The Etiology and Pathogenesis of Airway Disease in Children from Rural Communities

EPA Grant Number: R826711
Center: University of Iowa Children's Environmental Airway Disease Center
Center Director: Hunninghake, Gary W.
Title: The Etiology and Pathogenesis of Airway Disease in Children from Rural Communities
Investigators: Schwartz, David A.
Current Investigators: Hunninghake, Gary W. , Chrischilles, Elizabeth , Denning, Gerene , Merchant, James A. , Nauseef, William , Schwartz, David A.
Institution: University of Iowa
EPA Project Officer: Fields, Nigel
Project Period: August 1, 1998 through July 31, 2003
Project Amount: $2,660,847
RFA: Centers for Children's Environmental Health and Disease Prevention Research (1998) RFA Text |  Recipients Lists
Research Category: Children's Health , Health Effects , Human Health , Health

Objective:

The theme of our SCOR program is to investigate the etiology and pathogenesis of airway disease in children from rural communities.  We chose this theme for the following reasons: 1) asthma is the most common chronic illness in children; 2) the rural setting introduces unique environmental exposures that are known to play a role in the development of airway disease; 3) environmental models of asthma provide an ideal opportunity to investigate fundamental issues in childhood asthma such as the biological origin and persistence of airway disease; and 4) this theme builds on existing scientific expertise and ensures a highly interactive program.  Since grain dust and endotoxin are common in the rural setting and both are associated with acute and chronic forms of airway disease, we have used these very relevant exposures to further focus the projects in our SCOR program.  The end result is a highly integrated and focused program that, in aggregate, will substantially enhance our understanding of airway disease in children.  The primary hypothesis unifying this research program is that understanding the etiology and pathogenesis of airway disease in children from rural communities will provide the scientific rationale to develop primary, secondary, and tertiary preventive programs that reduce the morbidity and mortality of asthma in the rural setting.


Journal Articles: 32 Displayed | Download in RIS Format

Other center views: All 33 publications 32 publications in selected types All 32 journal articles
Type Citation Sub Project Document Sources
Journal Article Arbour NC, Lorenz E, Schutte BC, Zabner J, Kline JN, Jones M, Frees K, Watt JL, Schwartz DA. TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nature Genetics 2000;25(2):187-191. R826711 (Final)
R826711C001 (2000)
R826711C002 (2000)
R826711C004 (Final)
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  • Journal Article Brass DM, Savov JD, Gavett SH, Haykal-Coates N, Schwartz DA. Subchronic endotoxin inhalation causes persistent airway disease. American Journal of Physiology-Lung Cellular and Molecular Physiology 2003;285(3):L755-L761. R826711 (Final)
    R826711C004 (Final)
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  • Journal Article Butler NS, Monick MM, Yarovinsky TO, Powers LS, Hunninghake GW. Altered IL-4 mRNA stability correlates with Th1 and Th2 bias and susceptibility to hypersensitivity pneumonitis in two inbred strains of mice. Journal of Immunology 2002;169(7):3700-3709. R826711 (Final)
    R826711C003 (Final)
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  • Journal Article Carter AB, Donohue MR, Knudtson KL, Gudmundsson G, Monick MM, Hunninghake GW. Endotoxin augments viral replication and the inflammatory response in respiratory syncytial virus-infected epithelium. Journal of Immunology. R826711C001 (2000)
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    Journal Article Chen W, Hunninghake GW. Effects of ragweed and Th-2 cytokines on the secretion of IL-8 in human airway epithelial cells. Experimental Lung Research 2000;26(4):229-239. R826711 (Final)
    R826711C001 (2000)
    R826711C003 (Final)
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  • Journal Article Chen W, Monick MM, Carter AB, Hunninghake GW. Activation of ERK2 by respiratory syncytial virus in A549 cells is linked to the production of interleukin 8. Experimental Lung Research 2000;26(1):13-26. R826711 (Final)
    R826711C001 (2000)
    R826711C003 (Final)
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  • Journal Article Chrischilles E, Ahrens R, Kuehl A, Kelly K, Thorne P, Burmeister L, Merchant J. Asthma prevalence and morbidity among rural Iowa schoolchildren. Journal of Allergy and Clinical Immunology 2004;113(1):66-71. R826711 (Final)
    R826711C002 (Final)
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  • Journal Article George CL, Jin H, Wohlford-Lenane CL, O'Neill ME, Phipps JC, O'Shaughnessy P, Kline JN, Thorne PS, Schwartz DA. Endotoxin responsiveness and subchronic grain dust-induced airway disease. American Journal of Physiology-Lung Cellular and Molecular Biology 2001;280(2):L203-L213. R826711 (Final)
    R826711C001 (2000)
    R826711C002 (2000)
    R826711C004 (Final)
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  • Journal Article George CL, White ML, O'Neill ME, Thorne PS, Schwartz DA, Snyder JM. Altered surfactant protein A gene expression and protein metabolism associated with repeat exposure to inhaled endotoxin. American Journal of Physiology-Lung Cellular and Molecular Physiology 2003;285(6):L1337-L1344. R826711 (Final)
    R826711C004 (Final)
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  • Journal Article Hollingsworth II JW, Cook DN, Brass DM, Walker JK, Morgan DL, Foster WM, Schwartz DA. The role of toll-like receptor 4 in environmental airway injury in mice. American Journal of Respiratory and Critical Care Medicine 2004;170(2):126-132. R826711 (Final)
    R826711C004 (Final)
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  • Journal Article Kline JN, Jagielo PJ, Watt JL, Schwartz DA. Bronchial hyperreactivity is associated with enhanced grain dust-induced airflow obstruction. Journal of Applied Physiology 2000;89(3):1172-1178. R826711 (Final)
    R826711C001 (2000)
    R826711C002 (2000)
    R826711C004 (Final)
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  • Journal Article Kline JN, Cowden JD, Hunninghake GW, Schutte BC, Watt JL, Wohlford-Lenane CL, Powers LS, Jones MP, Schwartz DA. Variable airway responsiveness to inhaled lipopolysaccharide. American Journal of Respiratory and Critical Care Medicine 1999;160(1):297-303. R826711 (Final)
    R826711C001 (2000)
    R826711C002 (2000)
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  • Journal Article Lorenz E, Jones M, Wohlford-Lenane C, Meyer N, Frees KL, Arbour NC, Schwartz DA. Genes other than TLR4 are involved in the response to inhaled LPS. American Journal of Physiology-Lung Cellular and Molecular Physiology 2001;281(5):L1106-L1114. R826711 (Final)
    R826711C004 (Final)
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  • Journal Article Monick MM, Staber JM, Thomas KW, Hunninghake GW. Respiratory syncytial virus infection results in activation of multiple protein kinase C isoforms leading to activation of mitogen-activated protein kinase. Journal of Immunology 2001;166(4):2681-2687. R826711 (Final)
    R826711C001 (2000)
    R826711C003 (Final)
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  • Journal Article Monick MM, Yarovinsky TO, Powers LS, Butler NS, Carter AB, Gudmundsson G, Hunninghake GW. Respiratory syncytial virus up-regulates TLR4 and sensitizes airway epithelial cells to endotoxin. Journal of Biological Chemistry 2003;278(52):53035-53044. R826711 (Final)
    R826711C003 (Final)
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  • Journal Article Moreland JG, Fuhrman RM, Wohlford-Lenane CL, Quinn TJ, Benda E, Pruessner JA, Schwartz DA. TNF-α and IL-1β are not essential to the inflammatory response in LPS-induced airway disease. American Journal of Physiology-Lung Cellular and Molecular Biology 2001;280(1):L173-L180. R826711 (Final)
    R826711C001 (2000)
    R826711C002 (2000)
    R826711C004 (Final)
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  • Journal Article Moreland JG, Fuhrman RM, Pruessner JA, Schwartz DA. CD11b and intercellular adhesion molecule-1 are involved in pulmonary neutrophil recruitment in lipopolysaccharide-induced airway disease. American Journal of Respiratory Cell and Molecular Biology 2002;27(4):474-480. R826711 (Final)
    R826711C004 (Final)
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  • Journal Article Moreland JG, Bailey G, Nauseef WM, Weiss JP. Organism-specific neutrophil-endothelial cell interactions in response to Escherichia coli, Streptococcus pneumoniae, and Staphylococcus aureus. Journal of Immunology 2004;172(1):426-432. R826711 (Final)
    R826711C001 (Final)
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  • Journal Article Quinn TJ, Taylor S, Wohlford-Lenane CL, Schwartz DA. IL-10 reduces grain dust-induced airway inflammation and airway hyperreactivity. Journal of Applied Physiology 2000;88(1):173-179. R826711 (Final)
    R826711C001 (2000)
    R826711C002 (2000)
    R826711C004 (Final)
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  • Journal Article Savov JD, Gavett SH, Brass DM, Costa DL, Schwartz DA. Neutrophils play a critical role in development of LPS-induced airway disease. American Journal of Physiology-Lung Cellular and Molecular Physiology 2002;283(5):L952-L962. R826711 (Final)
    R826711C004 (Final)
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  • Journal Article Savov JD, Brass DM, Berman KG, McElvania E, Schwartz DA. Fibrinolysis in LPS-induced chronic airway disease. American Journal of Physiology-Lung Cellular and Molecular Physiology 2003;285(4):L940-L948. R826711 (Final)
    R826711C004 (Final)
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  • Journal Article Savov JD, Whitehead GS, Wang J, Liao G, Usuka J, Peltz G, Foster WM, Schwartz DA. Ozone-induced acute pulmonary injury in inbred mouse strains. American Journal of Respiratory Cell and Molecular Biology 2004;31(1):69-77. R826711 (Final)
    R826711C004 (Final)
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  • Journal Article Schwartz DA, Wohlford-Lenane CL, Quinn TJ, Krieg AM. Bacterial DNA or oligonucleotides containing unmethylated CpG motifs can minimize lipopolysaccharide-induced inflammation in the lower respiratory tract through an IL-12-dependent pathway. Journal of Immunology 1999;163(1):224-231. R826711 (Final)
    R826711C001 (2000)
    R826711C002 (2000)
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  • Journal Article Schwartz DA. Etiology and pathogenesis of airway disease in children and adults from rural communities. Environmental Health Perspectives 1999;107(Suppl 3):393-401. R826711 (Final)
    R826711C001 (2000)
    R826711C002 (2000)
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  • Journal Article Schwartz DA, Christ WJ, Kleeberger SR, Wohlford-Lenane CL. Inhibition of LPS-induced airway hyperresponsiveness and airway inflammation by LPS antagonists. American Journal of Physiology-Lung Cellular and Molecular Physiology 2001;280(4):L771-L778. R826711 (Final)
    R826711C004 (Final)
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  • Journal Article Schwartz DA. Does inhalation of endotoxin cause asthma? American Journal of Respiratory and Critical Care Medicine 2001;163(2):305-306. R826711 (Final)
    R826711C004 (Final)
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  • Journal Article Thomas KW, Monick MM, Staber JM, Yarovinsky T, Carter AB, Hunninghake GW. Respiratory syncytial virus inhibits apoptosis and induces NF-κB activity through a phosphatidylinositol 3-kinase-dependent pathway. Journal of Biological Chemistry 2002;277(1):492-501. R826711 (Final)
    R826711C003 (Final)
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  • Journal Article Walker JKL, Fong AM, Lawson BL, Savov JD, Patel DD, Schwartz DA, Lefkowitz RJ. β-Arrestin-2 regulates the development of allergic asthma. Journal of Clinical Investigation 2003;112(4):566-574. R826711 (Final)
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  • Journal Article Warshamana GS, Pociask DA, Sime P, Schwartz DA, Brody AR. Susceptibility to asbestos-induced and transforming growth factor-β1-induced fibroproliferative lung disease in two strains of mice. American Journal of Respiratory Cell and Molecular Biology 2002;27(6):705-713. R826711 (Final)
    R826711C004 (Final)
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  • Journal Article Whitehead GS, Walker JK , Berman KG, Foster WM, Schwartz DA. Allergen-induced airway disease is mouse strain dependent. American Journal of Physiology-Lung Cellular and Molecular Physiology 2003;285(1):L32-L42. R826711 (Final)
    R826711C004 (Final)
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  • Journal Article Wohlford-Lenane CL, Deetz DC, Schwartz DA. Cytokine gene expression after inhalation of corn dust. American Journal of Physiology 1999;276(5 Pt 1):L736-L743. R826711 (Final)
    R826711C001 (2000)
    R826711C002 (2000)
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  • Journal Article Zeldin DC, Wohlford-Lenane C, Chulada P, Bradbury JA, Scarborough PE, Roggli V, Langenbach R, Schwartz DA. Airway inflammation and responsiveness in prostaglandin H synthase-deficient mice exposed to bacterial lipopolysaccharide. American Journal of Respiratory Cell and Molecular Biology 2001;25(4):457-465. R826711 (Final)
    R826711C004 (Final)
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  • Supplemental Keywords:

    RFA, Health, Scientific Discipline, Geographic Area, Environmental Chemistry, Health Risk Assessment, State, Epidemiology, Risk Assessments, Allergens/Asthma, Children's Health, Biology, asthma, asthma triggers, environmental health, farmworkers, health effects, sensitive populations, airway disease, environmental risks, respiratory problems, exposure, asthma indices, persistent environmental airway disease, children, Human Health Risk Assessment, air pollution, airway inflammation, assessment of exposure, childhood respiratory disease, children's vulnerablity, asthmatic children, human exposure, IOWA (IA), children's environmental health, environmental health hazard, harmful environmental agents, epidemeology, grain dust, allergic response, agricultural community, allergen, genetic susceptibility, exposure assessment

    Progress and Final Reports:

    2000 Progress Report
    2001 Progress Report
    Final Report

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R826711C001 Mechanisms that Initiate, Promote, and Resolve Grain Dust/LPS Induced Inflammation
    R826711C002 Multi-component Intervention Study of Asthma in Children from Rural Communities
    R826711C003 Role of RSV Infection and Endotoxin in Airway Inflammation
    R826711C004 A Model to Study the Development of Persistent Environmental Airway Disease