Abnormalities in immune response to viral infections and the virulence patterns of certain respiratory viruses have been felt to contribute significantly to the inception, progression, and severity of childhood asthma through unknown mechanisms. Using a birth cohort to study these relationships, we have made a number of novel and important observations pertaining to immune response profiles and virus infections during early life, and more recently with continued maturation of the cohort, we have placed these findings in the context of gene-environment interactions, developmental aspects, and gender differences. The most novel finding thus far has been that moderate to severe rhinovirus (RV)-induced wheezing illnesses during infancy are the most significant event in early life that predicts the subsequent development of childhood asthma. Moreover, these outcomes appear to be related to deficiencies in the production of interferons in response to these infections. Thus, the overall hypothesis of this project is that susceptibility to, and the clinical severity and manifestations of RV infections throughout childhood and early adolescence, is related to a deficiency in interferon responses to viral infection. We therefore propose to continue evaluation of cytokine response profiles from three tissue compartments (blood, nasal aspirates, and induced sputum) that have been previously stored and prospectively obtained as they relate to the development and physiological consequences of wheezing illnesses with specific viral pathogens, the development of various atopic phenotypes, and the expression and remission of asthma through infancy, childhood and early adolescence. This project comprises the entire COAST cohort that, in addition to its own specific aims and objectives, provides all of the phenotypic characterization and biologic specimens and DMA for the remaining projects in this application. Defining mechanisms by which viral infections impact on the clinical expression of childhood asthma is clearly relevant to the development of therapies aimed at both acute treatment in the form of medications and primary prevention in the form of vaccines.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
Project #
Application #
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Wisconsin Madison
United States
Zip Code
Higano, Nara S; Hahn, Andrew D; Tkach, Jean A et al. (2016) Retrospective respiratory self-gating and removal of bulk motion in pulmonary UTE MRI of neonates and adults. Magn Reson Med :
Anderson, Halie M; Lemanske Jr, Robert F; Arron, Joseph R et al. (2016) Relationships among aeroallergen sensitization, peripheral blood eosinophils, and periostin in pediatric asthma development. J Allergy Clin Immunol :
Rubner, Frederick J; Jackson, Daniel J; Evans, Michael D et al. (2016) Early life rhinovirus wheezing, allergic sensitization, and asthma risk at adolescence. J Allergy Clin Immunol :
Bochkov, Yury A; Watters, Kelly; Basnet, Sarmila et al. (2016) Mutations in VP1 and 3A proteins improve binding and replication of rhinovirus C15 in HeLa-E8 cells. Virology 499:350-360
Fawkner-Corbett, David W; Khoo, Siew Kim; Duarte, Carminha M et al. (2016) Rhinovirus-C detection in children presenting with acute respiratory infection to hospital in Brazil. J Med Virol 88:58-63
Bochkov, Yury A; Gern, James E (2016) Rhinoviruses and Their Receptors: Implications for Allergic Disease. Curr Allergy Asthma Rep 16:30
Nicodemus-Johnson, Jessie; Myers, Rachel A; Sakabe, Noburu J et al. (2016) DNA methylation in lung cells is associated with asthma endotypes and genetic risk. JCI Insight 1:e90151
Anderson, Halie M; Lemanske Jr, Robert F; Evans, Michael D et al. (2016) Assessment of wheezing frequency and viral etiology on childhood and adolescent asthma risk. J Allergy Clin Immunol :
Nicodemus-Johnson, Jessie; Naughton, Katherine A; Sudi, Jyotsna et al. (2016) Genome-Wide Methylation Study Identifies an IL-13-induced Epigenetic Signature in Asthmatic Airways. Am J Respir Crit Care Med 193:376-85
Bønnelykke, Klaus; Ober, Carole (2016) Leveraging gene-environment interactions and endotypes for asthma gene discovery. J Allergy Clin Immunol 137:667-79

Showing the most recent 10 out of 133 publications