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The purpose of this study was to compare the effect of exercise treatment combined with breathing retraining (a computerized feedback program), with exercise treatment combined with heliox (a helium and oxygen combination), with exercise only in patients with moderate to severe chronic obstructive pulmonary disease. This was an 8-week intervention study.
Dynamic hyperinflation limits exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). Recently, several innovative approaches have been developed to reduce the burden of dynamic hyperinflation. Two such innovations, ventilation-feedback training and Heliox supplementation during exercise show great promise and posit a reduction in dynamic hyperinflation as a key to their effectiveness. In our recently completed trial, when age, FEV1 and RV/TLC were controlled, exercise plus VF (E+VF) was superior to E training alone (E only) or VF training alone in improving exercise tolerance. The mechanism responsible for this difference was, in part, a reduction in exercise-induced dynamic hyperinflation secondary to a change in breathing pattern. In additional preliminary studies, we determined that exercise tolerance can be increased when patients exercise while inhaling Heliox. Similar to VF, the mechanism for exercise improvement with Heliox was a reduction in exercise-induced dynamic hyperinflation. Although both interventions are promising, there are no definitive data to support use of either intervention as a standard of care for pulmonary rehabilitation.
Hypothesis/Research Questions Overview: The two primary hypotheses are that patients with moderate-severe COPD who successfully complete eight weeks of (a) E+VF training will achieve longer exercise duration than patients randomly assigned to E only and (b) E+heliox training will achieve longer exercise duration than patients randomly assigned to E only.
Methods: This study was a randomized controlled clinical trial. After baseline testing is completed, 103 subjects with moderate-severe COPD were randomized into one of three groups: E+VF, E+Heliox and E training only. Follow-up testing was completed at 8 weeks. testing, activity monitoring, and dyspnea measurements. After baseline testing was completed, randomized subjects trained in the Physical Performance Laboratory three times weekly. Exercise prescriptions were standardized and based on data from the exercise stress test.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Breathing retraining | Experimental | Exercise training with computerized training program |
|
| Heliox | Experimental | Exercise training with helium oxygen combination |
|
| Exercise | Active Comparator | Exercise training |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Breathing retraining | Behavioral | exercise training with computerized training program |
|
| Measure | Description | Time Frame |
|---|---|---|
| Exercise Endurance | Exercise endurance on a constant workrate treadmill test was measured at 14 weeks. The workload on the constant workrate treadmill test corresponded to the grade and speed that the participate had reached on a symptom-limited treadmill test when they reached 85% of their peak oxygen uptake value. | 14 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Inspiratory Capacity | Inspiratory capacity measured during exercise is a measure of air-trapping (dynamic hyperinflation). Inspiratory capacity was measured at an isotime (same time) during the constant workrate treadmill test at baseline and 14 weeks. | 14 weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Eileen G. Collins, PhD RN | Edward Hines Jr. VA Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Edward Hines, Jr. VA Hospital | Hines | Illinois | 60141-5000 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24238770 | Result | Collins EG, Jelinek C, O'Connell S, Butler J, McBurney C, Gozali C, Reda D, Laghi F. Contrasting breathing retraining and helium-oxygen during pulmonary rehabilitation in COPD: a randomized clinical trial. Respir Med. 2014 Feb;108(2):297-306. doi: 10.1016/j.rmed.2013.10.023. Epub 2013 Nov 5. |
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192 patients were screened for eligibility in the study. 103 patients were randomly assigned to the one of the 3 groups. Patients were not randomized for the following reasons: PFT did not qualify (n=47), cardiac problems (n=13), changed mind (n=9), non-compliant (n=6), time constraints (n=5), too debilitated (n=3), other (n=6).
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| ID | Title | Description |
|---|---|---|
| FG000 | Breathing Retraining | Exercise training with computerized training program Breathing retraining: exercise training with computerized training program |
| FG001 | Heliox | Exercise training with helium oxygen combination Heliox: exercise training with a helium oxygen combination |
| FG002 | Exercise | Exercise training Exercise: exercise training |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Breathing Retraining | Exercise training with computerized training program Breathing retraining: exercise training with computerized training program |
| BG001 | Heliox | Exercise training with helium oxygen combination Heliox: exercise training with a helium oxygen combination |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Exercise Endurance | Exercise endurance on a constant workrate treadmill test was measured at 14 weeks. The workload on the constant workrate treadmill test corresponded to the grade and speed that the participate had reached on a symptom-limited treadmill test when they reached 85% of their peak oxygen uptake value. | We used an intent-to treat analysis using the last value carried forward. All participants were included in the final analysis. | Mean | Standard Deviation | minutes | 14 weeks |
|
Adverse events were collected during the time period that the patient was enrolled in the study. When the patient completed the study (after 14 week testing was completed), we stopped collecting adverse event information.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Breathing Retraining | Exercise training with computerized training program Breathing retraining: exercise training with computerized training program |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiac Event | Cardiac disorders | Non-systematic Assessment | Patients had chest pain or needed an intervention such as angioplasty. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| COPD exacerbation | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment | Exacerbation of COPD that lasted over 2 weeks and caused the patient to be withdrawn from the study. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Eileen Collins | Edward Hines Jr. ,VA Hospital | 708-202-3525 | eileen.collins@va.gov |
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| ID | Term |
|---|---|
| D008171 | Lung Diseases |
| D011656 | Pulmonary Emphysema |
| ID | Term |
|---|---|
| D012140 | Respiratory Tract Diseases |
| D029424 | Pulmonary Disease, Chronic Obstructive |
| D008173 | Lung Diseases, Obstructive |
| D002908 | Chronic Disease |
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| ID | Term |
|---|---|
| C038949 | heliox |
| D015444 | Exercise |
| ID | Term |
|---|---|
| D009043 | Motor Activity |
| D009068 | Movement |
| D009142 | Musculoskeletal Physiological Phenomena |
| D055687 | Musculoskeletal and Neural Physiological Phenomena |
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| Heliox | Behavioral | exercise training with a helium oxygen combination |
|
| Exercise | Behavioral | exercise training |
|
| Lost to Follow-up |
|
| BG002 | Exercise | Exercise training Exercise: exercise training |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Smoking history | Smoking history was measured in pack/years. This is the number of packs of cigarettes smoked per day multiplied by the number of years of smoking. | Mean | Standard Deviation | pack/years |
|
| FEV1 percent predicted | The FEV1 (forced expiratory volume in 1 second) is a measure of pulmonary function. It is the amount of air that a person can blow out in one second. This value is reported as the percentage of predicted normal. | Mean | Standard Deviation | percent |
|
| RV/TLC percent predicted | The RV/TLC (residual volume/total lung capacity) is a pulmonary function measure. It is an indication of air-trapping in the lungs. In general, a value over 120 percent predicted indicates that there is significant air-trapping. | Mean | Standard Deviation | percent |
|
Exercise training with helium oxygen combination
Heliox: exercise training with a helium oxygen combination
| OG002 | Exercise | Exercise training Exercise: exercise training |
|
|
|
| Secondary | Inspiratory Capacity | Inspiratory capacity measured during exercise is a measure of air-trapping (dynamic hyperinflation). Inspiratory capacity was measured at an isotime (same time) during the constant workrate treadmill test at baseline and 14 weeks. | Intent-to-treat analysis was used so data on all randomized patients were analyzed. | Mean | Standard Deviation | Liters | 14 weeks |
|
|
|
|
| 1 |
| 35 |
| 1 |
| 35 |
| EG001 | Heliox | Exercise training with helium oxygen combination Heliox: exercise training with a helium oxygen combination | 0 | 33 | 2 | 33 |
| EG002 | Exercise | Exercise training Exercise: exercise training | 5 | 35 | 1 | 35 |
|
| lung cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Non-systematic Assessment | A patient developed lung cancer during the study. |
|
| intracerebral bleed | Blood and lymphatic system disorders | Non-systematic Assessment | Patient had a intercerebral bleed during the course of the study. |
|
|
| cellulitis | Blood and lymphatic system disorders | Non-systematic Assessment | Patient developed a cellulitis in his legs |
|
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| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |