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The Etiology and Pathogenesis of Airway Disease in Children from Rural Communities
EPA Grant Number: R826711Center: 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
Current Investigators: Hunninghake, Gary W. , Chrischilles, Elizabeth , Denning, Gerene , Merchant, James A. , Nauseef, William , Schwartz, David
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)
Research Category: Health Effects , Children's Health
Description:
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 | ||
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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) |
not available |
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Brass DM, Savov JD, Gavett SH, Haykal-Coates N, Schwartz DA. Subchronic endotoxin inhalation causes chronic airway disease. American Journal of Physiology-Lung Cellular and Molecular Physiology 2003;285(6):L755-L761. |
R826711 (Final) R826711C004 (Final) |
not available |
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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) |
not available |
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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) |
not available |
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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 and erratum in Journal of Allergy and Clinical Immunology 113(3):391. |
R826711 (Final) R826711C002 (Final) |
not available |
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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) |
not available |
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George CL, White M, 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) |
not available |
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Hollingsworth 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):106-107. |
R826711 (Final) R826711C004 (Final) |
not available |
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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) |
not available |
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Kline JN, Cowden JD, Hunninghake GW, 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, 1999. |
R826711C001 (2000) R826711C002 (2000) |
not available |
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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) |
not available |
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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) |
not available |
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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) |
not available |
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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) |
not available |
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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) |
not available |
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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) |
not available |
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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) |
not available |
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Savov JD, Gavett SH, Brass DM, Costa DL, Schwartz DA. Neutrophils play a critical role in the development of LPS-induced airway disease. American Journal of Physiology-Lung Cellular and Molecular Physiology 2002;283(5):L952-L962. |
R826711 (Final) R826711C004 (Final) |
not available |
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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) |
not available |
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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) |
not available |
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Schwartz DA, Wohlford-Lenane CL, Quinn TJ, Krieg AM. Bacterial DNA or oligonucleotides containing unmethylated CpG motifs can minimize LPS-induced inflammation in the lower respiratory tract through an IL-12 dependent pathway. Journal of Immunology 1999;163:224-231. |
R826711C001 (2000) R826711C002 (2000) |
not available |
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Schwartz DA. Etiology and pathogenesis of airway disease in children and adults from rural communities. Environmental Health Perspectives, 1999; 107 (Suppl 3):393-401. |
R826711C001 (2000) R826711C002 (2000) |
not available |
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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) |
not available |
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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) |
not available |
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Thomas KW, Monick MM, Staber JM, Yarovinsky TO, Carter AB, Hunninghake GW. RSV inhibits apoptosis and induces NF-κB activity through a PI-3K dependent pathway. Journal of Biological Chemistry 2002;277(1):492-501. |
R826711 (Final) R826711C003 (Final) |
not available |
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Walker JK , Fong AM, Lawson BL, Savov JD, Patel DD, Schwartz DA, Lefkowitz RJ. Beta-arrestin-2 regulates the development of allergic asthma. The Journal of Clinical Investigation 2003;112(4):566-574. |
R826711 (Final) R826711C004 (Final) |
not available |
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Warshamana GS, Pociask DA, Sime P, Schwartz DA, Brody AR. Susceptibility to asbestos-induced and transforming growth factor-beta 1-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) |
not available |
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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) |
not available |
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Wohlford-Lenane CL, Deetz DC, Schwartz DA. Cytokine gene expression following inhalation of corn dust. American Journal of Physiology: Lung Cell Molecular Biology 1999;276:L736-L743. |
R826711C001 (2000) R826711C002 (2000) |
not available |
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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) |
not available |
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Chen W, Monica 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;6(1):13-26. |
R826711 (Final) R826711C001 (2000) R826711C003 (Final) |
not available |
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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) |
not available |
Geographic Area, Scientific Discipline, Health, RFA, Biology, Risk Assessments, Health Risk Assessment, Epidemiology, Children's Health, Environmental Chemistry, Allergens/Asthma, State, exposure assessment, asthma indices, allergen, health effects, respiratory problems, children's environmental health, asthmatic children, assessment of exposure, childhood respiratory disease, farmworkers, harmful environmental agents, human health risk, genetic susceptibility, epidemeology, agricultural community, sensitive populations, grain dust, environmental health, air pollution, airway disease, children, environmental risks, IOWA (IA), exposure, children's vulnerablity, environmental health hazard, asthma triggers, allergic response, persistent environmental airway disease, asthma, human exposure, Human Health Risk 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