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Pedometer step count improves with pulmonary rehabilitation and deteriorates with time. The MCID for improvement and deterioration is 427 and -456 steps, respectively, but there is uncertainty about the reliability of these estimates. https://bit.ly/3ci97Jh., Competing Interests: Conflict of interest: O. Polgar has nothing to disclose. Conflict of interest: S. Patel has nothing to disclose. Conflict of interest: J.A. Walsh has nothing to disclose. Conflict of interest: R.E. Barker has nothing to disclose. Conflict of interest: S.F. Clarke has nothing to disclose. Conflict of interest: W.D-C. Man reports personal fees from Jazz Pharmaceuticals, Mundipharma and Novartis, grants from Pfizer, nonfinancial support from GSK, and grants from the National Institute for Health Research and the British Lung Foundation, outside the submitted work. Conflict of interest: C.M. Nolan reports personal fees for teaching on a course organised by Novartis outside the submitted work., (Copyright ©The authors 2021.)

Pulmonary rehabilitation (PR) following hospitalisations for acute exacerbation of COPD (AECOPD) is associated with improved exercise capacity and quality of life, and reduced readmissions. However, referral for, and uptake of, post-hospitalisation PR are low. In this prospective cohort study of 291 consecutive hospitalisations for AECOPD, COPD discharge bundles delivered by PR practitioners compared with non-PR practitioners were associated with increased PR referral (60% vs 12%, p<0.001; adjusted OR: 14.46, 95% CI: 5.28 to 39.57) and uptake (40% vs 32%, p=0.001; adjusted OR: 8.60, 95% CI: 2.51 to 29.50). Closer integration between hospital and PR services may increase post-hospitalisation PR referral and uptake., Competing Interests: Competing interests: REB, SSCK, SFC, JW, CMN, SEJ, SP, JAW, MM, MF and NSH have no competing interests to report. WM reports personal fees from Jazz Pharmaceuticals, personal fees from Mundipharma, personal fees from Novartis, grants from Pfizer, non-financial support from GSK, grants from National Institute for Health Research, grants from British Lung Foundation, outside the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Many trials supporting the benefits of pulmonary rehabilitation (PR) have used specialist exercise equipment, such as treadmills and cycle ergometers. However, access to specialist equipment may not be feasible in some settings. There is growing interest in delivering PR programmes with minimal, low-cost equipment, but uncertainty remains regarding their efficacy compared with programmes using specialist equipment., Methods: Using propensity score matching, 318 consecutive patients with COPD undergoing supervised PR using minimal equipment (PR-min) were compared 1:1 with a control group of 318 patients with COPD who underwent supervised PR using specialist equipment (PR-gym). A non-inferiority analysis was performed for the primary outcome (incremental shuttle walk (ISW)) and secondary outcomes (Chronic Respiratory Disease Questionnaire (CRQ)-domain and total scores)., Results: Similar improvements in ISW and CRQ-domains were observed in PR-min and PR-gym groups (mean difference ISW: 3 m (95% CI -16 to 9); CRQ-total: 0.9 (95% CI -2.7 to 4.5)). The 95% CI between group differences for ISW and CRQ-total did not cross the predefined non-inferiority margins. However, completion rates were lower in PR-min compared with PR-gym (64% vs 73%; p=0.014)., Conclusions: In patients with COPD, PR delivered using minimal equipment produces clinically significant benefits in exercise capacity and health-related quality of life that are non-inferior to rehabilitation delivered using specialist equipment. This study provides support for the provision of PR using minimal exercise equipment, particularly in areas where access to specialist exercise equipment is limited., Competing Interests: Competing interests: WDCM reports grants from the National Institute for Health Research, during the conduct of the study; grants from Pfizer and the British Lung Foundation, non-financial support from GSK, personal fees from Jazz Pharmaceuticals, Mundipharma and Novartis, outside the submitted work. CMN reports personal fees from Novartis, outside the submitted work. SSCK reports personal fees from Novartis, outside the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Polyneuropathy is defined as the simultaneous dysfunction of several peripheral nerves. In dogs, a number of breeds are predisposed to a variety of immune-mediated and/or degenerative inherited forms of polyneuropathy, with laryngeal paralysis and/or megaesophagus as important clinical features of many of these conditions. This case series describes degenerative and inflammatory polyneuropathies in 7 young Siberian huskies that were categorized based on clinicopathological characteristics as follows: (1) slowly progressive laryngeal paralysis and megaesophagus caused by primary axonal degeneration with large fiber loss (n = 2); (2) slowly progressive polyneuropathy without megaesophagus or laryngeal paralysis caused by primary axonal degeneration with large fiber loss (n = 2); (3) acute inflammatory demyelinating neuropathy causing sensory, motor and autonomic nerve deficits (n = 2); and (4) ganglioradiculitis (sensory neuronopathy; n = 1). Based on the predominantly young age at onset, slow progression, relatedness of affected dogs, and clinical and pathological similarities with inherited neuropathies reported in other dog breeds, a hereditary basis for the degenerative polyneuropathies in Siberian huskies is suspected. However, 5 different mutations in 3 genes known to cause polyneuropathy in other dog breeds ( NDRG1 , ARHGEF10 , or RAB3GAP1 ) were not detected in the affected Siberian huskies suggesting that more genetic variants remain to be identified. This study highlights the varied underlying lesions of polyneuropathies in young Siberian huskies.

Rationale: Pulmonary rehabilitation (PR) after hospitalizations for exacerbations of chronic obstructive pulmonary disease (COPD) improves exercise capacity and health-related quality of life and reduces readmissions. However, posthospitalization PR uptake is low. To date, no trials of interventions to increase uptake have been conducted. Objectives: To study the effect of a codesigned education video as an adjunct to usual care on posthospitalization PR uptake. Methods: The present study was an assessor- and statistician-blinded randomized controlled trial with nested, qualitative interviews of participants in the intervention group. Participants hospitalized with COPD exacerbations were assigned 1:1 to receive either usual care (COPD discharge bundle including PR information leaflet) or usual care plus the codesigned education video delivered via a handheld tablet device at discharge. Randomization used minimization to balance age, sex, FEV 1 % predicted, frailty, transport availability, and previous PR experience. Measurements and Main Results: The primary outcome was PR uptake within 28 days of hospital discharge. A total of 200 patients were recruited, and 196 were randomized (51% female, median FEV 1% predicted, 36 [interquartile range, 27-48]). PR uptake was 41% and 34% in the usual care and intervention groups, respectively ( P  = 0.37), with no differences in secondary (PR referral and completion) or safety (readmissions and death) endpoints. A total of 6 of the 15 participants interviewed could not recall receiving the video. Conclusions: A codesigned education video delivered at hospital discharge did not improve posthospitalization PR uptake, referral, or completion.

The aims of the study were to evaluate the responsiveness of Hospital Anxiety and Depression Scale-Anxiety (HADS-A) subscale and HADS-Depression (HADS-D) subscale to pulmonary rehabilitation (PR) in patients with bronchiectasis compared to a matched group of patients with chronic obstructive pulmonary disease (COPD) and provide estimates of the minimal clinically important difference (MCID) of HADS-A and HADS-D in bronchiectasis. Patients with bronchiectasis and at least mild anxiety or depression (HADS-A ≥ 8 or/and HADS-D ≥ 8), as well as a propensity score-matched control group of patients with COPD, underwent an 8-week outpatient PR programme (two supervised sessions per week). Within- and between-group changes were calculated in response to PR. Anchor- and distribution-based methods were used to estimate the MCID. HADS-A and HADS-D improved in response to PR in both patients with bronchiectasis and those with COPD (median (25th, 75th centile)/mean (95% confidence interval) change: HADS-A change: bronchiectasis -2 (-5, 0), COPD -2 (-4, 0); p = 0.43 and HADS-D change: bronchiectasis -2 (-2 to -1), COPD -2 (-3 to -2); p = 0.16). Using 26 estimates, the MCID for HADS-A and HADS-D was -2 points. HADS-A and HADS-D are responsive to PR in patients with bronchiectasis and symptoms of mood disorder, with an MCID estimate of -2 points.

Remote models of pulmonary rehabilitation (PR) are vital with suspension of face-to-face activity during the COVID-19 pandemic. We surveyed digital access and behaviours and PR delivery preferences of current PR service users. There was significant heterogeneity in access to and confidence in using the Internet with 31% having never previously accessed the Internet, 48% confident using the Internet and 29% reporting no interest in accessing any component of PR through a Web-based app. These data have implications for the remote delivery of PR during the COVID-19 pandemic and raise questions about the current readiness of service users to adopt Web-based delivered models of PR.

Exercise training confers health benefits for people with chronic obstructive pulmonary disease (COPD). This article reviews the evidence for several exercise training modalities shown to be beneficial among individuals with COPD. These modalities include aerobic, resistance, nonlinear periodized, upper limb and balance training, as well as yoga, Tai Chi, inspiratory muscle training, whole body vibration training and neuromuscular electrical stimulation. The literature pertaining to each modality was critically reviewed, and information on the rationale, mechanism(s) of action (where known), benefits, and exercise prescription is described to facilitate easy implementation into clinical practice.

Background: Cachexia is an important extra-pulmonary manifestation of chronic obstructive pulmonary disease (COPD) presenting as unintentional weight loss and altered body composition. Previous studies have focused on the relative importance of body composition compared with body mass rather than the relative importance of dynamic compared with static measures. We aimed to determine the prevalence of cachexia and pre-cachexia phenotypes in COPD and examine the associations between cachexia and its component features with all-cause mortality., Methods: We enrolled 1755 consecutive outpatients with stable COPD from two London centres between 2012 and 2017, stratified according to European Respiratory Society Task Force defined cachexia [unintentional weight loss >5% and low fat-free mass index (FFMI)], pre-cachexia (weight loss >5% but preserved FFMI), or no cachexia. The primary outcome was all-cause mortality. We calculated hazard ratios (HRs) using Cox proportional hazards regression for cachexia classifications (cachexia, pre-cachexia, and no cachexia) and component features (weight loss and FFMI) and mortality, adjusting for age, sex, body mass index, and disease-specific prognostic markers., Results: The prevalence of cachexia was 4.6% [95% confidence interval (CI): 3.6-5.6] and pre-cachexia 1.6% (95% CI: 1.0-2.2). Prevalence was similar across sexes but increased with worsening Global Initiative for Chronic Obstructive Pulmonary Disease spirometric stage and Medical Research Council dyspnoea score (all P < 0.001). There were 313 (17.8%) deaths over a median (interquartile range) follow-up duration 1089 (547-1704) days. Both cachexia [HR 1.98 (95% CI: 1.31-2.99), P = 0.002] and pre-cachexia [HR 2.79 (95% CI: 1.48-5.29), P = 0.001] were associated with increased mortality. In multivariable analysis, the unintentional weight loss feature of cachexia was independently associated with mortality [HR 2.16 (95% CI: 1.31-3.08), P < 0.001], whereas low FFMI was not [HR 0.88 (95% CI: 0.64-1.20), P = 0.402]. Sensitivity analyses using body mass index-specific, age-specific, and gender-specific low FFMI values found consistent findings., Conclusions: Despite the low prevalence of cachexia and pre-cachexia, both confer increased mortality risk in COPD, driven by the unintentional weight loss component. Our data suggest that low FFMI without concurrent weight loss may not confer the poor prognosis as previously reported for this group. Weight loss should be regularly monitored in practice and may represent an important target in COPD management. We propose the incorporation of weight monitoring into national and international COPD guidance., (© 2019 The Authors Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Home-based exercise has been proposed as an equivalent treatment strategy to supervised outpatient pulmonary rehabilitation (PR), but it is not known whether its implementation into clinical practice produces similar benefits to those observed in trials. We compared the real-world responses of 154 patients with COPD undergoing home-based exercise with a matched group attending supervised PR. We observed smaller improvements in exercise capacity with home-based exercise compared with PR, but similar improvements in quality of life. We propose that supervised PR remains the standard of care, with home-based exercise a less effective alternative for those unable to attend PR., Competing Interests: Competing interests: WM reports grants from National Institute for Health Research during the conduct of the study; grants from Pfizer, non-financial support from GSK, personal fees from Mundipharma, personal fees from Novartis, outside the submitted work., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Health status is increasingly used in clinical practice to quantify symptom burden and as a clinical trial end-point in patients with interstitial lung disease (ILD). The King's Brief Interstitial Lung Disease (KBILD) questionnaire is a brief, validated 15-item, disease-specific, health-related quality of life questionnaire that is increasingly used in clinical trials, but little data exist regarding the minimum clinically important difference (MCID). Using pulmonary rehabilitation as a model, we aimed to determine the responsiveness of KBILD and provide estimates of the MCID.KBILD scores, Chronic Respiratory Questionnaire (CRQ) scores, Medical Research Council (MRC) Dyspnoea score and incremental shuttle walk test (ISWT) distance were measured in 209 patients with ILD (105 with idiopathic pulmonary fibrosis (IPF)) before and after an outpatient pulmonary rehabilitation programme. Changes with intervention and Cohen's effect size were calculated. Anchor-based (linear regression and receiver operating characteristic plots) or distribution-based approaches (0.5 sd and standard error of measurement) were used to estimate the MCID of KBILD domain and total scores.KBILD, CRQ, MRC Dyspnoea and ISWT improved with intervention, and the effect sizes of KBILD domain and total scores ranged from 0.28 to 0.38. Using anchor-based estimates, the MCID estimates for KBILD-Psychological, KBILD-Breathlessness and activities, and KBILD-Total were 5.4, 4.4 and 3.9 points, respectively. Using distribution-based methods, the MCID estimate for KBILD-Chest symptoms was 9.8 points. The MCID estimates for KBILD in IPF patients were similar.In patients with ILD and IPF, KBILD is responsive to intervention with an estimated MCID of 3.9 points for the total score., Competing Interests: Conflict of interest: C.M. Nolan has nothing to disclose. Conflict of interest: S.S. Birring reports fees paid to King's College Hospital for use of KBILD from Roche, Boehringer Ingelheim and Galapagos, outside the submitted work. Conflict of interest: M. Maddocks reports grants (CDF-2017-10-009 and HSDR 16/02/18) from NIHR, outside the submitted work. Conflict of interest: T.M. Maher has, via his institution, received industry-academic funding from GlaxoSmithKline R&D and UCB, and has received consultancy or speakers fees from Apellis, AstraZeneca, aTyr Pharma, Bayer, Biogen Idec, Boehringer Ingelheim, Celgene, Galapagos, GlaxoSmithKline R&D, Indalo, Pliant, ProMetic, Roche, Samumed and UCB. Conflict of interest: S. Patel has nothing to disclose. Conflict of interest: R.E. Barker has nothing to disclose. Conflict of interest: S.E. Jones has nothing to disclose. Conflict of interest: J.A. Walsh has nothing to disclose. Conflict of interest: S.C. Wynne has nothing to disclose. Conflict of interest: P.M. George reports personal fees for lecturing and nonfinancial support for meeting attendance from Boehringer Ingelheim and Roche Pharmaceuticals, personal fees for lecturing from Teva, outside the submitted work. Conflict of interest: W.D-C. Man reports grants from National Institute for Health Research, during the conduct of the study; grants from Pfizer, nonfinancial support from GlaxoSmithKline, personal fees from Mundipharma and Novartis, outside the submitted work., (Copyright ©ERS 2019.)

This article contains highlights and a selection of the scientific advances from the European Respiratory Society's Clinical Assembly (Assembly 1 and its five respective groups) that were presented at the 2018 European Respiratory Society International Congress in Paris, France. The most relevant topics from each of the groups will be discussed, covering a wide range of areas including clinical problems, rehabilitation and chronic care, thoracic imaging, interventional pulmonology, and general practice and primary care. The newest research, actual data and highlight sessions will be discussed., Competing Interests: Conflict of interest: L.E.G.W. Vanfleteren reports receiving personal fees from AstraZeneca, Chiesi, PulmonX, GSK and Novartis, outside the submitted work. Conflict of interest: I. Ojanguren reports receiving grants from Mundipharma, speaker's fees from Boehringer Ingelheim, AstraZeneca, Teva and Novartis, and consulting fees from GSK, outside the submitted work. Conflict of interest: C.M. Nolan reports that she is co-author on one of the abstracts presented in this article. Conflict of interest: F.M.E. Franssen reports receiving personal fees from AstraZeneca, Chiesi, Boehringer Ingelheim, GSK, Teva and Novartis, outside the submitted work. Conflict of interest: V. Andrianopoulos has nothing to disclose Conflict of interest: A. Grgic has nothing to disclose. Conflict of interest: M. van Dijk has nothing to disclose. Conflict of interest: D.J. Slebos reports receiving reimbursement, devices for treatments for clinical trial trials performed at his institution (NCT01101958, NCT01796392 and NCT02025205), reimbursement for travel expenses, and speakers’ fees for presentations at scientific and educational meetings from PulmonX Inc. (USA); reimbursement for clinical trial trials performed in his institution (NCT02058459 and NCT01483534), devices for treatments, reimbursement for travel expenses, and speakers’ fees for presentations at scientific and educational meetings from Nuvaira Inc. (USA); reimbursement for clinical trial trials performed in his institution, devices for treatments, reimbursement for travel expenses and speakers’ fees for presentations at scientific and educational meetings from, and has acted as a physician advisor to CSA Medical (USA); reimbursement for clinical trial trials performed in his institution (NCT02059057, NCT02179125, NCT01608490, NCT01421082, NCT01328899 and NCT01220908), devices for treatments, reimbursement for travel expenses, speakers’ fees for presentations at scientific and educational meetings from, and has acted as a physician advisor to PneumRx/BTG (USA/UK), outside the submitted work. Conflict of interest: He is co-author on one of the abstracts presented in this article. Conflict of interest: L. Daines has nothing to disclose. Conflict of interest: J.W.H. Kocks reports receiving grants and personal fees from AstraZeneca and Boehringer Ingelheim, personal fees and nonfinancial support from GSK, grants from Chiesi and Mundi Pharma, outside the submitted work. He is an author of one of the presentations mentioned in this article. As Secretary of ERS Assembly 1, he was co-responsible in developing the symposium. Conflict of interest: N. Kahn has nothing to disclose.

The 4-m gait speed (4MGS), a simple physical performance measure and surrogate marker of frailty, consistently predicts adverse prognosis in older adults. We hypothesised that 4MGS could predict all-cause mortality and nonelective hospitalisation in patients with idiopathic pulmonary fibrosis (IPF).4MGS and lung function were measured at baseline in 130 outpatients newly diagnosed with IPF. Survival status and nonelective hospital admissions were recorded over 1 year. We assessed the predictive value of 4MGS (as a continuous variable and as a binary variable: slow versus preserved 4MGS) by calculating hazard ratios using Cox proportional regression, adjusting for potential confounding variables. Receiver operating characteristic curves assessed discrimination between the multivariable regression models and established prognostic indices.Continuous 4MGS and slow 4MGS were independent predictors of all-cause mortality (4MGS: HR 0.03, 95% CI 0.01-0.31; p=0.004; slow 4MGS: 2.63, 95% CI 1.01-6.87; p=0.049) and hospitalisation (4MGS: HR 0.02, 95% CI 0.01-0.14; p<0.001; slow 4MGS: 2.76, 95% CI 1.16-6.58; p=0.02). Multivariable models incorporating 4MGS or slow 4MGS had better discrimination for predicting mortality than either the gender, age and lung physiology index or Composite Physiologic Index.In patients with IPF, 4MGS is an independent predictor of all-cause mortality and nonelective hospitalisation., Competing Interests: Conflict of interest: C.M. Nolan has nothing to disclose. Conflict of interest: M. Maddocks reports fellowship and project grants CDF-2017-10-009 and HSDR 16/02/18 from the NIHR, outside the submitted work. Conflict of interest: T.M. Maher has, via his institution, received industry-academic funding from GSK R&D and UCB, and has received consultancy or speakers fees from Apellis, AstraZeneca, aTyr Pharma, Bayer, Biogen Idec, Boehringer Ingelheim, Celgene, Galapagos, GlaxoSmithKline R&D, Indalo, Pliant, ProMetic, Roche, Samumed and UCB. Conflict of interest: W. Banya has nothing to disclose. Conflict of interest: S. Patel has nothing to disclose. Conflict of interest: R.E. Barker has nothing to disclose. Conflict of interest: S.E. Jones has nothing to disclose. Conflict of interest: P. George reports speaker fees, honoraria and conference attendance support from Boehringer Ingelheim and Roche Pharmaceuticals, outside the submitted work. Conflict of interest: P. Cullinan has nothing to disclose. Conflict of interest: W.D-C. Man reports grants from the NIHR, during the conduct of the study; grants from Pfizer, nonfinancial support from GSK, and personal fees from Mundipharma and Novartis, outside the submitted work., (Copyright ©ERS 2019.)

International guidelines recommend pulmonary rehabilitation for patients with bronchiectasis, supported by small trials and data extrapolated from chronic obstructive pulmonary disease (COPD). However, it is unknown whether real-life data on completion rates and response to pulmonary rehabilitation are similar between patients with bronchiectasis and COPD.Using propensity score matching, 213 consecutive patients with bronchiectasis referred for a supervised pulmonary rehabilitation programme were matched 1:1 with a control group of 213 patients with COPD. Completion rates, change in incremental shuttle walk (ISW) distance and change in Chronic Respiratory Disease Questionnaire (CRQ) score with pulmonary rehabilitation were compared between groups.Completion rate was the same in both groups (74%). Improvements in ISW distance and most domains of the CRQ with pulmonary rehabilitation were similar between the bronchiectasis and COPD groups (ISW distance: 70 versus 63 m; CRQ-Dyspnoea: 4.8 versus 5.3; CRQ-Emotional Function: 3.5 versus 4.6; CRQ-Mastery: 2.3 versus 2.9; all p>0.20). However, improvements in CRQ-Fatigue with pulmonary rehabilitation were greater in the COPD group (bronchiectasis 2.1 versus COPD 3.3; p=0.02).In a real-life, propensity-matched control study, patients with bronchiectasis show similar completion rates and improvements in exercise and health status outcomes as patients with COPD. This supports the routine clinical provision of pulmonary rehabilitation to patients with bronchiectasis., Competing Interests: Conflict of interest: S. Patel has nothing to disclose. Conflict of interest: A.D. Cole has nothing to disclose. Conflict of interest: C.M. Nolan has nothing to disclose. Conflict of interest: R.E. Barker has nothing to disclose. Conflict of interest: S.E. Jones has nothing to disclose. Conflict of interest: S. Kon has nothing to disclose. Conflict of interest: J. Cairn has nothing to disclose. Conflict of interest: M. Loebinger has nothing to disclose. Conflict of interest: R. Wilson has nothing to disclose. Conflict of interest: W.D-C. Man reports grants from Pfizer, non-financial support from GSK, and personal fees from Mundipharma and Novartis, outside the submitted work., (Copyright ©ERS 2019.)

Imprinted genes are epigenetically modified in a parent-of-origin dependent manner and as a consequence are differentially expressed, with one allele typically expressed while the other is repressed. In canine, the insulin like growth factor 2 receptor gene (IGF2R) is imprinted with predominant expression of the maternally inherited allele. Because imprinted genes usually occur in clusters, we examined the allelic expression pattern of the gene encoding the canine Mas receptor (MAS1), which is located upstream of IGF2R on canine chromosome 1 and is highly conserved in mammals. In this report we describe monoallelic expression of canine MAS1 in the neonatal umbilical cord of several individuals and we identify the expressed allele as maternally inherited. These data suggest that canine MAS1 is an imprinted gene., (© 2018 Stichting International Foundation for Animal Genetics.)

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are one of the most common causes of emergency hospital admission and place great burden upon healthcare systems. Furthermore, AECOPD represent an important life event for patients, and are associated with significant reductions in physical activity, skeletal muscle function, exercise tolerance and health-related quality of life. Pulmonary rehabilitation, an intervention comprising supervised exercise-training and education, may counteract these negative consequences and target modifiable risk factors for hospital readmission. A recent Cochrane systematic review included 20 randomized controlled trials comparing pulmonary rehabilitation after exacerbation of COPD versus conventional care. Overall, the evidence supports moderate to large effects on health-related quality of life and exercise capacity. However, there is substantial heterogeneity across studies, and more recent studies have been more equivocal, including around hospital readmissions, particularly when rehabilitation is started in the inpatient setting. In this narrative review, we examine the rationale for pulmonary rehabilitation following AECOPD with a particular focus on skeletal muscle function, review the current evidence for pulmonary rehabilitation in the AECOPD setting, and identify areas that require future research, including the structure and nature of the intervention, improving uptake and adherence, and the role of alternative rehabilitation strategies for patients with AECOPD., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background and Objective: Usual gait speed over 4 m (4MGS) is an established functional performance measure in older adults that consistently predicts adverse health outcomes, but few data exist in idiopathic pulmonary fibrosis (IPF). We assessed the reliability of 4MGS, its relationship with established outcome measures and its responsiveness to pulmonary rehabilitation., Methods: In four prospective IPF cohorts, 4MGS inter-observer (n = 46) and test-retest (n = 46) reliability, concurrent validity (n = 65 and n = 62) and responsiveness (n = 60) were determined. The phenotypic characteristics of all patients stratified according to slow 4MGS (<0.8 m/s) were compared, including lung function parameters, HRCT of the chest, 6-min walking distance (6MWD), Medical Respiratory Council (MRC) dyspnoea score, King's Brief Interstitial Lung Disease (KBILD) questionnaire and Gender, Age and lung Physiology (GAP) prognostic index., Results: Intra-class correlation coefficients for inter-observer and test-retest reliability were 0.996 and 0.983, respectively. There was a strong association between 4MGS and 6MWD (r = 0.76; P < 0.0001) and moderate correlations with MRC (r = -0.56), KBILD (r = 0.44) and GAP index (r = -0.41); all P < 0.005. 4MGS improved significantly with pulmonary rehabilitation (mean (95% CI) change: 0.16 (0.12-0.20) m/s), effect size 0.65. Patients with slow 4MGS had significantly worse exercise performance (6MWD: -167 (-220 to -133) m), dyspnoea, health status and prognosis index than those with preserved 4MGS, despite similar lung function and HRCT parameters., Conclusion: 4MGS is a simple, reliable, valid and responsive tool that may detect a patient phenotype with worse exercise performance, dyspnoea, health status and prognosis index in stable IPF., (© 2017 Asian Pacific Society of Respirology.)

The incremental shuttle walk (ISW) is well validated in COPD but limited psychometric data restrict its use in idiopathic pulmonary fibrosis (IPF). Study 1: 50 patients performed the ISW and 6 min walk test (6MWT). Study 2: 72 patients completed the ISW before and after pulmonary rehabilitation (PR). The ISW correlated strongly with 6MWT distance (r=0.81,p<0.0001). Mean (95% confidence interval) improvement in ISW with PR was 54 (38 to 70) m with an effect size of 0.29. Distribution-based and anchor-based minimum clinically important difference (MCID) estimates ranged from 31 to 46 m. The ISW is valid and responsive in IPF, with an anchor-based MCID estimate similar to that observed in chronic obstructive pulmonary disease., Trial Registration Number: Pre-results; NCT02530736, NCT02436278., Competing Interests: Competing interests: VD, SP and REB are funded by the NIHR Respiratory Biomedical Research Unit, Royal Brompton and Harefield NHS Foundation Trust and Imperial College. VD is funded by NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for Northwest London. MM is supported by Cicely Saunders International and CLAHRC for South London. SSCK is funded by The Hillingdon Hospital and The Royal Brompton and Harefield NHS Foundation Trust. TMM is supported by an NIHR Clinician Scientist Fellowship (NIHR Ref: CS-2013-13-017). WDCM is partly funded by the NIHR CLAHRC for NW London. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. All other author have no competing interest to declare., (© 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.)

Rationale: Increasing physical activity is a key therapeutic aim in chronic obstructive pulmonary disease (COPD). Pulmonary rehabilitation (PR) improves exercise capacity, but there is conflicting evidence regarding its ability to improve physical activity levels., Objectives: To determine whether using pedometers as an adjunct to PR can enhance time spent in at least moderate-intensity physical activity (time expending ≥3 metabolic equivalents [METs]) by people with COPD., Methods: In this single-blind randomized controlled trial, participants were assigned 1:1 to receive a control intervention (PR comprising 8 wk, two supervised sessions per week) or the trial intervention (PR plus pedometer-directed step targets, reviewed weekly for 8 wk). In the randomization process, we used minimization to balance groups for age, sex, FEV 1 percent predicted, and baseline exercise capacity and physical activity levels. Outcome assessors and PR therapists were blinded to group allocation. The primary analysis was based on the intention-to-treat principle., Measurements and Main Results: The primary outcome was change from baseline to 8 weeks in accelerometer-measured daily time expending at least 3 METs. A total of 152 participants (72% male; mean [SD] FEV 1 percent predicted, 50.5% [21.2]; median [first quartile, third quartile] time expending ≥3 METs, 46 [21, 92] min) were enrolled and assigned to the intervention (n = 76) or control (n = 76) arm. There was no significant difference in change in time expending at least 3 METs between the intervention and control groups at 8 weeks (median [first quartile, third quartile] difference, 0.5 [-1.0, 31.0] min; P = 0.87) or at the 6-month follow-up (7.0 [-9, 27] min; P = 0.16)., Conclusions: Pedometer-directed step-count targets during an outpatient PR program did not enhance moderate-intensity physical activity levels in people with COPD. Clinical trial registered with www.clinicaltrials.gov (NCT01719822).

Background: The EQ-5D, a generic health status questionnaire that is widely used in health economic evaluation, was recently expanded to the EQ-5D-5L to address criticisms of unresponsiveness and ceiling effect., Aims: To describe the validity, responsiveness and minimum important difference of the EQ-5D-5L in COPD., Methods: Study 1: The validity of the EQ-5D-5L utility index and visual analogue scale (EQ-VAS) was compared with four established disease-specific health status questionnaires and other measures of disease severity in 616 stable outpatients with COPD. Study 2: The EQ-5D-5L utility index and EQ-VAS were measured in 324 patients with COPD before and after 8 weeks of pulmonary rehabilitation. Distribution and anchor-based approaches were used to estimate the minimum important difference., Results: There were moderate-to-strong correlations between utility index and EQ-VAS with disease-specific questionnaires (Pearson's r=0.47-0.72). A ceiling effect was seen in 7% and 2.6% of utility index and EQ-VAS. Utility index decreased (worsening health status) with indices of worsening disease severity. With rehabilitation, mean (95% CI) changes in utility index and EQ-VAS were 0.065 (0.047 to 0.083) and 8.6 (6.5 to 10.7), respectively, with standardised response means of 0.39 and 0.44. The mean (range) anchor estimates of the minimum important difference for utility index and EQ-VAS were 0.051 (0.037 to 0.063) and 6.9 (6.5 to 8.0), respectively., Conclusions: The EQ-5D-5L is a valid and responsive measure of health status in COPD and may provide useful additional cost-effectiveness data in clinical trials., (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: Skeletal muscle dysfunction and exercise intolerance are common in severe chronic obstructive pulmonary disease (COPD). We assessed the effectiveness of neuromuscular electrical stimulation (NMES) as a home-based exercise therapy., Methods: In this double-blind, placebo-controlled trial, undertaken across three UK National Health Service sites, we randomly assigned (1:1) adults with COPD, a forced expiratory volume in 1 s (FEV1) less than 50% predicted, and incapacitating breathlessness (Medical Research Council dyspnoea scale ≥4) to receive active or placebo NMES, daily over a 6-week period. Randomisation was by an independent system using minimisation to balance age, GOLD stage, and quadriceps strength. Participants and outcome assessors were masked to group allocation. The primary endpoint was change in 6-min walk test (6MWT) distance at 6 weeks. Analysis was by intention to treat. The trial was registered as ISRCTN15985261 and is now closed., Findings: Between June 29, 2012, and July 4, 2014, we enrolled 73 participants, of whom 52 participants were randomly assigned; 25 to receive active NMES and 27 to placebo NMES. Change in 6MWT distance was greater in the active NMES group (mean 29·9 [95% CI 8·9 to 51·0]) compared with in the placebo group (-5·7 [-19·9 to 8·4]; mean difference at 6 weeks 35·7 m [95% CI 10·5 to 60·9]; p=0·005). Sensitivity analyses for complete-cases and adjustment for baseline values showed similar results. 6 weeks after stopping the intervention the effect waned (7·3 m [95% CI -32·5 to 47·0]; p=0·50). The proportion of participants who had adverse events was similar between groups (five [20%] in the active NMES group and nine [33%] in the placebo group). Two participants, one from each group, reported persistent erythema, which was considered to be possibly related to NMES and the use of adhesive electrodes., Interpretation: NMES improves functional exercise capacity in patients with severe COPD by enhancing quadriceps muscle mass and function. These data support the use of NMES in the management of patients unable to engage with conventional pulmonary rehabilitation. More work is needed to study how to maintain the effect., Funding: National Institute for Health Research., (Copyright © 2016 Maddocks et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.)

Background: Hospitalisation for acute exacerbations of COPD is associated with high risk of readmission. However, no tool has been validated to stratify patients at discharge for risk of readmission., Aim: To evaluate the ability of the 4 m gait speed (4MGS), a surrogate marker of frailty, to predict risk of future readmission in hospitalised patients with an acute exacerbation of COPD (AECOPD)., Methods: 213 patients hospitalised with an AECOPD were recruited prospectively. 4MGS was measured on day of discharge. Logistic regression models were used to assess the association between 4MGS and readmission at 90 days after discharge., Results: Baseline characteristics of the cohort: 52% men; mean age 72 years; median FEV1 35%predicted. Mean (SD) 4MGS at hospital discharge was 0.61 (0.26) ms(-1). Significant increased rates of all-cause readmission at 90 days were seen across quartiles of decreasing 4MGS (Q4 fastest: 11.5%; Q3: 20.4%; Q2: 30.2%; Q1 slowest: 48.2%; p trend<0.001). Compared with Q4, those in the slowest 4MGS quartile had unadjusted ORs (95% CIs) for 90-day readmission of 7.12 (2.61 to 19.44) for the whole cohort and 11.56 (3.08 to 43.35) in those aged 65 or over. A multivariate model incorporating 4MGS, Charlson Index, hospital admission in past year, FEV1%predicted and number of exacerbations in past year in those aged 65 or over predicted 90-day readmission with a C-statistic of 0.86., Conclusions: The 4MGS, a surrogate marker of physical frailty, independently predicts the risk of readmission in older patients hospitalised for acute exacerbation of COPD., Trial Registration Number: NCT01507415., (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 & Aims: Bioelectrical impedance analysis (BIA) provides a simple method to assess changes in body composition. Raw BIA variables such as phase angle provide direct information on cellular mass and integrity, without the assumptions inherent in estimating body compartments, e.g. fat-free mass (FFM). Phase angle is a strong functional and prognostic marker in many disease states, but data in COPD are lacking. Our aims were to describe the measurement of phase angle in patients with stable COPD and determine the construct and discriminate validity of phase angle by assessing its relationship with established markers of function, disease severity and prognosis., Methods: 502 outpatients with stable COPD were studied. Phase angle and FFM by BIA, quadriceps strength (QMVC), 4-m gait speed (4MGS), 5 sit-to-stand time (5STS), incremental shuttle walk (ISW), and composite prognostic indices (ADO, iBODE) were measured. Patients were stratified into normal and low phase angle and FFM index., Results: Phase angle correlated positively with FFM and functional outcomes (r = 0.35-0.66, p < 0.001) and negatively with prognostic indices (r = -0.35 to -0.48, p < 0.001). In regression models, phase angle was independently associated with ISW, ADO and iBODE whereas FFM was removed. One hundred and seventy patients (33.9% [95% CI, 29.9-38.1]) had a low phase angle. Phenotypic characteristics included lower QMVC, ISW, and 4MGS, higher 5STS, ADO and iBODE scores, and more exacerbations and hospital days in past year. The proportion of patients to have died was significantly higher in patients with low phase angle compared to those with normal phase angle (8.2% versus 3.6%, p = 0.02)., Conclusion: Phase angle relates to markers of function, disease severity and prognosis in patients with COPD. As a directly measured variable, phase angle offers more useful information than fat-free mass indices., (Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Pulmonary rehabilitation (PR) can improve aerobic exercise capacity, health-related quality of life and dyspnoea in patients with chronic obstructive pulmonary disease (COPD). Recent studies have suggested that exercise training may improve blood pressure and arterial stiffness, albeit in small highly selected cohorts. The aim of the study was to establish whether supervised outpatient or unsupervised home PR can reduce peripheral blood pressure. Resting blood pressure was measured in 418 patients with COPD before and after outpatient PR, supervised by a hospital-based team (HOSP). Seventy-four patients with COPD undergoing an unsupervised home-based programme acted as a comparator group (HOME). Despite significant improvements in mean (95% confidence interval) exercise capacity in the HOSP group (56 (50-60) m, p < 0.001) and HOME group (30 (17-42) m, p < 0.001) systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MAP) did not change in either the HOSP (SBP: p = 0.47; DBP: p = 0.06; MAP: p = 0.38) or HOME group (SBP: p = 0.67; DBP: p = 0.38; MAP: p = 0.76). Planned subgroup analysis of HOSP patients with known hypertension and/or cardiovascular disease showed no impact of PR upon blood pressure. PR is unlikely to reduce blood pressure, and by implication, makes a mechanism of action in which arterial stiffness is reduced, less likely., (© The Author(s) 2015.)

An X-linked muscular dystrophy, with deficiency of full-length dystrophin and expression of a low molecular weight dystrophin-related protein, has been described in Japanese Spitz dogs. The aim of this study was to identify the causative mutation and develop a specific test to identify affected cases and carrier animals. Gene expression studies in skeletal muscle of an affected animal indicated aberrant expression of the Duchenne muscular dystrophy (dystrophin) gene and an anomaly in intron 19 of the gene. Genome-walking experiments revealed an inversion that interrupts two genes on the X chromosome, the Duchenne muscular dystrophy gene and the retinitis pigmentosa GTPase regulator gene. All clinically affected dogs and obligate carriers that were tested had the mutant chromosome, and it is concluded that the inversion is the causative mutation for X-linked muscular dystrophy in the Japanese Spitz breed. A PCR assay that amplifies mutant and wild-type alleles was developed and proved capable of identifying affected and carrier individuals. Unexpectedly, a 7-year-old male animal, which had not previously come to clinical attention, was shown to possess the mutant allele and to have a relatively mild form of the disease. This observation indicates phenotypic heterogeneity in Japanese Spitz muscular dystrophy, a feature described previously in humans and Golden Retrievers. With the availability of a simple, fast and accurate test for Japanese Spitz muscular dystrophy, detection of carrier animals and selected breeding should help eliminate the mutation from the breed., (© 2015 Stichting International Foundation for Animal Genetics.)

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

Background and Objective: The Clinical Chronic Obstructive Pulmonary Disease (COPD) Questionnaire (CCQ) is an easy to complete, health-related quality of life questionnaire which has been well-validated in COPD. The responsiveness of the CCQ in chronic respiratory disease patients other than COPD has not been previously described. The study aims were to determine if the CCQ in chronic respiratory disease correlates with other health related quality of life questionnaires, to assess the responsiveness of the CCQ to pulmonary rehabilitation and to determine the minimum important difference., Methods: The CCQ, COPD Assessment Test (CAT), the Chronic Respiratory Questionnaire (CRQ) and St George's Respiratory Questionnaire (SGRQ) were measured in 138 chronic respiratory disease patients completing pulmonary rehabilitation. Change in CCQ with pulmonary rehabilitation was correlated with change in the other questionnaires. The minimum important difference of the CCQ was calculated using distribution and anchor-based approaches., Results: The CCQ, CAT, CRQ and SGRQ improved significantly with rehabilitation with effect sizes of -0.43, -0.26, 0.62, -0.37. Change in CCQ correlated significantly with CAT, CRQ and SGRQ (r = 0.53, -0.64, 0.30, all P < 0.0001). The minimum important difference was -0.42 at the population level and -0.4 at the individual level., Conclusions: The CCQ is responsive to pulmonary rehabilitation in chronic respiratory disease patients, with an MID estimated at -0.4 at the individual level., (© 2014 Asian Pacific Society of Respirology.)

Non-suppurative meningoencephalitis is a breed-restricted canine neuroinflammatory disorder affecting young greyhounds in Ireland. A genetic risk factor is suspected because of the development of disease in multiple siblings and an inability to identify a causative infectious agent. The aim of this study was to examine potential associations between dog leucocyte antigen (DLA) class II haplotype and the presence of the disease. DLA three locus haplotypes were determined in 31 dogs with non-suppurative meningoencephalitis and in 115 healthy control dogs using sequence-based typing (SBT) methods. All dogs were unrelated at the parental level. Two haplotypes (DRB1*01802/DQA1*00101/DQB1*00802 and DRB1*01501/DQA1*00601/DQB1*02201) were significantly (P = 0.0099 and 0.037) associated with the presence of meningoencephalitis, with odds ratios (95% confidence interval) of 5.531 (1.168-26.19) and 3.736 (1.446-9.652), respectively. These results confirm that there is an association between DLA class II haplotype and greyhound meningoencephalitis, suggesting an immunogenetic risk factor for the development of the disease. Greyhound meningoencephalitis may be a suitable model for human neuroinflammatory diseases with an immunogenetic component., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The Clinical COPD Questionnaire (CCQ) is a simple 10-item, health-related quality of life questionnaire (HRQoL) with good psychometric properties. However, little data exists regarding the responsiveness of the CCQ to pulmonary rehabilitation (PR) or the minimal clinically important difference (MCID). The study aims were to assess the responsiveness of the CCQ to PR, to compare the responsiveness of the CCQ to other HRQoL questionnaires and to provide estimates for the MCID., Methods: The CCQ, St George's Respiratory Questionnaire (SGRQ), Chronic Respiratory Questionnaire (CRQ) and COPD Assessment Test (CAT) were measured in 261 patients with COPD before and after outpatient PR. Pre to post PR changes and Cohen's effect size were calculated. Changes in CCQ were compared with changes in other HRQoL questionnaires. Using an anchor-based approach and receiver operating characteristic (ROC) curves, the CCQ change cutoffs that identified patients achieving the known MCID for other health status questionnaires with PR were identified., Results: The CCQ, SGRQ, CRQ and CAT all significantly improved with PR with an effect size of -0.39, -0.33, 0.62 and -0.25, respectively. CCQ change correlated significantly with change in SGRQ, CRQ and CAT (r=0.48, -0.56, 0.54, respectively; all p<0.001). ROC curves consistently identified a CCQ change cutoff of -0.4 as the best discriminating value to identify the MCID for the SGRQ, CRQ and CAT (area under curve: 0.71, 0.75 and 0.77, respectively; all p<0.001)., Conclusions: The CCQ is responsive to PR with an estimated clinically important improvement of -0.4 points. The CCQ is a practical alternative to more time-consuming measures of HRQoL., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Usual gait speed is a consistent predictor of adverse outcomes in community-dwelling elderly people. The reliability and validity of the 4-m gait speed (4MGS) has recently been demonstrated in patients with chronic obstructive pulmonary disease (COPD). The aims of this study were to assess the responsiveness of the 4MGS and to estimate the minimal clinically important difference (MCID). In 301 COPD patients, 4MGS and incremental shuttle walk (ISW) were measured before and after pulmonary rehabilitation. 4MGS and ISW were also measured at baseline and 1 year later in a separate cohort of 162 COPD patients. The MCID of 4MGS was estimated using distribution and anchor-based methods. 4MGS improved significantly with pulmonary rehabilitation (mean change 0.08 m·s(-1), p<0.001). The minimal detectable change at 95% confidence was 0.11 m·s(-1). The MCID was estimated at 0.11 m·s(-1) (anchored against ISW) and 0.08 m·s(-1) (anchored against self-reported improvement). The effect size for 4MGS was greatest in frail individuals. After 12 months, mean 4MGS declined by 0.04 m·s(-1). When anchored against a decline of more than the MCID for ISW, change in 4MGS was -0.11 m·s(-1). The 4MGS is responsive to pulmonary rehabilitation and longitudinal change in COPD, and has potential as a simple functional assessment tool in COPD. The 4MGS may be particularly useful in frail individuals with COPD.

Background: The COPD Assessment Test (CAT) is responsive to change in patients with chronic obstructive pulmonary disease (COPD). However, the minimum clinically important difference (MCID) has not been established. We aimed to identify the MCID for the CAT using anchor-based and distribution-based methods., Methods: We did three studies at two centres in London (UK) between April 1, 2010, and Dec 31, 2012. Study 1 assessed CAT score before and after 8 weeks of outpatient pulmonary rehabilitation in patients with COPD who were able to walk 5 m, and had no contraindication to exercise. Study 2 assessed change in CAT score at discharge and after 3 months in patients admitted to hospital for more than 24 h for acute exacerbation of COPD. Study 3 assessed change in CAT score at baseline and at 12 months in stable outpatients with COPD. We focused on identifying the minimum clinically important improvement in CAT score. The St George's Respiratory Questionnaire (SGRQ) and Chronic Respiratory Questionnaire (CRQ) were measured concurrently as anchors. We used receiver operating characteristic curves, linear regression, and distribution-based methods (half SD, SE of measurement) to estimate the MCID for the CAT; we included only patients with paired CAT scores in the analysis., Findings: In Study 1, 565 of 675 (84%) patients had paired CAT scores. The mean change in CAT score with pulmonary rehabilitation was -2·5 (95% CI -3·0 to -1·9), which correlated significantly with change in SGRQ score (r=0·32; p<0·0001) and CRQ score (r=-0·46; p<0·0001). In Study 2, of 200 patients recruited, 147 (74%) had paired CAT scores. Mean change in CAT score from hospital discharge to 3 months after discharge was -3·0 (95% CI -4·4 to -1·6), which correlated with change in SGRQ score (r=0·47; p<0·0001). In Study 3, of 200 patients recruited, 164 (82%) had paired CAT scores. Although no significant change in CAT score was identified after 12 months (mean 0·6, 95% CI -0·4 to 1·5), change in CAT score correlated significantly with change in SGRQ score (r=0·36; p<0·0001). Linear regression estimated the minimum clinically important improvement for the CAT to range between -1·2 and -2·8 with receiver operating characteristic curves consistently identifying -2 as the MCID. Distribution-based estimates for the MCID ranged from -3·3 to -3·8., Interpretation: The most reliable estimate of the minimum important difference of the CAT is 2 points. This estimate could be useful in the clinical interpretation of CAT data, particularly in response to intervention studies., Funding: Medical Research Council and UK National Institute of Health Research., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Moving from sitting to standing is a common activity of daily living. The five-repetition sit-to-stand test (5STS) is a test of lower limb function that measures the fastest time taken to stand five times from a chair with arms folded. The 5STS has been validated in healthy community-dwelling adults, but data in chronic obstructive pulmonary disease (COPD) populations are lacking., Aims: To determine the reliability, validity and responsiveness of the 5STS in patients with COPD., Methods: Test-retest and interobserver reliability of the 5STS was measured in 50 patients with COPD. To address construct validity we collected data on the 5STS, exercise capacity (incremental shuttle walk (ISW)), lower limb strength (quadriceps maximum voluntary contraction (QMVC)), health status (St George's Respiratory Questionnaire (SGRQ)) and composite mortality indices (Age Dyspnoea Obstruction index (ADO), BODE index (iBODE)). Responsiveness was determined by measuring 5STS before and after outpatient pulmonary rehabilitation (PR) in 239 patients. Minimum clinically important difference (MCID) was estimated using anchor-based methods., Results: Test-retest and interobserver intraclass correlation coefficients were 0.97 and 0.99, respectively. 5STS time correlated significantly with ISW, QMVC, SGRQ, ADO and iBODE (r=-0.59, -0.38, 0.35, 0.42 and 0.46, respectively; all p<0.001). Median (25th, 75th centiles) 5STS time decreased with PR (Pre: 14.1 (11.5, 21.3) vs Post: 12.4 (10.2, 16.3) s; p<0.001). Using different anchors, a conservative estimate for the MCID was 1.7 s., Conclusions: The 5STS is reliable, valid and responsive in patients with COPD with an estimated MCID of 1.7 s. It is a practical functional outcome measure suitable for use in most healthcare settings.

In community-dwelling older adults, usual gait speed over 4 m (4MGS) consistently predicts greater risk of adverse health outcomes. The aims of the present study were to assess the reliability of the 4MGS and the relationship with established health outcome measures in chronic obstructive pulmonary disease (COPD). Test-retest and interobserver reliability of the 4MGS were measured in 80 and 58 COPD patients, respectively. In 586 COPD patients, the 4MGS, as well as forced expiratory volume in 1 s (FEV1), the incremental shuttle walk (ISW), Medical Research Council (MRC) dyspnoea scale and St George's Respiratory Questionnaire (SGRQ) were measured. Participants were stratified according to "slow" (<0.8 m·s(-1)) or "normal" 4MGS (≥0.8 m·s(-1)). Intra-class correlation coefficients for test-retest and interobserver reliability were 0.97 and 0.99, respectively. There was a significant positive correlation between 4MGS with ISW (ρ = 0.78; p<0.001) and a negative correlation with MRC dyspnoea scale and SGRQ (ρ = -0.55 and -0.44; p<0.001 for both). COPD patients with slow 4MGS had significantly reduced ISW and higher MRC dyspnoea scale and SGRQ than those with preserved walking speed, despite similar FEV1 % predicted. The 4MGS is reliable in COPD, correlates with exercise capacity, dyspnoea and health-related quality of life, and has potential as a simple assessment tool in COPD.

Placental development and genomic imprinting coevolved with parental conflict over resource distribution to mammalian offspring. The imprinted genes IGF2 and IGF2R code for the growth promoter insulin-like growth factor 2 (IGF2) and its inhibitor, mannose 6-phosphate (M6P)/IGF2 receptor (IGF2R), respectively. M6P/IGF2R of birds and fish do not recognize IGF2. In monotremes, which lack imprinting, IGF2 specifically bound M6P/IGF2R via a hydrophobic CD loop. We show that the DNA coding the CD loop in monotremes functions as an exon splice enhancer (ESE) and that structural evolution of binding site loops (AB, HI, FG) improved therian IGF2 affinity. We propose that ESE evolution led to the fortuitous acquisition of IGF2 binding by M6P/IGF2R that drew IGF2R into parental conflict; subsequent imprinting may then have accelerated affinity maturation.

Greyhound nonsuppurative meningoencephalitis is an idiopathic breed-associated fatal meningoencephalitis with lesions usually occurring within the rostral cerebrum. This disorder can only be confirmed by postmortem examination, with a diagnosis based upon the unique topography of inflammatory lesions. Our purpose was to describe the magnetic resonance (MR) imaging features of this disease. Four Greyhounds with confirmed Greyhound nonsuppurative meningoencephalitis were evaluated by MR imaging. Lesions predominantly affected the olfactory lobes and bulbs, frontal, and frontotemporal cortical gray matter, and caudate nuclei bilaterally. Fluid attenuation inversion recovery (FLAIR) and T2 weighted spin-echo (T2W) sequences were most useful to assess the nature, severity, extension, and topographic pattern of lesions. Lesions were predominantly T2-hyperintense and T1-isointense with minimal or absent contrast enhancement., (© 2012 Veterinary Radiology & Ultrasound.)

The clinical and clinicopathological features of non-suppurative meningoencephalitis in 30 greyhounds were reviewed. The dogs were from 21 separate litters, comprised both sexes (16 males and 14 females) and ranged in age from five to 18 months. In 14 (66.7 per cent) litters, more than one case was suspected or confirmed, and the number of siblings affected within individual litters ranged from one to seven. Clinical signs were progressive and varied from five days to 12 months in duration; 12 dogs had signs of two weeks' duration or less. The rate of progression of signs was variable. Common features included dullness or lethargy (22), altered behaviour (21), proprioceptive and postural reaction deficits (18), circling (17), ataxia (17), decreased appetite (15) and weight loss (13). No consistent haematological or biochemical abnormalities were identified and serology failed to implicate Toxoplasma gondii or Neospora caninum. Cerebrospinal fluid analysis revealed mild or moderate mononuclear pleocytosis in 12 (70.6 per cent) of 17 dogs. No definitive antemortem diagnosis could be made in any affected dog.

Transcription, translation and subsequent protein modification represent the transfer of genetic information from the archival copy of DNA to the short-lived messenger RNA, usually with subsequent production of protein. Although all cells in an organism contain essentially the same DNA, cell types and functions differ because of qualitative and quantitative differences in their gene expression. Thus, control of gene expression is at the heart of differentiation and development. Epigenetic processes, including DNA methylation, histone modification and various RNA-mediated processes, are thought to influence gene expression chiefly at the level of transcription; however, other steps in the process (for example, translation) may also be regulated epigenetically. The following paper will outline the role epigenetics is believed to have in influencing gene expression.