Clinical trial NCT00593918: Innate Immunity and Respiratory Syncytial Virus (RSV) Infection in Children
Official title: Innate Immunity and RSV Infection in Children
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Respiratory Syncytial Virus Infection
Keywords: RSV, asthma, innate immunity, gene, cytokines
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
First posted: 2008-01-15
Enrollment: 91
Sex: ALL
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Nasal Interferon (IFN)-a2
timeFrame: 1-5 days during acute illness (not after day 5 of illness)
measure: Percentage of Participants With Detected Nasal Interferon (IL)-2 Cytokine Expression
timeFrame: 1-5 days during acute illness (not after day 5 of illness)
Secondary outcomes:
Other outcomes:
Locations:
city: Madison
country: United States
facility: University of Wisconsin-Madison
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Theresa W. Guilbert, MD
role: PRINCIPAL_INVESTIGATOR
References: