Cystic Fibrosis
Conditions
Keywords
high frequency chest wall oscillation, cystic fibrosis
Brief summary
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
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.
Interventions
DEVICEHFCWC with higher pressure/variable-frequency settings
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.
DEVICEHFCWC with lower pressure/mid-frequency settings
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.
Sponsors
Hill-Rom
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of CF established by sweat chloride \> 60 mmol/L. 2. Age older than 18 years. 3. History of chronic daily sputum production. 4. 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. 5. 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). 6. Evaluated at the University of Minnesota CF Center 3 or more times in the preceding 12 months.
Exclusion criteria
1. Hospitalization for CF pulmonary complications in the 2 months preceding enrollment. 2. Hemoptysis \> 60 cc in a single episode in the 4 weeks preceding enrollment. 3. Chest pain requiring use of narcotic for pain control. 4. Current participation in another clinical trial. 5. Use of intravenous antibiotics for CF respiratory complications in the 2 months preceding enrollment. 6. No prior experience using HFCWO devices for airway clearance
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sputum Wet and Dry Weight | Produced during each airway clearance therapy session on days 1 and 4 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pre vs. Post Therapy Spirometry | Prior to and following each airway clearance therapy session on days 1 and 4 | 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. |
| Rheology and in Vitro Cough Transportability of Sputum Produced Immediately Following Airway Clearance Therapy Session | Sputum produced during the 15 minutes immediately following airway clearance therapy sessions on day 1 and day 4 | 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. |
| Patients' Perceived Comfort Using the Different Settings for the Vest Device | Immediately following each airway clearance therapy on day 1 and day 4 | 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). |
Countries
United States
Participant flow
Recruitment details
Potentially eligible patients were identified by query of the Minnesota CF database based on age and FEV1. This list was then reviewed and patients who met additional eligibility requirements were contacted by phone or recruited during a clinic visit by one of the study investigators. Enrollment was completed between 6/1/08 and 10/31/08.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Half patients randomly assigned to 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
VEST Airway Clearance System, Model 205 : 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 | 17 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1: First Intervention: 30 Minutes | Pulmonary lab plethysmography malfunctio | 1 | 0 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants |
| Age, Continuous | 33.3 years STANDARD_DEVIATION 7.3 |
| Region of Enrollment United States | 17 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 17 | 0 / 16 |
| serious Total, serious adverse events | 0 / 17 | 0 / 16 |
Outcome results
Primary
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.
Time frame: Produced during each airway clearance therapy session on days 1 and 4
Population: In a previous study with similar design,21 the standard deviation for the difference in the mean sputum wet weight between treatment arms was 4.6 g. Assuming the same standard deviation for the current study, enrollment of 16 subjects provided an 80% chance of detecting a 3.5-g difference in the sputum wet weights at a significance level of .05.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sputum Wet Weight Higher Pressure/Variable Frequency | Sputum Wet and Dry Weight | 6.4 grams |
| Sputum Wet Weight Lower Pressure/Mid-frequency | Sputum Wet and Dry Weight | 4.8 grams |
| Sputum Dry Weight Higher Pressure/Variable Frequency | Sputum Wet and Dry Weight | 0.20 grams |
| Sputum Dry Weight Lower Pressure/Mid-frequency | Sputum Wet and Dry Weight | 0.12 grams |
p-value: 0.02ANCOVA
Secondary
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).
Time frame: Immediately following each airway clearance therapy on day 1 and day 4
Population: power calculation not performed for secondary outcomes
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sputum Wet Weight Higher Pressure/Variable Frequency | Patients' Perceived Comfort Using the Different Settings for the Vest Device | 4.5 units on a scale |
| Sputum Wet Weight Lower Pressure/Mid-frequency | Patients' Perceived Comfort Using the Different Settings for the Vest Device | 5 units on a scale |
| Sputum Dry Weight Higher Pressure/Variable Frequency | Patients' Perceived Comfort Using the Different Settings for the Vest Device | 4 units on a scale |
| Sputum Dry Weight Lower Pressure/Mid-frequency | Patients' Perceived Comfort Using the Different Settings for the Vest Device | 4 units on a scale |
Secondary
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.
Time frame: Prior to and following each airway clearance therapy session on days 1 and 4
Population: Power calculation not performed for secondary outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sputum Wet Weight Higher Pressure/Variable Frequency | Pre vs. Post Therapy Spirometry | 70 ml | Standard Deviation 90 |
| Sputum Wet Weight Lower Pressure/Mid-frequency | Pre vs. Post Therapy Spirometry | 90 ml | Standard Deviation 120 |
| Sputum Dry Weight Higher Pressure/Variable Frequency | Pre vs. Post Therapy Spirometry | 80 ml | Standard Deviation 160 |
| Sputum Dry Weight Lower Pressure/Mid-frequency | Pre vs. Post Therapy Spirometry | 80 ml | Standard Deviation 230 |
Secondary
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.
Time frame: Sputum produced during the 15 minutes immediately following airway clearance therapy sessions on day 1 and day 4
Population: power calculation not performed for secondary outcomes
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sputum Wet Weight Higher Pressure/Variable Frequency | Rheology and in Vitro Cough Transportability of Sputum Produced Immediately Following Airway Clearance Therapy Session | 4.43 dynes/cm^2 |
| Sputum Wet Weight Lower Pressure/Mid-frequency | Rheology and in Vitro Cough Transportability of Sputum Produced Immediately Following Airway Clearance Therapy Session | 4.61 dynes/cm^2 |
| Sputum Dry Weight Higher Pressure/Variable Frequency | Rheology and in Vitro Cough Transportability of Sputum Produced Immediately Following Airway Clearance Therapy Session | 107.3 dynes/cm^2 |
| Sputum Dry Weight Lower Pressure/Mid-frequency | Rheology and in Vitro Cough Transportability of Sputum Produced Immediately Following Airway Clearance Therapy Session | 130.7 dynes/cm^2 |
| G Loss Modulus 1 Rad/Sec Higher Pressure/Variable Frequency | Rheology and in Vitro Cough Transportability of Sputum Produced Immediately Following Airway Clearance Therapy Session | 10.7 dynes/cm^2 |
| G Loss Modulus 1 Rad/Sec Lower Pressure/Mid-frequency | Rheology and in Vitro Cough Transportability of Sputum Produced Immediately Following Airway Clearance Therapy Session | 7.4 dynes/cm^2 |
| G Loss Modulus 100 Rad/Sec Higher Pressure/Variable Frequency | Rheology and in Vitro Cough Transportability of Sputum Produced Immediately Following Airway Clearance Therapy Session | 1,224 dynes/cm^2 |
| G Loss Modulus 100 Rad/Sec Lower Pressure/Mid-frequency | Rheology and in Vitro Cough Transportability of Sputum Produced Immediately Following Airway Clearance Therapy Session | 862 dynes/cm^2 |