Exercise and Oscillatory Positive Expiratory Pressure Therapy in Cystic Fibrosis

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

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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Device: Flutter®; Device: No Flutter®

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Zurich, Switzerland, 8091
    • University Hospital Zurich
  • Zurich, Switzerland, 8092
    • ETH Zurich
  • Zurich, Switzerland, 8001
    • University of Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cycling in combination with Flutter® therapy; 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®; Acute exercise with Flutter® breathing therapy.
Active Comparator: Cycling without Flutter® therapy; 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®; Acute exercise without Flutter® breathing therapy.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Zurich
• Investigators: Principal Investigator: Thomas Radtke, PhD, University of Zurich

Publications and helpful links

General Publications

• Radtke T, Boni L, Bohnacker P, Maggi-Beba M, Fischer P, Kriemler S, Benden C, Dressel H. Acute effects of combined exercise and oscillatory positive expiratory pressure therapy on sputum properties and lung diffusing capacity in cystic fibrosis: a randomized, controlled, crossover trial. BMC Pulm Med. 2018 Jun 14;18(1):99. doi: 10.1186/s12890-018-0661-1.

Study record dates

Study Major Dates

• Study Start: May 1, 2016
• Primary Completion (Actual): January 19, 2017
• Study Completion (Actual): January 19, 2017

Study Registration Dates

• First Submitted: April 12, 2016
• First Submitted That Met QC Criteria: April 20, 2016
• First Posted (Estimate): April 25, 2016

Study Record Updates

• Last Update Posted (Estimate): January 25, 2017
• Last Update Submitted That Met QC Criteria: January 24, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Exercise; Lung disease; Lung diffusion capacity; Sputum viscoelasticity
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: 2015-00153

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED