Understanding the effectiveness of different exercise training programme designs on V̇O2peak in COPD: a component network meta-analysis.

Pulmonary rehabilitation programmes including aerobic training improve cardiorespiratory fitness in patients with COPD, but the optimal programme design is unclear. We used random effects additive component network meta-analysis to investigate the relative effectiveness of different programme components on fitness measured by V̇O2peak in COPD. The included 59 studies involving 2191 participants demonstrated that V̇O2peak increased after aerobic training of at least moderate intensity with the greatest improvement seen following high intensity training. Lower limb aerobic training (SMD 0.56 95% CI 0.32;0.81, intervention arms=86) and the addition of non-invasive ventilation (SMD 0.55 95% CI 0.04;1.06, intervention arms=4) appeared to offer additional benefit but there was limited evidence for effectiveness of other exercise and non-exercise components.

Lung volume reduction surgery versus endobronchial valves: a randomised controlled trial.

BACKGROUND: Lung volume reduction surgery (LVRS) and bronchoscopic lung volume reduction (BLVR) with endobronchial valves can improve outcomes in appropriately selected patients with emphysema. However, no direct comparison data exist to inform clinical decision making in people who appear suitable for both procedures. Our aim was to investigate whether LVRS produces superior health outcomes when compared with BLVR at 12 months. METHODS: This multicentre, single-blind, parallel-group trial randomised patients from five UK hospitals, who were suitable for a targeted lung volume reduction procedure, to either LVRS or BLVR and compared outcomes at 1 year using the i-BODE score. This composite disease severity measure includes body mass index, airflow obstruction, dyspnoea and exercise capacity (incremental shuttle walk test). The researchers responsible for collecting outcomes were masked to treatment allocation. All outcomes were assessed in the intention-to-treat population. RESULTS: 88 participants (48% female, mean±sd age 64.6±7.7 years, forced expiratory volume in 1 s percent predicted 31.0±7.9%) were recruited at five specialist centres across the UK and randomised to either LVRS (n=41) or BLVR (n=47). At 12 months follow-up, the complete i-BODE was available in 49 participants (21 LVRS/28 BLVR). Neither improvement in the i-BODE score (LVRS -1.10±1.44 versus BLVR -0.82±1.61; p=0.54) nor in its individual components differed between groups. Both treatments produced similar improvements in gas trapping (residual volume percent predicted: LVRS -36.1% (95% CI -54.6- -10%) versus BLVR -30.1% (95% CI -53.7- -9%); p=0.81). There was one death in each treatment arm. CONCLUSION: Our findings do not support the hypothesis that LVRS is a substantially superior treatment to BLVR in individuals who are suitable for both treatments.

Whole-body and muscle responses to aerobic exercise training and withdrawal in ageing and COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) patients exhibit lower peak oxygen uptake (V'O2 peak), altered muscle metabolism and impaired exercise tolerance compared with age-matched controls. Whether these traits reflect muscle-level deconditioning (impacted by ventilatory constraints) and/or dysfunction in mitochondrial ATP production capacity is debated. By studying aerobic exercise training (AET) at a matched relative intensity and subsequent exercise withdrawal period we aimed to elucidate the whole-body and muscle mitochondrial responsiveness of healthy young (HY), healthy older (HO) and COPD volunteers to whole-body exercise. METHODS: HY (n=10), HO (n=10) and COPD (n=20) volunteers were studied before and after 8 weeks of AET (65% V'O2 peak) and after 4 weeks of exercise withdrawal. V'O2 peak, muscle maximal mitochondrial ATP production rate (MAPR), mitochondrial content, mitochondrial DNA (mtDNA) copy number and abundance of 59 targeted fuel metabolism mRNAs were determined at all time-points. RESULTS: Muscle MAPR (normalised for mitochondrial content) was not different for any substrate combination in HO, HY and COPD at baseline, but mtDNA copy number relative to a nuclear-encoded housekeeping gene (mean±sd) was greater in HY (804±67) than in HO (631±69; p=0.041). AET increased V'O2 peak in HO (17%; p=0.002) and HY (21%; p<0.001), but not COPD (p=0.603). Muscle MAPR for palmitate increased with training in HO (57%; p=0.041) and HY (56%; p=0.003), and decreased with exercise withdrawal in HO (-45%; p=0.036) and HY (-30%; p=0.016), but was unchanged in COPD (p=0.594). mtDNA copy number increased with AET in HY (66%; p=0.001), but not HO (p=0.081) or COPD (p=0.132). The observed changes in muscle mRNA abundance were similar in all groups after AET and exercise withdrawal. CONCLUSIONS: Intrinsic mitochondrial function was not impaired by ageing or COPD in the untrained state. Whole-body and muscle mitochondrial responses to AET were robust in HY, evident in HO, but deficient in COPD. All groups showed robust muscle mRNA responses. Higher relative exercise intensities during whole-body training may be needed to maximise whole-body and muscle mitochondrial adaptation in COPD.

Deriving personalised physical activity intensity thresholds by merging accelerometry with field-based walking tests: Implications for pulmonary rehabilitation.

During pulmonary rehabilitation (PR), patients receive individually tailored walking exercise training. The personalised nature of exercise prescription is a fundamental component of PR. Despite this, the measurement of physical activity (PA) has been limited to a 'one size fits all' approach and can be challenging to translate into clinically meaningful or real-world units, such as cadence. This discrepancy may partly explain the inconsistent evidence for the impact of PR on PA. It may also provide an opportunity to standardise PA assessment in the context of chronic respiratory disease (CRD) and PR, where field-based walking tests are routine measures. This technical note provides an example of how to develop personalised PA intensity thresholds, calibrated against an individual's performance on the Incremental Shuttle Walking Test (ISWT; maximal) and Endurance Shuttle Walk Test (ESWT; sub-maximal). These are externally paced tests, with each level (speed) of the tests denoting a specific speed (intensity); ranging 1.8 km/h (ISWT Level 1) to 8.5 km/h (ISWT Level 12). From the ESWT, it becomes possible to evaluate adherence to each individual's walking exercise prescription. Future research should explore this approach and its responsiveness to PR. It may be possible to extend this methodology with the inclusion of physiological parameters (e.g., heart rate, calorimetry, and oxygen consumption) to derive relative intensity markers (e.g. moderate-to-vigorous), accounting for individual differences in exercise capacity, under the same paradigm as PR exercise prescription.

ERS International Congress 2023: highlights from the Respiratory Clinical Care and Physiology Assembly.

It is a challenge to keep abreast of all the clinical and scientific advances in the field of respiratory medicine. This article contains an overview of laboratory-based science, clinical trials and qualitative research that were presented during the 2023 European Respiratory Society International Congress within the sessions from the five groups of Assembly 1 (Respiratory Clinical Care and Physiology). Selected presentations are summarised from a wide range of topics: clinical problems, rehabilitation and chronic care, general practice and primary care, electronic/mobile health (e-health/m-health), clinical respiratory physiology, exercise and functional imaging.

Effect of aerobic exercise training on pulse wave velocity in adults with and without long-term conditions: a systematic review and meta-analysis.

RATIONALE: There is conflicting evidence whether aerobic exercise training (AET) reduces pulse wave velocity (PWV) in adults with and without long-term conditions (LTCs). OBJECTIVE: To explore whether PWV improves with AET in adults with and without LTC, to quantify the magnitude of any effect and understand the influence of the exercise prescription. DATA SOURCES: CENTRAL, MEDLINE and EMBASE were among the databases searched. ELIGIBILITY CRITERIA: We included studies with a PWV measurement before and after supervised AET of at least 3 weeks duration. Exclusion criteria included resistance exercise and alternative measures of arterial stiffness. DESIGN: Controlled trials were included in a random effects meta-analysis to explore the effect of AET on PWV. Uncontrolled studies were included in a secondary meta-analysis and meta-regression exploring the effect of patient and programme factors on change in PWV. The relevant risk of bias tool was used for each study design. RESULTS: 79 studies (n=3729) were included: 35 controlled studies (21 randomised control trials (RCT) (n=1240) and 12 non-RCT (n=463)) and 44 uncontrolled (n=2026). In the controlled meta- analysis, PWV was significantly reduced following AET (mean (SD) 11 (7) weeks) in adults with and without LTC (mean difference -0.63; 95% CI -0.82 to -0.44; p<0.0001). PWV was similarly reduced between adults with and without LTC (p<0.001). Age, but not specific programme factors, was inversely associated with a reduction in PWV -0.010 (-0.020 to -0.010) m/s, p<0.001. DISCUSSION: Short-term AET similarly reduces PWV in adults with and without LTC. Whether this effect is sustained and the clinical implications require further investigation.

The effect of COVID rehabilitation for ongoing symptoms Post HOSPitalisation with COVID-19 (PHOSP-R): protocol for a randomised parallel group controlled trial on behalf of the PHOSP consortium.

INTRODUCTION: Many adults hospitalised with COVID-19 have persistent symptoms such as fatigue, breathlessness and brain fog that limit day-to-day activities. These symptoms can last over 2 years. Whilst there is limited controlled studies on interventions that can support those with ongoing symptoms, there has been some promise in rehabilitation interventions in improving function and symptoms either using face-to-face or digital methods, but evidence remains limited and these studies often lack a control group. METHODS AND ANALYSIS: This is a nested single-blind, parallel group, randomised control trial with embedded qualitative evaluation comparing rehabilitation (face-to-face or digital) to usual care and conducted within the PHOSP-COVID study. The aim of this study is to determine the effectiveness of rehabilitation interventions on exercise capacity, quality of life and symptoms such as breathlessness and fatigue. The primary outcome is the Incremental Shuttle Walking Test following the eight week intervention phase. Secondary outcomes include measures of function, strength and subjective assessment of symptoms. Blood inflammatory markers and muscle biopsies are an exploratory outcome. The interventions last eight weeks and combine symptom-titrated exercise therapy, symptom management and education delivered either in a face-to-face setting or through a digital platform ( www.yourcovidrecovery.nhs.uk ). The proposed sample size is 159 participants, and data will be intention-to-treat analyses comparing rehabilitation (face-to-face or digital) to usual care. ETHICS AND DISSEMINATION: Ethical approval was gained as part of the PHOSP-COVID study by Yorkshire and the Humber Leeds West Research NHS Ethics Committee, and the study was prospectively registered on the ISRCTN trial registry (ISRCTN13293865). Results will be disseminated to stakeholders, including patients and members of the public, and published in appropriate journals. Strengths and limitations of this study • This protocol utilises two interventions to support those with ongoing symptoms of COVID-19 • This is a two-centre parallel-group randomised controlled trial • The protocol has been supported by patient and public involvement groups who identified treatments of symptoms and activity limitation as a top priority.

Effects of combining electrical stimulation of the calf and thigh muscles in patients with osteoarthritis of the knee: protocol for a double-blind, randomised, sham-controlled trial.

INTRODUCTION: Knee osteoarthritis (KOA) is a leading cause of disability and is characterised by degenerative changes causing pain and loss of function. Neuromuscular electrical stimulation (NMES) has been shown to influence muscle size and strength in healthy subjects. A novel self-administered NMES device has been developed to help manage the symptoms of KOA. This study aims to investigate the effects of combining NMES of the calf and quadriceps on individuals with KOA. METHODS AND ANALYSIS: 193 individuals with KOA will be recruited to a single-centre, double-blind, randomised, sham-controlled trial at the Respiratory Biomedical Research Centre, Leicester, UK. Participants will be randomised (1:1) to follow an 8-week home-based intervention using a NMES device or sham device. The NMES device consists of footplate electrodes and two quadriceps electrodes. Footplate stimulation will be completed daily for 30 min and quadriceps stimulation for 20 min, five times a week (compliance is recorded in a self-reported participant diary). The primary outcome is the Western Ontario and McMaster Universities Arthritis Index pain domain, taken at 8 weeks follow-up. Secondary outcomes will explore quadriceps muscle strength, swelling, health-related quality of life, exercise capacity, anxiety and depression, sleep, physical activity and self-reported compliance. A powered subgroup analysis for compliance to the active device will be complete for the primary outcome. Participant focus groups will be completed following recruitment of half of the participants and after all participants have been recruited. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the North-West Preston ethics committee (17/NW/0081). Participants are required to provide informed consent following review of the participant information sheet and discussion regarding study procedures with a member of the research team. The study results will be disseminated to the appropriate stakeholders through presentations, conferences and peer-reviewed journals. Results will be presented to participants following study completion at the Biomedical Research Centre-Respiratory, Glenfield Hospital, Leicester. TRIAL REGISTRATION NUMBER: ISRCTN registry, ISRCTN12112819 (date registered 1 May 2019). IRAS registry 219 693. University Hospitals of Leicester registry 91 017. Protocol Version 8.

Impact of transcutaneous neuromuscular electrical stimulation or resistance exercise on skeletal muscle mRNA expression in COPD.

Background: Voluntary resistance exercise (RE) training increases muscle mass and strength in patients with chronic obstructive pulmonary disease (COPD). Nonvolitional transcutaneous neuromuscular electrical stimulation (NMES) may be an alternative strategy for reducing ambulatory muscle weakness in patients unable to perform RE training, but little comparative data are available. This study, therefore, investigated changes in muscle mRNA abundance of a number of gene targets in response to a single bout of NMES compared with RE. Methods: Twenty-six patients with stable COPD (15 male; FEV1, 43±18% predicted; age, 64±8 years; fat free mass index, 16.6±1.8 kg/m2) undertook 30 minutes of quadriceps NMES (50 Hz, current at the limit of tolerance) or 5×30 maximal voluntary isokinetic knee extensions. Vastus lateralis muscle biopsies were obtained at rest immediately before and 24 hours after intervention. Expression of 384 targeted mRNA transcripts was assessed by real time TaqMan PCR. Significant change in expression from baseline was determined using the ΔΔCT method with a false discovery rate (FDR) of <5%. Results: NMES and RE altered mRNA abundance of 18 and 68 genes, respectively (FDR <5%), of which 14 genes were common to both interventions and of the same magnitude of fold change. Biological functions of upregulated genes included inflammation, hypertrophy, muscle protein turnover, and muscle growth, whilst downregulated genes included mitochondrial and cell signaling functions. Conclusions: Compared with NMES, RE had a broader impact on mRNA abundance and, therefore, appears to be the superior intervention for maximizing transcriptional responses in the quadriceps of patients with COPD. However, if voluntary RE is not feasible in a clinical setting, NMES by modifying expression of genes known to impact upon muscle mass and strength may have a positive influence on muscle function.

ERS International Congress 2019: highlights from Best Abstract awardees.

#ERSCongress 2019: highlights from Best Abstract awardees http://bit.ly/2XWlD7Y.