Clinical trial NCT04716023: Physiology and Structure of the Small Airways in Patients With Chronic Airflow Obstruction or COVID-19
Official title: Physiology and Structure of the Small Airways in Patients With Chronic Airflow Obstruction or COVID-19
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Copd
COVID-19
Asthma
Small Airways Disease
Lead sponsor: Imperial College London
Sponsor class: OTHER
First posted: 2021-01-20
Enrollment: 42
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subjects over the age of 16 with either chronic airflow obstruction or COVID-19

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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)
timeFrame: Baseline, pre-procedure
Secondary outcomes:
measure: Respiratory reactance at 5Hz: X5 (kPa/l/s)
timeFrame: Baseline, pre-procedure
measure: Reactance area: Ax (kPa/l/s)
timeFrame: Baseline, pre-procedure
measure: Functional residual capacity by MBNW: FRCgas (L)
timeFrame: Baseline, pre-procedure
measure: Lung clearance index: LCI
timeFrame: Baseline, pre-procedure
measure: Ventilation heterogeneity conducting airways: Scond (L/s)
timeFrame: Baseline, pre-procedure
measure: Ventilation heterogeneity acinar airways: Sacin (L/s)
timeFrame: Baseline, pre-procedure
measure: Forced expiratory volume in 1 second: FEV1 (L)
timeFrame: Baseline, pre-procedure
measure: Forced vital capacity: FVC (L)
timeFrame: Baseline, pre-procedure
measure: Total lung capacity: TLC (L)
timeFrame: Baseline, pre-procedure
measure: Residual volume: RV (L)
timeFrame: Baseline, pre-procedure
measure: Functional residual capacity by plethysmography: FRCpleth (L)
timeFrame: Baseline, pre-procedure
measure: Airway mean luminal diameter (Dmean)
timeFrame: Baseline, during the procedure
measure: Airway inner lumen area (Ai)
timeFrame: Baseline, during the procedure
measure: Airway wall area (Aw), airway wall percentage (Aw%) as determined by [Aw/(Ai + Aw) × 100%]
timeFrame: Baseline, during the procedure
measure: Air trapping - expiratory phase low attenuation area <856 HU (%LAA <856 HU)
timeFrame: Baseline, pre-procedure
measure: Modified MRC dyspnoea score
timeFrame: Baseline, pre-procedure
measure: St George's Respiratory Questionnaire Score
timeFrame: Baseline, pre-procedure
measure: Asthma-related Quality of Life Questionnaire (AQLQ) (if asthmatic)
timeFrame: Baseline, pre-procedure
measure: Asthma Control Questionnaire (ACQ) (if asthmatic)
timeFrame: Baseline, pre-procedure
measure: 6-minute walk distance (m)
timeFrame: Baseline, pre-procedure
Other outcomes:
measure: Exploratory: Inflammatory and pathological studies of airways brush, wash and cryobiopsy samples
timeFrame: Baseline, during the procedure
Locations:
city: London
country: United Kingdom
facility: The Royal Brompton
Study officials:
References: