):1497-1502. |
R834596 (2010) R834596 (2011) R834596 (2012) R834596 (Final) R835435 (Final) |
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Nadeau K, McDonald-Hyman C, Noth EM, Pratt B, Hammond SK, Balmes J, Tager I. Ambient air pollution impairs regulatory T-cell function in asthma. Journal of Allergy and Clinical Immunology 2010;126(4):845-852.e10. |
R834596 (2010) R834596 (2011) R834596C003 (2010) R834596C003 (2011) R834786 (2011) R835435 (Final) |
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Noth EM, Hammond SK, Biging GS, Tager IB. Mapping and modeling airborne urban phenanthrene distribution using vegetation biomonitoring. Atmospheric Environment 2013;77:518-524. |
R834596 (Final) R835435 (Final) |
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Padula AM, Mortimer K, Hubbard A, Lurmann F, Jerrett M, Tager IB. Exposure to traffic-related air pollution during pregnancy and term low birth weight: estimation of causal associations in a semiparametric model. American Journal of Epidemiology 2012;176(9):815-824. |
R834596 (2010) R834596 (2011) R834596 (2012) R834596 (Final) R834596C001 (2011) R834596C001 (2012) R834596C001 (Final) |
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Padula AM, Tager IB, Carmichael SL, Hammond SK, Yang W, Lurmann F, Shaw GM. Ambient air pollution and traffic exposures and congenital heart defects in the San Joaquin Valley of California. Paediatric and Perinatal Epidemiology 2013;27(4):329-339. |
R834596 (2011) R834596 (2012) R834596 (Final) R834596C002 (2011) R834596C002 (2012) R834596C002 (Final) R835435 (Final) |
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Padula AM, Tager IB, Carmichael SL, Hammond SK, Lurmann F, Shaw GM. The association of ambient air pollution and traffic exposures with selected congenital anomalies in the San Joaquin Valley of California. American Journal of Epidemiology 2013;177(10):1074-1085. |
R834596 (2011) R834596 (2012) R834596 (Final) R834596C002 (2011) R834596C002 (2012) R834596C002 (Final) R835435 (Final) |
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Padula AM, Tager IB, Carmichael SL, Hammond SK, Yang W, Lurmann FW, Shaw GM. Traffic-related air pollution and selected birth defects in the San Joaquin Valley of California. Birth Defects Research, Part A: Clinical and Molecular Teratology 2013;97(11):730-735. |
R834596 (2012) R834596 (Final) R834596C002 (2012) R834596C002 (Final) R835435 (Final) |
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Padula AM, Mortimer KM, Tager IB, Hammond SK, Lurmann FW, Yang W, Stevenson DK, Shaw GM. Traffic-related air pollution and risk of preterm birth in the San Joaquin Valley of California. Annals of Epidemiology 2014;24(12):888-895e4. |
R834596 (2012) R834596 (Final) R834596C001 (2012) R834596C001 (Final) R835435 (2015) R835435 (2016) R835435 (2018) R835435 (Final) |
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Padula AM, Balmes JR, Eisen EA, Mann J, Noth EM, Lurmann FW, Pratt B, Tager IB, Nadeau K, Hammond SK. Ambient polycyclic aromatic hydrocarbons and pulmonary function in children. Journal of Exposure Science & Environmental Epidemiology 2015;25(3):295-302. |
R834596 (2012) R834596 (Final) R835435 (2014) R835435 (2015) R835435 (2016) R835435 (Final) |
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Yang W, Carmichael SL, Roberts EM, Kegley SE, Padula AM, English PB, Shaw GM. Residential agricultural pesticide exposures and risk of neural tube defects and orofacial clefts among offspring in the San Joaquin Valley of California. American Journal of Epidemiology 2014;179(6):740-748. |
R834596 (Final) R834596C002 (Final) |
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Supplemental Keywords:
congenital abnormalities, pregnancy, air pollution, allergic, allergy, asthma, childhood asthma, environmental health, epidemiologic studies, human health, immune system, immune tolerance, immunopathology, inflammation, lung, pollutant, regulatory T-lymphocyte;Relevant Websites:
Children's Health & Air Pollution Study - San Joaquin Valley ExitProgress and Final Reports:
Original Abstract Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R834596C001 Effect of Multi-Level Environmental Exposure on Birth Outcomes
R834596C002 Exposure to Air Pollutants and Risk of Birth Defects
R834596C003 Ambient Pollutant/Bioaerosol Effects on Treg Function
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.