Forty healthy volunteers split in different age ranges (20-30 years n=10, 30-40 years n=10, 40-50 years n=10 and 50-60 years n=10) will undergo two airway assessments at rest and during exercise. The exercise assessments will be a continuous bronchoscopy during exercise (CBE-1st visit) and magnetic resonance imaging during exercise (MRIE-2nd visit) separated by at least three days to ensure for a sufficient cardiorespiratory and musculoskeletal recovery.

Airway Disease

The diagnostic tests will be consisted by two visits.
In the first visit participants will undergo a medical history assessment and they will complete questionnaires related to the lung function (MRC Dyspnoea score, Dyspnoea-12 questionnaire, and Visual Analogue Scale). A spirometry will be performed to assess the lung function. Bronchoscopy will be performed at rest in a semi-supine position (on a reclined bed) and then during exercise on a treadmill.
In the second visit, spirometry and questionnaires will be performed prior to resting and during exercise measurements on a magnetic resonance imaging (MRI) scan.
Rest: Structural imaging of the neck and chest will be performed followed by dynamic imaging of the airways during several inspiratory and expiratory manoeuvres. No IV contrast media will be used.
Exercise: After obtaining the baseline images, the participants will be asked to cycle using a programmable supine ergometer placed on the MRI.

CBE & MRIE

Characterisation of Large Airway Collapse During Exercise (LACE)

The Feasibility of Continuous Bronchoscopy During Exercise in Healthy Adults in Assessing Large Airways Collapse

Primary outcome will be the feasibility of continuous bronchoscopy during continuous exercise in healthy adults. Feasibility will be assessed via a post CBE tolerability questionnaire.
The post exercise tolerability questionnaire aims to evaluate the upper airways function during exercise and the discomfort that the participant might experience during the test. It consists of 5 questions (Part A) where the score ranges from 1 (strongly disagree) to 5 (strongly agree), and 2 questions (Part B) where the score ranges from 1 (None at all) to 10 (Unbearable amount).
The total score that will confirm the feasibility of CBE should be < 3 or < 5, for Part A and B, respectively.
The questions relate to the tolerability of the CBE test (e.g., Exercise with the camera in place cause discomfort, 1 (strongly agree) to 5 (strongly disagree).

To evaluate the degree of large airway collapse (LAC) apparent in normal subjects via continuous bronchoscopy during exercise (CBE) and to compare this with static forced expiratory manoeuvres in magnetic resonance imaging (MRI) and MRI during exercise (MRIE).
Flexible bronchoscopy and MRI at rest will be performed using dynamic inspiratory and expiratory manoeuvres.
CBE will be performed on a treadmill utilising a linear individualised ramp protocol. Heart rate and electrocardiogram will be monitored throughout the test.
MRIE will be performed on the MRI with and feet will be placed on a cycle ergometer fitted on the MRI (MR Pedal, Lode, Netherlands).
The degree of LAC will be estimated in percentage reduction of the airway lumen in several sites of the trachea and main bronchi. In bronchoscopy the reduction will be classified as 0 to 50% / 50 to 75% / 75 to 100% / 100% airway closure. In MRI LAC will be diagnosed as >50% airway closure.

To estimate the percentage of LAC from MRI in normal subjects during forced expiratory manoeuvres at rest and during exercise for both modalities.
More specifically, the reduction (%) of LAC will be estimated in bronchoscopy at rest and will be compared with CBE to evaluate whether physical exertion can induce the similar response to dynamic expiratory manoeuvres. Similarly, percentage of LAC will be estimated in MRI at rest and compared with MRIE.
Comparisons will be performed using statistical tests (e.g., Paired sample T-tests).

To compare findings between modalities (treadmill vs supine cycling).
The percentages of LAC between CBE and MRIE will be compared (via statistical tests such as t-tests and Pearson's correlation tests.

Imperial College London

Royal Brompton & Harefield NHS Foundation Trust

Eligible patients will have 6-Minute Walk Test (6-MWT) on self ventilation and on CPAP

Those patients who improve their 6-MWT by more than 30 meters will then be randomised to either:
Treatment arm - Patients will be setup onto portable CPAP during the day

Those patients who improve their 6-MWT by more than 30 meters will then be randomised to either:
Control Arm - Standard care arm.

Excessive Dynamic Airway Collapse

Tracheobronchomalacia

Participants will be established on portable CPAP during the day with nasal pillows as an interface and requested to use it at least 8 hours/day.

Experimental: Treatment

Participants will undergo a run-in phase during which they will undergo baseline assessments. If they tolerate the portable CPAP and if their 6-MWT improves by more than 30m when performed on CPAP, they will be randomised into the trial.

Experimental: Run In Phase

No change will be made to participants care

Sham Comparator: Stand Care Arm

Guys and St Thomas NHS Foundation

Symptomatic Treatment of Excessive Dynamic Airway Collapse Using Daytime Portable Continuous Positive Airway Pressure

Daytime activity assessed by an accelerometer. Participants will be assessed at baseline and at 4 weeks in the control arm and in the treatment arm with participants on portable CPAP to see if there is any change between the time frames and between the groups on daytime activity measured by accelerometers that all participants randomised into the trial will wear from baseline to follow up at 4 weeks.

Is there a change in exercise capacity measured by 6-MWT for all patients in the study from baseline to 4 weeks. All walk tests will be performed on portable Continuous Positive Airway Pressure (CPAP)

Is there a change in quality of life from baseline to 4 weeks measured by Severe Respiratory Insufficiency Questionnaire

Is there a change in quality of life from baseline to 4 weeks measured by St George's Respiratory Questionnaire.

Is there a change in neural respiratory drive measured by parasternal electromyography both at rest and whilst using portable CPAP at baseline and at 4 weeks

Is there a change in lung homogeneity in participants from baseline to 4 weeks. Measured by electrical impedence tomography whilst all participants are using portable CPAP

Is there a change in the area of the quadriceps rectus femoris in participants from baseline to 4 weeks. Measured using ultrasound which will be performed on all participants

tracheobronchomalacia/ضيق النفس

Characterisation of Large Airway Collapse During Exercise (LACE)

Symptomatic Treatment of Excessive Dynamic Airway Collapse Using Daytime Portable Continuous Positive Airway Pressure

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