Grantee Research Project Results
2010 Progress Report: Endotoxin Exposure and Asthma in Children
EPA Grant Number: R834515Center: Denver Childrens Environmental Health Center - Environmental Determinants of Airway Disease in Children
Center Director: Guo, Yanbing
Title: Endotoxin Exposure and Asthma in Children
Investigators: Schwartz, David A. , Covar, Ronina A , Litonjua, Augusto A. , Liu, Andrew H. , Murphy, Amy J , Strand, Mathew J. , Van Dyke, Michael V. , White, Carl W. , Martyny, John W. , Forssen, Anna , Dakhama, Azzeddine , Yang, Ivana , Sordillo, Joanne , Rabinovitch, Nathan , Szefler, Stanley
Current Investigators: Schwartz, David A. , Covar, Ronina A , Litonjua, Augusto A. , Liu, Andrew H. , Murphy, Amy J , Strand, Mathew J. , Van Dyke, Michael V. , Martyny, John W. , Rabinovitch, Nathan
Institution: National Jewish Health
EPA Project Officer: Hahn, Intaek
Project Period: June 22, 2010 through June 21, 2015 (Extended to June 21, 2017)
Project Period Covered by this Report: June 22, 2010 through June 21,2011
Project Amount: $1,897,209
RFA: Children's Environmental Health and Disease Prevention Research Centers (with NIEHS) (2009) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health
Objective:
The Denver Children's Environmental Health Center is conducting three projects and the Community Outreach and Translation Core (COTC). The objectives of the projects and COTC are below.
Project 1: Endotoxin Exposure and Asthma in Children
Objective: We hypothesize that higher levels of endotoxin exposure cause persistent, problematic asthma and that key environmental (ozone and allergens) and genetic modifiers (endotoxin receptor polymorphisms) contribute to endotoxin susceptibility and pathological asthmatic responses. We are studying these endotoxin-induced airway conditions in children through three complementary clinical investigations.
Project 2: Environmental Determinants of Early Host Response to RSV
Objective: The overall hypothesis of this project is that ozone exposure, in the early postnatal phase, alters lung development and modifies the host immune response to early life viral infection and allergen exposure, thereby contributing to the development of reactive airway disease. In the presence of bacterial endotoxin (LPS), however, lung development will be sustained and the host immune response will mature and protect the newborn against the development of altered airway responses to viral infection and allergen exposure. The specific aims are to: (1) define the influence of ozone exposure on Toll-like receptor (TLR) expression and airway structure and function; (2) define the influence of ozone exposure on airway responsiveness to respiratory syncytial virus (RSV) and allergen; and (3) determine if and how LPS can modify airway responsiveness to RSV infection and allergen, following postnatal exposure to ozone.
Project 3: Environmental Determinants of Host Defense
Objective: The overall goal of this project is to understand how and why air pollution alters lung hose defense. The overall hypothesis of this project is that the expression of TLR in the lung are influenced by environmental (ozone and/or pathogen associated molecular patterns [PAMPs]) and genetic factors, and the dynamic expression of TLRs has profound effects on lung host defense and, consequently, the development of lung infections and allergic airway disease.
Community Outreach and Translation Core (COTC)
The COTC forms a bidirectional bridge between researchers, community stakeholders, and community residents for:
- sharing thoughts, perceptions, information and needs;
- applying existing evidence; and
- informing and shaping future research that is responsive to the community.
A Community Advisory Board (CAB) serves as a forum for investigators, practitioners, and community stakeholders to discuss the activities of the Denver Children's Environmental Health Center (CEHC) and the priorities of the community.), The CAB is composed of members of multidisciplinary, multi-regional, and multi-lateral stakeholders, serves as the direct link between investigators and the various communities in Colorado. The work of the COTC follows the principles of community engagement. CAB members are involved in the scientific process of the CEHC through a variety of means, including proposal review, question-and-answer sessions between CAB members and investigators, and CAB-led "community fireside chats" where community needs, potential targeted interventions, responsive research, and issues of feasibility are discussed. In addition, a central activity of the COTC is to work with community stakeholders and members to identify and share the key messages of the Center’s research findings, so that the community is able to take advantage of new discoveries.
Progress Summary:
Project 1: Endotoxin Exposure and Asthma in Children
As proposed, three complementary studies address the aims and hypotheses of Project 1: (1) Childhood Asthma Management Program (CAMP) ancillary study; (2) Denver Panel Study (DPS); and (3) Housing and Urban Development (HUD) ancillary study. For the CAMP study, house dust samples from 980 CAMP study participants were shipped to the Denver site for endotoxin measurement. An important decision was made to change the lab assay for dust endotoxin from one based on the limulus amebocyte lysate (LAL) to recombinant Factor C (rFC) derived from the Limulus amebocyte. rFC has significant technical advantages compared to LAL. In lab pilot studies to validate rFC measures, a high correlation was observed between rFC and LAL (19 dust samples, correlation r = 0.92). Other rFC lab method refinements were made, based on additional lab pilots. These rFC methods will be used to measure dust endotoxin in all of our Children's Environmental Health Center studies. In Aim 2, for the DPS study, we completed a lab pilot to determine the induced sputum yield for airway macrophages from people with asthma via bead separation methods. There was high variability in the proportion and number of airway macrophages from different samples (10 participant samples: median 75,000 airway macrophages/sample; range 5,000-510,000). Accordingly, we plan a screening visit for potential study participants to assess their induced sputum yield prior to enrollment in the DPS study. For Aim 4, the original investigation of 7 functional polymorphisms and 31 SNPs in 3 endotoxin receptor complex genes has been expanded due to the availability of extensive genotyping of CAMP study participants in a separate effort via Illumina 550K SNP genotyping methods. With this expanded scope of envirogenomic investigation, innovative observations in this study will benefit from validation in replication cohort investigations. Therefore, we have identified potential race-matched cohorts for such validation studies, in case they become necessary.
Project 2: Environmental Determinants of Early Host Response to RSV
This project has made substantial progress in achieving its overall objective to characterize the influence of postnatal ozone exposure on TLR expression and on airway structure and function. Our initial studies, using pathway focused qPCR arrays, have shown significant changes in TLR expression in the airways of newborn mice at 24 h after postnatal ozone exposure. Analyses of lung tissues collected from these mice showed a significant thickening of the alveolar septae. This thickening was associated with peripheral (parenchymal) airway tissue infiltration with neutrophils, and was not due to cell proliferation or accumulation of myofibroblasts within the alveolar wall tissue. However, unlike ozone-exposed dam (mothers) where large numbers of neutrophils were recovered in the bronchoalveolar lavage (BAL) fluids, newborn mice showed only few neutrophils in their BAL. Comparison of the results of ozone exposure between different age groups of mice (i.e.,. 1, 2, 3, and 6 weeks) further established an age-dependent increase in airway responses to ozone. Thus, as the lung developed, the neutrophilic response increased and was associated with greater lung permeability and anti-‐oxidant response.
Depletion of neutrophils in the 3 or 6 weeks old mice did not alter ozone-induced lung permeability, suggesting that this alteration develops independent of neutrophil recruitment/accumulation in the airways of these mice. Studies of airway function are currently ongoing, as planned, to define the nature and extent of ozone-induced airways dysfunction that may associate with neutrophil accumulation in peripheral airways or lung permeability and tissue damage in central/proximal airways, following ozone exposure. To further define the effects of postnatal ozone exposure on the developing newborn mouse lung, we used a global approach of gene expression analysis to identify the genes and pathways that are perturbed by ozone. A large number of genes were found to be downregulated (n=115) while others were upregulated (n=63) at the mRNA level, following ozone exposure. In addition to their functional role, some of these genes also may serve as reliable markers of biological response to ozone exposure. Gene expression pathway analyses revealed that ozone exposure inhibited a large number of genes (at least 25) involved in cell cycle, repair, cellular movement, cellular assembly and reorganization. Other pathways including cellular development, inflammatory response, cell-to-cell signaling and interaction were also significantly modified after ozone exposure.
Project 3: Environmental Determinants of Host Defense
Optimization of ozone and PAMP exposures for in vivo studies has been completed and the experimental design will be used for further studies. To initiate in vivo studies, we focused on C57BL/6J strain of mice and two PAMPs--LPS or
Pam3Cys. Our initial experiments included cell counts (total and differential) in the BAL, collection of BAL fluid and serum for cytokine measurements, and collection of lung tissue for RNA extractions and histology. Our future studies will also include assessment of airway hyperresponsiveness (AHR) by Flexivent. To determine TLR cell surface expression on alveolar macrophages, BAL cells from different treatment groups were fixed and stained with a panel of antibodies conjugated to fluorochromes, followed by flow cytometry using FAC Scan (Becton-Dickinson, V5.2). The flow cytometry on Pam3Cys treatment groups is completed and we are in the process of completing flow cytometry experiments on LPS treatment groups.
COTC
Six CAB meetings were held. The CAB was expanded to include Dr. Mark Anderson and Ms. Alicia Aalto. Dr. Mark Anderson is a pediatrician for Denver Health (which serves Denver’s inner-city and un/underinsured), runs a school-based health center, and is the Director of the Pediatric Environmental Health Specialty Unit for EPA Region 8. Ms. Alicia Aalto is an environmental engineer and the Children’s Health Coordinator for EPA Region 8. All CEHC investigators presented their research projects to the community advisory board. As a result of the opportunities for CAB member and CEHC investigators to discuss their work, CAB members were able to inform investigators of priority topics and questions in their communities (e.g., diesel, particulate matter), potential hotspots, and areas/communities to involve for project recruitment/sampling. The CAB is actively planning the priorities and activities of the COTC. To support the process, an environmental scan was initiated and is nearing completion. Thus far, key informant interviews have been completed with teachers, science curriculum consultants, and community non-governmental organizations involved in schools related to environmental health. A guiding principle of our work is to avoid duplication and reinvention of the wheel thus the environmental scan was a key activity.
The COTC also was involved in the training of graduate students. An MPH student from the Colorado School of Public Health worked with COTC staff to complete her capstone research project that explored traffic density and asthma in Denver.
Future Activities:
Project 1:
For the CAMP study, we will complete EPA, GCP, and IRB approval processes. We plan to complete house dust endotoxin measures and expand genotyping of CAMP participants, analyze endotoxin exposure and genetic modifiers of asthma outcomes, and submit results for presentation and publication. For the HUD study, study participant enrollment and house dust sample collection will be completed, allergen and endotoxin levels in dust samples will be measured, and the effect of the home intervention on dust endotoxin levels and asthma outcomes will be analyzed. Over the course of the coming year, we aim to complete the endotoxin measures and analyses for the CAMP and HUD studies, while planning and organizing for the DPS asthma study.
Project 2:
Complete Aim 1 by Summer 2011 and publish results by the end of this year. Initiate Aim 2 studies in June and pursue the sub-aims as planned in the original application.
Project 3:
The planned future activities are to: (1) determine the effect of in vitro exposures to ozone and/or PAMPs on the expression of TLRs in murine macrophages and dendritic cells; (2) determine the effect of in vivo exposures to ozone and/or PAMPs on the expression of TLRs in mouse lungs; (3) determine the effect of in vivo exposures to ozone and/or PAMPs on susceptibility of mice to lung pathogens; and (4) determine the effect of in vivo exposures to ozone and/or PAMPs on house dust mite (HDM) sensitization and the development of HDM induced allergic airway disease in mice.
COTC:
The CAB and COTC will plan, develop and implement an environmental lung health program that emphasizes critical thinking skills and integrates the Colorado Student Aptitude Assessment Program's standards. The COTC's objectives for the next year are to: (1) develop and disseminate a resource guide that compiles and reviews existing lesson plans and resources for integrating lung health, environmental health and critical thinking into the curricula of grades K-12; and (2) identify models for integrating lung health, environmental health, and critical thinking into the curricula of grades K-12. Along with CAB members, CEHC investigators will review the developed resource guide and participate in the identification and selection of models for curriculum integration and proposal development. The CAB also will continue to follow the CEHC's projects while assisting CEHC investigators to understand issues and perspectives of communities. This process will support a bridge between scientific discoveries and the translation and application of that new knowledge.
Journal Articles: 31 Displayed | Download in RIS Format
Other center views: | All 51 publications | 30 publications in selected types | All 30 journal articles |
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Alper S, Warg LA, De Arras L, Flatley BR, Davidson EJ, Adams J, Smith K, Wohlford-Lenane CL, McCray Jr PB, Pedersen BS, Schwartz DA, Yang IV. Novel Innate Immune Genes Regulating the Macrophage Response to Gram Positive Bacteria. Genetics 2016;204(1):327-336. |
R834515 (Final) |
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Breton CV, Marsit CJ, Faustman E, Nadeau K, Goodrich JM, Dolinoy DC, Herbstman J, Holland N, LaSalle JM, Schmidt R, Yousefi P, Perera F, Joubert BR, Wiemels J, Taylor M, Yang IV, Chen R, Hew KM, Freeland DM, Miller R, Murphy SK. Small-magnitude effect sizes in epigenetic end points are important in children's environmental health studies:the Children's Environmental Health and Disease Prevention Research Center's Epigenetics Working Group. Environmental Health Perspectives 2017;125(4):511-526. |
R834515 (Final) R835436 (2017) R836159 (2018) |
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Das R, Subrahmanyan L, Yang IV, van Duin D, Levy R, Piecychna M, Leng L, Montgomery RR, Shaw A, Schwartz DA, Bucala R. Functional polymorphisms in the gene encoding macrophage migration inhibitory factor are associated with gram-negative bacteremia in older adults. Journal of Infectious Diseases 2014;209(5):764-768. |
R834515 (2013) R834515 (2014) R834515 (2015) R834515 (Final) R834515C001 (2014) R834515C002 (2014) R834515C003 (2014) R834515C003 (2016) |
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De Arras L, Seng A, Lackford B, Keikhaee MR, Bowerman B, Freedman JH, Schwartz DA, Alper S. An evolutionarily conserved innate immunity protein interaction network. Journal of Biological Chemistry 2013;288(3):1967-1978. |
R834515 (2013) R834515 (2014) R834515 (2015) R834515 (Final) R834515C001 (2014) R834515C002 (2014) R834515C003 (2014) R834515C003 (2016) |
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Gabehart K, Correll KA, Yang J, Collins ML, Loader JE, Leach S, White CW, Dakhama A. Transcriptome profiling of the newborn mouse lung response to acute ozone exposure. Toxicological Sciences 2014;138(1):175-190. |
R834515 (2011) R834515 (2013) R834515 (2014) R834515 (2015) R834515 (Final) R834515C001 (2014) R834515C002 (2014) R834515C002 (2015) R834515C003 (2014) |
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Gabehart K, Correll KA, Loader JE, White CW, Dakhama A. The lung response to ozone is determined by age and is partially dependent on toll-like receptor 4. Respiratory Research 2015;16:117. |
R834515 (2013) R834515 (2014) R834515 (2015) R834515 (Final) R834515C001 (2014) R834515C002 (2014) R834515C002 (2015) R834515C003 (2014) |
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Gao Z, Dosman JA, Rennie DC, Schwartz DA, Yang IV, Beach J, Senthilselvan A. NOS3 polymorphism, lung function, and exposure in swine operations: results of 2 studies. Journal of Allergy and Clinical Immunology 2014;134(2):485-488. |
R834515 (2013) R834515 (2014) R834515 (2015) R834515 (Final) R834515C001 (2014) R834515C002 (2014) R834515C003 (2014) R834515C003 (2016) |
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Henao-Martinez AF, Agler AH, LaFlamme D, Schwartz DA, Yang IV. Polymorphisms in the SUFU gene are associated with organ injury protection and sepsis severity in patients with Enterobacteriacea bacteremia. Infection, Genetics and Evolution 2013;16:386-391. |
R834515 (2013) R834515 (2014) R834515 (2015) R834515 (Final) R834515C001 (2014) R834515C002 (2014) R834515C003 (2014) R834515C003 (2016) |
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Jing J, Yang IV, Hui L, Patel JA, Evans CM, Prikeris R, Kobzik L, O'Connor BP, Schwartz DA. Role of macrophage receptor with collagenous structure in innate immune tolerance. Journal of Immunology 2013;190(12):6360-6367. |
R834515 (2013) R834515 (2014) R834515 (2015) R834515 (Final) R834515C001 (2014) R834515C002 (2014) R834515C003 (2014) R834515C003 (2016) |
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Kelada SN, Wilson MS, Tavarez U, Kubalanza K, Borate B, Whitehead GS, Maruoka S, Roy MG, Olive M, Carpenter DE, Brass DM, Wynn TA, Cook DN, Evans CM, Schwartz DA, Collins FS. Strain-dependent genomic factors affect allergen-induced airway hyperresponsiveness in mice. American Journal of Respiratory Cell and Molecular Biology 2011;45(4):817-824. |
R834515 (2013) R834515 (2014) R834515 (2015) R834515 (Final) R834515C001 (2014) R834515C003 (2014) R834515C003 (2016) |
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Lai PS, Hofmann O, Baron RM, Cernadas M, Meng QR, Bresler HS, Brass DM, Yang IV, Schwartz DA, Christiani DC, Hide W. Integrating murine gene expression studies to understand obstructive lung disease due to chronic inhaled endotoxin. PLoS One 2013;8(5):e62910. |
R834515 (2013) R834515 (2014) R834515 (2015) R834515 (Final) R834515C001 (2014) R834515C002 (2014) R834515C003 (2014) R834515C003 (2016) |
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Long H, O'Connor BP, Zemans RL, Zhou X, Yang IV, Schwartz DA. The Toll-like receptor 4 polymorphism Asp299Gly but not Thr399Ile influences TLR4 signaling and function. PLoS One 2014;9(4):e93550 (10 pp.). |
R834515 (2013) R834515 (2014) R834515 (2015) R834515 (Final) R834515C001 (2014) R834515C002 (2014) R834515C003 (2014) R834515C003 (2016) |
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Matsui EC, Hansel NN, Aloe C, Schiltz AM, Peng RD, Rabinovitch N, Ong MJ, Williams DL, Breysse PN, Diette GB, Liu AH. Indoor pollutant exposures modify the effect of airborne endotoxin on asthma in urban children. American Journal of Respiratory and Critical Care Medicine 2013;188(10):1210-1215. |
R834515 (2012) R834515 (2013) R834515 (2014) R834515 (2015) R834515 (Final) R834515C001 (2014) R834515C001 (2015) R834515C002 (2014) R834515C003 (2014) R834510 (2014) |
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Oakes JL, O'Connor BP, Warg LA, Burton R, Hock A, Loader J, LaFlamme D, Jing J, Hui L, Schwartz DA, Yang IV. Ozone enhances pulmonary innate immune response to a Toll-like receptor-2 agonist. American Journal of Respiratory Cell and Molecular Biology 2013;48(1):27-34. |
R834515 (2013) R834515 (2014) R834515 (2015) R834515 (Final) R834515C001 (2014) R834515C002 (2014) R834515C003 (2014) R834515C003 (2016) |
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Szefler SJ, Dakhama A. New insights into asthma pathogenesis and treatment. Current Opinion in Immunology 2011;23(6):801-807. |
R834515 (2011) R834515 (Final) |
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Szefler SJ. Advancing asthma care: the glass is only half full! Journal of Allergy and Clinical Immunology 2011;128(3):485-494. |
R834515 (2011) R834515 (Final) |
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Szefler SJ. Advances in pediatric asthma in 2011: moving forward. Journal of Allergy and Clinical Immunology 2012;129(1):60-68. |
R834515 (2011) R834515 (Final) |
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Warg LA, Oakes JL, Burton R, Neidermyer AJ, Rutledge HR, Groshong S, Schwartz DA, Yang IV. The role of the E2F1 transcription factor in the innate immune response to systemic LPS. American Journal of Physiology-Lung Cellular and Molecular Physiology 2012;303(5):L391-L400. |
R834515 (2013) R834515 (2014) R834515 (2015) R834515C001 (2014) R834515C002 (2014) R834515C003 (2014) R834515C003 (2016) |
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Warg LA, Oakes JL, Burton R, Neidermyer AJ, Rutledge HR, Groshong S, Schwartz DA, Yang IV. The role of the E2F1 transcription factor in the innate immune response to systemic LPS. American Journal of Physiology-Lung Cellular and Molecular Physiology 2012; 303(5):L391-L400.. |
R834515 (Final) |
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Warg LA, Oakes JL, Burton R, Neidermyer AJ, Rutledge HR, Groshong S, Schwartz DA, Yang IV. The role of the E2F1 transcription factor in the innate immune response to systemic LPS. American Journal of Physiology-Lung Cellular and Molecular Physiology 2012;303(5):L391-L400. |
R834515 (2013) R834515 (2014) R834515 (2015) R834515C001 (2014) R834515C002 (2014) R834515C003 (2014) R834515C003 (2016) |
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Yang IV, Alper S, Lackford B, Rutledge H, Warg LA, Burch LH, Schwartz DA. Novel regulators of the systemic response to lipopolysaccharide. American Journal of Respiratory Cell and Molecular Biology 2011;45(2):393-402. |
R834515 (2013) R834515 (2014) R834515 (2015) R834515 (Final) R834515C001 (2014) R834515C002 (2014) R834515C003 (2014) R834515C003 (2016) |
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Yang IV, Tomfohr J, Singh J, Foss CM, Marshall HE, Que LG, McElvania-Tekippe E, Florence S, Sundy JS, Schwartz DA. The clinical and environmental determinants of airway transcriptional profiles in allergic asthma. American Journal of Respiratory and Critical Care Medicine 2012;185(6):620-627. |
R834515 (Final) |
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Julian CG, Yang IV, Browne VA, Vargas E, Rodriguez C, Pedersen BS, Moore LG, Schwartz DA. Inhibition of peroxisome proliferator-activated receptor gamma: a potential link between chronic maternal hypoxia and impaired fetal growth. FASEB Journal 2014;28(3):1268-1279. |
R834515 (Final) |
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Kelada SN, Carpenter DE, Aylor DL, Chines P, Rutledge H, Chesler EJ, Churchill GA, Pardo-Manuel de Villena F, Schwartz DA, Collins FS. Integrative genetic analysis of allergic inflammation in the murine lung. American Journal of Respiratory Cell and Molecular Biology 2014;51(3):436-445. |
R834515 (Final) |
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Liang L, Willis-Owen SAG, Laprise C, Wong KCC, Davies GA, Hudson TJ, Binia A, Hopkin JM, Yang IV, Grundberg E, Busche S, Hudson M, Ronnblom L, Pastinen TM, Schwartz DA, Lathrop GM, Moffatt MF, Cookson W. An epigenome-wide association study of total serum immunoglobulin E concentration. Nature 2015;520(7549):670-674. |
R834515 (Final) |
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Eyring KR, Pedersen BS, Yang IV, Schwartz DA. In Utero Cigarette Smoke Affects Allergic Airway Disease But Does Not Alter the Lung Methylome. PloS one 2015;10(12):e0144087 (10 pp.). |
R834515 (Final) |
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Julian CG, Pedersen BS, Salmon CS, Yang IV, Gonzales M, Vargas E, Moore LG, Schwartz DA. Unique DNA Methylation Patterns in Offspring of Hypertensive Pregnancy. Clinical and Translational Science 2015;8(6):740-745. |
R834515 (Final) |
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Yang IV, Pedersen BS, Liu A, O’Connor GT, Teach SJ, Kattan M, Misiak RT, Gruchalla R, Steinbach SF, Szefler SJ, Gill MA, Calatroni A, David G, Hennessy CE, Davidson EJ, Zhang W, Gergen P, Togias A, Busse WW, Schwartz DA. DNA methylation and childhood asthma in the inner city. Journal of Allergy and Clinical Immunology 2015;136(1):69-80. |
R834515 (Final) |
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Lai PS, Liang L, Cibas ES, Liu AH, Gold DR, Baccarelli A, Phipatanakul W. Alternate methods of nasal epithelial cell sampling for airway genomic studies. Journal of Allergy and Clinical Immunology 2015;136(4):1120-1123.e4. |
R834515 (Final) |
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Yang IV, Richards A, Davidson EJ, Stevens AD, Kolakowski CA, Martin RJ, Schwartz DA. The nasal methylome: a key to understanding allergic asthma. American Journal of Respiratory and Critical Care Medicine 2017;195(6):829-831. |
R834515 (Final) |
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Yang IV, Pedersen BS, Liu AH, O'Connor GT, Pillai D, Kattan M, Misiak RT, Gruchalla R, Szefler SJ, Khurana Hershey GK, Kercsmar C, Richards A, Stevens AD, Kolakowski CA, Makhija M, Sorkness CA, Krouse RZ, Visness C, Davidson EJ, Hennessy CE, Martin RJ, Togias A, Busse WW, Schwartz DA. The nasal methylome and childhood atopic asthma. Journal of Allergy and Clinical Immunology 2017;139(5):1478-1488. |
R834515 (Final) |
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Supplemental Keywords:
Endotoxin, exposure, children, asthma, risk, health effects, susceptibility, sensitive populations, genetic predisposition, genetic polymorphism, indoor air, dose-response, ozone, remediation, human health, health, health effects, biology, health risk assessment, children's health, allergens/asthma, asthma indices, intervention, RFA, Health, Scientific Discipline, HUMAN HEALTH, Health Risk Assessment, Allergens/Asthma, Health Effects, Children's Health, Biology, asthma, asthma triggers, sensitive populations, endotoxin, asthma indices, airway inflammation, children, allergic responseRelevant Websites:
Children's Environmental Health Center (CEHC) - National Jewish HealthProgress 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).
R834515C001 Endotoxin Exposure and Asthma in Children
R834515C002 Environmental Determinants of Early Host Response to RSV
R834515C003 Environmental Determinants of Host Defense
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.
Project Research Results
- Final Report
- 2015 Progress Report
- 2014 Progress Report
- 2013 Progress Report
- 2012 Progress Report
- 2011 Progress Report
- Original Abstract
30 journal articles for this center