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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
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| 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) |
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Inclusion Criteria:
Exclusion Criteria:
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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.
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| Name | Affiliation | Role |
|---|---|---|
| Theresa W. Guilbert, MD | University of Wisconsin, Madison | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Wisconsin-Madison | Madison | Wisconsin | 53792-9988 | United States |
Patients were enrolled if they met the enrollment criteria
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 | Toll-like Receptor 4 AG/AA Genotypes |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Nasal Interferon (IFN)-a2 | Interferon a2 was measured from nasal lavage samples by Luminex multiplex assay. | Analysis was per protocol based on the number of children enrolled by genotype and completed nasal washes at first visit. | Posted | Mean | Standard Deviation | pg/ml | 1-5 days during acute illness (not after day 5 of illness) |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 |
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Subject withdraw before blood draw on second visit and small numbers recruited lead to small numbers of subjects analyzed.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Theresa Guilbert, MD | University of Wisconsin-Madison | 608-263-9608 | tguilbert@wisc.edu |
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| ID | Term |
|---|---|
| D018357 | Respiratory Syncytial Virus Infections |
| D001249 | Asthma |
| ID | Term |
|---|---|
| D018186 | Pneumovirus Infections |
| D018184 | Paramyxoviridae Infections |
| D018701 | Mononegavirales Infections |
| D012327 | RNA Virus Infections |
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Nasal samples Supernatant from Peripheral mononuclear cell stimulation cultures DNA
Toll-like Receptor 4 (TLR4) -2026/AG and AA control genotypes hypothesized to be associated with more inflammation during Respiratory syncytial virus (RSV) infection
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Primary | Percentage of Participants With Detected Nasal Interferon (IL)-2 Cytokine Expression | IL-2 measured from nasal lavage samples by Luminex multiplex assay | Posted | Number | Percentage of Participants | 1-5 days during acute illness (not after day 5 of illness) |
|
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|
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| 0 |
| 17 |
| 0 |
| 17 |
| EG001 | 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 | 0 | 74 | 0 | 74 |
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| D014777 | Virus Diseases |
| D007239 | Infections |
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012130 | Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |