Effect of Blood Flow Restriction Resistance Exercises in COPDAE In-patient Rehabilitation

Effects on Muscle Strength After Blood Flow Restriction Resistance Exercise (BFR-RE) in Early In-patient Rehabilitation of Chronic Obstructive Pulmonary Disease Acute Exacerbation (COPDAE), a Single Blinded, Randomized Controlled Study

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.

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.

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.

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.

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)

Same standardized 2-week in-patient rehabilitation and same amount of the above-mentioned resistance training without the "BFR device".

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

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.

a non-invasive marker of systemic skeletal muscle strength and function, is assessed by handheld grip dynamometer of dominant hand

Measure pain score by visual analog scale (0-10) before, immediate and 5-minute post exercise. least pain=0 ; most severe pain=10

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

Acceptance scale will be assessed immediately after the program after 3 (after 10-12 sessions of training)

Inclusion Criteria: COPD acute exacerbation (COPDAE) as the primary diagnosis for hospitalization or transfer to pulmonary wards of the Haven of Hope Hospital Able to walk under supervision Understand instruction in Cantonese and can give informed consent. Exclusion Criteria: Concomitant acute cardiac event Severe hypertension (BP > 180/100) History of venous thromboembolism History of peripheral vascular disease Absence of posterior tibial or dorsalis pedal pulse History of revascularization of the extremity History of lymphectomies Extremities with dialysis access Vascular grafting Current extremity infection Active malignancy Open fracture / soft tissue injuries Amputation to the lower extremity Expected hospitalization less than 2 weeks on admission Medications known to increase clotting risks

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