A Rhinovirus Challenge Study to Investigate Exacerbations and Immune Responses in Bronchiectasis (BARRIER)

Description

Study Rationale:

Bronchiectasis is a chronic respiratory disease affective >200,000 individuals in the UK. We are aiming to develop an experimental rhinovirus challenge model for bronchiectasis. This model could provide crucial insights into how viral infections trigger exacerbations (flare-ups) in bronchiectasis patients. Recent studies have found that viruses, especially rhinoviruses, are present in a significant number of bronchiectasis exacerbations. However, their exact role and the mechanisms behind increased viral susceptibility in these patients remain unclear. This model will allow us to study how factors like altered lung microbiota, might influence viral susceptibility. By enabling controlled sampling of both upper and lower airways at specific times during an infection, this study offers a opportunity to understand the complex immunological responses involved. Currently we have a poor understanding of exacerbation mechanisms in bronchiectasis and future development of treatment strategies require a suitable translational system for testing. This research could shed light on why bronchiectasis patients are more vulnerable to viral infections and potentially pave the way for new strategies to predict, prevent, or manage exacerbations.

End of Study:

• Follow-up period of 42 days.

Study Centres:

• There will be 1 study centre, ICRRU within Imperial College Healthcare NHS site at St Mary's Hospital London, United Kingdom.

Study Intervention:

• All participants will be inoculated intra-nasally with rhinovirus A-16.

Study Procedures:

• Screening period (lung function tests (FEV1, FVC and PEF), height and weight/BMI, Medical and surgical history, drug history, pregnancy test for females, Lung function tests (FEV1, FVC, PEF), blood sample, nasosorption and nasal brushing.
• Baseline visit to clinic (Blood tests including for haematology, biochemistry and coagulation), vital signs, physical examination, nasosorption, nasal brushings, spontaneous sputum collection, chest x-ray, lung function tests (FEV1, FVC, PEF and FeNO) and a stool sample.
• Baseline bronchoscopy: (Blood tests, nasosorption, nasal brushings and bronchoscopy including bronchoabsorption, bronchioalveolar lavage, bronchial brushings and bronchial biopsies)
• Viral inoculation: (Vital signs, physical examination, nasal lavage, spontaneous sputum collection and intranasal RV-A16 challenge)
• Visit Day 1: (Vital signs, physical examination, review of symptom scores, nasosorption, nasal lavage, nasal brushing, spontaneous sputum collection and lung function tests (FEV1, FVC and PEF))
• Visit Day 2: (Vital signs, physical examination, review of symptom scores, bloods, nasal lavage, spontaneous sputum collection and lung function tests (FEV1, FVC and PEF))
• Visit Day 4: (Vital signs, physical examination, review of symptom scores, nasal lavage, spontaneous sputum collection and lung function tests (FEV1, FVC and PEF))
• Visit Day 7 and Bronchoscopy: (Vital signs, physical examination, review of symptom scores, blood tests, nasosorption, nasal lavage, nasal brushings, lung function tests (FEV1, FVC, PEF and FeNO), stool sample and bronchoscopy including bronchoabsorption, bronchioalveolar lavage, bronchial brushings and bronchial biopsies)
• Visit Day 10: (Vital signs, physical examination, review of symptom scores, nasal lavage, spontaneous sputum collection and lung function tests (FEV1, FVC and PEF))
• Visit Day 14: (Vital signs, physical examination, review of symptom scores, bloods, nasosorption, nasal lavage, spontaneous sputum collection and lung function tests (FEV1, FVC and PEF))
• Visit Day 21: (Vital signs, physical examination, review of symptom scores, nasal lavage, spontaneous sputum collection and lung function tests (FEV1, FVC and PEF))
• Visit Day 28: (Vital signs, physical examination, review of symptom scores, nasal lavage, spontaneous sputum collection and lung function tests (FEV1, FVC and PEF))
• Visit Day 42: (Vital signs, physical examination, review of symptom scores, bloods, nasosorption, nasal lavage, nasal brush, spontaneous sputum collection and lung function tests (FEV1, FVC and PEF) and stool sample)

Study Sample Size:

• 18 participants will be recruited with bronchiectasis, 18 patients with bronchiectasis and chronic pseudomonas colonisation and 18 healthy participants will be recruited.

Statistical Methods:

• Using an independent two-sided t-test a sample size of 15 participants per group will allow the detection of a significant difference in lower respiratory tract symptom scores and secondary endpoints.

Details