Respiratory Syncytial Virus Infection
Conditions
Keywords
RSV, asthma, innate immunity, gene, cytokines
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.
Interventions
None listed
Sponsors
University of Wisconsin, Madison
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
No minimum to 24 Months
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Nasal Interferon (IFN)-a2 | 1-5 days during acute illness (not after day 5 of illness) | Interferon a2 was measured from nasal lavage samples by Luminex multiplex assay. |
| Percentage of Participants With Detected Nasal Interferon (IL)-2 Cytokine Expression | 1-5 days during acute illness (not after day 5 of illness) | IL-2 measured from nasal lavage samples by Luminex multiplex assay |
Countries
United States
Participant flow
Recruitment details
Study details planned during the first 4 months of the study. Recruitment period began during the RSV seasons from November to May each year from 2003-2008 in medical clinics.
Pre-assignment details
Patients were enrolled if they met the enrollment criteria
Participants by arm
| Arm | Count |
|---|---|
| Toll-like Receptor 4 GG Genotype Toll-like Receptor 4 (TLR4) -2026/GG gentoype hypothesized to be associated with less inflammation during Respiratory syncytial virus (RSV) infection | 17 |
| Toll-like Receptor 4 AG/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 | 74 |
| Total | 91 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 5 | 24 |
Baseline characteristics
| Characteristic | Toll-like Receptor 4 AG/AA Genotypes | Toll-like Receptor 4 GG Genotype | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 74 Participants | 17 Participants | 91 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 0.82 years STANDARD_DEVIATION 0.54 | 0.78 years STANDARD_DEVIATION 0.56 | 0.82 years STANDARD_DEVIATION 0.55 |
| Region of Enrollment United States | 74 participants | 17 participants | 91 participants |
| Sex: Female, Male Female | 32 Participants | 7 Participants | 39 Participants |
| Sex: Female, Male Male | 42 Participants | 10 Participants | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 17 | 0 / 74 |
| serious Total, serious adverse events | 0 / 17 | 0 / 74 |
Outcome results
Primary
Nasal Interferon (IFN)-a2
Interferon a2 was measured from nasal lavage samples by Luminex multiplex assay.
Time frame: 1-5 days during acute illness (not after day 5 of illness)
Population: Analysis was per protocol based on the number of children enrolled by genotype and completed nasal washes at first visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Toll-like Receptor 4 GG Genotype | Nasal Interferon (IFN)-a2 | 10 pg/ml | Standard Deviation 3 |
| Toll-like Receptor 4 AG/AA Genotypes | Nasal Interferon (IFN)-a2 | 26 pg/ml | Standard Deviation 31 |
p-value: 0.04Mixed Models Analysis
Primary
Percentage of Participants With Detected Nasal Interferon (IL)-2 Cytokine Expression
IL-2 measured from nasal lavage samples by Luminex multiplex assay
Time frame: 1-5 days during acute illness (not after day 5 of illness)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Toll-like Receptor 4 GG Genotype | Percentage of Participants With Detected Nasal Interferon (IL)-2 Cytokine Expression | 0 Percentage of Participants |
| Toll-like Receptor 4 AG/AA Genotypes | Percentage of Participants With Detected Nasal Interferon (IL)-2 Cytokine Expression | 44 Percentage of Participants |
p-value: 0.14Mixed Models Analysis