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

• Conditions: COVID-19; Copd; Asthma; Small Airways Disease

• Registration Number: NCT04716023
• Lead Sponsor: Imperial College London

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-08-23
• Study First Submitted: 2020-07-02
• Status Verified: 2021-01
• Study First Submitted QC: 2021-01-18
• Last Update Submitted: 2021-01-18
• Study First Posted: 2021-01-20
• Last Update Posted: 2021-01-20
• Primary Completion: 2021-08-22
• Study Completion: 2022-02-02

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 42

Inclusion Criteria

1. Age 16 or over

2. Scheduled for bronchoscopy as part of clinical care or research protocol

3. No bleeding diathesis or therapeutic anticoagulation

4. 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

1. Unable to provide informed consent

2. 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

3. 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

4. Contra-indications to passing oesophageal balloons

   • Oesophageal ulceration or varices
   • Sinusitis, recent nasal surgery or epistaxis

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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)	Baseline, pre-procedure	Impulse Oscillometry

Secondary Outcome Measures

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

Trial Locations

Locations (1)

The Royal Brompton; 🇬🇧 London, United Kingdom