Comparison of Airway Clearance Therapy in Cystic Fibrosis Using the Same VEST Therapy Device But With Different Settings

Study Overview
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Brief Summary
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Our primary hypothesis is that airway clearance therapy with sine waveform HFCWO using higher inflation pressures combined with both low and high oscillator frequencies will result in greater sputum production compared to sine waveform HFCWO with lower inflation pressures and mid-frequency oscillations.

Detailed Description
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Patients with cystic fibrosis (CF) perform daily airway clearance therapy to facilitate removal of secretions from their airways. Many different techniques are available to achieve this and there is currently no consensus as to which form of therapy is most effective. High frequency chest wall oscillation (HFCWO) is used by CF patients throughout the United States and abroad. To perform this therapy, the patient wears a vest which fits over the entire torso and is connected to an air compressor. The compressor generates oscillating air pulses that are transmitted to the lungs, thereby mobilizing secretions. The most commonly used device is The Vest™ Airway Clearance System, (Hill-Rom Inc, St Paul, MN). Adjustment of the inflation pressure and frequency of oscillations affects the volume of displaced air and flow of air measured at the mouth of the patient. Previous studies indicate this form of therapy is as effective as more traditional and cumbersome forms of therapy. However, it is unclear which inflation pressures and oscillator frequencies provide optimal airway clearance. Some studies of sine waveform HFCWO reported the largest volume of air displacement and highest air flow measured at the mouth when using a combination of high inflation pressures with either low (7 - 10 Hz) or high frequencies (18 - 20 Hz), but most CF centers in the United States use HFCWO with lower pressures combined with mid-range frequencies (10 - 14 Hz). Furthermore, there are no previous studies assessing the affect of sine waveform HFCWO settings on sputum production. As a result, there is no consensus on which pressure and frequency settings are most efficacious for CF patients.

Official Title
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Comparison of Sine Waveform High Frequency Chest Wall Oscillation Using Different Settings in Cystic Fibrosis

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Device: HFCWC with higher pressure/variable-frequency settings
* Device: HFCWC with lower pressure/mid-frequency settings


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of CF established by sweat chloride > 60 mmol/L. Age older than 18 years. History of chronic daily sputum production. Currently on a home therapeutic regimen that includes some form of airway clearance performed with a HFCWO device at least once daily that also includes concomitant use of an inhaled mucolytic and inhaled bronchodilator. FVC and FEV1 > 40%-predicted, and with stable lung function (no greater than a 10% variation in lung function parameters over the preceding 3 months). Evaluated at the University of Minnesota CF Center 3 or more times in the preceding 12 months. Exclusion criteria: Hospitalization for CF pulmonary complications in the 2 months preceding enrollment. Hemoptysis > 60 cc in a single episode in the 4 weeks preceding enrollment. Chest pain requiring use of narcotic for pain control. Current participation in another clinical trial. Use of intravenous antibiotics for CF respiratory complications in the 2 months preceding enrollment. No prior experience using HFCWO devices for airway clearance

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: HFCWC with higher pressure/variable frequency settings<br>Half patients randomly assigned to perform HFCWC therapy first with a higher pressure/variable frequency protocol. This entailed performing a 30 minute session with pressure of 10 and 5 minutes each at frequencies of 8,9, and 10 Hz followed by pressure of 6 and 5 minutes each at frequencies of 18, 19, and 20 Hz. This group subsequently crossed-over to the lower-pressure/mid-frequency HFCWC protocol after a washout period of 2 days. This entailed performing a HFCWC session using a pressure of 5 and frequency of 12 Hz for the entire 30 minute session. The other half of subjects were randomly assigned to perform the lower-pressure/mid-frequency protocol first followed by the higher pressure/mixed-frequency after the 2 day washout period | Device: HFCWC with higher pressure/variable-frequency settings<br>* Randomized crossover trial of airway clearance therapy comparing sine wave HFCWO with high pressures and variable frequency (pressure 10, frequencies 8,9,10 and pressure 6, frequencies 18,19,20) to low pressure and mid frequency (pressure 5, frequency 12). Subjects will have 2-day washout between airway clearance sessions. All sputum collected during sessions.<br>* Other names: High frequency chest wall oscillation;Device: HFCWC with lower pressure/mid-frequency settings<br>* Subjects will perform pulmonary function tests prior to and following each airway clearance therapy. All sputum produced during, and for 15 minutes following airway clearance therapy will be collected. Subjects will complete a questionnaire addressing the comfort of therapy upon completion of the session.<br>* Other names: high frequency chest wall oscillation;|
| Active Comparator: HFCWC with lower pressure/mid-frequency settings<br>lower-pressure/mid-frequency protocol first followed by the higher pressure/mixed-frequency | Device: HFCWC with higher pressure/variable-frequency settings<br>* Randomized crossover trial of airway clearance therapy comparing sine wave HFCWO with high pressures and variable frequency (pressure 10, frequencies 8,9,10 and pressure 6, frequencies 18,19,20) to low pressure and mid frequency (pressure 5, frequency 12). Subjects will have 2-day washout between airway clearance sessions. All sputum collected during sessions.<br>* Other names: High frequency chest wall oscillation;Device: HFCWC with lower pressure/mid-frequency settings<br>* Subjects will perform pulmonary function tests prior to and following each airway clearance therapy. All sputum produced during, and for 15 minutes following airway clearance therapy will be collected. Subjects will complete a questionnaire addressing the comfort of therapy upon completion of the session.<br>* Other names: high frequency chest wall oscillation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sputum Wet and Dry Weight | All sputum expectorated during all HFCWC sessions was collected in a pre-weighed specimen container and immediately sealed. Half the subjects used higher pressure/mixed frequency on day 1 followed by lower pressure/mid-frequency on day 4. Half the patients performed lower pressure/mid-frequency on day 1 followed by higher pressure/mixed frequency on day 4. All specimens were immediately centrifuged at 21,150 g for 15 min at 4°C, and the supernatant was completely removed to eliminate saliva. The sputum wet weight was calculated after re-weighing the container with the sputum pellet. The container was then left open in an oven with the temperature set at 65°C for a minimum of 3 days to allow for complete desiccation. The sputum dry weight was calculated after re-weighing the container. | Produced during each airway clearance therapy session on days 1 and 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pre vs. Post Therapy Spirometry | Spirometry was performed prior to, and immediately following, all HCWC sessions on Day 1. Spirometry was performed immediately prior to, and immediately following, all HFCWC sessions on Day 4. Spirometry was performed according to American Thoracic Society/European Respiratory Society standards. | Prior to and following each airway clearance therapy session on days 1 and 4 | 
| Rheology and in Vitro Cough Transportability of Sputum Produced Immediately Following Airway Clearance Therapy Session | Sputum was collected during the 15 minutes immediately following HFCWC sessions on day 1 and day 4. Half the subjects performed higher-pressure/mixed frequency HFCWC on Day 1 followed by lower pressure/mid-frequency HFCWC on Day 4. The other half of subjects performed lower pressure/mid-frequency on Day 1 followed by higer pressure/mixed-frequency on Day 4. Samples were studied with a rheometer (AR1000, TA Instruments, New Castle, Delaware) to assess the dynamic frequency range of stress-strain of a 20 microliter sputum sample over driving frequencies of 1-100 rad/s. Shear storage modulus (G') and shear loss modulus (G) were determined from these curves after nondestructive creep transformation. G' (or dynamic elasticity) measures stored energy and is a property of ideal solids. G is directly proportional to viscosity (viscosity x frequency) and is a property of ideal liquids. | Sputum produced during the 15 minutes immediately following airway clearance therapy sessions on day 1 and day 4 | 
| Patients' Perceived Comfort Using the Different Settings for the Vest Device | Following each HFCWC session on day 1 and day 4, subjects completed a questionnaire that rated the comfort and efficacy of each HFCWC session using a 5-point scale. The questionnaire was entitled Post-Therapy Questionnaire. Scale range for comfort ranged from 1 (very uncomfortable) to 3 (neutral) to 5 (very comfortable). Scale range for how effective the HFCWC session was ranged from 1 (minimally effective) to 3 (neutral) to 5 (very effective). | Immediately following each airway clearance therapy on day 1 and day 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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high frequency chest wall oscillation, cystic fibrosis