For many asthmatic patients, the syndrome or disease has its roots in infancy. From preliminary observations in humans, and from experiments performed in a rodent model of virus-induced airway dysfunction in our laboratory, two factors appear to influence the development of persistent wheezing or the asthmatic phenotype. First a hereditary component which is clinically manifested by the development of allergic diseases, and immunologically mediated by the presence of increased levels of IgE antibody and/or a dysregulation in cytokine production [most likely a decreased production of interferon gamma (IFN-gamma)]. Second, an environmental component, which appears biologically related to the development of a significant viral lower respiratory tract illness (most likely respiratory syncytial virus), and temporally related to a critical stage in the physiological development of the lower airway. However, the relative contribution of either of these factors, either alone or in combination, has yet to be clearly established during infancy and/or early childhood. To establish and advance our knowledge about these very important relationships, this study proposes to conduct experiments designed to answer the following questions. Is IFN-gamma dysregulated in persistent wheezers or asthmatic children? If so, how early in life can these abnormalities be demonstrated? At birth? Following infection? As the child encounters his/her environment for various periods of time? Is IFN-gamma the only cytokine that can be linked with such outcomes, or can other cytokines be involved as well? If IFN-gamma dysregulation can be shown to be causally linked with various outcomes, what is the mechanism of the defect? How closely do any demonstrable abnormalities in cytokine responses or regulation track with the development of clinically apparent allergic disease such as atopic dermatitis, allergic rhinitis, and or asthma? To answer these questions, a prospective longitudinal study has been designed that will evaluate the interactions and time dependencies of relevant immunological, microbiological, and clinical parameters. The results of these studies will provide information that will be a major step forward in our understanding of the relative influences that genetic and environmental risk factors have on the development of childhood asthma.

Project Start
1999-12-01
Project End
2000-11-30
Budget Start
Budget End
Support Year
15
Fiscal Year
2000
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Burgess-Hull, Albert J; Roberts, Linda J; Piper, Megan E et al. (2018) The social networks of smokers attempting to quit: An empirically derived and validated classification. Psychol Addict Behav 32:64-75
Kelly, Elizabeth A; Esnault, Stephane; Liu, Lin Ying et al. (2017) Mepolizumab Attenuates Airway Eosinophil Numbers, but Not Their Functional Phenotype, in Asthma. Am J Respir Crit Care Med 196:1385-1395
Shen, Zhong-Jian; Hu, Jie; Kashi, Venkatesh P et al. (2017) Epstein-Barr Virus-induced Gene 2 Mediates Allergen-induced Leukocyte Migration into Airways. Am J Respir Crit Care Med 195:1576-1585
Anderson, Halie M; Lemanske Jr, Robert F; Evans, Michael D et al. (2017) Assessment of wheezing frequency and viral etiology on childhood and adolescent asthma risk. J Allergy Clin Immunol 139:692-694
Gomez, Jose L; Yan, Xiting; Holm, Carole T et al. (2017) Characterisation of asthma subgroups associated with circulating YKL-40 levels. Eur Respir J 50:
Kelly, Elizabeth A; Esnault, Stephane; Johnson, Sean H et al. (2016) Human eosinophil activin A synthesis and mRNA stabilization are induced by the combination of IL-3 plus TNF. Immunol Cell Biol 94:701-8
Bray, Bethany C; Smith, Rachel A; Piper, Megan E et al. (2016) Transitions in Smokers' Social Networks After Quit Attempts: A Latent Transition Analysis. Nicotine Tob Res 18:2243-2251
Dougherty, Ryan J; Ellingson, Laura D; Schultz, Stephanie A et al. (2016) Meeting physical activity recommendations may be protective against temporal lobe atrophy in older adults at risk for Alzheimer's disease. Alzheimers Dement (Amst) 4:14-7
Johansson, Mats W; Evans, Michael D; Crisafi, Gina M et al. (2016) Serum periostin is associated with type 2 immunity in severe asthma. J Allergy Clin Immunol 137:1904-1907.e2
Vreede, Andrew P; Jones, Andrea N; Hansen, Karen E (2015) Can serum isotope levels accurately measure intestinal calcium absorption compared to gold-standard methods? Nutr J 14:73

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