Chronic Obstructive Pulmonary Disease, Acute Exacerbation of COPD
Conditions
Keywords
muscle strength, COPDAE, BFRRE, isometric knee extension
Brief summary
This is a randomised controlled trial of the blood flow restriction resistance exercise (BFR-RE) for early rehabilitation of chronic obstructive pulmonary disease acute exacerbation (COPDAE) in the Haven of Hope Hospital. BFR-RE was invented by Dr. Yoshiaki Sato in Japan 40 years ago. This exercise was newly introduced to the Physiotherapy Department of Haven of Hope Hospital in March, 2020 and not a routine common training in Hospital Authority. However, currently the BFR-device is in its 3rd generation. Under the guidance of a certified physiotherapist, a low load intensity can be used for resistance training to build up muscle mass and strength by applying the device over the thigh to partially limit the blood flow to the distal limb. BFR-RE is well studied in athletes, elderlies and patients for rehabilitation after orthopaedics surgeries. A large amount of literature reveals BFR-RE with low load intensity shows comparable increase of muscle mass as high load intensity resistance training and more increase of muscle strength than those only undergoing low load intensity resistance training. The objective of this study is to investigate the additional effects of 2-week BFR-RE in patients with COPDAE on top of the conventional in-patient rehabilitation training. The primary outcome is effect on localized muscle strength. The secondary outcomes include mobility function, systemic muscle strength as reflected by handgrip strength(HGS), health related quality of life, unplanned readmission to acute hospital rate within 1 month for COPDAE.
Detailed description
Chronic obstructive pulmonary disease (COPD) is a prevalent disease around the world particularly in developed countries. COPD often has frequent admissions for acute exacerbation which increase the risks of mortality. Muscular dysfunction is one of extra-pulmonary morbidity of COPD. Reduced muscle strength is associated with increased mortality in moderate to severe COPD. However, at least 70% of 1-repetition maximum (1-RM) of weight is needed to achieve muscle growth in resistance training. This might not be feasible particularly to the patients admitted for COPD acute exacerbation (COPDAE). Blood flow restriction resistance training (BFR-RE), Kaatsu training, was developed by Dr. Yoshiaki Sato more than 40 years ago. The basic physiological mechanism of BFR-RE to increase muscle mass and strength is by metabolite accumulation, e.g. lactate. The metabolites lead to increase of serum growth hormone (GH) which promotes the collagen synthesis for tissue repair and recovery. The surge of GH leads to release of insulin-like growth factor (IGF-1) which is a protein related to muscle growth. IGF-1 contributes the muscle gain, which is a muscular anabolic process, by enhancing satellite cell proliferation. Concerning growth of muscle mass, BFR-RE leads to a comparable increase when compared to high load resistance exercise (HL-RE). However, concerning increase of muscle strength, BFR-RE is less effective in gain than that in HL- RE but more effective than that in low load resistance exercise (LL-RE) alone. Therefore, BFR-RE can be considered when HL- RE is not advisable. (e.g. frail elderly, post-operative rehabilitation, etc.) BFR-RE is well studied among healthy adult, elderly and musculoskeletal rehabilitation patients, but not in COPDAE patients. Standardized isotonic knee extension resistance training on alternate day with a load of 15-30% of 1-Repetition Maximum (1-RM) with BFR-device will be compared with the control arm having same set of exercise training without the device in COPDAE patient during 2-week of inpatient stay. Referred to previous study with 30% drop out rate estimation, 24 patients for each arm will be needed. Study period will be set to be 9 months or until expected recruitment achieved. Though there no adverse risk responses were reported in published randomized controlled trials in clinical populations in the literature, there are some expected transient perceptual type responses, e.g. dizziness, limb numbness, perceived exertion, delayed onset muscle soreness. There are no significant risks of complications if BFR-RE is prescribed by certified trainers who have knowledge of appropriate protocols and contraindications to the use of occlusive stimuli. The effect on muscle strength in COPDAE inpatient, which is not well studied in the literatures, will be the primary outcome of this study. The effect on mobility functions, systemic muscle strength, health related quality of life, unplanned readmission rate within 1 month of discharge for COPDAE, acceptability and feasibility of the BFR-RE will be evaluated as secondary outcomes.
Interventions
Application the Blood flow restriction device over the proximal thigh to have 80% of the limb occlusion pressure to accumulate the metabolite generated during knee extension
Sponsors
Hospital Authority, Hong Kong
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
The Assessor for the primary outcome (maximum voluntary isometric contraction, MVIC) of knee extension, functional outcomes(6-minute walk test, Short Physical Performance Battery), will be blinded to the allocated study group.
Intervention model description
Participants are randomized into one of the two treatment groups by drawing enclosed envelops which contain the random allocation of participants to intervention group (training with BFR-device and control group (training without the device). The envelopes are opened after inclusion for the individual participant only. Stratification of participants into two groups by maximum voluntary isometric contraction (MVIC) at baseline before randomization will be done. The cutoff for the stratification will be determined from the data in the recent service.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. COPD acute exacerbation (COPDAE) as the primary diagnosis for hospitalization or transfer to pulmonary wards of the Haven of Hope Hospital 2. Able to walk under supervision 3. Understand instruction in Cantonese and can give informed consent.
Exclusion criteria
1. Concomitant acute cardiac event 2. Severe hypertension (BP \> 180/100) 3. History of venous thromboembolism 4. History of peripheral vascular disease 5. Absence of posterior tibial or dorsalis pedal pulse 6. History of revascularization of the extremity 7. History of lymphectomies 8. Extremities with dialysis access 9. Vascular grafting 10. Current extremity infection 11. Active malignancy 12. Open fracture / soft tissue injuries 13. Amputation to the lower extremity 14. Expected hospitalization less than 2 weeks on admission 15. Medications known to increase clotting risks
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of Maximal Voluntary Isometric Contraction (MVIC) of Knee Extension of the Dominant Leg in 3 Weeks | baseline and 3 weeks (after 10-12 sessions of training) | To measure the change of the force-producing capabilities of a muscle group objectively during its isometric contraction condition which means muscle group under contraction with a constant velocity of joint motion and muscle length. Computer dynamometer will be used to measure the MVIC of the isometric knee extension of the dominant leg. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change of Hand Grip Strength in 3 Weeks | baseline and 3 weeks (after 10-12 sessions of training) | a non-invasive marker of systemic skeletal muscle strength and function, is assessed by handheld grip dynamometer of dominant hand |
| Change of Health Related Quality of Life in 3 Weeks | baseline and 3 weeks (after 10-12 sessions of training) | Self-administered Chinese version of Chronic obstructive pulmonary disease(COPD) assessment test (CAT) It contains 8 questions and 6 points each (0 to 5). Higher score means worse health status. The Minimal clinical important difference of CAT score was 2 to 3. Minimum score=0 Maximum score=40 (worst health status) |
| Average Pain Score of Each Training | pain score before, immediate and 5-minute post exercise; | Visual analog scale (0-10) for before, immediate and 5-minute post exercise. least pain=0 ; most severe pain=10 |
| Reasons of Drop-out of Blood Flow Restriction Resistance Exercise | baseline to 3 weeks (after 10-12 sessions of training) | Examination the reasons of drop-out in those discontinuing the training |
| Change of Scores of Short Physical Performance Battery (SPPB) in 3 Weeks | baseline and 3 weeks (after 10-12 sessions of training) | SPPB is the sum of the points from the following 3 measures, high the point, better performance * Time needed to walk 4m distance: less than 4.82s=4 points, 4.82-6.2s=3 points, 6.21-8.7s=2 points, \>8.7s=1 point; if unable to do the walk=0 point * Balance test: can hold side by side stand 10s= 1 point; semi-tandem stand 10s=1 point; tandem stand 10s=2 point; tandem stand 3-9.99s=1 point; if unable to do the stand=0 point * Repeated chair stands test:; Participant unable to complete 5 chair stands or completes stands in \>60s =0 point; If chair stand time is 16.70s or more= 1 point; If chair stand time is 13.70 to 16.69s = 2 points; If chair stand time is 11.20 to 13.69s=3 points; If chair stand time is 11.19s or less= 4 points Minimum score=0 Maximum score=12(best performance) |
| Unplanned Readmission Rate on 1 Month Post Discharge | 1 month after the discharge of patients in the study | Unplanned readmission rate within 1 month of discharge for Chronic Obstructive Pulmonary Disease Acute Exacerbation (COPDAE) |
| 6-minute Walk Test Distance Gain | baseline and 3 weeks (after 10-12 sessions of training) | the distance can achieved in 6-minute walk test |
| Acceptability of Blood Flow Restriction Resistance Exercise | Acceptance scale will be assessed immediately after the program after 3 (after 10-12 sessions of training) | Measure the patient's acceptance by a 5-point categorical scale after the whole program. 1=very dislike, 2=dislike,3=no comment, 4= like, 5=very like Lowest score=1 Highest score=5(Higher score means better acceptance) |
| Feasibility of BFR Exercise | baseline and 3 weeks (after 10-12 sessions of training) | Examination of drop-out rate |
Countries
Hong Kong
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BFR-RE Intervention Group The participants will have the standardised 2 week resistance training with BFR-device with details as follows:
* Cuff size: medium
* Restriction time: 5- 10 mins (stop after finishing 4 sets of training or terminating by Physiotherapists)
* Applied location: alternate quadriceps in consecutive day
* Applied pressure: 80% limb occlusion pressure (LOP)
Blood flow restriction resistance exercise: Application the Blood flow restriction device over the proximal thigh to have 80% of the limb occlusion pressure to accumulate the metabolite generated during knee extension | 20 |
| Control Group Same standardized 2-week in-patient rehabilitation and same amount of the above-mentioned resistance training without the BFR device. | 25 |
| Total | 45 |
Baseline characteristics
| Characteristic | Control Group | Total | BFR-RE Intervention Group |
|---|---|---|---|
| Age, Continuous | 77.4 year STANDARD_DEVIATION 8.9 | 76.3 year STANDARD_DEVIATION 10.1 | 74.9 year STANDARD_DEVIATION 11.9 |
| body mass index (BMI) | 19.8 kg/m^2 STANDARD_DEVIATION 3 | 19.4 kg/m^2 STANDARD_DEVIATION 3 | 19 kg/m^2 STANDARD_DEVIATION 3.1 |
| Body mass index, obstruction, dyspnea, exercise (BODE) index | 5 units on a scale | 5 units on a scale | 5 units on a scale |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment Hong Kong | 25 participants | 45 participants | 20 participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 24 Participants | 43 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 25 |
| other Total, other adverse events | 11 / 20 | 4 / 25 |
| serious Total, serious adverse events | 0 / 20 | 0 / 25 |
Outcome results
Primary
Change of Maximal Voluntary Isometric Contraction (MVIC) of Knee Extension of the Dominant Leg in 3 Weeks
To measure the change of the force-producing capabilities of a muscle group objectively during its isometric contraction condition which means muscle group under contraction with a constant velocity of joint motion and muscle length. Computer dynamometer will be used to measure the MVIC of the isometric knee extension of the dominant leg.
Time frame: baseline and 3 weeks (after 10-12 sessions of training)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Blood Flow Restriction Resistance Exercise (BFR-RE) Intervention Group | Change of Maximal Voluntary Isometric Contraction (MVIC) of Knee Extension of the Dominant Leg in 3 Weeks | 25.9 kgf |
| Control Group | Change of Maximal Voluntary Isometric Contraction (MVIC) of Knee Extension of the Dominant Leg in 3 Weeks | 24.7 kgf |
Secondary
6-minute Walk Test Distance Gain
the distance can achieved in 6-minute walk test
Time frame: baseline and 3 weeks (after 10-12 sessions of training)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Blood Flow Restriction Resistance Exercise (BFR-RE) Intervention Group | 6-minute Walk Test Distance Gain | 5.5 m |
| Control Group | 6-minute Walk Test Distance Gain | 37 m |
Secondary
Acceptability of Blood Flow Restriction Resistance Exercise
Measure the patient's acceptance by a 5-point categorical scale after the whole program. 1=very dislike, 2=dislike,3=no comment, 4= like, 5=very like Lowest score=1 Highest score=5(Higher score means better acceptance)
Time frame: Acceptance scale will be assessed immediately after the program after 3 (after 10-12 sessions of training)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Blood Flow Restriction Resistance Exercise (BFR-RE) Intervention Group | Acceptability of Blood Flow Restriction Resistance Exercise | Very dislike / dislike / no comment | 5 Participants |
| Blood Flow Restriction Resistance Exercise (BFR-RE) Intervention Group | Acceptability of Blood Flow Restriction Resistance Exercise | like / very like | 15 Participants |
| Control Group | Acceptability of Blood Flow Restriction Resistance Exercise | Very dislike / dislike / no comment | 10 Participants |
| Control Group | Acceptability of Blood Flow Restriction Resistance Exercise | like / very like | 15 Participants |
Secondary
Average Pain Score of Each Training
Visual analog scale (0-10) for before, immediate and 5-minute post exercise. least pain=0 ; most severe pain=10
Time frame: pain score before, immediate and 5-minute post exercise;
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Blood Flow Restriction Resistance Exercise (BFR-RE) Intervention Group | Average Pain Score of Each Training | Before training | 0 score on a scale |
| Blood Flow Restriction Resistance Exercise (BFR-RE) Intervention Group | Average Pain Score of Each Training | Immediate after training | 3.4 score on a scale |
| Blood Flow Restriction Resistance Exercise (BFR-RE) Intervention Group | Average Pain Score of Each Training | 5 mins after training | 0 score on a scale |
| Control Group | Average Pain Score of Each Training | Before training | 0 score on a scale |
| Control Group | Average Pain Score of Each Training | Immediate after training | 0 score on a scale |
| Control Group | Average Pain Score of Each Training | 5 mins after training | 0 score on a scale |
Secondary
Change of Hand Grip Strength in 3 Weeks
a non-invasive marker of systemic skeletal muscle strength and function, is assessed by handheld grip dynamometer of dominant hand
Time frame: baseline and 3 weeks (after 10-12 sessions of training)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Blood Flow Restriction Resistance Exercise (BFR-RE) Intervention Group | Change of Hand Grip Strength in 3 Weeks | 1 kg |
| Control Group | Change of Hand Grip Strength in 3 Weeks | 2 kg |
Secondary
Change of Health Related Quality of Life in 3 Weeks
Self-administered Chinese version of Chronic obstructive pulmonary disease(COPD) assessment test (CAT) It contains 8 questions and 6 points each (0 to 5). Higher score means worse health status. The Minimal clinical important difference of CAT score was 2 to 3. Minimum score=0 Maximum score=40 (worst health status)
Time frame: baseline and 3 weeks (after 10-12 sessions of training)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Blood Flow Restriction Resistance Exercise (BFR-RE) Intervention Group | Change of Health Related Quality of Life in 3 Weeks | 6.5 units on a scale |
| Control Group | Change of Health Related Quality of Life in 3 Weeks | 6 units on a scale |
Secondary
Change of Scores of Short Physical Performance Battery (SPPB) in 3 Weeks
SPPB is the sum of the points from the following 3 measures, high the point, better performance * Time needed to walk 4m distance: less than 4.82s=4 points, 4.82-6.2s=3 points, 6.21-8.7s=2 points, \>8.7s=1 point; if unable to do the walk=0 point * Balance test: can hold side by side stand 10s= 1 point; semi-tandem stand 10s=1 point; tandem stand 10s=2 point; tandem stand 3-9.99s=1 point; if unable to do the stand=0 point * Repeated chair stands test:; Participant unable to complete 5 chair stands or completes stands in \>60s =0 point; If chair stand time is 16.70s or more= 1 point; If chair stand time is 13.70 to 16.69s = 2 points; If chair stand time is 11.20 to 13.69s=3 points; If chair stand time is 11.19s or less= 4 points Minimum score=0 Maximum score=12(best performance)
Time frame: baseline and 3 weeks (after 10-12 sessions of training)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Blood Flow Restriction Resistance Exercise (BFR-RE) Intervention Group | Change of Scores of Short Physical Performance Battery (SPPB) in 3 Weeks | 8.5 score on a scale |
| Control Group | Change of Scores of Short Physical Performance Battery (SPPB) in 3 Weeks | 7 score on a scale |
Secondary
Feasibility of BFR Exercise
Examination of drop-out rate
Time frame: baseline and 3 weeks (after 10-12 sessions of training)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Blood Flow Restriction Resistance Exercise (BFR-RE) Intervention Group | Feasibility of BFR Exercise | 7 Participants |
| Control Group | Feasibility of BFR Exercise | 1 Participants |
Secondary
Reasons of Drop-out of Blood Flow Restriction Resistance Exercise
Examination the reasons of drop-out in those discontinuing the training
Time frame: baseline to 3 weeks (after 10-12 sessions of training)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Blood Flow Restriction Resistance Exercise (BFR-RE) Intervention Group | Reasons of Drop-out of Blood Flow Restriction Resistance Exercise | Due to contact contact precaution requirement | 3 Participants |
| Blood Flow Restriction Resistance Exercise (BFR-RE) Intervention Group | Reasons of Drop-out of Blood Flow Restriction Resistance Exercise | Due to hospitalization less than 2 weeks | 2 Participants |
| Blood Flow Restriction Resistance Exercise (BFR-RE) Intervention Group | Reasons of Drop-out of Blood Flow Restriction Resistance Exercise | Due to failure to complete training | 2 Participants |
| Control Group | Reasons of Drop-out of Blood Flow Restriction Resistance Exercise | Due to contact contact precaution requirement | 0 Participants |
| Control Group | Reasons of Drop-out of Blood Flow Restriction Resistance Exercise | Due to hospitalization less than 2 weeks | 1 Participants |
| Control Group | Reasons of Drop-out of Blood Flow Restriction Resistance Exercise | Due to failure to complete training | 0 Participants |
Secondary
Unplanned Readmission Rate on 1 Month Post Discharge
Unplanned readmission rate within 1 month of discharge for Chronic Obstructive Pulmonary Disease Acute Exacerbation (COPDAE)
Time frame: 1 month after the discharge of patients in the study
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Blood Flow Restriction Resistance Exercise (BFR-RE) Intervention Group | Unplanned Readmission Rate on 1 Month Post Discharge | Not COPDAE related | 2 Participants |
| Blood Flow Restriction Resistance Exercise (BFR-RE) Intervention Group | Unplanned Readmission Rate on 1 Month Post Discharge | COPDAE related | 2 Participants |
| Blood Flow Restriction Resistance Exercise (BFR-RE) Intervention Group | Unplanned Readmission Rate on 1 Month Post Discharge | No admission | 16 Participants |
| Control Group | Unplanned Readmission Rate on 1 Month Post Discharge | Not COPDAE related | 3 Participants |
| Control Group | Unplanned Readmission Rate on 1 Month Post Discharge | COPDAE related | 1 Participants |
| Control Group | Unplanned Readmission Rate on 1 Month Post Discharge | No admission | 21 Participants |