Innate Immunity and Respiratory Syncytial Virus (RSV) Infection in Children

Study Overview
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Brief Summary
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In this project we will study the capacity for single nucleotide polymorphisms (SNP) in TLR4 gene to induce varying levels of inflammatory chemokine and cytokine production.

Detailed Description
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Infection with RSV is the most common cause of respiratory tract illnesses (LRIs) in the first 3 years of life. There are significant social and health care costs associated with RSV-LRIs. More than 3% of US children are hospitalized each year due to RSV and 500 die annually. Several longitudinal studies have also suggested that children who have RSV-LRIs are at substantially increased risk of developing asthma in the first 3 years after infection and bronchial hyperresponsiveness (BHR) many years after the primary infection. Mechanisms involved in RSV disease are not well understood. Recent reports suggest that RSV may initiate the innate immune response through the pattern recognition receptor, Toll like receptor-4 (TLR4). In this project we will study the capacity for single nucleotide polymorphisms (SNP) in TLR4 gene to induce varying levels of inflammatory chemokine and cytokine production. It has been suggested that such a mechanism may result in altered immune responses to RSV infection and different clinical outcomes. This research has direct application to improving our understanding of bronchiolitis in early childhood, particularly those factors that influence severity of the disease, and may have implications for possible therapy of patients with bronchiolitis in the future.

Official Title
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Innate Immunity and RSV Infection in Children

Conditions
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Respiratory Syncytial Virus Infection

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Parental or sibling history of asthma. Child must be less than 24 months of age. Presence of viral upper or lower respiratory tract symptoms. Exclusion Criteria: History of recurrent wheezing requiring systemic corticosteroids. Prior history of lung disease. Birth < 36 weeks gestation. Immunodeficiency Treatment with ribavirin, systemic or inhaled corticosteroids during the RSV infection. Congenital heart disease. No history of parental or sibling asthma. Less than 48 hour or more than 5 day duration of viral URI symptoms since the peak symptoms from RSV would be expected to occur from 2-5 days into course of infection.

Ages Eligible for Study
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Maximum Age: 24 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Toll-like Receptor 4 -2026/GG Genotype<br>Toll-like Receptor 4 (TLR4) -2026/GG Genotype of interest hypothesized to be associated with less inflammation during Respiratory Syncytial virus (RSV) infection | |
| Toll-like Receptor 4 -2026/AG and AA Genotypes<br>Toll-like Receptor 4 (TLR4) -2026/AG and AA control genotypes hypothesized to be associated with more inflammation during respiratory syncytial virus (RSV) infection | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nasal Interferon (IFN)-a2 | Interferon a2 was measured from nasal lavage samples by Luminex multiplex assay. | 1-5 days during acute illness (not after day 5 of illness) | 
| Percentage of Participants With Detected Nasal Interferon (IL)-2 Cytokine Expression | IL-2 measured from nasal lavage samples by Luminex multiplex assay | 1-5 days during acute illness (not after day 5 of illness) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RSV, asthma, innate immunity, gene, cytokines