Influence of microbiome disruption on expressed immune phenotype in health and in asthma Other
Conditions
Interventions
Two cohorts: healthy volunteers (n = 34), asthmatics (n = 34). Total participants n = 68.
Within each cohort, participants are randomised using double-blinded sequential block randomisation to ensure
Sponsors
University of Manchester
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1. Males and Females 2. Mild asthma patients aged between 18 and 80 years, inclusive 3. Healthy volunteers aged between 18 and 80 years, inclusive 4. Non-smokers or Ex-smokers with fewer than 10 pack years and >6 months abstinence 5. Healthy volunteers: no clinically relevant abnormalities based on history, examination, vital signs, and no history of respiratory disease 6. Asthma cohort participants only: confirmed airway responsiveness via methacholine challenge at screening visit 7. Asthma cohort participants only: good or partial symptom control according to GINA classification and corticosteroid naïve 8. Capacity to consent
Exclusion criteria
Exclusion criteria: 1. Have received any systemic antibiotic medication: 1.1. To treat an infection arising during the participant’s potential study participation 1.2. Within the year prior to potential inclusion 2. Have received any topical or systemic treatment for oral thrush in the year prior to inclusion. 3. Have received any leukotriene antagonist medication within the year prior to the inclusion. 4. History of hypersensitivity or allergy to penicillins or other beta-lactam antibiotics. 5. Treatment for asthma beyond intermittent inhaled salbutamol use– i.e. regular inhaled corticosteroids or above or any use of systemic or inhaled corticosteroids - during or within one year prior to inclusion in the study 6. Baseline FEV1 <70% (asthma cohort) or <80% (healthy volunteers). 7. Current smokers or ex-smokers with over 10 pack years or under 6 months abstinence. 8. Current regular smokers (over once a month) of cannabis or other illicit drugs. 9. Conditions or medications that may affect the safety of bronchoscopy, sedation, amoxicillin administration, or have an independent effect on airway immune responses and reactivity: a. any pulmonary or chest wall disease other than asthma (including but not limited to chronic obstructive pulmonary disease, interstitial lung disease, significant chest wall deformities); b. other disease states that increase the risk of hypoxaemia, or the risk of serious sequalae of hypoxaemia; c. regular use of anti-histamine medications – unless participant able to discontinue during bronchoscopy phase of the study; d. regular anticoagulant therapy; e. upper or lower respiratory tract infection within 4 weeks prior to enrolment; f. history of adverse reactions to sedative or anaesthetic agents beyond expected side effects. 10. Conditions or medications that have an independent effect on the host gut or respiratory flora and microbiome (including but not limited to inflammatory bowel disease, irritable bowel syndrome, small intestinal bacterial overgrowth) 11. Pregnant 12. Other severe, acute or chronic, medical or psychiatric conditions that may increase the risk associated with trial participation or interfere with the interpretation of trial results. 13. Inability to collect and provide a stool sample. 14. Participation in other interventional research trials within the study period – except where appropriate cross-enrolment has been agreed by both Chief Investigators.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. In-depth immune cell characterisation to quantify the degree of expression of interleukins and immune cell surface markers associated with type 2 inflammation in paired broncho-alveolar fluid (BAL) and blood at baseline (day 0) and post-intervention (day 7) 2. Matched to fraction of exhaled nitric oxide (FeNO) measurements (in parts per billion [ppb]) at baseline (day 0) and post-intervention (day 7) 3. Blood immune cell characterisation to quantify the degree of expression of interleukins and immune cell surface markers associated with type 2 inflammation will be repeated at follow-up at approximately 6, 12, 26 and 52 weeks post-intervention 4. FeNO measurements (ppb) will be repeated at follow-up at approximately 6, 12, 26 and 52 weeks post-intervention | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Characterisation of the gut bacterial microbiome composition pre- and post-intervention (day 0 and day 7) by microbiome sequencing techniques performed on paired BAL and stool samples, including analysis of the change in microbiota attributable to antibiotic administration 2. Assessment of the recovery of the gut microbiome over the following year through serial microbiome sequencing on stool samples at approximately 6, 12, 26 and 52 weeks post-intervention 3. Quantification and characterisation of stool and blood bacterial metabolites by short chain fatty acid assay at baseline (day 0), post-intervention (day 7) and at approximately 6, 12, 26 and 52 weeks post-intervention | — |
Countries
England, United Kingdom
Contacts
Public ContactTim Felton
Outcome results
None listed