Physiology and Structure of the Small Airways in Patients With Chronic Airflow Obstruction or COVID-19

Study Overview
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Brief Summary
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The purpose of this research project is to study small airways physiological function in patients with chronic obstructive lung disease or COVID-19 and explore the relationship with in-vivo microanatomical small airway structure as measured by OCT. Correlating endobronchial assessment with multiple breath nitrogen washout and impulse oscillometry will allow the characterisation of the relationship between small airway structural findings and these validated investigations. A small volume lung wash, endobronchial brushings and the collection of a limited number of endobronchial cryobiopsy samples will be performed to better understand the endobronchial environment of the small airways through inflammatory studies. Following the completion of any such work, residual samples will be stored in a bio-bank to enable the completion of future work. Understanding the relationship with symptom-based quality of life scoring questionnaires and a functional assessment of exercise capacity will help elucidate the clinical impact of in-vivo small airways findings.

Official Title
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Physiology and Structure of the Small Airways in Patients With Chronic Airflow Obstruction or COVID-19

Conditions
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Copd, COVID-19, Asthma, Small Airways Disease

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 16 or over Scheduled for bronchoscopy as part of clinical care or research protocol No bleeding diathesis or therapeutic anticoagulation COPD: FEV1/FVC ratio <70% or Asthma: Diagnosed by standard clinical methods Post-bronchodilator FEV1 ≥60% predicted or COVID-19 infection or previous COVID-19 infection (confirmed as per local guidelines) Exclusion Criteria: Unable to provide informed consent Exacerbation of obstructive airways disease or respiratory infection requiring systemic antibiotics or corticosteroids in the 6 weeks prior to enrolment unless suffering from COVID-19 infection and bronchoscopy is required for clinical reasons Contra-indications to performing lung function testing Aortic aneurysm >6cm Unstable cardiovascular disease (unstable angina, myocardial infarction or pulmonary embolism <4 weeks prior) Severe aortic stenosis Pneumothorax Cerebral aneurysm Thoracic or abdominal surgery <4 weeks prior Contra-indications to passing oesophageal balloons Oesophageal ulceration or varices Sinusitis, recent nasal surgery or epistaxis

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Chronic Airflow obstruction / COVID-19<br>Patients with either chronic airflow obstruction of COVID-19 | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Respiratory resistance at 5Hz - 20Hz (R5-R20) (kPa/l/s) related to airtrapping as determined by quantitative CT (Expiratory phase low attenuation area <856 HU (%LAA <856 HU) | Impulse Oscillometry | Baseline, pre-procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Respiratory reactance at 5Hz: X5 (kPa/l/s) | Impulse Oscillometry | Baseline, pre-procedure | 
| Reactance area: Ax (kPa/l/s) | Impulse Oscillometry | Baseline, pre-procedure | 
| Functional residual capacity by MBNW: FRCgas (L) | Multiple Breath Nitrogen Washout | Baseline, pre-procedure | 
| Lung clearance index: LCI | Multiple Breath Nitrogen Washout | Baseline, pre-procedure | 
| Ventilation heterogeneity conducting airways: Scond (L/s) | Multiple Breath Nitrogen Washout | Baseline, pre-procedure | 
| Ventilation heterogeneity acinar airways: Sacin (L/s) | Multiple Breath Nitrogen Washout | Baseline, pre-procedure | 
| Forced expiratory volume in 1 second: FEV1 (L) | Spirometry | Baseline, pre-procedure | 
| Forced vital capacity: FVC (L) | Spirometry | Baseline, pre-procedure | 
| Total lung capacity: TLC (L) | Plethysmography | Baseline, pre-procedure | 
| Residual volume: RV (L) | Plethysmography | Baseline, pre-procedure | 
| Functional residual capacity by plethysmography: FRCpleth (L) | plethysmography | Baseline, pre-procedure | 
| Airway mean luminal diameter (Dmean) | Optical Coherence Tomography | Baseline, during the procedure | 
| Airway inner lumen area (Ai) | Optical Coherence Tomography | Baseline, during the procedure | 
| Airway wall area (Aw), airway wall percentage (Aw%) as determined by [Aw/(Ai + Aw) × 100%] | Optical Coherence Tomography | Baseline, during the procedure | 
| Air trapping - expiratory phase low attenuation area <856 HU (%LAA <856 HU) | Quantitative CT | Baseline, pre-procedure | 
| Modified MRC dyspnoea score | Patient reported outcome measure | Baseline, pre-procedure | 
| St George's Respiratory Questionnaire Score | Patient reported outcome measure | Baseline, pre-procedure | 
| Asthma-related Quality of Life Questionnaire (AQLQ) (if asthmatic) | Patient reported outcome measure | Baseline, pre-procedure | 
| Asthma Control Questionnaire (ACQ) (if asthmatic) | Patient reported outcome measure | Baseline, pre-procedure | 
| 6-minute walk distance (m) | 6-minute walk distance (m) | Baseline, pre-procedure |