Matthew Maddocks

Sarcopenia in COPD: prevalence, clinical correlates and response to pulmonary rehabilitation

Background Age-related loss of muscle, sarcopenia, is recognised as a clinical syndrome with multiple contributing factors. International European Working Group on Sarcopenia in Older People (EWGSOP) criteria require generalised loss of muscle mass and reduced function to diagnose sarcopenia. Both are common in COPD but are usually studied in isolation and in the lower limbs. Objectives To determine the prevalence of sarcopenia in COPD, its impact on function and health status, its relationship with quadriceps strength and its response to pulmonary rehabilitation (PR). Methods EWGSOP criteria were applied to 622 outpatients with stable COPD. Body composition, exercise capacity, functional performance, physical activity and health status were assessed. Using a case–control design, response to PR was determined in 43 patients with sarcopenia and a propensity score-matched non-sarcopenic group. Results Prevalence of sarcopenia was 14.5% (95% CI 11.8% to 17.4%), which increased with age and Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) stage, but did not differ by gender or the presence of quadriceps weakness (14.9 vs 13.8%, p=0.40). Patients with sarcopenia had reduced exercise capacity, functional performance, physical activity and health status compared with patients without sarcopenia (p<0.001), but responded similarly following PR; 12/43 patients were no longer classified as sarcopenic following PR. Conclusions Sarcopenia affects 15% of patients with stable COPD and impairs function and health status. Sarcopenia does not impact on response to PR, which can lead to a reversal of the syndrome in select patients.

Is exercise an acceptable and practical therapy for people with or cured of cancer?: A systematic review

INTRODUCTION Therapeutic exercise, although potentially beneficial, does not appear acceptable to many cancer patients. A greater understanding of the reasons for this is required. We have systematically reviewed the use of exercise in this group, identifying rates of uptake, adherence and completion along with factors influencing acceptability. METHODS Searches were completed using relevant key words. Data on study design, patient group, exercise intervention, patient flow data and reasons for declining or withdrawing from a programme were independently extracted by two researchers. Rates of study uptake, completion and adherence were compared according to dichotomised patient or programme characteristics using Mann Whitney U test (p=0.05). Reasons provided when declining or withdrawing from a study were categorised. RESULTS Sixty five studies were included. The majority contained groups made up entirely or predominantly of patients with breast cancer offered an aerobic or resistance exercise programme. The median [IQR] rates of uptake, adherence and completion were 63 [33-80]%, 84 [72-93]% and 87 [80-96]%, respectively. No characteristic influenced the proportion of patients taking up or completing a programme. The main reasons for refusal were disinterest or the impracticality of undertaking the programme and for withdrawal, medical complication or deterioration. CONCLUSIONS The invitation to undertake a programme of therapeutic exercise is accepted by about two-thirds of patients. Rates of adherence and completion are relatively high, but overall, only about half of patients offered a programme complete one. There is a need to modify exercise programmes if they are to be acceptable for the majority of patients.

Muscle function in COPD: a complex interplay

The skeletal muscles play an essential role in life, providing the mechanical basis for respiration and movement. Skeletal muscle dysfunction is prevalent in all stages of chronic obstructive pulmonary disease (COPD), and significantly influences symptoms, functional capacity, health related quality of life, health resource usage and even mortality. Furthermore, in contrast to the lungs, the skeletal muscles are potentially remedial with existing therapy, namely exercise-training. This review summarizes clinical and laboratory observations of the respiratory and peripheral skeletal muscles (in particular the diaphragm and quadriceps), and current understanding of the underlying etiological processes. As further progress is made in the elucidation of the molecular mechanisms of skeletal muscle dysfunction, new pharmacological therapies are likely to emerge to treat this important extra-pulmonary manifestation of COPD.

Validity of three accelerometers during treadmill walking and motor vehicle travel

Objective To determine the relative accuracy during treadmill walking and motor vehicle travel of the ActivPAL, PALlite and Digi-Walker accelerometers. Methods Forty healthy volunteers wearing all accelerometers undertook either five treadmill walks (n=20) at speeds ranging between 0.6 and 1.4 m/s or a 15 min motor vehicle journey (n=20). Step counts recorded by each accelerometer were compared with the actual step count determined by video analysis (treadmill walking) or with an actual step count of zero (motor vehicle). Mean percentage measurement error was calculated and compared between devices by one-way ANOVA and Student t test. Results For treadmill walking, the measurement error was lowest for the ActivPAL, with no significant differences between the ActivPAL and the PALlite monitors. The measurement error was significantly higher for the Digi-Walker at speeds of ≤1 m/s. During vehicle travel erroneous steps were recorded by the PALlite (254 steps) and Digi-Walker (25 steps), but not the ActivPAL monitor (0 steps). Conclusions The ActivPAL accelerometer accurately measures step count over a range of walking speeds and, unlike the other accelerometers tested, is not falsely triggered by motor vehicle travel.

Physical frailty and pulmonary rehabilitation in COPD: a prospective cohort study

Background Frailty is an important clinical syndrome that is consistently associated with adverse outcomes in older people. The relevance of frailty to chronic respiratory disease and its management is unknown. Objectives To determine the prevalence of frailty among patients with stable COPD and examine whether frailty affects completion and outcomes of pulmonary rehabilitation. Methods 816 outpatients with COPD (mean (SD) age 70 (10) years, FEV1% predicted 48.9 (21.0)) were recruited between November 2011 and January 2015. Frailty was assessed using the Fried criteria (weight loss, exhaustion, low physical activity, slowness and weakness) before and after pulmonary rehabilitation. Predictors of programme non-completion were identified using multivariate logistic regression, and outcomes were compared using analysis of covariance, adjusting for age and sex. Results 209/816 patients (25.6%, 95% CI 22.7 to 28.7) were frail. Prevalence of frailty increased with age, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage, Medical Research Council (MRC) score and age-adjusted comorbidity burden (all p≤0.01). Patients who were frail had double the odds of programme non-completion (adjusted OR 2.20, 95% CI 1.39 to 3.46, p=0.001), often due to exacerbation and/or hospital admission. However, rehabilitation outcomes favoured frail completers, with consistently better responses in MRC score, exercise performance, physical activity level and health status (all p<0.001). After rehabilitation, 71/115 (61.3%) previously frail patients no longer met case criteria for frailty. Conclusions Frailty affects one in four patients with COPD referred for pulmonary rehabilitation and is an independent predictor of programme non-completion. However, patients who are frail respond favourably to rehabilitation and their frailty can be reversed in the short term.

Neuromuscular electrical stimulation to improve exercise capacity in patients with severe COPD: a randomised double-blind, placebo-controlled trial.

BACKGROUND Skeletal muscle dysfunction and exercise intolerance are common in severe chronic obstructive pulmonary disease (COPD). We assessed the effectiveness of neuromuscular electrical stimulation (NMES) as a home-based exercise therapy. METHODS In this double-blind, placebo-controlled trial, undertaken across three UK National Health Service sites, we randomly assigned (1:1) adults with COPD, a forced expiratory volume in 1 s (FEV1) less than 50% predicted, and incapacitating breathlessness (Medical Research Council dyspnoea scale ≥4) to receive active or placebo NMES, daily over a 6-week period. Randomisation was by an independent system using minimisation to balance age, GOLD stage, and quadriceps strength. Participants and outcome assessors were masked to group allocation. The primary endpoint was change in 6-min walk test (6MWT) distance at 6 weeks. Analysis was by intention to treat. The trial was registered as ISRCTN15985261 and is now closed. FINDINGS Between June 29, 2012, and July 4, 2014, we enrolled 73 participants, of whom 52 participants were randomly assigned; 25 to receive active NMES and 27 to placebo NMES. Change in 6MWT distance was greater in the active NMES group (mean 29·9 [95% CI 8·9 to 51·0]) compared with in the placebo group (-5·7 [-19·9 to 8·4]; mean difference at 6 weeks 35·7 m [95% CI 10·5 to 60·9]; p=0·005). Sensitivity analyses for complete-cases and adjustment for baseline values showed similar results. 6 weeks after stopping the intervention the effect waned (7·3 m [95% CI -32·5 to 47·0]; p=0·50). The proportion of participants who had adverse events was similar between groups (five [20%] in the active NMES group and nine [33%] in the placebo group). Two participants, one from each group, reported persistent erythema, which was considered to be possibly related to NMES and the use of adhesive electrodes. INTERPRETATION NMES improves functional exercise capacity in patients with severe COPD by enhancing quadriceps muscle mass and function. These data support the use of NMES in the management of patients unable to engage with conventional pulmonary rehabilitation. More work is needed to study how to maintain the effect. FUNDING National Institute for Health Research.

Exercise for cancer cachexia in adults

Cancer cachexia is a complex syndrome characterized by an ongoing loss of skeletal muscle mass and progressive functional impairment. A proactive management approach is recommended, including physical exercise to maintain function via modulation of muscle metabolism, insulin sensitivity and levels of inflammation. The review aimed to determine the safety, acceptability and effectiveness of exercise in adults with cancer cachexia. Secondary aims, subject to the data availability, were to compare effectiveness according to the characteristics of the study intervention or population.

Exercise for cancer cachexia in adults: Executive summary of a Cochrane Collaboration systematic review

Cancer cachexia is a complex syndrome characterized by an ongoing loss of skeletal muscle mass and progressive functional impairment. A proactive management approach is recommended, including physical exercise to maintain function via modulation of muscle metabolism, insulin sensitivity and levels of inflammation. The review aimed to determine the safety, acceptability and effectiveness of exercise in adults with cancer cachexia. Secondary aims, subject to the data availability, were to compare effectiveness according to the characteristics of the study intervention or population.

Improving muscle mass and function in cachexia: non-drug approaches

Purpose of reviewTherapeutic exercise may help maintain or slow down the rate of decline in muscle mass and physical function that occurs with cachexia. This review considers recent evidence in relation to patients with cachexia as regards the rationale for the use of exercise, the challenges in its clinical application and future developments. Recent findingsExercise may attenuate the effects of cachexia by modulating muscle metabolism, insulin sensitivity and levels of inflammation. Studies targeting cachectic patients have demonstrated that even in advanced disease peripheral muscle has the capacity to respond to exercise training. Nonetheless, there are challenges in implementing the use of exercise, particularly once cachexia is established in which tolerance to even low levels of exercise is poor. Strategies to make exercise a more accessible therapy are required and could include offering exercise earlier on in the course of the disease, at lower intensities and in various forms, including more novel approaches. SummaryThe use of therapeutic exercise has a sound rationale, even in patients with advanced disease and cachexia. Because of practical issues with its application, further study is required to examine if benefits achieved in small studies can be translated to a wider clinical population.

Exercise as a supportive therapy in incurable cancer: exploring patient preferences

Objective: Therapeutic exercise may benefit patients with incurable cancer, but there is little data on its practicality. We have explored the acceptability of six exercise programmes based on different types of exercise, the preferred delivery method, location and time relative to anticancer treatments and whether various patient characteristics influence choice of exercise.