PROJECT 1: RSV bronchiolitis and early childhood asthma are the most common, serious, acute, and chronic conditions of infancy and childhood, respectively, and diseases that disproportionately burden vulnerable populations. Opportunity and Impact. This project draws together three important elements in understanding the role of RSV on recurrent wheezing and asthma inception - RSV infection severity, host response and susceptibility. In studying the association of RSV with asthma inception, studies have overwhelmingly focused on the 3-5% of RSV-infected infants requiring hospitalization, while the vast majority of RSV infections are mild. Whether mild infection confers intermediate risk or has a protective effect is an important question. The answer will influence proposals for primary asthma prevention strategies. The proposed series of investigations will aid in our understanding of the role and mechanisms through which RSV may both lead to chronic lung disease, and may protect from chronic lung disease. Approach. Utilizing the ReSPIRA cohort, established for this investigation and described in Core B, we will investigate the relationship between infant RSV infection, host response to infection, and genetic determinants of recurrent wheezing, asthma and allergic disease development following RSV infection.
Our specific aims are to: (1) Establish the association between RSV LRTI, RSV URI/exposure, and no RSV infection in the first 6 months of life on the risk of recurrent wheezing and asthma, (2) Define whether host immune response and/or airway injury biomarkers assessed during infant RSV infection are associated with recurrent wheezing, atopic disease or early childhood asthma, and (3) Identify the genetic determinants of the phenotype of recurrent wheezing, early childhood asthma and atopy following infant RSV infection. Utilizing the ReSPIRA cohort which includes 2000 infants followed from early infancy through early childhood, and established through this U19 grant, this project will answer the following questions: (1) how does RSV cause asthma, (2) does mild RSV infection during infancy increase or decrease the risk of asthma, and (3) what host factors are important in the progression from infant RSV infection to early childhood asthma. Answering these questions will allow us to develop preventive interventions for chronic lung disease in children, and ultimately improve the health of infants and children with bronchiolitis and asthma in the U.S. and worldwide.

Public Health Relevance

Respiratory syncytial virus (RSV) and asthma are the major causes of infant and early childhood morbidity, respectively. Severe RSV infection has also been linked to subsequent asthma development. This project will answer the following questions: (1) how does RSV cause asthma, (2) does mild RSV infection during infancy increase or decrease the risk of asthma, and (3) which host, environmental and genetic factors are important in the progression from infant RSV infection to early childhood asthma. Answering these questions will allow us to develop preventive interventions for chronic lung disease in children.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI095227-03
Application #
8511345
Study Section
Special Emphasis Panel (ZAI1-PA-I)
Project Start
Project End
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
3
Fiscal Year
2013
Total Cost
$218,666
Indirect Cost
$64,328
Name
Vanderbilt University Medical Center
Department
Type
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
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Kwon, Young-Man; Hwang, Hye Suk; Lee, Jong Seok et al. (2014) Maternal antibodies by passive immunization with formalin inactivated respiratory syncytial virus confer protection without vaccine-enhanced disease. Antiviral Res 104:1-6
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Zhou, Weisong; Goleniewska, Kasia; Zhang, Jian et al. (2014) Cyclooxygenase inhibition abrogates aeroallergen-induced immune tolerance by suppressing prostaglandin I2 receptor signaling. J Allergy Clin Immunol 134:698-705.e5
Yan, Dan; Lee, Sujin; Thakkar, Vidhi D et al. (2014) Cross-resistance mechanism of respiratory syncytial virus against structurally diverse entry inhibitors. Proc Natl Acad Sci U S A 111:E3441-9

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