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

Innate Immunity and RSV Infection in Children

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.

Study Overview

• Status: Completed
• Conditions: Respiratory Syncytial Virus Infection

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 91

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53792-9988
      • University of Wisconsin-Madison

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 2 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Children who present with viral upper respiratory infections or bronchiolitis to their primary care physician. Upon consent, children willl have cheek samples for genotyping and nasal secretion samples to determine RSV infection.

Description

Inclusion Criteria:

1. Parental or sibling history of asthma.
2. Child must be less than 24 months of age.
3. Presence of viral upper or lower respiratory tract symptoms.

Exclusion Criteria:

1. History of recurrent wheezing requiring systemic corticosteroids.
2. Prior history of lung disease.
3. Birth < 36 weeks gestation.
4. Immunodeficiency
5. Treatment with ribavirin, systemic or inhaled corticosteroids during the RSV infection.
6. Congenital heart disease.
7. No history of parental or sibling asthma.
8. 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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Toll-like Receptor 4 -2026/GG Genotype; 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; 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?

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)

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Investigators: Principal Investigator: Theresa W. Guilbert, MD, University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start: November 1, 2003
• Primary Completion (Actual): May 1, 2008
• Study Completion (Actual): June 1, 2008

Study Registration Dates

• First Submitted: January 3, 2008
• First Submitted That Met QC Criteria: January 14, 2008
• First Posted (Estimate): January 15, 2008

Study Record Updates

• Last Update Posted (Estimate): October 20, 2015
• Last Update Submitted That Met QC Criteria: September 30, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: RSV, asthma, innate immunity, gene, cytokines
• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Disease Attributes; Paramyxoviridae Infections; Mononegavirales Infections; Pneumovirus Infections; Infections; Communicable Diseases; Respiratory Syncytial Virus Infections
• Other Study ID Numbers: 7K08HL071742-05 (U.S. NIH Grant/Contract)