Exercise and Oscillatory Positive Expiratory Pressure Therapy in Cystic Fibrosis

Study Overview
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Brief Summary
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The investigators aim to compare a single bout of moderately intense cycling exercise incorporating Flutter® breathing maneuvers with a single bout of moderately intense cycling exercise alone on sputum viscoelasticity (primary endpoint) and the diffusion capacity of the lungs in adult patients with cystic fibrosis. The investigators further aim to analyze the short-term variability of resting diffusion capacity of carbon monoxide (DLCO) and nitric oxide (DLNO) in patients with cystic fibrosis.

Detailed Description
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Regular airway clearance is an integral component of cystic fibrosis care and of critical importance to lung health. Exercise and standardized chest physiotherapy are accepted airway clearance techniques in cystic fibrosis. Different airway clearance techniques are available, but there is no evidence that one technique or a combination is superior. Oscillatory positive expiratory pressure with the Flutter® is a widely used airway clearance technique in the European countries and has been shown to favourably alter sputum viscoelasticity in cystic fibrosis. This randomized crossover study is designed to assess the acute effects of combined cycling exercise and Flutter® therapy on sputum viscoelasticity (primary outcome measure) and gas diffusion in adults with cystic fibrosis.

Official Title
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Acute Effects of Combined Exercise and Oscillatory Positive Expiratory Pressure Therapy on Sputum Properties and Lung Diffusion Capacity in Cystic Fibrosis: a Randomized Crossover Trial

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Device: Flutter®
* Device: No Flutter®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of CF based on either two CF-causing mutations and/or a sweat chloride concentration during two tests of > 60 mmol/l Patients that are able to provide sputum samples Adult age ≥ 18 years Exclusion Criteria: Unstable condition affecting participation in the exercise experiments (i.e., major hemoptysis or pneumothorax within the last 3 months, acute exacerbation and iv-antibiotics during the last 4 weeks, unstable allergic bronchopulmonary aspergillosis, listed for lung transplantation, major musculoskeletal injuries such as fractures or sprains during the last 2 months, others according to the impression of the doctor) Cardiac arrhythmias with exercise Requiring additional oxygen with exercise Colonization with Burkholderia cenocepacia Status post lung transplantation

Ages Eligible for Study
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Minimum Age: 18 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cycling in combination with Flutter® therapy<br>Participants perform 30 minutes of moderately intense cycling exercise in 4-min intervals at 75% of their maximal heart rate and interspersed with 2-min resting periods during which 6-8 breathing maneuvers are performed with the Flutter®. | Device: Flutter®<br>* Acute exercise with Flutter® breathing therapy.<br>|
| Active Comparator: Cycling without Flutter® therapy<br>Participants perform 30 minutes of continuous moderately intense cycling exercise at 75% of their maximal heart rate without additional Flutter® breathing maneuvers. | Device: No Flutter®<br>* Acute exercise without Flutter® breathing therapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in sputum viscoelasticity (G*) over a broad frequency range (1-100 rad.s-1) | Sputum viscoelasticity measured by stress/strain controlled rheometer (Anton Paar, MCR 301/MCR 501). | Baseline - immediately post exercise - 45min post exercise | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in shear viscosity (η) | Shear viscosity measured by stress/strain controlled rheometer (Anton Paar, MCR 301/MCR 501). | Baseline - immediately post exercise - 45min post exercise | 
| Change in sputum spinnability (mm) | Measured with a Capillary Breakup Extensional Rheometer (CaBER). | Baseline - immediately post exercise - 45min post exercise | 
| Change in sputum solids content (%) | Sputum weight of a 50 μL aliquot before and after lyophilization to dryness using a freeze dryer. | Baseline - immediately post exercise - 45min post exercise | 
| Change in lung diffusion capacity for nitric oxide (DLNO) | Single-breath measurements with MasterScreenTM PFT system | Baseline - immediately post exercise - 45min post exercise | 
| Change in lung diffusion capacity for carbon monoxide (DLCO) | Single-breath measurements with MasterScreenTM PFT system | Baseline - immediately post exercise - 45min post exercise | 
| Change in DLNO/DLCO ratio | Single-breath measurements with MasterScreenTM PFT system | Baseline - immediately post exercise - 45min post exercise | 
| Change in alveolar volume | Single-breath measurements with MasterScreenTM PFT system | Baseline - immediately post exercise - 45min post exercise | 
| Change in pulmonary capillary blood volume | Single-breath measurements with MasterScreenTM PFT system | Baseline - immediately post exercise - 45min post exercise | 
| Change in pulmonary membrane diffusion capacity | Single-breath measurements with MasterScreenTM PFT system | Baseline - immediately post exercise - 45min post exercise | 
| Change in ease of sputum expectoration (cm) | Assessed by a visual analogue scale (0-10) | Baseline - immediately post exercise - 45min post exercise | 
| Change in oxygen saturation (%) | Measured by pulse oximetry. | Baseline - immediately post exercise - 45min post exercise | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Exercise, Lung diffusion capacity, Sputum viscoelasticity, Lung disease