BARRIER
Research type
Research Study
Full title
Human BronchiectAsis RhinoviRus challenge to define Immunopathogenesis of ExaceRbation
IRAS ID
332594
Contact name
Aran Singanayagam
Contact email
Sponsor organisation
Imperial College London
Duration of Study in the UK
3 years, 6 months, 1 days
Research summary
Bronchiectasis is a chronic lung condition characterised by progressive susceptibility to symptomatic flare-ups (exacerbations). These episodes are a major cause of morbidity and mortality with limited treatment options. Historically, bacteria have been deemed responsible for most exacerbations leading to widespread treatment with prolonged antibiotics, however, there is increasing antimicrobial resistance and we urgently need new approaches.
We have recently found that, contrary to previous belief, a significant proportion of exacerbations (~40%) are associated with detection of viruses (most commonly rhinovirus) which may be an unrecognised trigger for bronchiectasis exacerbations. It remains unclear however whether viruses can directly trigger exacerbations in bronchiectasis and the mechanisms that predispose individuals to viral infections are unknown.
This project asks the following questions:
1. Does deliberately infecting bronchiectasis subjects with rhinovirus lead to development of an exacerbation?
2. Does bronchiectasis reduce the immune system's ability to respond to and fight off viral infection?
3. What are the changes that occur in the lungs during a viral infection that lead to bronchiectasis exacerbation?In this study, we will administer rhinovirus into the nose of 36 subjects with bronchiectasis and 18 healthy control subjects to induce infection and record respiratory symptoms and lung function daily to determine whether rhinovirus infection causes greater symptoms in bronchiectasis compared to healthy individuals. We will take samples from the nose and also mucus coughed up by these individuals to analyse the antiviral immune response. We will additionally take cells from the lungs of these individuals using bronchoscopy (where a telescope is inserted into the airways). We will culture these cells in the laboratory and infect them with rhinovirus before again measuring how much interferon and other substances they produce. This will determine if bronchiectasis is associated with a reduced ability of the immune system to respond to a viral infection.
REC name
South West - Central Bristol Research Ethics Committee
REC reference
24/SW/0025
Date of REC Opinion
12 Mar 2024
REC opinion
Further Information Favourable Opinion