Studying Innate Immune Responses in Infants With Bronchiolitis

Terminated

• Conditions: Bronchiolitis

• Registration Number: NCT01159795
• Lead Sponsor: Imperial College London

Brief Summary

This study aims to establish whether impaired innate immune responses are associated with severity of Respiratory syncytial virus (RSV) infection.

Detailed Description

Respiratory syncytial virus (RSV) causes a spectrum of illness in healthy infants, ranging from asymptomatic infection to life threatening bronchiolitis with respiratory failure. The reasons for the differences in clinical presentation remain unknown. Interferons are natural antiviral factors and components of the innate immune response, which play a role in limiting viral replication.

We postulate that differences in clinical severity of RSV infection may be due to innate immune differences in the production of type I and III interferons (innate interferons). To test this hypothesis, we will recruit infants with mild, moderate and severe RSV bronchiolitis and compare production of innate interferons in blood and respiratory samples, using quantitative and functional analysis. We will determine whether interferon responses differ across a spectrum of clinical severity, and will relate them to viral load.

To establish whether defects in interferon production persist in those infants with severe infection, we will retest them following recovery and measure interferon responses after challenge with live RSV. Demonstrating a persisting defect may suggest a genetically determined defect requiring further investigation. Identification of the mechanisms of severe disease in patients without known risk-factors could lead to targeted therapy to prevent or treat severe disease.

Study Timeline

• Study First Submitted: 2010-07-06
• Study First Submitted QC: 2010-07-08
• Study First Posted: 2010-07-09
• Study Start: 2010-10
• Status Verified: 2012-04
• Primary Completion: 2013-03
• Study Completion: 2013-03
• Last Update Submitted: 2016-11-10
• Last Update Posted: 2016-11-11

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 250

Inclusion Criteria

• Bronchiolitis
• Infant

Exclusion Criteria

• Age over 1 year
• Underlying chronic lung disease, prematurity, congenital heart disease

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Nasal and blood interferon alpha, beta, lambda levels(protein level and gene expression)	At presentation (average = day 4 of symptoms)	Interferon alpha, beta and lambda protein levels will be measured by ELISA and gene expression by quantitative real-time PCR, on paired nasal and blood samples.

Secondary Outcome Measures

Name	Time	Method
RSV viral load	At presentation (average = day 4 of symptoms)	RSV viral load will be measured by quantitataive real-time PCR on nasal epithelium samples.

Trial Locations

Locations (1)

St Mary's Hospital; 🇬🇧 London, United Kingdom