Asthma is the result of host and environment interactions. Lower respiratory tract infections (LRTI), caused by viruses such as respiratory syncytial virus (RSV) and rhinovirus (RV), are a leading cause of bronchiolitis in infants. Infants hospitalized with bronchiolitis not only experience significant morbidity, but are also at significantly increased risk for both recurrent wheezing and childhood asthma. We have established that respiratory syncytial viral infections appear to directly contribute to asthma causation, not just simply identify persons at risk for subsequent wheezing. Viral infections outside the infant period are also important, as they are modifiable environmental factors that have been established to be the most common cause of asthma exacerbations in both children and adults. This proposal uses a combined, parallel clinical and experimental approach to evaluate the contribution of, causality, and mechanisms through which respiratory syncytial virus, and human rhinovirus, contribute to asthma development and disease natural history. These studies all relate to the central hypothesis that viruses, as one significant environmental factor, alter the risk for developing asthma, as well as the natural history of prevalent disease. Specific testable questions related to this hypothesis include: 1) to determine the host factors among those with RSV and HRV infection that contribute to asthma development, 2) to determine the timing of infection during infancy and how that impacts the risk of developing childhood asthma;3) to determine the mechanisms through which RSV and HRV contribute to asthma development, specifically focusing on lung injury and differential immune response to infection;4) to determine if there are allelic variations in host genes involved with severity of respiratory viral infection that correlate with a predisposition or resistance to both infant bronchiolitis and childhood asthma;5) to determine if there are allelic variation in RSV genes that are associated with both infant LRTI severity, and subsequent risk of asthma development. PROJECT NARRATIVE The aims of this mid-career investigator award will be met by allowing the candidate to translate her experimental expertise to both mentor trainees and to direct patient-oriented studies of the progression and functional outcome of childhood viral illness in asthma development, moving from risk factor determination to intervention studies, and ultimately to disease prevention.

Public Health Relevance

The aims of this mid-career investigator award will be met by allowing the candidate to translate her experimental expertise to both mentor trainees and to direct patient-oriented studies of the progression and functional outcome of childhood viral illness in asthma development, moving from risk factor determination to intervention studies, and ultimately to disease prevention. PUBLIC HEALTH RELEVANCE: The aims of this mid-career investigator award will be met by allowing the candidate to translate her experimental expertise to both mentor trainees and to direct patient-oriented studies of the progression and functional outcome of childhood viral illness in asthma development, moving from risk factor determination to intervention studies, and ultimately to disease prevention.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
2K24AI077930-06
Application #
8443115
Study Section
Allergy & Clinical Immunology-1 (AITC)
Program Officer
Prograis, Lawrence J
Project Start
2008-03-15
Project End
2018-02-28
Budget Start
2013-03-01
Budget End
2014-02-28
Support Year
6
Fiscal Year
2013
Total Cost
$108,340
Indirect Cost
$8,025
Name
Vanderbilt University Medical Center
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Wu, Pingsheng; Escobar, Gabriel J; Gebretsadik, Tebeb et al. (2018) Effectiveness of Respiratory Syncytial Virus Immunoprophylaxis in Reducing Bronchiolitis Hospitalizations Among High-Risk Infants. Am J Epidemiol 187:1490-1500
Turi, Kedir N; Gebretsadik, Tebeb; Lee, Rees L et al. (2018) Seasonal patterns of Asthma medication fills among diverse populations of the United States. J Asthma 55:764-770
Stone, Cosby; Gebretsadik, Tebeb; Lee, Rees L et al. (2018) Trends in health care utilization for asthma exacerbations among diverse populations with asthma in the United States. J Allergy Clin Immunol Pract 6:295-297.e5
Stone Jr, Cosby; Qiu, Yunping; Kurland, Irwin J et al. (2018) Effect of Maternal Smoking on Plasma and Urinary Measures of Vitamin E Isoforms in the First Month after Extreme Preterm Birth. J Pediatr 197:280-285.e3
Donovan, Brittney M; Ryckman, Kelli K; Breheny, Patrick J et al. (2018) Association of newborn screening metabolites with risk of wheezing in childhood. Pediatr Res 84:619-624
Turi, Kedir N; Shankar, Jyoti; Anderson, Larry J et al. (2018) Infant Viral Respiratory Infection Nasal Immune-Response Patterns and Their Association with Subsequent Childhood Recurrent Wheeze. Am J Respir Crit Care Med 198:1064-1073
Stone Jr, Cosby A; McEvoy, Cindy T; Aschner, Judy L et al. (2018) Update on Vitamin E and Its Potential Role in Preventing or Treating Bronchopulmonary Dysplasia. Neonatology 113:366-378
Rosas-Salazar, Christian; Shilts, Meghan H; Tovchigrechko, Andrey et al. (2018) Nasopharyngeal Lactobacillus is associated with a reduced risk of childhood wheezing illnesses following acute respiratory syncytial virus infection in infancy. J Allergy Clin Immunol 142:1447-1456.e9
Beigelman, Avraham; Rosas-Salazar, Christian; Hartert, Tina V (2018) Childhood Asthma: Is It All About Bacteria and Not About Viruses? A Pro/Con Debate. J Allergy Clin Immunol Pract 6:719-725
Turi, Kedir N; Romick-Rosendale, Lindsey; Ryckman, Kelli K et al. (2018) A review of metabolomics approaches and their application in identifying causal pathways of childhood asthma. J Allergy Clin Immunol 141:1191-1201

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