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Background: COPD is characterized by reduced exercise tolerance, and improving physical performance is an important therapeutic goal. A variety of exercise tests are commonly used to assess exercise tolerance, including laboratory and field-based tests. The responsiveness of these various tests to common COPD interventions is yet to be compared, but the results may inform test selection in clinical and research settings., Research Question: What exercise test possesses the greatest sensitivity to change from before to after intervention in patients with COPD?, Study Design and Methods: One hundred fifty-four patients with symptomatic COPD were recruited and randomized (2:1:1) to 6 weeks of long-acting muscarinic antagonist, pulmonary rehabilitation (PR), or usual care. Before and after intervention, participants performed an incremental cycle exercise test and constant work rate cycle test (CWRCT), incremental shuttle walk test and endurance shuttle walk test (ESWT), 6-min walk test, and 4-m gait speed test., Results: One hundred three participants (mean ± SD age, 67 ± 8 years; 75 male participants [73%]; FEV 1 , 50.6 ± 16.8% predicted) completed the study. Significant improvements in the incremental cycle exercise test, CWRCT, incremental cycle exercise test, ESWT, and 6-min walk test results were observed after PR (P < .05), with the greatest improvements seen in the constant work rate protocols (percentages change: CWRCT, 42%; ESWT, 41%)., Interpretation: The ESWT and CWRCT seemed to be the most responsive exercise test protocols to long-acting muscarinic antagonist and PR therapy. The magnitude of change was much greater after a program of rehabilitation compared with bronchodilator therapy., Clinical Trial Registry: International Standard Randomised Controlled Trial Number (ISRCTN): No. 64759523; URL: https://www.isrctn.com/ISRCTN64759523., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: R. T.-S. is a retiree and shareholder of GlaxoSmithKline since 2019. M. A. is a former employee of GlaxoSmithKline. A.H is a former employee of Boehringer Ingelheim (Canada) Ltd. M. C. S reports personal fees and non-financial support from Boehringer Ingelheim and GlaxoSmithKline, outside the submitted work. None declared (T. C.H.-D., M. M. B, M. I. P, M. R, S. A. E, M. D. M, S. J. S)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Rationale: As the prevalence of multimorbidity increases, understanding the impact of isolated comorbidities in people COPD becomes increasingly challenging. A simplified model of common comorbidity patterns may improve outcome prediction and allow targeted therapy., Objectives: To assess whether comorbidity phenotypes derived from routinely collected clinical data in people with COPD show differences in risk of hospitalisation and mortality., Methods: Twelve clinical measures related to common comorbidities were collected during annual reviews for people with advanced COPD and k-means cluster analysis performed. Cox proportional hazards with adjustment for covariates was used to determine hospitalisation and mortality risk between clusters., Measurements and Main Results: In 203 participants (age 66 ± 9 years, 60 % male, FEV 1 %predicted 31 ± 10 %) no comorbidity in isolation was predictive of worse admission or mortality risk. Four clusters were described: cluster A (cardiometabolic and anaemia), cluster B (malnourished and low mood), cluster C (obese, metabolic and mood disturbance) and cluster D (less comorbid). FEV 1 %predicted did not significantly differ between clusters. Mortality risk was higher in cluster A (HR 3.73 [95%CI 1.09-12.82] p = 0.036) and B (HR 3.91 [95%CI 1.17-13.14] p = 0.027) compared to cluster D. Time to admission was highest in cluster A (HR 2.01 [95%CI 1.11-3.63] p = 0.020). Cluster C was not associated with increased risk of mortality or hospitalisation., Conclusions: Despite presence of advanced COPD, we report striking differences in prognosis for both mortality and hospital admissions for different co-morbidity phenotypes. Objectively assessing the multi-system nature of COPD could lead to improved prognostication and targeted therapy for patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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 V̇O 2peak in COPD. The included 59 studies involving 2191 participants demonstrated that V̇O 2peak 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

In 2014, the European Respiratory Society published a statement on nutritional assessment and therapy in COPD. Since then, increasing research has been performed on the role of diet and nutrition in the prevention and management of COPD. Here, we provide an overview of recent scientific advances and clinical implications. Evidence for a potential role of diet and nutrition as a risk factor in the development of COPD has been accumulating and is reflected in the dietary patterns of patients with COPD. Consuming a healthy diet should, therefore, be promoted in patients with COPD. Distinct COPD phenotypes have been identified incorporating nutritional status, ranging from cachexia and frailty to obesity. The importance of body composition assessment and the need for tailored nutritional screening instruments is further highlighted. Dietary interventions and targeted single or multi-nutrient supplementation can be beneficial when optimal timing is considered. The therapeutic window of opportunity for nutritional interventions during and recovering from an acute exacerbation and hospitalisation is underexplored., Competing Interests: Conflicts of interest: All authors have no conflicts of interest to declare., (Copyright ©The authors 2023.)

Chronic Obstructive Pulmonary Disease (COPD) is a common disease associated with significant morbidity and mortality that is both preventable and treatable. However, a major challenge in recognizing, preventing, and treating COPD is understanding its complexity. While COPD has historically been characterized as a disease defined by airflow limitation, we now understand it as a multi-component disease with many clinical phenotypes, systemic manifestations, and associated co-morbidities. Evidence is rapidly emerging in our understanding of the many factors that contribute to the pathogenesis of COPD and the identification of "early" or "pre-COPD" which should provide exciting opportunities for early treatment and disease modification. In addition to breakthroughs in our understanding of the origins of COPD, we are optimizing treatment strategies and delivery of care that are showing impressive benefits in patient-centered outcomes and healthcare utilization. This special issue of Respiratory Medicine, "COPD: Providing the Right Treatment for the Right Patient at the Right Time" is a summary of the proceedings of a conference held in Stresa, Italy in April 2022 that brought together international experts to discuss emerging evidence in COPD and Pulmonary Rehabilitation in honor of a distinguished friend and colleague, Claudio Ferdinando Donor (1948-2021). Claudio was a true pioneer in the field of pulmonary rehabilitation and the comprehensive care of individuals with COPD. He held numerous leadership roles in in the field, provide editorial stewardship of several respiratory journals, authored numerous papers, statement and guidelines in COPD and Pulmonary Rehabilitation, and provided mentorship to many in our field. Claudio's most impressive talent was his ability to organize spectacular conferences and symposia that highlighted cutting edge science and clinical medicine. It is in this spirit that this conference was conceived and planned. These proceedings are divided into 4 sections which highlight crucial areas in the field of COPD: (1) New concepts in COPD pathogenesis; (2) Enhancing outcomes in COPD; (3) Non-pharmacologic management of COPD; and (4) Optimizing delivery of care for COPD. These presentations summarize the newest evidence in the field and capture lively discussion on the exciting future of treating this prevalent and impactful disease. We thank each of the authors for their participation and applaud their efforts toward pushing the envelope in our understanding of COPD and optimizing care for these patients. We believe that this edition is a most fitting tribute to a dear colleague and friend and will prove useful to students, clinicians, and researchers as they continually strive to provide the right treatment for the right patient at the right time. It has been our pleasure and a distinct honor to serve as editors and oversee such wonderful scholarly work., Competing Interests: Declaration of competing interest To the best of my knowledge as editor and corresponding author for the above manuscript, neither I nor any of the coauthors or editor have any perceived conflict of interest with respect to the subject matter of this paper. This, by necessity, must be a preliminary statement, as I assume each author must at a later date submit a personal COI statement., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Physical activity (PA) intensity of people living with chronic obstructive pulmonary disease (COPD) is typically evaluated using intensity thresholds developed in younger, healthier populations with greater exercise capacity and free from respiratory symptoms. This study therefore compared (i) PA differences between COPD and non-COPD controls using both traditional intensity thresholds and threshold-free metrics that represent the volume and intensity of the whole PA profile, and (ii) explored the influence of exercise capacity on observed differences. Moderate-to-vigorous physical activity (MVPA), average acceleration (proxy for volume, mg) and intensity distribution of activity were calculated for 76 individuals with COPD and 154 non-COPD controls from wrist-worn ActiGraph accelerometry. PA profiles representing the minimum intensity (acceleration, mg) during the most active accumulated 5-960 min were plotted. Estimated VO 2peak and relative intensity were derived from the incremental shuttle walk test distance. Compared to the non-COPD control group, individuals with COPD recorded fewer MVPA minutes (59 vs. 83 min/day), lower overall waking activity (29.1 vs. 36.4 mg) and a poorer waking intensity distribution (-2.73 vs. -2.57). Individuals with COPD also recorded a lower absolute intensity (acceleration, mg) for their most active 5-960 min, but higher intensity relative to their estimated exercise capacity derived from the ISWT. People with COPD have a lower volume and absolute intensity of PA than controls but perform PA at a higher relative intensity. There is a need to move away from absolute intensity thresholds, and towards personalised or relative-intensity thresholds, to reflect reduced exercise capacity in COPD populations.

Background: Chronic obstructive pulmonary disease (COPD) patients exhibit lower peak oxygen uptake ( V ' O 2 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 ' O 2 peak ) and after 4 weeks of exercise withdrawal. V ' O 2 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 ' O 2 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., Competing Interests: Conflict of Interest: L.E. Latimer has nothing to disclose. Conflict of interest: D. Constantin-Teodosiu has nothing to disclose. Conflict of interest: B. Popat has nothing to disclose. Conflict of interest: D. Constantin has nothing to disclose. Conflict of interest: L. Houchen-Wolloff has nothing to disclose. Conflict of interest: C.E. Bolton reports, during the course of the study, funding from the MRC/ABPI COPD consortium and the National Institute for Health Research; grants or contracts from British Lung Foundation, H2020, GSK and Pfizer; travel support from Chiesi, outside the submitted work. Conflict of interest: M.C. Steiner has nothing to disclose. Conflict of interest: P.L. Greenhaff has nothing to disclose., (Copyright ©The authors 2022.)

Background: The use of vital signs monitoring in the early recognition of an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) post-hospital discharge is limited. This study investigated whether continuous vital signs monitoring could predict an AECOPD and readmission., Methods: 35 people were recruited at discharge following hospitalisation for an AECOPD. Participants were asked to wear an Equivital LifeMonitor during waking hours for 6 weeks and to complete the Exacerbations of Chronic Pulmonary Disease Tool (EXACT), a 14-item symptom diary, daily. The Equivital LifeMonitor recorded respiratory rate (RR), heart rate (HR), skin temperature (ST) and physical activity (PA) every 15-s. An AECOPD was classified as mild (by EXACT score), moderate (prescribed oral steroids/antibiotics) or severe (hospitalisation)., Results: Over the 6-week period, 31 participants provided vital signs and symptom data and 14 participants experienced an exacerbation, of which, 11 had sufficient data to predict an AECOPD. HR and PA were associated with EXACT score (p < 0.001). Three days prior to an exacerbation, RR increased by mean ± SD 2.0 ± 0.2 breaths/min for seven out of 11 exacerbations and HR increased by 8.1 ± 0.7 bpm for nine of these 11 exacerbations., Conclusions: Increased heart rate and reduced physical activity were associated with worsening symptoms. Even with high-resolution data, the variation in vital signs data remains a challenge for predicting AECOPDs. Respiratory rate and heart rate should be further explored as potential predictors of an impending AECOPD., Trial Registration: ISRCTN registry; ISRCTN12855961. Registered 07 November 2018-Retrospectively registered, https://www.isrctn.com/ISRCTN12855961., (© 2022. The Author(s).)

Introduction: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide, corresponding to 5% of all deaths globally, with more than 90% occurring in low- and middle-income countries (LMIC). Pulmonary Rehabilitation (PR) is a routine clinical service for COPD management, often used in western countries. At present, there is no formal PR in Sri Lanka; a culturally appropriate programme is required that considers the views of adults living with COPD and healthcare providers (HCPs) who would be involved in the referral or delivery of PR., Purpose: The study assessed the attitudes and preferences of Sri Lankan adults living with COPD and attitudes and barriers of HCPs making PR referrals to inform an appropriate PR programme., Methodology: A descriptive cross-sectional study was conducted with the ethical clearance of Colombo south teaching hospital ERC committee (ERC Application No. 674), among adults living with COPD and HCPs in Colombo district, Sri Lanka. Adults living with COPD were enrolled August 2018-December 2018 using systematic random sampling from Colombo South Teaching Hospital and were assessed using a pre-tested interviewer administered questionnaire. HCPs were recruited from Colombo South Teaching Hospital and Jaffna Teaching Hospital between August 2018 and November 2018 and assessed using self-administered questionnaire., Results: Responses from 138 adults living with COPD (53% male, 52% aged ≥60 years) and 277 HCPs were collected. The majority of adults living with COPD were interested in participating in PR (80%) and would prefer PR to be delivered in a supervised, group-based, setting with hospital-based (49%). Adults living with COPD were mostly (73%) willing to spend between 30 minutes and 2 hours per day for PR-related activities. Among HCPs, 234 (83%) were nurses, 29 (11%) were hospital doctors and 14 (4%) were family physicians. The majority of HCPs stated that they were unsure about referring adults with COPD for PR (86%) and 61% stated considerable uncertainty regarding the availability of resources for PR. Nearly half of the HCPs (45%) felt they were not adequately prepared to refer adults living with COPD to PR programmes. Most HCPs (92%) reported that PR is worthwhile for COPD management., Conclusion: Adults living with COPD in Sri Lanka are willing to attend PR and would prefer group-based programmes delivered in hospitals, under the supervision of qualified personnel. Awareness about PR is poor and there is a lack of readiness to refer to PR amongst HCPs. There is an urgent need to train HCPs on PR and develop effective referral strategies to support PR uptake and delivery for adults living with COPD in Sri Lanka., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Perera et al.)

Introduction: Pulmonary rehabilitation (PR) is a programme of individually prescribed physical exercise, education and self-management activities. PR is recommended in international guidelines for managing chronic obstructive pulmonary disease (COPD) and other chronic respiratory diseases. PR is still under-recognised in tuberculosis (TB) guidelines and PR is not available in many low and middle-income countries and for people with post-TB lung disease (PTBLD). The main aims of the study are to adapt and define a culturally appropriate PR programme in Kyrgyzstan for people living with PTBLD and to test, in a fully powered randomised controlled trial (RCT), the effectiveness of PR in improving exercise capacity for people living with PTBLD., Methods and Analysis: The study will be divided into three stages: stage 1: focus group discussions with patients living with PTBLD and interviews with PR referrers will be conducted to explore initial perceptions and inform the cultural adaptation, structure and content of PR. Stage 2a: a single-blind RCT evaluating the effectiveness of a culturally adapted 6-week PR programme on maximal exercise capacity, assessed by the incremental shuttle walking test, before and after PR. Participants will be additionally followed-up 12 weeks postbaseline. Additional outcomes will include health-related quality of life, respiratory symptoms, psychological well-being and physical function. Stage 2b: participants' experience of PR will be collected through interviews and using a log book and a patient evaluation form. Staff delivering PR will be interviewed to explore their experience of delivering the intervention and refining the delivery for future implementation., Ethics and Dissemination: The study was approved 22/07/2019 by Ethics Committee National Center for Cardiology and Internal Medicine (reference number 17) and by University of Leicester ethics committee (reference number 22293). Study results will be disseminated through appropriate peer-reviewed journals, national and international respiratory/physiotherapy conferences, social media, and through patient and public involvement events in Kyrgyzstan and in the UK., Trial Registration Number: ISRCTN11122503., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: Low body mass index (BMI) is associated with COPD, but temporal relationships between airflow obstruction (AO) development and emphysematous change are unclear. We investigated longitudinal changes in BMI, AO, and lung density throughout adulthood using data from the Framingham Offspring Cohort (FOC)., Methods: BMI trajectories were modelled throughout adulthood in 4587 FOC participants from Exam 2 (mean age = 44), through Exam 9 (mean age = 71), in AO participants and non-AO participants (AO n = 1036), determined by spirometry, using fractional polynomial growth curves. This process was repeated for low lung density (LLD) and non LLD participants (LLD n = 225) determined by Computed Tomography. Spirometry decline was compared separately between tertiles of BMI in those aged <40 years and associations between fat and lean mass (measured using Dual Energy X-ray Absorptiometry, DEXA) and development of AO and LLD were also assessed. Additional analyses were performed with adjustment for smoking volume., Results: The BMI trajectory from 30 years of age was visually lower in the AO group than both non-AO smokers (non-1 /FVC ratio in both sexes., Conclusion: Mean BMI is lower throughout adulthood in AO and LLD participants. Lower BMI is associated with a steeper decline in the ratio of FEV 1 /FVC. These findings suggest body mass may precede and potentially have a role in the development of COPD lung pathophysiology.

Introduction: Pulmonary rehabilitation (PR) is a low cost, high impact intervention that ameliorates the disability associated with chronic respiratory diseases (CRD). PR is becoming increasingly recognized in low resource settings where the burden of CRD is rapidly increasing. To aid the implementation of PR in Uganda, we conducted a study to assess the attitudes and opinions towards PR among patients with CRD in Uganda and explore barriers faced by health care workers (HCWs) in referring to PR., Methods: A cross-sectional study comprising two survey populations: people living with CRD and HCWs regarded as potential PR referrers and PR deliverers. This exploratory study sought initial opinions and thoughts regarding PR, as well as baseline knowledge and potential barriers faced in the referral process., Results: Overall, 30 HCWs (53% female, 43% doctors) and 51 adults with CRD (63% female) participated in the survey. Among those with CRD, the majority reported breathlessness as a major problem (86%) and breathlessness affected their ability to do paid and unpaid work (70%). Interest in PR was high amongst adults with CRD (92%) with preference for a hospital-based programme (67%) as opposed to community-based (16%) or home-based (17%). All HCWs considered PR important in lung disease management, but 77% do not refer patients due to a lack of information about PR. HCWs' free-text responses identified the need for training in PR, patient education and streamlining the referral process as key elements to develop successful PR referral services., Conclusion: To successfully set up a PR service for people with CRD in Uganda, there is a great need for appropriately tailored training and education of prospective referrers about CRD and PR programs. Educating patients about the benefits of PR as well as streamlining the referral process is critical in expanding PR services across Uganda to fulfill this unmet need., Competing Interests: The authors report no conflicts of interest in this work. This research was funded by the National Institute for Health Research (NIHR) (17/63/20) using UK aid from the UK Government to support global health research. The views expressed in this publication are those of the authors and not necessarily those of the NIHR or the UK Department of Health and Social Care., (© 2021 Katagira et al.)

Objective: Multi-morbidity contributes to mortality and hospitalisation in COPD, but it is uncertain how this interacts with disease severity in risk prediction. We compared contributions of multi-morbidity and disease severity factors in modelling future health risk using UK primary care healthcare data., Methods: Health records from 103,955 patients with COPD identified from the Clinical Practice Research Datalink were analysed. We compared area under the curve (AUC) statistics for logistic regression (LR) models incorporating disease indices with models incorporating categorised comorbidities. We also compared these models with performance of The John Hopkins Adjusted Clinical Groups ® System (ACG) risk prediction algorithm., Results: LR models predicting all-cause mortality outperformed models predicting hospitalisation. Mortality was best predicted by disease severity (AUC & 95% CI: 0.816 (0.805-0.827)) and prediction was enhanced only marginally by the addition of multi-morbidity indices (AUC & 95% CI: 0.829 (0.818-0.839)). The model combining disease severity and multi-morbidity indices was a better predictor of hospitalisation (AUC & 95% CI: 0.679 (0.672-0.686)). ACG-derived LR models outperformed conventional regression models for hospitalisation (AUC & 95% CI: 0.697 (0.690-0.704)) but not for mortality (AUC & 95% CI: 0.816 (0.805-0.827))., Conclusion: Stratification of future health risk in COPD can be undertaken using clinical and demographic data recorded in primary care, but the impact of disease severity and multi-morbidity varies depending on the choice of health outcome. A more comprehensive risk modelling algorithm such as ACG offers enhanced prediction for hospitalisation by incorporating a wider range of coded diagnoses., Competing Interests: JB and SS report personal fees from Johns Hopkins Health Solutions, outside the submitted work; JKQ reports grants and personal fees from AstraZeneca, grants and personal fees from Bayer, grants from Boehringer Ingelheim, grants from Chiesi, grants from Asthma UK, grants and personal fees from GSK, grants from MRC, grants from The Health Foundation, outside the submitted work; MS reports personal fees from GSK, non-financial support from Boehringer Ingelheim, outside the submitted work; NG reports grants, personal fees and non-financial support from GlaxoSmithKline, personal fees and non-financial support from Chiesi, personal fees and non-financial support from Boehringer Ingelheim, personal fees from AstraZeneca, outside the submitted work; RAE reports grants from CLARHC, during the conduct of the study; personal fees from Chiesi, personal fees from GSK, personal fees from TEVA, personal fees from BMJ, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2021 Groves et al.)

Background: Eccentric cycling (ECC) may be an attractive exercise method in COPD because of both low cardiorespiratory demand and perception of effort compared with conventional concentric cycling (CON) at matched mechanical loads. However, it is unknown whether ECC can be performed by individuals with COPD at an intensity able to cause sufficient metabolic stress to improve aerobic capacity., Research Question: What are the cardiopulmonary and metabolic responses to ECC in people with COPD and healthy volunteers when compared with CON at matched mechanical loads?, Study Design and Methods: Thirteen people with COPD (mean ± SD age, 64 ± 9 years; FEV 1 , 45 ± 19% predicted; BMI, 24 ± 4 kg/m 2 ; oxygen uptake at peak exercise [V̇O 2peak ], 15 ± 3 mL/kg/min) and 9 age-matched control participants (FEV 1 , 102 ± 13% predicted; BMI, 28 ± 5 kg/m 2 ; V̇O 2peak , 23 ± 5 mL/kg/min), performed up to six 4-min bouts of ECC and CON at matched mechanical loads of increasing intensity. In addition, 12 individuals with COPD underwent quadriceps muscle biopsies before and after 20 min of ECC and CON at 65% peak power., Results: At matched mechanical loads, oxygen uptake, minute ventilation, heart rate, systolic BP, respiratory exchange ratio (all P < .001), capillary lactate, perceived breathlessness, and leg fatigue (P < .05) were lower in both groups during ECC than CON. Muscle lactate content increased (P = .008) and muscle phosphocreatine decreased (P = .012) during CON in COPD, which was not evident during ECC., Interpretation: Cardiopulmonary and blood lactate responses during submaximal ECC were less compared with during CON at equivalent mechanical workloads in healthy participants and COPD patients, and this was confirmed at a muscle level in COPD patients. Submaximal ECC was well tolerated and allowed greater mechanical work at lower ventilatory cost. However, in people with COPD, a training intervention based on ECC is unlikely to stimulate cardiovascular and metabolic adaptation to the same extent as CON., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Cognitive impairment (CI) is prevalent in COPD and is associated with poor health-related quality of life. Recovery of cognition following an acute exacerbation of COPD (AECOPD), the impact of CI on pulmonary rehabilitation (PR) uptake and the effect of PR on CI are not fully understood., Methods: This 6-week prospective study analysed 67 people with stable COPD symptoms who completed PR (PR group) and the recovery of 45 people admitted for AECOPD (AECOPD group). All participants were assessed for cognitive function (Montreal Cognitive Assessment [MoCA]), health status (COPD Assessment Test, Chronic Respiratory Questionnaire), lower extremity function (Short Physical Performance Battery), and psychological well-being (Hospital Anxiety and Depression Score). Follow up assessments were carried out after a 6-week recovery post-discharge in AECOPD group and after PR in the PR group., Results: AECOPD group showed no improvement in MoCA following a 6-week recovery post-discharge (Δ-0.8 ± 3.2, p = 0.205), despite improvements in all other clinical outcomes. PR uptake among the AECOPD group was not associated with the presence of CI (p = 0.325). Participants in the PR group with CI at baseline showed a significant improvement in MoCA score following PR (Δ1.6 ± 2.4, p = 0.004)., Conclusions: Cognition does not improve following 6-week recovery post-AECOPD, and CI may influence patients' response to PR referral as an inpatient. PR improves cognition in people with stable COPD symptoms and CI. People with AECOPD should be actively encouraged to attend PR irrespective of mild-moderate cognition but may require additional support or opportunities to take part., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: To establish what proportion of patients completing a UK pulmonary rehabilitation (PR) programme meet the 2018 National Institute for Health and Care Excellence (NICE) chronic obstructive pulmonary disease (COPD) guideline (NG115) criteria to have a respiratory review to establish whether referral to a lung volume reduction multidisciplinary team would be appropriate. This respiratory review would include evaluation of the presence of hyperinflation and the presence of emphysema on CT scan. The NICE criteria include measures of breathlessness and exercise capacity but these parameters are not completely defined., Design: Observational study., Setting: PR programmes across the UK in 2015 (210 centres) and 2017 (184 centres) entering data into the Royal College of Physicians' National Asthma and COPD Audit Programme., Participants: 8295 (55.7%) of 14 889 patients in programmes using incremental shuttle walk test (ISWT) or 6-minute walk test (6MWT) as an outcome measure completed PR, and 4856 (32.6%) had complete data recorded (6MWT/ISWT, baseline spirometry, Medical Research Council (MRC) dyspnoea score)., Results: Depending on the walking test safety threshold adopted for the ISWT (≥140 m or ≥ 80 m) and the MRC dyspnoea score threshold used (MRC score ≥3 or ≥4 at the end of PR), between 4.9% and 18.1% of PR completers met the NICE criteria for a lung volume reduction-focused respiratory review., Conclusions: Lung volume reduction therapies are beneficial in appropriately selected patients with COPD, but few procedures are performed, and treatment pathways are unclear. These data help to inform the feasibility of the approach recommended by NICE and highlight the need for future systematic pathways to reduce inequalities in patients being considered for effective treatments., Competing Interests: Competing interests: SCB, AL, NSH and WB have no competing interests to declare. SVK reports other relationship with PulmonX during the conduct of the study and personal fees from Boston Scientific, outside of the submitted work. JQ reports grants from the RCP during the conduct of the study and is the analysis lead for the NACAP. MCS reports personal fees from GSK and non-financial support from Boehringer-Ingelheim, outside the submitted work., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: International guidelines recommend pulmonary rehabilitation (PR) should be offered to adults living with chronic obstructive pulmonary disease (COPD), but PR availability is limited in Sri Lanka. Culturally appropriate PR needs to be designed and implemented in Sri Lanka. The study aims to adapt PR to the Sri Lankan context and determine the feasibility of conducting a future trial of the adapted PR in Sri Lanka., Methods and Analysis: Eligible participants will be identified and will be invited to take part in the randomised controlled feasibility trial, which will be conducted in Central Chest Clinic, Colombo, Sri Lanka. A total of 50 participants will be recruited (anticipated from April 2021) to the trial and randomised (1:1) into one of two groups; control group receiving usual care or the intervention group receiving adapted PR. The trial intervention is a Sri Lankan-specific PR programme, which will consist of 12 sessions of exercise and health education, delivered over 6 weeks. Focus groups with adults living with COPD, caregivers and nurses and in-depth interviews with doctors and physiotherapist will be conducted to inform the Sri Lankan specific PR adaptations. After completion of PR, routine measures in both groups will be assessed by a blinded assessor. The primary outcome measure is feasibility, including assessing eligibility, uptake and completion. Qualitative evaluation of the trial using focus groups with participants and in-depth interviews with PR deliverers will be conducted to further determine feasibility and acceptability of PR, as well as the ability to run a larger future trial., Ethics and Dissemination: Ethical approval was obtained from the ethics review committee of Faculty of Medical Sciences, University of Sri Jayewardenepura, Sri Lanka and University of Leicester, UK. The results of the trial will be disseminated through patient and public involvement events, local and international conference proceedings, and peer-reviewed journals., Trial Registration Number: ISRCTN13367735., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Background: A large proportion of people with COPD are not referred to pulmonary rehabilitation (PR) despite its proven benefits. No previous studies have examined predictors of referral to PR., Objective: To determine the characteristics of people with COPD associated with referral to PR., Methods: Cross-sectional analysis of a primary care cohort of 82,696 Welsh people with COPD generated as part of a UK national audit of COPD care. Data represent care received by patients as of 31/03/2017. Referral to PR was defined as any code in the patient record indicating referral to PR in the last 3 years. Potential predictors of referral to PR were chosen based on clinical judgement and data availability. Independent predictors of PR referral were determined using backward stepwise mixed-effects logistic regression with a random effect for practice. Variables assessed were: age, gender, deprivation, MRC recorded in past year, MRC grade, smoking status recorded in past year, smoking status, number of exacerbations in past year, inhaled therapy prescription, influenza vaccination, and comorbidities of diabetes, hypertension, coronary heart disease, stroke, heart failure, lung cancer, asthma, bronchiectasis, depression, anxiety, severe mental illness, osteoporosis, and painful condition., Results: A total of 13,297 people (16%) with COPD were referred from primary care for PR. Patients with a comorbidity of bronchiectasis or depression, MRC recorded in the last year, higher MRC grade, more exacerbations in the last year, a greater level of inhaled therapy, an influenza vaccination, or were an ex-smoker had significantly higher odds of referral to PR. Patients that were older, female, more deprived, or had a comorbidity of diabetes, asthma, or painful condition had significantly lower odds of referral to PR., Conclusion: Generally appropriate patients are being prioritised for PR referral; however, it is concerning that women, current smokers, and more deprived patients appear to have lower odds of referral., Competing Interests: The authors worked on the National COPD Audit Programme which was funded by the Healthcare Quality Improvement Partnership. Philip Stone reports grants from the Royal College of Physicians, during the conduct of the study. C Michael Roberts reports personal fees from educational lectures on role of audit in COPD care, outside the submitted work. Jennifer Quint reports grants from the Royal College of Physicians, during the conduct of the study. The authors report no other potential conflicts of interest for this work., (© 2020 Stone et al.)

Background: Despite the wide-ranging benefits of pulmonary rehabilitation, conflicting results remain regarding whether people with COPD can improve their peak oxygen uptake (V˙O 2peak) with aerobic training., Research Question: The goal of this study was to investigate the effect of aerobic training and exercise prescription on V˙O 2peak in COPD., Study Design and Methods: A systematic review was performed by using MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, and Cochrane databases for all studies measuring V˙O 2peak prior to and following supervised lower-limb aerobic training in COPD. A random effects meta-analysis limited to randomized controlled trials comparing aerobic training vs usual care was conducted. Other study designs were included in a secondary meta-analysis and meta-regression to investigate the influence of program and patient factors on outcome., Results: A total of 112 studies were included (participants, N = 3,484): 21 controlled trials (n = 489), of which 13 were randomized (n = 288) and 91 were uncontrolled (n = 2,995) studies. Meta-analysis found a moderate positive change in V˙O 2peak (standardized mean difference, 0.52; 95% CI, 0.34-0.69) with the intervention. The change in V˙O 2peak was positively associated with target duration of exercise session (P = .01) and, when studies > 1 year duration were excluded, greater total volume of exercise training (P = .01). Similarly, the change in V˙O 2peak was greater for programs > 12 weeks compared with those 6 to 12 weeks when adjusted for age and sex. However, reported prescribed exercise intensity (P = .77), training modality (P > .35), and mode (P = .29) did not affect V˙O 2peak . Cohorts with more severe airflow obstruction exhibited smaller improvements in V˙O 2peak (P < .001)., Interpretation: Overall, people with COPD achieved moderate improvements in V˙O 2peak through supervised aerobic training. There is sufficient evidence to show that programs with greater total exercise volume, including duration of exercise session and program duration, are more effective. Reduced effects in severe disease suggest alternative aerobic training methods may be needed in this population., Clinical Trial Registration: PROSPERO; No.: CRD42018099300; URL: https://www.crd.york.ac.uk/prospero/., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of complications and death following surgery. Pulmonary complications are particularly prominent.  Pulmonary rehabilitation is a course of physical exercise and education that helps people with COPD manage their condition.  Although proven to improve health outcomes in patients with stable COPD, it has never been formally tested as a pre-surgical intervention in patients scheduled for non-cardiothoracic surgery.  If a beneficial effect were to be demonstrated, pulmonary rehabilitation for pre-surgical patients with COPD might be rapidly implemented across the National Health Service, as pulmonary rehabilitation courses are already well established across much of the United Kingdom (UK). Methods: We performed a feasibility study to test study procedures and barriers to identification and recruitment to a randomised controlled trial testing whether pulmonary rehabilitation, delivered before major abdominal surgery in a population of people with COPD, would reduce the incidence of post-operative pulmonary complications.  This study was run in two UK centres (Oxford and Newcastle upon Tyne). Results:   We determined that a full randomised controlled trial would not be feasible, due to failure to identify and recruit participants.  We identified an unmet need to identify more effectively patients with COPD earlier in the surgical pathway.  Service evaluations suggested that barriers to identification and recruitment would likely be the same across other UK hospitals. Conclusions:   Although pulmonary rehabilitation is a potentially beneficial intervention to prevent post-operative pulmonary complications, a randomised controlled trial is unlikely to recruit sufficient participants to answer our study question conclusively at the present time, when spirometry is not automatically conducted in all patients planned for surgery.  As pulmonary rehabilitation is a recommended treatment for all people with COPD, alternative study methods combined with earlier identification of candidate patients in the surgical pathway should be considered. Trial registration: ISRCTN29696295, 31/08/2017., Competing Interests: Competing interests: LM, AL, EH, JDY, NR, CS, KP no competing interests. MS reports personal fees from GSK, Boehringer Ingelheim, and Nutricia, non-financial support from Boehringer Ingelheim, GSK, outside the submitted work. MG received programmed activities for their role in the NELA Project Team, is a medical adviser for Sphere Medical Ltd and director of Oxygen Control Systems Ltd and received an honorarium and travel expenses from Edwards Lifesciences in 2016., (Copyright: © 2020 Marlow LL et al.)

Background: Randomised control trial (RCT)-derived survival figures for acute exacerbation of chronic obstructive pulmonary disease admissions managed with non-invasive ventilation (NIV) have not been replicated in UK clinical audits. Subsequent guidelines have emphasised the need for timely NIV application., Methods: Data from the 2008 and 2014 national chronic obstructive pulmonary disease audits was used to analyse the association between time to NIV and mortality., Results: 1032 patients received NIV in 2008, and 1612 in 2014. Overall mortality rates reduced between the audits from 24.9% in 2008 to 16.8% in 2014 but time to NIV lengthened. In 2014, 20.9% of patients received NIV within 60 min versus 24.9% in 2008 (p=0.001). The proportion of patients receiving NIV between 3 and 24 hours increased from 31.3% in 2008 to 39% in 2014 (p=0.001). Patients admitted with hypercapnic acidotic respiratory failure who received NIV within 3 hours had lower in-patient mortality than those who received NIV between 3 and 24 hours, 15.9% versus 18.4%, but this did not reach statistical significance (p=0.425), but acidotic patients receiving NIV >24 hours after admission had significantly higher mortality (28.9%, p=0.002). A second cohort admitted with hypercapnia but normal range pH, who developed later acidosis, had higher mortality (24.6%), compared with those acidotic on admission (18% p≤0.001) and an extremely high mortality when NIV was given >24 hours after admission (42.6%)., Conclusion: Survival rates for those treated with NIV has improved between the two audits but remains lower than reported in RCTs. Patients who developed acidosis after admission and received NIV later in the hospital stay have even higher mortality and deserve further study and clinical attention., Competing Interests: Competing interests: None declared.

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; FEV 1 , 43±18% predicted; age, 64±8 years; fat free mass index, 16.6±1.8 kg/m 2 ) 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 ΔΔC T 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., Competing Interests: NJG reports personal fees from AstraZeneca, GlaxoSmithKline (GSK), and Boehringer Ingelheim outside the submitted work. MCS reports personal fees and non-financial support from Boehringer Ingelheim, GSK and Nutricia outside the submitted work, and grants from the Medical Research Council and NIHR East Midlands CLAHRC during the conduct of the study. PLG reports grants from the MRC/ARUK Centre for Musculoskeletal Ageing Research, and a grant from Remedi, during the conduct of the study. LEL was funded by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care, Leicestershire, Northamptonshire, and Rutland (CLAHRC LNR); CLAHRC East Midlands; and the NIHR Leicester Biomedical Research Centre – Respiratory, who also provided facilities at the University Hospitals of Leicester NHS Trust during the conduct of the study. DC was funded by the MRC/ARUK Centre for Musculoskeletal Ageing Research during the conduct of this study. The authors report no other conflicts of interest in this work.

Introduction: Although the effectiveness of domiciliary monitoring (telehealth) to improve outcomes in chronic obstructive pulmonary disease (COPD) is controversial, it is being used in the National Health Service (NHS)., Aim: To explore the use of teleheath for COPD across England and Wales, to assess the perceptions of clinicians employing telehealth in COPD and to summarise the techniques that have been used by healthcare providers to personalise alarm limits for patients with COPD enrolled in telehealth programmes., Methods: A cross-sectional survey consisting of 14 questions was sent to 230 COPD community services in England and Wales. Questions were designed to cover five aspects of telehealth in COPD: purpose of use, equipment type, clinician perceptions, variables monitored and personalisation of alarm limits., Results: 65 participants completed the survey from 52 different NHS Trusts. 46% of Trusts had used telehealth for COPD, and currently, 31% still provided telehealth services to patients with COPD. Telehealth is most commonly used for baseline monitoring and to allow early detection of exacerbations, with 54% believing it to be effective. The three most commonly monitored variables were oxygen saturation, heart rate and breathlessness. A variety of methods were used to set alarm limits with the majority of respondents believing that at least 40% of alarms were false., Conclusion: Around one-third of responded community COPD services are using telehealth, believing it to be effective without robust evidence, with a variety of variables monitored, a variety of hardware and varying techniques to set alarm limits with high false alarm frequencies., Competing Interests: Competing interests: None declared.

Background: The constructs and interdependency of physical behaviors are not well described and the complexity of physical activity (PA) data analysis remains unexplored in COPD. This study examined the interrelationships of 24-hour physical behaviors and investigated their associations with participant characteristics for individuals with mild-moderate airflow obstruction and healthy control subjects., Patients and Methods: Vigorous PA (VPA), moderate-to-vigorous PA (MVPA), light PA (LPA), stationary time (ST), average movement intensity (vector magnitude counts per minute), and sleep duration for 109 individuals with COPD and 135 healthy controls were obtained by wrist-worn accelerometry. Principal components analysis (PCA) examined interrelationships of physical behaviors to identify distinct behavioral constructs. Using the PCA component loadings, linear regressions examined associations with participant (+, positive correlation; -, negative correlation), and were compared between COPD and healthy control groups., Results: For both groups PCA revealed ST, LPA, and average movement intensity as distinct behavioral constructs to MVPA and VPA, labeled "low-intensity movement" and "high-intensity movement," respectively. Sleep was also found to be its own distinct behavioral construct. Results from linear regressions supported the identification of distinct behavioral constructs from PCA. In COPD, low-intensity movement was associated with limitations with mobility (-), daily activities (-), health status (+), and body mass index (BMI) (-) independent of high-intensity movement and sleep. High-intensity movement was associated with age (-) and self-care limitations (-) independent of low-intensity movement and sleep. Sleep was associated with gender (0= female, 1= male; [-]), lung function (-), and percentage body fat (+) independent of low-intensity and high-intensity movement., Conclusion: Distinct behavioral constructs comprising the 24-hour day were identified as "low-intensity movement," "high-intensity movement," and "sleep" with each construct independently associated with different participant characteristics. Future research should determine whether modifying these behaviors improves health outcomes in COPD., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Rationale: Bimagrumab is a fully human monoclonal antibody that blocks the activin type II receptors, preventing the activity of myostatin and other negative skeletal muscle regulators., Objectives: To assess the effects of bimagrumab on skeletal muscle mass and function in patients with chronic obstructive pulmonary disease (COPD) and reduced skeletal muscle mass., Methods: Sixty-seven patients with COPD (mean FEV 1 , 1.05 L [41.6% predicted]; aged 40-80 yr; body mass index < 20 kg/m 2 or appendicular skeletal muscle mass index ≤ 7.25 [men] and ≤ 5.67 [women] kg/m 2 ), received two doses of either bimagrumab 30 mg/kg intravenously (n = 33) or placebo (n = 34) (Weeks 0 and 8) over 24 weeks., Measurements and Main Results: We assessed changes in thigh muscle volume (cubic centimeters) as the primary endpoint along with 6-minute-walk distance (meters), safety, and tolerability. Fifty-five (82.1%) patients completed the study. Thigh muscle volume increased by Week 4 and remained increased at Week 24 in bimagrumab-treated patients, whereas no changes were observed with placebo (Week 4: +5.9% [SD, 3.4%] vs. 0.0% [3.3%], P < 0.001; Week 8: +7.0% [3.7%] vs. -0.7% [2.8%], P < 0.001; Week 16: +7.8% [5.1%] vs. -0.9% [4.5%], P < 0.001; Week 24: +5.0% [4.9%] vs. -1.3% [4.3%], P < 0.001). Over 24 weeks, 6-minute-walk distance did not increase significantly in either group. Adverse events in the bimagrumab group included muscle-related symptoms, diarrhea, and acne, most of which were mild in severity., Conclusions: Blocking the action of negative muscle regulators through the activin type II receptors with bimagrumab treatment safely increased skeletal muscle mass but did not improve functional capacity in patients with COPD and low muscle mass. Clinical trial registered with www.clinicaltrials.gov (NCT01669174).

Despite the high prevalence of osteoporosis in chronic obstructive pulmonary disease (COPD) patients, the fracture risk prediction tools are not routinely undertaken in the management of COPD. We quantified fracture risk using a validated risk prediction tool (Fracture Risk Assessment (FRAX®)) and determined potential bone-protection treatment needs in patients with advanced COPD. The 10-year probability of major osteoporotic or hip fracture was calculated using the FRAX tool in a cohort of patients attending a hospital complex COPD service. Patients were identified to be at low, intermediate and high risk based on their FRAX scores, in accordance with the National Osteoporosis Guideline Group recommendations, to assess the number of patients requiring bone mineral density (BMD) testing or bone protection therapy. Two hundred forty-seven patients [mean (standard deviation (SD)) age 66 (9.1) years, 26% current smokers, 40% women and median (interquartile range (IQR)) Medical Research Council (MRC) breathlessness scale 4 (0)] had a 10-year probability of 9.5% (6.1) and 3.8% (4.6) for major osteoporotic and hip fractures, respectively. Thirty-six percentage of patients were identified to be at intermediate risk of developing fragility fracture, requiring BMD assessment, while 9% were at high risk, requiring treatment. Thirty-two percentage of high-risk patients were on bisphosphonates. The FRAX score can be used to assess the fracture risk within the COPD cohort and assist with decision-making about BMD measurement and provision of bone protection therapy.

We investigated whether the differences in exercise limitation between patients with chronic obstructive pulmonary disease (COPD) or chronic heart failure (CHF) affect the repeatability or responsiveness of incremental exercise tests. Patients with COPD (Medical Research Council dyspnoea grade 2-5) and patients with CHF (New York Heart Association class II-IV) performed two incremental shuttle walk tests (ISWT) following familiarisation and two incremental cycle ergometer tests (ICE) within 2 weeks. Both tests were repeated on completion of a pulmonary rehabilitation (PR) programme. One hundred and twelve patients were recruited. In response to exercise, patients with COPD were more likely than patients with CHF to have a ventilatory limitation ( p < 0.001) and less likely to have a cardiovascular limitation ( p < 0.001). The ISWT distance and ICE peak volume of oxygen uptake (VO 2 Peak) were similarly repeatable ( p = 0.11 and p = 0.47 for time and disease effect) and responsive to PR ( p = 0.44 and p = 0.67) between diseases. There was no difference in repeatability or responsiveness with either a ventilatory or cardiovascular limitation to exercise ( p > 0.20 for all comparisons). The coefficient of repeatability across the cohort was 60 m for the ISWT and 0.270 L/minute for ICE VO 2 Peak. The minimum important difference (MID) for the ISWT in both diseases for PR was 30 m. The repeatability and responsiveness of the ISWT distance and ICE VO 2 Peak are similar between patients with COPD and CHF and are unaffected by differences in exercise limitation. A change of 60 m in the ISWT or 0.270 L/minute in ICE VO 2 Peak is required to be 95% certain that a true change has occurred within an individual patient. For a group of patients with either COPD or CHF, the MID for the ISWT distance is estimated to be 30 m.

Introduction and Objectives: There are various recommendations for physical activity (PA). However agreement between all of these measures has not been established. Furthermore, given the challenges of measuring PA there is interest in evaluating whether a measure of exercise performance can be used as a surrogate measure to identify who is likely to achieve the recommendations., Methods: A total of 184 people with COPD were recruited, 128 of which had complete data for these analyses. Participants wore the SenseWear Armband for 7 consecutive days and all performed an incremental shuttle walk test (ISWT). We extracted moderate to vigorous physical activity (MVPA) in bouts of ≥10 min using a 3 metabolic equivalent (MET) threshold and an individually prescribed MET threshold (based on performance on the ISWT). Average daily step count and the physical activity level were also calculated., Results: There was poor agreement between the four PA recommendations, with agreement on all four achieved in only 30 participants. People were least likely to be active using MVPA in ≥10 min bouts using 3 MET threshold (21.1% active), and most likely to be active using MVPA in ≥10 min bouts using an individually prescribed threshold (64.9% active). It was not possible to identify a threshold on the ISWT that would reliably predict those that achieved any of the four recommendations., Conclusion: Agreement between various physical activity recommendations is poor. This should be considered when measuring and describing physical activity adherence. The ISWT cannot be used to reliably predict adherence to physical activity guidelines., (© 2016 John Wiley & Sons Ltd.)

Rationale: Pulmonary rehabilitation (PR) in patients with COPD has consistently been shown to produce benefits in exercise capacity, symptoms, and health status. The data surrounding survival following PR are less clear. Our aims were to compare the long-term survival in two cohorts of patients referred for PR; those who successfully completed PR, and a comparator group constructed from patients who either did not complete PR or did not start the program. Additionally, we compared survival between those people who were able to achieve a clinically meaningful improvement in exercise capacity (incremental shuttle walking test) following PR with those who were not., Methods: A retrospective longitudinal analysis of clinical service outcomes was conducted to compare the long-term survival in "completers" and "non-completers" of rehabilitation at two hospitals within the University Hospitals of Leicester NHS Trust from January 1, 2000 to February 23, 2012. For "completers", we also analyzed survival in those meeting (and not meeting) the desired level of change in the incremental shuttle walking test (≥50 m vs <50 m)., Results: We present to you the largest dataset on this topic (n=1,515). Survival data were ascertained for 823 (54.3%) patients with COPD who had completed a course of PR and for 692 (45.7%) patients who dropped out. Survival time was significantly greater in "completers" compared to "non-completers" of PR ( p <0.001). In addition, PR success (≥50 m change in walking distance) was also associated with improved survival ( p <0.05)., Conclusion: The data show an association between completion of PR and survival. In addition, PR success (>50 m change in walking distance) was also associated with improved survival., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Our aim was to evaluate the use and impact of the practice walk test on enrolment, completion, and clinical functional response to pulmonary rehabilitation (PR) using the 2015 UK National Chronic Obstructive Pulmonary Disease (COPD) Pulmonary Rehabilitation audit data. Patients were assessed according to whether a baseline practice walk test was performed or not. Study outcomes included use of the practice walk test, baseline and change in incremental shuttle walk test distance (ISWD) or 6-minute walk test distance (6MWD), and enrolment to and completion of PR program. Of 7,355 patients, only 1,666 (22.6%) had a baseline practice test. At baseline, the practice walk test group walked further as compared to the no practice walk test group: ISWD, 17.9 m [95% confidence interval (CI) 8.2-27.5 m] and 6MWD, 34.8 m (95% CI 24.7-44.9 m). The practice walk test group were 2.2 times (95% CI 1.8-2.6) more likely to enroll and 17% (95% CI 1.03-1.34) more likely to complete PR. Although the change in ISWD and 6MWD with PR was lower in the practice walk test group, they walked further at discharge assessment. Only 22.6% of the patients in the 2015 National PR audit had a practice walk test at assessment. Those who did had better enrolment, completion, and better baseline walking distance, from which the prescription is set., Competing Interests: Disclosure AH has carried out this study as part of his PhD program at University of Nottingham. He has received a scholarship award from Ministry of Education (Saudi Arabia). The authors report no other conflicts of interest in this work.

Objective: To evaluate if observed increased weekend mortality was associated with poorer quality of care for patients admitted to hospital with chronic obstructive pulmonary disease (COPD) exacerbation., Design: Prospective case ascertainment cohort study., Setting: 199 acute hospitals in England and Wales, UK., Participants: Consecutive COPD admissions, excluding subsequent readmissions, from 1 February to 30 April 2014 of whom 13 414 cases were entered into the study., Main Outcomes: Process of care mapped to the National Institute for Health and Care Excellence clinical quality standards, access to specialist respiratory teams and facilities, mortality and length of stay, related to time and day of the week of admission., Results: Mortality was higher for weekend admissions (unadjusted OR 1.20, 95% CI 1.00 to 1.43), and for case-mix adjusted weekend mortality when calculated for admissions Friday morning through to Monday night (adjusted OR 1.19, 95% CI 1.00 to 1.43). Median time to death was 6 days. Some clinical processes were poorer on Mondays and during normal working hours but not weekends or out of hours. Specialist respiratory care was less available and less prompt for Friday and Saturday admissions. Admission to a specialist ward or high dependency unit was less likely on a Saturday or Sunday., Conclusions: Increased mortality observed in weekend admissions is not easily explained by deficiencies in early clinical guideline care. Further study of out-of-hospital factors, specialty care and deaths later in the admission are required if effective interventions are to be made to reduce variation by day of the week of admission., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Chronic obstructive pulmonary disease (COPD) is characterized in the later stages by acute exacerbations that often require hospitalization. Pulmonary rehabilitation is recommended for patients with COPD to aid symptom control, improve quality of life and increase physical activity. We have previously reported a large intervention trial commenced during a hospital admission. The aim of this sub-study was to evaluate the patients' experiences of discharge following the hospitalization for an acute exacerbation of COPD. During a programme of early rehabilitation (ER) patient perceptions, experiences and healthcare use were collated during the month that followed their discharge. ER (started during their admission) was comprised of exercise training techniques that were modified to suit the environment of acute illness, together with an education and self-management programme. Each patient was then supported on the programme by telephone contact, following their discharge home, at 48 hours, 2 weeks and 4 weeks. We collected information in relation to the walking and exercise progression; we monitored patient recall of healthcare use, compliance/understanding of medical therapy, as well as their wider perceptions that may have influenced the recovery process. Healthcare use was captured using GP records and data analysis. Of the 100 patients, 47 males, (mean (standard deviation)) 71 (9.3) years, FEV 1 1.14 L (0.6), BMI 26.6 (6.9), pack smoked years 45.8 (29.6), ethnicity White British 97%, were discharged home following an acute exacerbation of their respiratory symptoms, to an ER programme. At 48 hours following discharge, a minority (20%) of patients stated their symptoms were 'feeling better'; 15% highlighted that they found the prescribed 'exercise difficult'; 44% of patients felt at the end of the month that prescribed exercise programme had a 'positive effect' on their recovery from their exacerbation; 38% of patients felt their family had a positive effect on their recovery; 11% felt their family hindered. Patients reported a mean confidence score of 8.21 (2.1) for exercise that did not vary over the three contacts ( p = 0.166). A similar mean confidence score of 7.76 (2.6) was reported for walking with a non-statistical change also noted ( p = 0.223). When patient recall of primary health care contact was compared with actual use, there was statistical significance shown ( p = 0.002); patients underestimated the amount of care they received. The data indicate that patients do recover at home within the support of an early intervention. Patients are positive about the benefit of ER in the process of recovery; however, this is uncontrolled data.

Background: Pulmonary rehabilitation (PR) improves exercise capacity and health status in patients with COPD, but many patients assessed for PR do not complete therapy. It is unknown whether socioeconomic deprivation associates with rates of completion of PR or the magnitude of clinical benefits bequeathed by PR., Methods: PR services across England and Wales enrolled patients to the National PR audit in 2015. Deprivation was assessed using Index of Multiple Deprivation (IMD) derived from postcodes. Study outcomes were completion of therapy and change in measures of exercise performance and health status. Univariate and multivariate analyses investigated associations between IMD and these outcomes., Results: 210 PR programmes enrolled 7413 patients. Compared with the general population, the PR sample lived in relatively deprived neighbourhoods. There was a statistically significant association between rates of completion of PR and quintile of deprivation (70% in the least and 50% in the most deprived quintiles). After baseline adjustments, the risk ratio (95% CI) for patients in the most deprived relative to the least deprived quintile was 0.79 (0.73 to 0.85), p<0.001. After baseline adjustments, IMD was not significantly associated with improvements in exercise performance and health status., Conclusions: In a large national dataset, we have shown that patients living in more deprived areas are less likely to complete PR. However, deprivation was not associated with clinical outcomes in patients who complete therapy. Interventions targeted at enhancing referral, uptake and completion of PR among patients living in deprived areas could reduce morbidity and healthcare costs in such hard-to-reach populations., Competing Interests: Competing interests: Professor Steiner reports personal fees from Boehringer Ingelheim, non-financial support from Boehringer Ingelheim and GlaxoSmithKline (GSK), personal fees from Boehringer Ingelheim and GSK, grants from Medical Research Council (MRC) and East Midlands Collaboration for Leadership in Applied Health Research and Care (CLAHRC), outside the submitted work. Dr Bolton reports grants from MRC/Association of British Pharmaceutical Industry (ABPI) and GSK, personal fees from Chiesi, other support from GSK, outside the submitted work. Dr Blakey reports personal fees and non-financial support from GSK, personal fees and non-financial support from Napp, personal fees from Novartis and AstraZeneca, grants from Pfizer, outside the submitted work. Dr Man reports grants and other support from Pfizer, Boehringer Ingelheim, grants from National Institute for Health Research and Medical Research Council, outside the submitted work. Professor Singh reports personal fees from GSK, AstraZeneca and Novartis, grants from MRC/ABPI, National Institute for Health Research and East Midlands CLAHRC, outside the submitted work. PW reports personal fees from Chiesi and AstraZeneca, outside the submitted work., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Introduction: An acute exacerbation of chronic obstructive pulmonary disease (COPD) marks a critical life event, which can lower patient quality of life and ability to perform daily activities. Patients with COPD tend to lead inactive and highly sedentary lifestyles, which may contribute to reductions in functional capacity. Targeting sedentary behaviour (SB) may be more attainable than exercise (at a moderate-to-vigorous intensity) for behaviour change in patients following an exacerbation. This study aims to evaluate the feasibility and acceptability of a 2-week at-home intervention providing education and self-monitoring to reduce prolonged periods of SB in patients with COPD discharged following an acute exacerbation., Methods and Analysis: Patients will be randomised into 1 of 3 conditions: usual care (control), education or education+feedback. The education group will receive information and suggestions about reducing long periods of sitting. The education+feedback group will receive real-time feedback on their sitting time, stand-ups and step count at home through an inclinometer linked to a smart device app. The inclinometer will also provide vibration prompts to encourage movement when the wearer has been sedentary for too long. Data will be collected during hospital admission and 2 weeks after discharge. Qualitative interviews will be conducted with patients in the intervention groups to explore patient experiences. Interviews with healthcare staff will also be conducted. All data will be collected January to August 2016. The primary outcomes are feasibility and acceptability, which will be assessed by qualitative interviews, uptake and drop-out rates, reasons for refusing the intervention, compliance, app usage and response to vibration prompts., Ethics and Dissemination: The research ethics committee East Midlands Leicester-Central has provided ethical approval for the conduct of this study. The results of the study will be disseminated through appropriate conference proceedings and peer-reviewed journals., Trial Registration Number: ISRCTN13790881; Pre-results., Competing Interests: Conflicts of Interest: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Patients with moderate exacerbations of COPD and the eosinophilic phenotype have better outcomes with prednisolone. Whether this outcome is similar in patients hospitalized with a severe exacerbation of COPD is unclear. We investigated the rate of recovery of eosinophilic and noneosinophilic exacerbations in patients participating in a multicenter randomized controlled trial assessing health outcomes in hospitalized exacerbations., Methods: Patients were recruited at presentation to the hospital with an exacerbation of COPD. They were stratified into groups according to eosinophilic exacerbations if the peripheral blood eosinophil count on admission was ≥ 200 cells/μL and/or ≥ 2% of the total leukocyte count. Admission details, serum C-reactive protein levels, length of stay, and subsequent rehospitalization data were compared between groups., Results: A total of 243 patients with COPD (117 men) with a mean age of 71 years (range, 45-93 years) were recruited. The inpatient mortality rate was 3% (median time to death, 12 days; range, 9-16 days). The median absolute eosinophil count was 100 cells/μL (range, 10-1,500 cells/μL), and 25% met our criteria for an eosinophilic exacerbation; in this population, the mean length of stay (in days) was shorter than in patients with noneosinophilic exacerbations (5.0 [range, 1-19] vs 6.5 [range, 1-33]; P = .015) following treatment with oral corticosteroids and independent of treatment prior to admission. Readmission rates at 12 months were similar between groups., Conclusions: The study patients presenting to the hospital with a severe eosinophilic exacerbation of COPD had a shorter length of stay. The exacerbations were usually not associated with elevated C-reactive protein levels, suggesting that better treatment stratification of exacerbations can be used., Trial Registry: http://www.isrctn.com/ISRCTN05557928., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Nutrition and metabolism have been the topic of extensive scientific research in chronic obstructive pulmonary disease (COPD) but clinical awareness of the impact dietary habits, nutritional status and nutritional interventions may have on COPD incidence, progression and outcome is limited. A multidisciplinary Task Force was created by the European Respiratory Society to deliver a summary of the evidence and description of current practice in nutritional assessment and therapy in COPD, and to provide directions for future research. Task Force members conducted focused reviews of the literature on relevant topics, advised by a methodologist. It is well established that nutritional status, and in particular abnormal body composition, is an important independent determinant of COPD outcome. The Task Force identified different metabolic phenotypes of COPD as a basis for nutritional risk profile assessment that is useful in clinical trial design and patient counselling. Nutritional intervention is probably effective in undernourished patients and probably most when combined with an exercise programme. Providing evidence of cost-effectiveness of nutritional intervention is required to support reimbursement and thus increase access to nutritional intervention. Overall, the evidence indicates that a well-balanced diet is beneficial to all COPD patients, not only for its potential pulmonary benefits, but also for its proven benefits in metabolic and cardiovascular risk., (©ERS 2014.)

Background: Nutritional depletion is an important manifestation of chronic obstructive pulmonary disease (COPD), which has been related to systemic inflammation. It remains unclear to what degree airway inflammation contributes to the presence or progression of nutritional depletion., Objectives: To determine whether airway inflammation and lung bacterial colonization are related to nutritional status or predict progressive weight loss and muscle atrophy in patients with COPD., Methods: Body composition using dual energy X-ray absorptiometry, indices of airway inflammation, and bacterial colonization were measured in 234 COPD patients. Systemic inflammation was assessed from serum C reactive protein (CRP) and circulating total and differential leukocyte counts. Nutritional depletion was defined as a body mass index (BMI) less than 21 kg/m(2) and/or fat-free mass index (FFMI) less than 15 or 17 kg/m(2) in women and men, respectively. FFMI was calculated as the fat-free mass (FFM) corrected for body surface area. Measurements were repeated in 94 patients after a median 16-month follow-up. Regression analysis was used to assess the relationships of weight change and FFM change with indices of bacterial colonization and airway and systemic inflammation., Results: Nutritional depletion occurred in 37% of patients. Lung function was worsened in patients with nutritional depletion compared to those without (forced expiratory volume in 1 second 1.17 L versus 1.41 L, mean difference 0.24, 95% confidence interval 0.10 to 0.38, P<0.01). There were no differences in airway inflammation and bacterial colonization in patients with and without nutritional depletion. At baseline, BMI correlated positively with serum CRP (rs=0.14, P=0.04). Change in weight and change in FFM over time could not be predicted from baseline patient characteristics., Conclusion: Nutritional depletion and progressive muscle atrophy are not related to airway inflammation or bacterial colonization. Overspill of pulmonary inflammation is not a key driver of muscle atrophy in COPD.

Objective: To investigate whether an early rehabilitation intervention initiated during acute admission for exacerbations of chronic respiratory disease reduces the risk of readmission over 12 months and ameliorates the negative effects of the episode on physical performance and health status., Design: Prospective, randomised controlled trial., Setting: An acute cardiorespiratory unit in a teaching hospital and an acute medical unit in an affiliated teaching district general hospital, United Kingdom., Participants: 389 patients aged between 45 and 93 who within 48 hours of admission to hospital with an exacerbation of chronic respiratory disease were randomised to an early rehabilitation intervention (n=196) or to usual care (n=193)., Main Outcome Measures: The primary outcome was readmission rate at 12 months. Secondary outcomes included number of hospital days, mortality, physical performance, and health status. The primary analysis was by intention to treat, with prespecified per protocol analysis as a secondary outcome., Interventions: Participants in the early rehabilitation group received a six week intervention, started within 48 hours of admission. The intervention comprised prescribed, progressive aerobic, resistance, and neuromuscular electrical stimulation training. Patients also received a self management and education package., Results: Of the 389 participants, 320 (82%) had a primary diagnosis of chronic obstructive pulmonary disease. 233 (60%) were readmitted at least once in the following year (62% in the intervention group and 58% in the control group). No significant difference between groups was found (hazard ratio 1.1, 95% confidence interval 0.86 to 1.43, P=0.4). An increase in mortality was seen in the intervention group at one year (odds ratio 1.74, 95% confidence interval 1.05 to 2.88, P=0.03). Significant recovery in physical performance and health status was seen after discharge in both groups, with no significant difference between groups at one year., Conclusion: Early rehabilitation during hospital admission for chronic respiratory disease did not reduce the risk of subsequent readmission or enhance recovery of physical function following the event over 12 months. Mortality at 12 months was higher in the intervention group. The results suggest that beyond current standard physiotherapy practice, progressive exercise rehabilitation should not be started during the early stages of the acute illness.Trial registration Current Controlled Trials ISRCTN05557928., (© Greening et al 2014.)

Background: It is proposed that resistance training (RT) does not activate the cardiopulmonary system to the same extent as whole-body exercise. This is important for patients with chronic obstructive pulmonary disease (COPD) who are ventilatory limited., Objective: The aim was to assess the ventilatory response to an isokinetic quadriceps RT program in people with COPD and healthy controls., Design: Observational., Registration Number: ISRCTN22764439., Setting: Outpatient, university teaching hospital., Participants and Outcome Measures: People with COPD (n=14) and healthy controls (n=11) underwent breath-by-breath analysis of their ventilation during an RT session (five sets of 30 maximal knee extensions at 180°/sec). Subjects performed a maximal cycle ergometry test (CET) at baseline. Peak ventilation (VE; L/min) and oxygen consumption (VO2; mL/kg/min) were collected. The same system measured VO2 and VE during the RT session. Parameters are presented as a percentage of the maximal CET. Isokinetic workload, symptom scores, heart rate (HR), and oxygen saturation were documented post-training., Results: People with COPD worked at higher percentages of their maximal capacity than controls (mean range between sets 1-5 for VO2 =49.1%-60.1% [COPD], 45.7%-51.43% [controls] and for VE =57.6%-72.2% [COPD], 49.8%-63.6% [controls]), although this was not statistically significant (P>0.1 in all cases). In absolute terms, the difference between groups was only significant for actual VO2 on set 2 (P<0.05). Controls performed more isokinetic work than patients with COPD (P<0.05). Median Borg symptom scores after RT were the same in both groups (3 breathlessness, 13 exertion), no de-saturation occurred, and both groups were training at ≥65% of their maximum HR., Conclusion: No statistically significant differences were found between people with COPD and healthy controls for VO2 and VE achieved during training. The symptoms associated with training were within acceptable limits.

Objective: To derive an improved understanding of how patients respond to, appraise, and understand the experience of an acute exacerbation of chronic obstructive pulmonary disease via a critical interpretive meta-synthesis., Methods: Search terms - Exacerbate* OR hospital* AND 'Chronic obstructive' OR emphysema OR bronchitis AND interview* OR qualitative. Inclusion criteria - Primary research published in English of patients' experiences of an acute exacerbation of chronic obstructive pulmonary disease. Data extraction and synthesis - eight papers were identified. Data were extracted by three researchers and constructs elicited via reciprocal translational analysis., Findings: Themes reflected two domains of understanding an acute exacerbation: (1) Acute effect - encompassing intense emotions, somatic awareness and patients need for rescue. (2) Sustained regulation - reflecting life as interrupted, ongoing beliefs and behaviour and help-seeking., Discussion: Acute exacerbations of chronic obstructive pulmonary disease result in heightened patient arousal, vigilance and powerlessness in response to symptoms. Ongoing, psychological interventions which promote partnership working by both acknowledging patients fear and shaping their appraisals may mitigate distress, enhancing the impact of health messages and engagement in pulmonary rehabilitation.

Introduction: Pulmonary Rehabilitation (PR) reduces hospital admissions following an acute exacerbation of Chronic Obstructive Pulmonary Disease (COPD) but adherence is known to be poor. Patients' illness perceptions may affect adherence to disease-management strategies but to date have not been explored following an exacerbation. The study aim is two-fold; firstly to prospectively explore acceptance and uptake of post-exacerbation PR and secondly to identify possible clusters of patients' illness perceptions following hospitalisation for an exacerbation of COPD., Methods: Patients admitted to hospital with an exacerbation of COPD were recruited to a prospective observational study. Self-reported illness perceptions, mood, health status and self-efficacy were assessed. Acceptance and uptake of PR were recorded at six months. Cluster analysis of Illness Perceptions Questionnaire-Revised data was used to establish groups of patients holding distinct beliefs., Results: 128 patients were recruited. Acceptance and uptake of PR following an acute exacerbation was poor with only 9% (n = 11) completing the programme. Cluster analysis revealed three distinct groups: Cluster 1 'in control' (n = 52), Cluster 2 'disengaged' (n = 36) and Cluster 3 'distressed' (n = 40). Significant between-cluster differences were observed in mood, health status and self-efficacy (p < 0.01). Acceptance and uptake of PR did not differ between clusters., Conclusions: Acceptance/uptake of post-exacerbation PR was found to be poor. Three distinct illness schema exist in patients following an acute exacerbation. This information may be useful in developing novel psychologically-informed interventions designed to reduce feelings of distress and perhaps facilitate a PR intervention for this vulnerable population., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: To test the accuracy of a multi-sensor activity monitor (SWM) in detecting slow walking speeds in patients with chronic obstructive pulmonary disease (COPD)., Background: Concerns have been expressed regarding the use of pedometers in patient populations. Although activity monitors are more sophisticated devices, their accuracy at detecting slow walking speeds common in patients with COPD has yet to be proven., Methods: A prospective observational study design was employed. An incremental shuttle walk test (ISWT) was completed by 57 patients with COPD wearing an SWM. The ISWT was repeated by 20 patients wearing the same SWM., Results: Differences were identified between metabolic equivalents (METS) and between step-count across five levels of the ISWT (p < 0.001). Good within monitor reproducibility between two ISWT was identified for total energy expenditure and step-count (p < 0.001)., Conclusions: The SWM is able to detect slow (standardized) speeds of walking and is an acceptable method for measuring physical activity in individuals disabled by COPD., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Neuromuscular electrical stimulation (NMES) has shown to improve skeletal muscle strength and exercise capacity in stable patients with chronic obstructive pulmonary disease (COPD). Variations in NMES protocols are considerable. We aimed to compare changes in muscle strength after high-frequency and low-frequency NMES in patients admitted to hospital with an acute exacerbation of COPD., Methods: Patients were referred for inpatient (IP) rehabilitation during hospitalisation for an acute worsening of their COPD. They received 30-minute daily NMES to both quadriceps at a frequency of 35 or 50 Hz. NMES intensity was titrated to patients' tolerance. Isometric quadriceps muscle strength and endurance walking (ESWT) time were measured at baseline and on hospital discharge., Results: A total of 10 patients in each treatment group underwent NMES during hospitalisation (mean [SD] age 68.0 [±7.4] years, FEV1 0.99 L [±0.58], FEV1/FVC 47% [± 27%], MRC 5 [IQR ±1]). There were no significant differences in baseline characteristics between groups. Muscle strength (legs combined) increased in both groups regardless of the NMES frequency used (35 Hz--3.8 ± 4.9; 50 Hz--3.4 ± 5.5 kg). This was only significant within the 35 Hz group. The change in ESWT also showed a trend to increase in both groups (35 Hz--109 ± 92.7; 50 Hz--145.6 ± 94.7). There was no significant difference between groups for either outcome., Conclusion: NMES is a feasible intervention to improve muscle strength in a cohort of patients admitted with an exacerbation of COPD. The response appears to be independent of the frequency used and both were well-tolerated., (Copyright © 2012 John Wiley & Sons, Ltd.)

Background: Skeletal muscle dysfunction is a systemic feature of chronic obstructive pulmonary disease (COPD), contributing to morbidity and mortality. Physical training improves muscle mass and function in COPD, but the molecular regulation therein is poorly understood., Methods: Candidate genes and proteins regulating muscle protein breakdown (ubiquitin proteasome pathway), muscle protein synthesis (phosphatidylinositol 3 kinase/Akt/mammalian target of rapamycin pathway), myogenesis (MyoD, myogenin and myostatin) and transcription (FOXO1, FOXO3 and RUNX1) were determined in quadriceps muscle samples taken at four time points over 8 weeks of knee extensor resistance training (RT) in patients with COPD and healthy controls (HCs). Patients with COPD were randomly allocated to receive protein/carbohydrate or placebo supplements during RT., Results: 59 patients with COPD (mean (SD) age 68.0 (9.3) years, forced expiratory volume in 1 s (FEV1) 46.9 (17.8) % predicted) and 21 HCs (66.1 (4.8) years, 105.0 (21.6) % predicted) were enrolled. RT increased lean mass (~5%) and strength (~20%) in all groups. Absolute work done during RT was lower throughout in patients with COPD compared with HCs. RT resulted in increases (from basal) in catabolic, anabolic, myogenic and transcription factor protein expression at 24 h, 4 weeks and 8 weeks of exercise in HCs. This response was blunted in patients with COPD, except for myogenic signalling, which was similar. Nutritional supplementation did not augment functional or molecular responses to RT., Conclusions: The potential for muscle rehabilitation in response to RT is preserved in COPD. Except for markers of myogenesis, molecular responses to RT are not tightly coupled to lean mass gains but reflect the lower work done during RT, suggesting some caution when identifying molecular targets for intervention. Increasing post-exercise protein and carbohydrate intake is not a prerequisite for a normal training response in COPD.

Background: Quantifying the improvements in lower limb or quadriceps muscle mass following resistance training (RT), is an important outcome measure in COPD. Ultrasound is a portable, radiation free imaging technique that can measure the size of superficial muscles belonging to the quadriceps group such as the rectus femoris, but has not been previously used in COPD patients following RT. We compared the responsiveness of ultrasound derived measures of quadriceps mass against dual energy x-ray absorptiometry (DEXA), in patients with COPD and healthy controls following a programme of high intensity knee extensor RT., Methods: Portable ultrasound was used to assess the size of the dominant quadriceps in 45 COPD patients and 19 healthy controls-before, during, and after 8 weeks of bilateral high intensity isokinetic knee extensor RT. Scanning was performed at the mid-thigh region, and 2 indices of quadriceps mass were measured-rectus femoris cross-sectional area (RFcsa) and quadriceps muscle thickness (Qt). Thigh lean mass (Tdexa) was determined by DEXA., Results: Training resulted in a significant increase in Tdexa, RFcsa and Qt in COPD patients [5.7%, 21.8%, 12.1% respectively] and healthy controls [5.4%, 19.5%, 10.9 respectively]. The effect size for the changes in RFcsa (COPD= 0.77; Healthy=0.83) and Qt (COPD=0.36; Healthy=0.78) were greater than the changes in Tdexa (COPD=0.19; Healthy=0.26) following RT., Conclusions: Serial ultrasound measurements of the quadriceps can detect changes in muscle mass in response to RT in COPD. The technique has good reproducibility, and may be more sensitive to changes in muscle mass when compared to DEXA., Trial Registration: http://www.controlled-trials.com (Identifier: ISRCTN22764439).