Respiratory Respiratory
Conditions
Interventions
1. Healthy young participants.
Adverts will be distributed in Newcastle University by email and poster, and through appropriate other channels, seeking healthy participants aged 18-30. Those respondin
Sponsors
Newcastle upon Tyne Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: Younger healthy participants: 1. Aged 18-30 years old 2. World Health Organization (WHO) Performance Status Score 0 3. Provision of informed, written consent from the participant 4. A negative highly sensitive urine pregnancy test for women of childbearing potential (WOCBP)* (*A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile**. The post-menopausal state is defined as “no menses for 12 months without an alternative medical cause.” When it cannot be confirmed that a participant is post-menopausal a pregnancy test will be conducted. **Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.) Older healthy participants: 1. Aged > = 60 years old 2. WHO Performance Status Score 0 3. Provision of informed, written consent from the participant 4. A negative highly sensitive urine pregnancy test for women of childbearing potential (WOCBP) Patients in the ICU: 1. Patients intubated and mechanically ventilated in ICU for > = 2 days 2. Provision of informed, written consent from a personal or legal representative 3. A negative highly sensitive urine pregnancy test for WOCBP Bronchoscopy only: 1. Aged 18 or over old 2. WHO Performance Status Score 0 3. Provision of informed, written consent from the participant 4. A negative highly sensitive urine pregnancy test for women of childbearing potential (WOCBP)
Exclusion criteria
Exclusion criteria: Younger healthy participants: 1. SARS-CoV-2 positive 2. Current smoker of cigarettes or e-cigarettes 3. Past smoking history of > = 2 pack-years 4. Any smoking in the last year 5. Pregnancy or lactation 6. Temperature > = 38ºc 7. Systolic blood pressure = 2 pack-years any smoking in the last year 4. Pregnancy or lactation 5. Temperature > = 38ºc 6. Systolic blood pressure 3) 9. Intracranial pressure greater than 20 mmhg 10. Estimated GFR = 2 pack-years 4. Any cigarette smoking in the last year 5. Pregnancy or lactation 6. Temperature > = 38ºc 7. Systolic blood pressure < 90 mmhg 8. Evidence of atrial or ventricular arrhythmia on ECG 9. Oxygen saturations < 94% breathing room air 10. FEV1 < 80% of predicted 11. FEV1:FVC ratio < 70% predicted 12
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The proportion of alveolar macrophages phagocytosing =2 zymosan particles measured using laboratory phagocytosis assays in each bronchoscopy sample obtained for the duration of the study | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Bronchoscopy Safety measured by recording oxygen saturations and continuous ECG monitoring following standard clinical SOPs during each bronchoscopy 2. Safety of nebulised interventions measured by the recording of oxygen saturations, post-inhalation spirometry and the recording of serious adverse reactions during each nebulisation 3. The function of alveolar macrophages measured using functional assays (including phagocytosis, efferocytosis and bacterial killing), cell signalling analyses, receptor expression and cell surface marker analyses, cytokine levels, transcriptomics and proteomics after each bronchoscopy 4. The function of neutrophils in blood measured using phagocytosis assays, bacterial killing, reactive oxygen species generation, and flow cytometry for cell surface markers after blood sampling in each participant 5. The function of monocytes in blood measured using flow cytometry to measure mHLA-DR after blood sampling in each participant Exploratory outcome measurements (applicable to parallel group element only): Safety will be measured using data collected through a review of patient records at day 30 following inclusion. This will include the following variables: 1. 30-day all-cause mortality 2. Length of ICU stay (data collected at day 30 and not beyond) 3. Frequency of serious adverse reactions overall and between groups (SAEs will be collected from the start of the first nebulisation until 24 hours after the BAL) 4. Duration of intubation and mechanical ventilation (data collected at day 30 and not beyond) 5. Blood tests at 24 hours post-intervention for toxicity assessment (blood white cell count, blood neutrophil count, serum liver transaminases and serum creatinine) 6. Respiratory infections (data collected at day 30 and not beyond; principally to assess the safety of BAL in parallel group element). | — |
Countries
England, United Kingdom
Contacts
Public ContactRichard;Other public and Davidson;general enquiries
;
Outcome results
None listed