We followed the Medical Research Council framework for design of complex interventions (Figure 1). 14 We describe each phase of development in accordance with the template for intervention description and replication (TIDieR)15 and the Consensus on Exercise Reporting Template (CERT).16 Subsequently, we describe required intervention adaptations resulting from the impact of the COVID-19 pandemic on face-to-face clinical services.
Stage 1a: Systematic review of exercise interventions for pulmonary hypertension
Stage 1a Methods
We completed a systematic review12 of intervention content of completed and registered studies of exercise-based interventions for pulmonary hypertension. We identified 19 studies (n=673 participants), of which six were randomised controlled trials. Although exercise prescription was generally well reported, interventions were not described in sufficient detail to allow replication. The key findings from our review are summarised in Supplementary file 1.12
Stage 1a Results from systematic review
All studies focused mainly on inpatient exercise programmes for people in Groups 1 or 4, thus it was not possible to generalise the results of the systematic review across the spectrum of people living with pulmonary hypertension. Our review provided a broad framework within which our intervention could be developed. As many people with pulmonary hypertension have a primary diagnosis of heart failure or respiratory disease, we also reviewed published guidelines for cardiopulmonary rehabilitation.
Stage 1b: Review of Rehabilitation Guidelines
Stage 1b Methods
We reviewed UK and other international guidance applicable to people living with chronic respiratory and cardiovascular conditions. The key guidelines include those published by the British Association of Cardiovascular Prevention and Rehabilitation17, the American Association of Cardiovascular and Pulmonary Rehabilitation18 and the European Association of Cardiovascular Prevention & Rehabilitation.19
Stage 1b Results
Findings from our review of cardiac rehabilitation guidelines are presented in Table 1.
International guidelines were broadly in agreement in relation to the safe and effective duration, intensity, frequency and type of exercise for cardiopulmonary rehabilitation. Guidelines were sufficiently flexible to allow different models of programme delivery, including home or centre based. None of the clinical guidelines included recommendations or guidance for online support for people with pulmonary hypertension. We used these findings, combined with the evidence systematic review, to develop a broad outline of an exercise programme for people with pulmonary hypertension (Stage 2).
Table 1. International guidelines for cardiopulmonary rehabilitation
Source
|
Country
|
Type
|
Intensity
|
Subjective intensity
RPE/ Dyspnoea scale
|
Frequency
per week
|
Duration
|
ACPICR/
BACPR
17 20
|
UK
|
Aerobic
Resistance
|
60-80% max. heart rate
40-70% HRR
30-40% 1RM upper body
50-60% 1RM lower body
|
RPE: 11-14
(Dyspnoea:3-4)
|
2-3
2-4
|
20-60 mins
|
CACPR 21
|
Canada
|
Aerobic
Resistance
|
40-85% HRR
30-40% 1RM upper body
50-60% 1RM lower body
|
Not specified
|
3-5
|
20-40 mins
1-3 sets of
12-15 reps
for 6-10
exercises
|
EAPC 19
|
Europe
|
Aerobic
Resistance
|
50-80% max. heart rate
40-60% HRR
|
RPE: 10-14
To moderate fatigue
|
³3
2
|
20-30 mins
10-15
repetitions
per exercise
|
ACRA 22
|
Australia
|
Aerobic
Resistance
|
Low to moderate
intensity physical activity
As appropriate
|
|
1-2
Not specified
|
30-60 mins
|
JCS 23
|
Japan
|
Aerobic
|
40-60% HRR
|
RPE: 12-13
|
1-3
|
15-60 mins
|
AACVPR (22)
|
USA
|
Aerobic
Resistance
|
40-80% HRR
50% 1RM progressing
to 60-70% 1RM
|
RPE:11-16
(Dyspnoea:3-4)
RPE: 11-13
|
3-5
2-3
|
20-60 mins
1-3 sets of
10-15
Repetitions
for 8-10
exercises
|
ACPICR; Association of Chartered Physiotherapists in Cardiac Rehabilitation, BACPR; British Association of Cardiovascular Prevention & Rehabilitation, CACPR; Canadian Association of Cardiac Rehabilitation, EAPC; European Association of Cardiovascular Prevention & Rehabilitation, ACRA; Australian Cardiovascular Health & Rehabilitation Association, JCS; Japanese Circulation Society, AACVPR; American Association of Cardiovascular & Pulmonary Rehabilitation, HRR; Heart Rate Reserve, 1RM; One Repetition Maximum. RPE; Rating of Perceived Exertion.
Stage 2: Expert opinion, patient and public involvement, and stakeholder engagement
Stage 2 Methods
Patients were involved at multiple stages in the development of the SPHERe intervention. To holistically appraise the needs of people with pulmonary hypertension and their support network, we engaged widely with patients, lay people, multi-disciplinary professional agencies, and the Pulmonary Hypertension Association, identified through formal working relationships and informal networks. The SPHERe research team (n=14) consisted of clinical academics with expertise in the development and implementation of complex exercise rehabilitation interventions. The research team identified key themes and priorities to form the outline for discussions, based on up-to-date evidence from Stage 1. We held a series of consensus meetings at the Warwick Clinical Trials Unit from April 2018 to September 2019. All stakeholders were invited to either attend in person or contribute remotely through telephone, e-mail, and video conference. Workshops included trained facilitators to direct discussions which were recorded, also observers took notes. Workshops started with overview presentations before group discussion. Consensus responses were recorded and collated into the following categories: exercise dose (Frequency, Intensity, Time and Type (FITT) principles), exercise progression, psychosocial support and the feasibility of incorporating the intervention into existing NHS rehabilitation programmes. Summaries from the workshops were circulated and agreed amongst the group by email and at subsequent meetings.
Stage 2 Results
Findings from the co-production stakeholder meetings are summarised in Table 2. Following these meetings, we generated a framework for the draft intervention programme for pre-pilot testing.
Table 2. Key findings from stakeholder consensus meetings for SPHERe intervention development
Component
|
Outcome/consensus (s)
|
Exercise dose
|
All agreed that two supervised and one unsupervised session per week of 20-60 minutes duration, dependent on fitness level, should be tested for acceptability during the pre-pilot phase. Some concerns were expressed by patients and respiratory physicians that this may not be tolerated by more debilitated patients.
Patients requested inclusion of functional strength exercise to improve ease of activities of daily living, and a home exercise programme to include functional and whole-body movements.
All agreed that aerobic exercise at an intensity of 40-70% Heart Rate Reserve, RPE- 11-14 could be achieved after participants had received induction/familiarisation session.
Strength training exercise intensity was discussed at length: there was some reticence for moderate intensity (CR 10 scale 3-4) due to perceived risk of dizziness/syncope from respiratory medicine/patients. Exercise physiologists/researchers felt that moderate intensity exercise would be safe following an appropriate warm-up and under careful supervision. All agreed to test acceptability during pre-pilot.
|
Exercise progression
|
Patients with pulmonary hypertension requested a one-to-one induction to overcome learned fear of activity. They agreed that two familiarisation sessions should be incorporated and piloted to ensure all participants felt safe exercising as many will be new to exercise.
Duration of exercise should be progressed primarily until at least 20 minutes of aerobic exercise could be achieved for maximal therapeutic benefit. Researchers requested that exercise physiologists review participant programmes weekly and progress the prescription if intensity or duration targets were not met. This was agreed by all.
|
Psychosocial support
|
Fear avoidance and anxiety about activities that bring on breathlessness was emphasised heavily and identified as main barrier to adherence. It was agreed by all, further to a suggestion from the health psychologist, that six one-to-one psychosocial education sessions should be included. It was considered that participant numbers at any one time were unlikely to be great enough to deliver these sessions in group format. Motivation/goal setting, pacing of activities and managing negative emotions were chosen as topics.
|
Delivery within NHS
|
Exercise physiologist, GP, cardiology and respiratory medicine highlighted potential obstacles to delivery within the NHS rehabilitation setting: retention, busy classes, accurate intensity monitoring and psychosocial intervention training. Actions were agreed to mitigate these issues: (1) deliver up to three days training for practitioners led by health psychologist and research fellow and (2) provide a comprehensive manual for participants practitioners to follow.
|
Stage 3: Pre-Pilot testing of draft intervention and refinement
Stage 3 Methods
The draft intervention programme was pre-piloted for acceptability testing with a small sample of people living with pulmonary hypertension. Ethical approval was received via the Integrated Research Application System (261218) and the West Midlands Coventry & Warwickshire Research Ethics Committee (19/WM/0155) and Health Research Authority (13/7/2019). We obtained informed signed consent from each participant. We delivered the pre-pilot phase in a community NHS exercise rehabilitation facility at one NHS Trust (Atrium Health Centre for Exercise and Health, Coventry). We gathered data on the acceptability and practicality of the intervention from the eight participants and healthcare practitioners. Each particpant was invited to a one-hour appointment then continued to attend on a weekly basis, supported by a trained exerice facilitator. We collected data on attendance, adherence to exercises and acceptability of prescription.. No formal statistical analyses were undertaken with pre-pilot data, rather we collated feedback on written trial materials and practitioner/participant manuals to refine and develop the intervention for the internal pilot phase before launching the main trial
Stage 3 Findings from pre-pilot phase
Eight people diagnosed with pulmonary hypertension took part in the pre-pilot study between November 2019 and February 2020. All participants attended assessments and were prescribed the draft SPHERe intervention programme (components included assessment, exercise and behavioural support). They also completed trial baseline and follow-up outcome assessments. Findings are summarised in Table 3.
Table 3. Main findings from pre-pilot study testing SPHERe intervention delivery
Component
|
Finding(s)
|
Implications for SPHERe Intervention
|
Intensity of exercise
|
Participants were unwilling at first to exert themselves to target intensity due to fear it would be harmful.
|
Two familiarisation sessions and a one-to-one fear avoidance session introduced in the first week of programme
|
Progression
|
Participants found the progression more acceptable once they had gained confidence in the gym environment and felt included in the decision-making process jointly with the practitioner.
|
Intervention protocol amended so that Practitioners review the programme with participant each week and jointly decide how to progress the programme.
|
Home exercise plan
|
Clearer explanations were needed on format and some exercises of home circuit.
Concern over? risk of overexertion during the unsupervised component. Adequate initial explanation, and demonstration of home programme took longer than anticipated.
|
Additional explanation added to the participant manual. Thirty minutes was allocated following the 2nd supervised session for the practitioner to comprehensively explain the home programme and select appropriate exercises with the participant.
|
Very debilitated participants
|
One participant could only walk 20 metres at assessment with a rollator, therefore conventional exercise e.g. bike/treadmill was too difficult and heart rate unreliable as intensity measure.
|
Provision of adapted functional exercises; e.g., sit to stand, step ups with handrail, added for those too debilitated to exercise. Breathlessness rating used alongside heart rate and perceived exertion as a measure of intensity.
|
Behavioural education
|
Participants preferred behavioural education to be called ‘coaching’ to reduce mental illness stigma. Participants required more support stopping negative thoughts around physical activity.
|
Additional material included in the participant workbook on negative thought patterns. Thought diary home worksheet introduced for those that request more support.
|
Practitioner training (based on site delivery rather than online revised model)
|
Sites could not spare exercise staff for three days. Training was condensed into one long day with provision of written materials in advance.
Practitioners requested crib sheets to guide and standardise behaviour sessions.
|
Duration of practitioner training reduced from three days to one. This was tested at one site. Practitioner assessment was introduced after training and more support given where necessary. Crib sheets for each behavioural session and laminated visual aids produced for all practitioners to support with delivery of behavioural coaching sessions.
|
Rationale for content within SPHERe intervention
Type of Exercise
One key finding from the systematic review12 was that most cardiopulmonary exercise programmes included both aerobic and resistance exercise. This is appropriate for this population; regular aerobic and resistance exercise training in pulmonary hypertension Groups 1 and 4, and in other clinical populations (heart failure and pulmonary disease), leads to adaptations that attenuate many of the histochemical features of skeletal myopathy.24-26 Engagement with patients with pulmonary hypertension, through stakeholder workshops and pre-pilot testing, revealed that patients wanted types of exercise that reduced their breathlessness and improved their ability to perform activities of everyday living. Functional exercises, such as sit to stand and/or step-ups, may help reduce atrophy and restore muscle function, improving mobility and balance.27 Therefore, four to six resistance or functional exercises were included in the programme, to target all the major muscle groups, and compound (more than one muscle) rather than isolation (single muscle) exercises were incorporated,28 to ensure that fewer exercises were required for whole body training. At the time of development, we intended for each clinical site to adapt standardised exercise principles according to availability of resistance equipment.
Exercise Dose and Setting
During the stakeholder meetings, it was agreed that the SPHERe intervention should include three exercise sessions per week: ideally, two supervised in a rehabilitation centre and one unsupervised at home, as per international rehabilitation guidelines. The supervised exercise sessions were originally planned to last up to an hour (including, warm-up, aerobic component, muscle strength and endurance (MSE) component, and cool down) and home exercise sessions to last up to 45 minutes. These components could be altered, initially dependant on the degree of limitation in our population, and then up-titrated during the programme.
Exercise Intensity
The stakeholder engagement and pre-pilot experiences revealed a general reluctance amongst healthcare professionals to prescribe exercise greater than low-moderate intensity for people with pulmonary hypertension, due to concerns of exercise-induced adverse events e.g. syncope, severe dyspnoea.29 However, moderate intensity exercise (40-70% heart rate reserve, Borg scale 12-14, breathlessness scale 3-4)17, is recommended for other rehabilitation populations, some of whom may have pulmonary hypertension (Groups 2 and 3) as a secondary condition.17 28 During our pre-pilot study, we found that participants were also, at first, very unwilling to exert themselves to this level due to repeated historical warnings not to exercise from health professionals, family, friends etc. This was particularly evident during resistance exercise. Some participants required substantial reassurance and encouragement from the practitioner to achieve moderate intensity levels. We therefore included initial familiarisation sessions with early behavioural support, to ameliorate fear and avoidance of physical activity. The intention was to educate participants that exercise, contrary to being detrimental to health, may be safe and beneficial.
Monitoring Intensity
The intensity of exercise should be high enough to stimulate beneficial adaptations by gradually overloading the cardiovascular and musculoskeletal system. This must be standardised and monitored at each session to ensure all participants receive the same intervention dose. Heart rate is commonly used to prescribe intensity in exercise programmes at percentages of maximum or predicted maximum.28 However, heart rate monitoring is not always reliable e.g. due to arrhythmias, medication, caffeine, anxiety etc, therefore the Borg scales of perceived exertion and dyspnoea (breathlessness)30 were included so that target heart rate could be crosschecked with the subjective perception of the participant.
Starting Levels of Exercise
The stakeholder group agreed that starting prescription level of exercise intensity and duration should be calculated from the results of an individual assessment. Resting heart rate was recorded after the participant sat in a quiet room and completed a medical history consultation with the practitioner. The peak heart rate response from participants during an Incremental Shuttle Walk Test31 was used as the maximum heart rate required to calculate 40-70% heart rate reserve using the Karvonen formula.32 During the pre-pilot, practitioners found it preferable to initially prescribe exercise at the lower end of this heart rate range to avoid creating undue participant anxiety around excessive fatigue and breathlessness. We opted to include the MSE component exercises as soon as possible, i.e. from week two onwards. Older adults (>65 years) or those new to exercise, were asked to undertake 10–15 repetitions at first to improve strength28 at an intensity/weight resistance of 4-6 on the Borg Category Ratio (CR-10) scale after two repetitions.17 The CR-10 scale is a 10 point scale that differs from the 15 point RPE scale and is more accurate for resistance exercise.33
Criteria for Progression
The duration and intensity of exercise prescribed must be progressed regularly for participants to receive a continual stimulus for adaptation and improvement for the whole programme. Therefore, we recommended that initially the duration of exercise was increased by 1-5 minutes per session until therapeutic levels of exercise were achieved i.e. at least 20 minutes duration at a moderate intensity range. During the pre-pilot, participants found the exercise sessions more acceptable once they had gained confidence in the gym environment, even as their programme became more challenging. Rate of progression was based on heart rate, perceived exertion and breathlessness recorded during exercise and through careful discussion with the participant. An exercise prescription booklet, designed for participants, was used during the pre-pilot to record measures of intensity. Progress was reviewed each week jointly by the practitioner and participant – exercises were progressed if intensity fell below the desired target range.17
Progression of Resistance Training
We agreed that MSE exercise sets, repetitions or resistance should be progressed if the CR-10 score was lower than 3-4. One general rule for MSE progression is that where participants can perform 20 repetitions on their last set28 then resistance is almost certainly too low to produce an adaptation in strength. Therefore, it should be increased, allowing for the fact that perhaps as few as 8-12 repetitions could be performed at the new resistance level.
Home Exercise Programme
Pre-COVID pandemic, our draft home exercise plan was tested by four participants. We received helpful feedback on how to improve materials, for example; being clearer about the explanation of the format of exercises and weekly progression. The risk of participants potentially over-exerting themselves whilst unsupervised at home was highlighted when one participant took two hours to complete the 30-45 minute home exercise plan, requiring rest periods in between. There was no adverse event on this occasion but the need for greater explanation was apparent. Our training day materials, practitioner manuals and participant materials were adapted to ensure that practitioners reviewed all home exercise plan record sheets weekly, during any face-to-face or online supervised session. During the pre-pilot study, we found that thirty minutes was required to adequately explain and demonstrate the home exercise plan in the first week of the programme.
Duration of SPHERe Programme
Most other clinical trials report exercise programmes lasting four to 15 weeks.13 In the UK, NICE34 recommend 12 weeks as the optimal length for cardiac rehabilitation programmes. In practice however, longer programmes require more capacity/resource and can result in longer wait times for patients. In addition, adherence to longer programmes becomes difficult due to ill health, return to work or loss of motivation. The most common length of UK cardiac rehabilitation programmes in the eight partner sites we had approached was eight weeks (16 sessions), slightly shorter than the national average of 10.3 weeks 35. As the intention of SPHERe was to embed participants in existing cardiac rehabilitation programmes, the study team took a pragmatic decision for an eight week exercise programme to encourage engagement and uptake by clinical rehabiltation centres.
Promoting Adherence
Behavioural interventions have been shown to increase adherence to physical activity interventions in adults.36 This, in combination with our patient stakeholder feedback, led to the inclusion of behavioural sessions, referred to by practitioners as ‘coaching’ sessions (after participant feedback), to run in parallel with the supervised exercise sessions. The six coaching sessions were designed in collaboration with an experienced health psychologist (HS) with the objective of attenuating the most common psychosocial barriers to exercise for this group. We focused on increasing participants’ awareness of how irrational thoughts and feelings can influence their behaviour. Sessions were designed to investigate the pros and cons of changing a specific behaviour, for example; fear avoidance of exercise, assistance to develop a specific management plan, incorporating motivation and goal setting. This was encouraged from the first assessment so that the exercise prescriptions were targeted at physical goals identified as important by patients during the stakeholder meetings. These goals included becoming less fatigued and breathless on exertion, being able to walk further, being able to climb stairs, generally increasing fitness, and regaining independence. There is evidence that linking exercise to daily activities can encourage adherence over the longer term.27 Once goals were jointly agreed, a written ‘contract’ signed by both the practitioner and participant was recommended, as per best practice to encourage adherence.37 This was incorporated into the participant workbook for completion during week one of the programme.
Condition Specific Considerations for the Exercise Programme
Due to the higher risk of syncope in people with pulmonary hypertension, a thorough warm-up and cool-down are particularly important. A gradual increase in oxygen demand whilst muscles reach optimal metabolic efficiency and the cardiopulmonary blood vessels have had time to dilate fully, helps to avoid unnecessary breathlessness during activity. Likewise, the avoidance of sudden cessation of exercise via a gradual cool-down can reduce pooling of blood in the working muscles38, light headedness, and vasovagal syncope.17
We underestimated how ingrained activity avoidance was in this population, as result of years of health professional advice to avoid activity. We placed extra emphasis on this by introducing behavioural coaching, individual assessment and exercise familiarisation sessions. Another consideration was that many people living with pulmonary hypertension were on long term oxygen therapy and were extremely debilitated. During the pre-pilot, one participant could only walk 30 metres with a rollator that carried her oxygen cylinder. Exercise programmes for the extremely debilitated cannot always use conventional exercise equipment as the minimum level of difficulty maybe too hard for patients to achieve for a meaningful duration. For some people, even getting onto some equipment, for example, an upright exercise bike or rower, may induce severe breathlessness. The introduction of adapted functional exercises, such as sit to stand from an elevated chair and step ups with a handrail, are more achievable and appropriate for the severely impaired. Furthermore, the necessity for ratings of breathlessness and exertion over heart rate was underlined by our experiences with participants who were severely limited.
Adaptations due to Covid-19 pandemic
The SPHERe intervention was developed for supervised delivery in gym settings but subsequently adapted for online delivery in light of the COVID-19 pandemic. All online exercise and behavioural coaching sessions are delivered using a secure password-protected online platform and delivered by practitioners at a central location (Atrium Health Ltd, Coventry). The revised protocol was approved by the funder and independent committees.39 The online SPHERe intervention was then tested in an internal pilot study.
Overview of SPHERE Intervention
The final, online, eight-week SPHERe programme has three core components after initial familiarisation sessions (Figure 2):
Week 1: Online Familiarisation Sessions
One-on-one, online familiarisation sessions are undertaken in the first week to introduce participants to the online platform and their home exercise programme. The familarisation sessions include a comprehensive medical and physical activity history.29 On recruitment to the trial, all participants complete an Incremental Shuttle Walk Test31 at a local healthcare centre so that symptom thresholds (saturated oxygen drop in level, dysnpnoa scale >4) can be linked to walking speed which inform exercise prescription. The SPHERe practitioner then develops the exercise prescription, in agreement with the participant, at a level adapted for ability. A copy of the individualised exercise programme is sent to the participant by email.
Weeks 1 to 8: Supervised, live online exercise sessions
Participants are invited to attend practitioner-led, online group exercise sessions held weekly over eight weeks, each session lasting for one hour, for up to 8 sessions. Sessions consist of warm-up and mobility, followed by moderate intensity exercise (40-70% heart rate reserve, Borg scale of perceived exertion;12-14, and breathlessness; 3-4)17, that includes aerobic, MSE and ‘functional’ exercise. During these sessions, practitioners closely monitor the group and suggest alternative or adapted exercises to individualise these for participants as much as possible.
Weeks 2 to 8: Behavioural coaching sessions
All participants are invited to attend weekly 30-minute, online group behavioural coaching support sessions with a trained SPHERe practitioner, over six of the eight weeks. These online sessions are held either before or after exercise, wherever possible. The primary goal of the psychosocial and motivational support sessions is to promote adherence to exercise and allay fears and worries around fatigue and breathlessness.
Weeks 1 to 8: Home unsupervised exercise programme
An individualised, unsupervised home exercise plan is to be followed at least twice per week. Each participant has a stationary exercise bike/recumbent bike delivered to their home, except in circumstances where this is not feasible e.g. lack of space. In agreement with their practitioner, particpants complete a fixed duration and intensity at least once a week on their bike. They are also given a ‘home exercise circuit’ with 6-8 of the menu of 24 available exercises from the online platform. The participant is instructed to perform these selected exercises in a ‘circuit’; i.e., one after another, and multiple circuits repeated as required. The practitioner reviews the supervised and home exercise plan weekly with the participant and modify/progress exercises as necessary. The home programme is based on functional fitness, supplemented with access to a suite of recorded exercise sessions and demonstration videos on the online platform.
Intervention Fidelity: Practitioner Training and Quality Control
To ensure standardisation of intervention delivery, all practitioners involved in the SPHERe trial have a full day of face to face practical and theoretical training with a clinical exercise physiologist (SE) and health psychologist (HS), who provide guidance on how to deliver behavioural education sessions, utilising motivational interviewing techniques and the COM-B model.40 All practitioners complete an assessment after training, to gauge readiness to deliver the intervention and/or the need for further training. Practitioners are provided with comprehensive manuals for intervention delivery and phone call support as required. The SPHERe intervention is designed for delivery by NHS clinical exercise physiologists (i.e. in possession of sport science degree) or chartered physiotherapists with a minimum of two years’ experience working with clinical populations.
Although adaptations to the trial format due to Covid-19 resulted in delivery of the online programme from a central NHS trust rather than multiple healthcare sites, all practitioners are subject to regular quality control inspections. This is to ensure that exercise and behavioural education sessions are being delivered in a standardised manner and also to provide support to rehabilitation teams. All familiarisation and group sessions are video recorded for review by an independent researcher not involved with intervention delivery. A separate process evaluation will assess programme acceptability amongst participants and practitioners.39