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No additional data available. Originally Published in: Patel, S., Jones, S.E., Walsh, J.A., Barker, R.E., Polgar, O., Maddocks, M., Hopkinson, N.S., Nolan, C.M. and Man, W.D.-C. (2022) 'The Six-Minute Step Test as an Exercise Outcome in COPD', Annals ATS, 0 (in press), pp. 1-11. DOI: 10.1513/AnnalsATS.202206-516RL. Copyright © 2022 by the American Thoracic Society. The final publication is available at https://www.atsjournals.org/doi/10.1513/AnnalsATS.202206-516RL. NIHR Clinical Doctoral Research Fellowship (NIHR300566); NIHR Clinical Doctoral Research Fellowship (ICA-CDRF-2017-03-018); NIHR Clinical Trials Fellowship (CTF-2017-06-005); British Lung Foundation Project Grant (IPFPG17-15); National Institute Health Research (NIHR) Doctoral Research Fellowship (DRF-2015-08-004); NIHR Research for Patient Benefit PB-PG-0816-20022; NIHR Career Development Fellowship (CDF-2017-10-009); NIHR Applied Research Collaboration South London (NIHR ARC South London) at King’s College Hospital NHS Foundation Trust.

INTRODUCTION Although e-cigarettes can be an effective form of nicotine substitution for adults attempting to quit smoking, their use among children and young people is a concern. Accurate data about this are needed to inform debates over policy and regulation in the UK and elsewhere. METHODS Using data from an online survey of 2,613 people aged 11 to 18 years, conducted by the market research company YouGov in March 2022, we present prevalence estimates of e-cigarette and tobacco use.We use logistic regression models to assess differences in e-cigarette use, tobacco use and use of disposable e-cigarettes across a range of covariates including age, sex, tobacco smoking status, social class and country. RESULTS Among the 18.0% of those surveyed who reported ever having smoked a cigarette, 83.9% were not regular (at least once per week) smokers and 16.1% were (15.1% and 2.9% of the total sample respectively). Among the 19.2% of those surveyed who had ever used an e-cigarette, 79.2% were not regular users, while 20.8% were (15.2% and 4.0% respectively. Regular e-cigarette use was more common than regular tobacco smoking (4.0% vs 2.9%). E-cigarette use was more common among those who also smoked tobacco, with 9.0% of never e-cigarette users ever smoking tobacco, compared with 89.4% of regular e-cigarette users. Both smoking and e-cigarette use were associated with increasing age and use by others within the home, but not with social class. Use of disposable e-cigarettes was reported by 53.8% of those who have ever used an e-cigarette, and more common among girls than boys. DISCUSSION Regular e-cigarette use is now more common than smoking in children and youth, though the majority of this is among those who have also smoked tobacco. Measures to reduce the appeal of e-both e-cigarettes and tobacco to children and young people are warranted.

BackgroundLung volume reduction surgery (LVRS) and bronchoscopic lung volume reduction (BLVR) with endobronchial valves can improve outcomes in appropriately selected patients with emphysema. However, no direct comparison data exist to inform clinical decision making in people who appear suitable for both procedures. Our aim was to investigate whether LVRS produces superior health outcomes when compared with BLVR at 12 months.MethodsThis multicentre, single-blind, parallel-group trial randomised patients from five UK hospitals, who were suitable for a targeted lung volume reduction procedure, to either LVRS or BLVR and compared outcomes at 1 year using the i-BODE score. This composite disease severity measure includes body mass index, airflow obstruction, dyspnoea and exercise capacity (incremental shuttle walk test). The researchers responsible for collecting outcomes were masked to treatment allocation. All outcomes were assessed in the intention-to-treat population.Results88 participants (48% female, mean±sdage 64.6±7.7 years, forced expiratory volume in 1 s percent predicted 31.0±7.9%) were recruited at five specialist centres across the UK and randomised to either LVRS (n=41) or BLVR (n=47). At 12 months follow-up, the complete i-BODE was available in 49 participants (21 LVRS/28 BLVR). Neither improvement in the i-BODE score (LVRS −1.10±1.44versusBLVR −0.82±1.61; p=0.54) nor in its individual components differed between groups. Both treatments produced similar improvements in gas trapping (residual volume percent predicted: LVRS −36.1% (95% CI −54.6– −10%)versusBLVR −30.1% (95% CI −53.7– −9%); p=0.81). There was one death in each treatment arm.ConclusionOur findings do not support the hypothesis that LVRS is a substantially superior treatment to BLVR in individuals who are suitable for both treatments.

Introduction: Although mean physical activity in COPD patients declines by 400–500 steps/day annually, it is unknown whether the natural progression is the same for all patients. We aimed to identify distinct physical activity progression patterns using a hypothesis-free approach and to assess their determinants. Methods: We pooled data from two cohorts (usual care arm of Urban Training [NCT01897298] and PROactive initial validation [NCT01388218] studies) measuring physical activity at baseline and 12 months (Dynaport MoveMonitor). We identified clusters (patterns) of physical activity progression (based on levels and changes of steps/day) using k-means, and compared baseline sociodemographic, interpersonal, environmental, clinical and psychological characteristics across patterns. Results: In 291 COPD patients (mean ± SD 68 ± 8 years, 81% male, FEV1 59 ± 19%pred) we identified three distinct physical activity progression patterns: Inactive (n = 173 [59%], baseline: 4621 ± 1757 steps/day, 12-month change (Δ): −487 ± 1201 steps/day), Active Improvers (n = 49 [17%], baseline: 7727 ± 3275 steps/day, Δ: + 3378 ± 2203 steps/day) and Active Decliners (n = 69 [24%], baseline: 11 267 ± 3009 steps/day, Δ: −2217 ± 2085 steps/day). After adjustment in a mixed multinomial logistic regression model using Active Decliners as reference pattern, a lower 6-min walking distance (RRR [95% CI] 0.94 [0.90–0.98] per 10 m, P = .001) and a higher mMRC dyspnea score (1.71 [1.12–2.60] per 1 point, P = .012) were independently related with being Inactive. No baseline variable was independently associated with being an Active Improver. Conclusions: The natural progression in physical activity over time in COPD patients is heterogeneous. While Inactive patients relate to worse scores for clinical COPD characteristics, Active Improvers and Decliners cannot be predicted at baseline. Introducción: Aunque la actividad física en pacientes con EPOC declina una media anual de 400-500 pasos/día, se desconoce si esta progresión es igual en todos los pacientes. Este estudio pretendió identificar los patrones de progresión de la actividad física mediante métodos libres de hipótesis y evaluar sus determinantes. Métodos: Se estudiaron 291 pacientes con EPOC estable (media ± DE: 68 ± 8 años, 81% hombres, VEMS 59 ± 19%pred) de dos cohortes europeas con actividad física basal y a 12 meses (acelerómetro Dynaport MoveMonitor). Se identificaron conglomerados (patrones) de progresión de actividad física basados en los niveles y cambios de pasos/día usando k-means, y se compararon entre patrones las características sociodemográficas, interpersonales, ambientales, clínicas y psicosociales basales. Resultados: Se identificaron tres patrones: inactivo (n = 173 [59%], basal: 4.621 ± 1.757 pasos/día, cambio en 12 meses (Δ): −487 ± 1.201 pasos/día), activo que aumenta (n = 49 [17%], basal: 7.727 ± 3.275 pasos/día, Δ: +3.378 ± 2.203 pasos/día) y activo que reduce (n = 69 [24%], basal: 11.267 ± 3.009 pasos/día, Δ: −2.217 ± 2.085 pasos/día). La distancia en la prueba de la marcha de 6 minutos (6MWD) y la disnea se asociaron independientemente con ser inactivo: RRR [IC 95%] 0,94 [0,90-0,98] por cada 10 m de 6MWD (p = 0,001) y 1,71 [1,12-2,60] por cada punto en la escala mMRC (p = 0,012), respectivamente, en comparación con el patrón activo que reduce. No se encontraron variables basales independientemente asociadas con ser activo que aumenta. Conclusiones: La progresión natural de la actividad física en pacientes con EPOC es heterogénea. Mientras que el patrón de pacientes inactivo se relaciona con peores características clínicas de EPOC, no se pudo predecir la evolución de los activos a aumentar o reducir. info:eu-repo/semantics/acceptedVersion

Imperial College Clinician Investigator Scholarship

Background The association between current tobacco smoking, the risk of developing COVID-19 and the severity of illness is an important information gap. Methods UK users of the COVID Symptom Study app provided baseline data including demographics, anthropometrics, smoking status and medical conditions, were asked to log symptoms daily from 24th March 2020 to 23rd April 2020. Participants reporting that they did not feel physically normal were taken through a series of questions, including 14 potential COVID-19 symptoms and any hospital attendance. The main study outcome was the association between current smoking and the development of “classic” symptoms of COVID-19 during the pandemic defined as fever, new persistent cough and breathlessness. The number of concurrent COVID-19 symptoms was used as a proxy for severity. In addition, association of subcutaneous adipose tissue expression of ACE2, both the receptor for SARS-CoV-2 and a potential mediator of disease severity, with smoking status was assessed in a subset of 541 twins from the TwinsUK cohort. Results Data were available on 2,401,982 participants, mean(SD) age 43.6(15.1) years, 63.3% female, overall smoking prevalence 11.0%. 834,437 (35%) participants reported being unwell and entered one or more symptoms. Current smokers were more likely to develop symptoms suggesting a diagnosis of COVID-19; classic symptoms adjusted OR[95%CI] 1.14[1.10 to 1.18]; >5 symptoms 1.29[1.26 to 1.31]; >10 symptoms 1.50[1.42 to 1.58]. Smoking was associated with reduced ACE2 expression in adipose tissue (Beta(SE)=-0.395(0.149); p=7.01×10-3). Interpretation These data are consistent with smokers having an increased risk from COVID-19. Funding Zoe provided in kind support for all aspects of building, running and supporting the app and service to all users worldwide. The study was also supported by grants from the Wellcome Trust, UK Research and Innovation and British Heart Foundation.

Although Influenza vaccination is recommended for healthcare workers, vaccination rates in UK healthcare workers are only around 50%. We investigated the association between NHS sickness absence rates (using data from Health and Social Care Information Centre quarterly reports), staff vaccination rates and influenza vaccine efficacy (from Public Health England), influenza deaths (from the Office of National Statistics) and staff satisfaction (from www.NHSstaffsurveys.com). Data from 223 healthcare trusts covered approximately 800,000 staff in each of four influenza seasons from 2011; overall staff sickness rate was roughly 4.5%. Annual vaccination rates varied between 44% and 54%. Higher NHS trust vaccination rates were associated with reduced sickness absence (β = –0.425 [95% CI –0.658 to –0.192], p

What you need to know There are 1.3 million people in the UK with a diagnosis of chronic obstructive pulmonary disease (COPD) and the condition is responsible for considerable morbidity and mortality.1 COPD is also a common cause of hospital admission. NHS England has now recognised respiratory disease as a priority area in the Long Term Plan,2 but Royal College of Physicians COPD Audits3 identify substantial deficiencies across the healthcare system, including marked under-provision of pulmonary rehabilitation, flu vaccination, and smoking cessation treatment. This article summarises the most recent recommendations from the National Institute for Health and Care Excellence (NICE).10 The updated areas are mainly concerned with the management of stable COPD and include self management and education, assessment for lung volume reduction procedures, and home oxygen use. This article focuses on the newly updated sections, with reference to older recommendations where they are particularly important or needed for context. Effective COPD management pathways require an integrated approach across primary and secondary care and involve a multidisciplinary team of health professionals. The guidance focuses on the need to ensure that good quality care is delivered wherever patients are seen. Specialist care, whether delivered in a hospital or community setting, may be indicated for people …

ispartof: Journal of Medical Internet Research status: accepted

Introduction Complete foreign body airway obstruction is a life-threatening emergency, but there are limited data on its epidemiology. Methods We conducted a retrospective analysis of data collected routinely from London Ambulance Service calls coded as being for choking was undertaken for the calendar year of 2016. Results There were 1916 choking episodes of significant severity to call for emergency assessment in London during 2016, 0.2% of total calls requiring an ambulance response, an average of 5.2 per day. The incidence increased at the extremes of age. Calls coded as choking occurred at times consistent with lunch and dinner and less frequently at breakfast. Peak incidence occurred at Sunday lunchtimes and on Wednesday evenings. Conclusions Choking is a substantial health problem for Londoners to seek emergency assistance. Choking is more frequent at the extremes of age with a higher incidence at lunch and dinner time. Greater public awareness of choking and its management could help to prevent avoidable deaths.

Introduction Endobronchial valve placement has potential as a treatment for patients with chronic obstructive pulmonary disease (COPD). However, a robust evidence base will be needed to convince commissioners of healthcare that it is a high-value treatment. We sought to develop the evidence base by performing an individual patient-level analysis of randomised controlled trials in people with heterogeneous emphysema and an absence of collateral ventilation. Methods A literature search (PROSPERO register CRD42016048127) identified two trials meeting these criteria, the BelieVeR-HIFi and STELVIO studies. Anonymised individual patient data were obtained from investigators and analysed. The primary outcome measure was a comparison of change in forced expiratory volume in 1 s (FEV1) from baseline between the treatment and control groups. Secondary end points were change from baseline in 6 min walk distance (6MWD), Medical Research Council dyspnoea score and St George’s Respiratory Questionnaire (SGRQ). Results 114 individuals were treated with 3-month to 6-month follow-up data available for 101 individuals. FEV1 improved by 23.1 (±28.3)% in patients treated with valves with a mean (95% CI) difference in response between groups of 17.8 (26.5, 9.2)% (p

RATIONALE: Reduced physical activity (PA) in patients with COPD is associated with a poor prognosis. Increasing PA is a key therapeutic target, but thus far few strategies have been found effective in this patient group. OBJECTIVES: To investigate the effectiveness of a 12-week semiautomated telecoaching intervention on PA in patients with COPD in a multicentre European randomised controlled trial. METHODS: 343 patients from six centres, encompassing a wide spectrum of disease severity, were randomly allocated to either a usual care group (UCG) or a telecoaching intervention group (IG) between June and December 2014. This 12-week intervention included an exercise booklet and a step counter providing feedback both directly and via a dedicated smartphone application. The latter provided an individualised daily activity goal (steps) revised weekly and text messages as well as allowing occasional telephone contacts with investigators. PA was measured using accelerometry during 1 week preceding randomisation and during week 12. Secondary outcomes included exercise capacity and health status. Analyses were based on modified intention to treat. MAIN RESULTS: Both groups were comparable at baseline in terms of factors influencing PA. At 12 weeks, the intervention yielded a between-group difference of mean, 95% CI (lower limit - upper limit; ll-ul) +1469, 95% CI (971 to 1965) steps/day and +10.4, 95% CI (6.1 to 14.7) min/day moderate PA; favouring the IG (all p, Rationale Reduced physical activity (PA) in patients with COPD is associated with a poor prognosis. Increasing PA is a key therapeutic target, but thus far few strategies have been found effective in this patient group. Objectives To investigate the effectiveness of a 12-week semiautomated telecoaching intervention on PA in patients with COPD in a multicentre European randomised controlled trial. Methods 343 patients from six centres, encompassing a wide spectrum of disease severity, were randomly allocated to either a usual care group (UCG) or a telecoaching intervention group (IG) between June and December 2014. This 12-week intervention included an exercise booklet and a step counter providing feedback both directly and via a dedicated smartphone application. The latter provided an individualised daily activity goal (steps) revised weekly and text messages as well as allowing occasional telephone contacts with investigators. PA was measured using accelerometry during 1 week preceding randomisation and during week 12. Secondary outcomes included exercise capacity and health status. Analyses were based on modified intention to treat. Main results Both groups were comparable at baseline in terms of factors influencing PA. At 12 weeks, the intervention yielded a between-group difference of mean, 95% CI (lower limit – upper limit; ll-ul) +1469, 95% CI (971 to 1965) steps/day and +10.4, 95% CI (6.1 to 14.7) min/day moderate PA; favouring the IG (all p≤0.001). The change in 6-min walk distance was significantly different (13.4, 95% CI (3.40 to 23.5) m, p

BACKGROUND: Skeletal muscle impairment is a recognized complication of COPD, predicting mortality in severe disease. Increasing evidence implicates the renin-angiotensin system in control of muscle phenotype. We hypothesized that angiotensin-converting enzyme (ACE) inhibition would improve quadriceps function and exercise performance in COPD. METHODS: This double-blind, randomized placebo-controlled trial investigated the effect of the ACE inhibitor, fosinopril, on quadriceps function in patients with COPD with quadriceps weakness. Primary outcomes were change in quadriceps endurance and atrophy signaling at 3 months. Quadriceps maximum voluntary contraction (QMVC), mid-thigh CT scan of the cross-sectional area (MTCSA), and incremental shuttle walk distance (ISWD) were secondary outcomes. RESULTS: Eighty patients were enrolled (mean [SD], 65 [8] years, FEV1 43% [21%] predicted, 53% men). Sixty-seven patients (31 fosinopril, 36 placebo) completed the trial. The treatment group demonstrated a significant reduction in systolic BP (Δ−10.5 mm Hg; 95% CI, −19.9 to −1.1; P = .03) and serum ACE activity (Δ−20.4 IU/L; 95% CI, −31.0 to −9.8; P < .001) compared with placebo. No significant between-group differences were observed in the primary end points of quadriceps endurance half-time (Δ0.5 s; 95% CI, −13.3-14.3; P = .94) or atrogin-1 messenger RNA expression (Δ−0.03 arbitrary units; 95% CI, −0.32-0.26; P = .84). QMVC improved in both groups (fosinopril: Δ1.1 kg; 95% CI, 0.03-2.2; P = .045 vs placebo: Δ3.6 kg; 95% CI, 2.1-5.0; P < .0001) with a greater increase in the placebo arm (between-group, P = .009). No change was shown in the MTCSA (P = .09) or ISWD (P = .51). CONCLUSIONS: This randomized controlled trial found that ACE inhibition, using fosinopril for 3 months, did not improve quadriceps function or exercise performance in patients with COPD with quadriceps weakness. TRIAL REGISTRY: Current Controlled Trials; No.: ISRCTN05581879; URL: www.controlled-trials.com

Breathlessness is a common symptom which may have multiple causes in any one individual and causes which may change over time. Breathlessness campaigns encourage people to see their GP if they are unduly breathless. Members of the London Respiratory Network collaborated to develop a tool which would encourage a holistic approach to breathlessness, which was applicable both at the time of diagnosis and during ongoing management. This has led to the development of the aide memoire “Breathing SPACE” which encompasses 5 key themes – Smoking, Pulmonary disease, Anxiety/psychosocial factors, Cardiac disease and Exercise/fitness. A particular concern was to ensure that high value interventions (smoking cessation and exercise interventions) are prioritised across the life-course and throughout the course of disease management. The approach is relevant both to well people and in those with an underling diagnosis or diagnoses. The inclusion of anxiety draws attention to the importance of mental health issues. Parity of esteem requires the physical health problems of people with mental illness to be addressed. The SPACE mnemonic also addresses the problem of underdiagnosis of heart disease in people with lung disease and vice versa, as well as the systematic undertreatment of these conditions where they do co-occur.

There is growing interest in Singing for Lung Health (SLH), an approach where patients with respiratory disease take part in singing groups, intended to improve their condition. A consensus group was convened in early 2016 to address issues including: the specific features that make SLH distinct from other forms of participation in singing; the existing evidence base via a systematic review; gaps in the evidence base including the need to define value-based outcome measures for sustainable commissioning of SLH; defining the measures needed to evaluate both individuals' responses to SLH and the quality of singing programmes. and core training, expertise and competencies required by singing group leaders to deliver high-quality programmes. A systematic review to establish the extent of the evidence base for SLH was undertaken. Electronic databases, including Pubmed, OVID Medline and Embase, Web of Science, Cochrane central register of controlled trials and PEDro, were used. Six studies were included in the final review. Quantitative data suggest that singing has the potential to improve health-related quality of life, particularly related to physical health, and levels of anxiety without causing significant side effects. There is a significant risk of bias in many of the existing studies with small numbers of subjects overall. Little comparison can be made between studies owing to their heterogeneity in design. Qualitative data indicate that singing is an enjoyable experience for patients, who consistently report that it helps them to cope with their condition better. Larger and longer-term trials are needed. NIHR Respiratory Biomedical Research Unit at Royal Brompton; Harefield NHS Foundation Trust and Imperial College London

There is growing interest in Singing for Lung Health (SLH), an approach where patients with respiratory disease take part in singing groups, intended to improve their condition. A consensus group was convened in early 2016 to address issues including; the specific features that make SLH distinct from other forms of participation in singing; the existing evidence base via a systematic review; gaps in the evidence base including the need to define value-based outcome measures for sustainable commissioning of SLH; defining the measures needed to evaluate individuals' responses to SLH and the quality of singing programmes; core training, expertise and competencies required by singing group leaders to deliver high quality programmes. A systematic review to establish the extent of the evidence base for Singing for Lung Health was undertaken. Electronic databases including Pubmed, OVID Medline and Embase, Web of Science, Cochrane central register of controlled trials and PEDro were used. Six studies were included in the final review. Quantitative data suggest singing has the potential to improve health related quality of life, particularly related to physical health, and levels of anxiety without causing significant side effects. There is a significant risk of bias in many of the existing studies with small numbers of subjects overall. Little comparison can be made between studies due to their heterogeneity in design. Qualitative data indicate that singing is an enjoyable experience for patients who consistently report that it helps them to cope with their condition better. Larger and longer term trials are needed.

Outcomes in early trials of bronchoscopic lung volume reduction using endobronchial valves for the treatment of patients with advanced emphysema were inconsistent. However improvements in patient selection with focus on excluding those with interlobar collateral ventilation and homogeneous emphysema resulted in significant benefits in the BeLieVeR-HIFi study compared to sham treated controls. In this manuscript we present data from the control patients in the BeLieVeR-HIFi study who went on to have open label endobronchial valve treatment after completion of the clinical trial (n=12), combined with data from those in the treatment arm who did not have collateral ventilation (n=19). Three months after treatment the forced expiratory volume in the 1st second increased by 27.3(36.4)%, residual volume reduced by 0.49(0.76)L, the 6 minute walk distance increased by 32.6(68.7) m, and the St George Respiratory Questionnaire for COPD score improved by 8.2(20.2) points. These data extend the evidence for endobronchial valve placement in appropriately selected patients with COPD.

Background Loss of muscle mass is a co‐morbidity common to a range of chronic diseases including chronic obstructive pulmonary disease (COPD). Several systemic features of COPD including increased inflammatory signalling, oxidative stress, and hypoxia are known to increase the expression of growth differentiation factor‐15 (GDF‐15), a protein associated with muscle wasting in other diseases. We therefore hypothesized that GDF‐15 may contribute to muscle wasting in COPD. Methods We determined the expression of GDF‐15 in the serum and muscle of patients with COPD and analysed the association of GDF‐15 expression with muscle mass and exercise performance. To determine whether GDF‐15 had a direct effect on muscle, we also determined the effect of increased GDF‐15 expression on the tibialis anterior of mice by electroporation. Results Growth differentiation factor‐15 was increased in the circulation and muscle of COPD patients compared with controls. Circulating GDF‐15 was inversely correlated with rectus femoris cross‐sectional area (P

Rationale: Epidemiological studies in older individuals have found an association between use of ACE-inhibition (ACE-I) therapy and preserved locomotor muscle mass, strength and walking speed. ACE-I therapy might therefore have a role in the context of pulmonary rehabilitation. Objectives: We investigated the hypothesis that enalapril, an ACE-inhibitor, would augment the improvement in exercise capacity seen during pulmonary rehabilitation. Methods: We performed a double-blind, placebo-controlled, parallel-group randomised controlled trial. COPD patients, with at least moderate airflow obstruction and taking part in pulmonary rehabilitation, were randomised to either 10 weeks therapy with an ACE-inhibitor (10mg enalapril) or placebo. Measurements: The primary outcome measurement was the change in peak power (assessed using cycle ergometry) from baseline. Main Results: Eighty patients were enrolled, seventy-eight randomised (age 67±8years, FEV1 48±21% predicted), and sixty-five completed the trial (34 placebo, 31 ACE-inhibitor). The ACE-inhibitor treated group demonstrated a significant reduction in systolic blood pressure (Δ-16mmHg, 95% CI -22 to -11) and serum ACE activity (Δ-18IU/L, 95% CI -23 to -12) versus placebo (between group differences p

Acting to address the amount of physical activity of patients with chronic obstructive pulmonary disease (COPD) is recommended as part of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations [1]. A level lower than approximately 5000 steps for day (sedentary lifestyle index) is associated with significantly increased health risks [2, 3]. Actively screening to identify patients below this threshold could be an important step towards targeting interventions to increase physical activity. Potential screening tools include activity monitors (objective assessment) or self-reported questionnaires (subjective assessment) to measure the amount of physical activity [4]. The latter method, which is feasible in clinical practice, may not result in an accurate representation in an individual patient, as questionnaire responses tend to misclassify physical activity [5]. Although more accurate and widely used in research, activity monitoring is not yet commonly included in patients' routine assessment. Several health status questionnaires in routine clinical use contain a domain or dimension related to physical activity [6]. In the analytical framework of Leidy [7], functional performance has been defined as the physical, psychological, social, occupational and spiritual activities that people actually do in the normal course of their lives to meet basic needs, fulfil usual roles, and maintain their health and wellbeing. A review by Kocks et al . [8] proposed that these questionnaires could be used in the measurement of functional performance (defined as “what a patient is actually doing”) and that this would be a more practical alternative to physical activity monitoring. Whether this approach is sufficiently valid as a representation of physical activity levels in clinical practice remains to be established. Health status questionnaires provide only limited insight into the physical activity of patients with COPD The PROactive Consortium members are as follows. Nathalie Ivanoff: Almirall, Barcelona, Spain; Niklas Karlsson and Solange Corriol-Rohou: AstraZeneca AB, Molndal, Sweden; Ian Jarrod: British Lung Foundation, London, UK; Damijen Erzen: Boehringer Ingelheim, Nieder-Ingelheim, Germany; Mario Scuri and Roberta Montacchini: Chiesi Farmaceutici S.A. Parma, Italy; Paul McBride: Choice Healthcare Solutions, Hitchin, UK; Nadia Kamel: European Respiratory Society, Lausanne, Switzerland; Margaret Tabberer: GlaxoSmithKline, Uxbridge, UK; Thierry Troosters, Wim Janssens and Fabienne Dobbels,: Katholieke Universiteit Leuven, Leuven, Belgium; Judith Garcia-Aymerich, Municipal Institute of Medical Research, Barcelona, Spain; Pim de Boer: Netherlands Lung Foundation, Amersfoort, The Netherlands; Karoly Kulich and Alastair Glendenning: Novartis, Basel, Switzerland; Michael I. Polkey and Nick S. Hopkinson: Royal Brompton and Harefield NHS Foundation Trust, London, UK; Ioannis Vogiatzis: Thorax Research Foundation, Athens, Greece; Enkeleida Nikai: UCB, Brussels, Belgium; Thys van der Molen and Corina De Jong: University Medical Center, Groningen, The Netherlands; Roberto A. Rabinovich and Bill MacNee: University of Edinburgh, Edinburgh, UK; Milo A. Puhan and Anja Frei: University of Zurich, Zurich, Switzerland.

© 2016 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society of Sarcopenia, Cachexia and Wasting DisordersBackground: Loss of muscle mass and strength is a significant comorbidity in patients with chronic obstructive pulmonary disease (COPD) that limits their quality of life and has prognostic implications but does not affect everyone equally. To identify mechanisms that may contribute to the susceptibility to a low muscle mass, we investigated microRNA (miRNA) expression, methylation status, and regeneration in quadriceps muscle from COPD patients and the effect of miRNAs on myoblast proliferation in vitro. The relationships of miRNA expression with muscle mass and strength was also determined in a group of healthy older men. Methods: We identified miRNAs associated with a low fat-free mass (FFM) phenotype in a small group of patients with COPD using a PCR screen of 750 miRNAs. The expression of two differentially expressed miRNAs (miR-675 and miR-519a) was determined in an expanded group of COPD patients and their associations with FFM and strength identified. The association of these miRNAs with FFM and strength was also explored in a group of healthy community-dwelling older men. As the expression of the miRNAs associated with FFM could be regulated by methylation, the relative methylation of the H19 ICR was determined. Furthermore, the proportion of myofibres with centralized nuclei, as a marker of muscle regeneration, in the muscle of COPD patients was identified by immunofluorescence. Results: Imprinted miRNAs (miR-675 and from a cluster, C19MC which includes miR-519a) were differentially expressed in the quadriceps of patients with a low fat-free mass index (FFMI) compared to those with a normal FFMI. In larger cohorts, miR-675 and its host gene (H19) were higher in patients with a low FFMI and strength. The association of miR-519a expression with FFMI was present in male patients with severe COPD. Similar associations of miR expression with lean mass and strength were not observed in healthy community dwelling older men participating in the Hertfordshire Sarcopenia Study. Relative methylation of the H19 ICR was reduced in COPD patients with muscle weakness but was not associated with FFM. In vitro, miR-675 inhibited myoblast proliferation and patients with a low FFMI had fewer centralized nuclei suggesting miR-675 represses regeneration. Conclusions: The data suggest that increased expression of miR-675/H19 and altered methylation of the H19 imprinting control region are associated with a low FFMI in patients with COPD but not in healthy community dwelling older men suggesting that epigenetic control of this loci may contribute to a susceptibility to a low FFMI.

No current patient-centred instrument captures all dimensions of physical activity in chronic obstructive pulmonary disease (COPD). Our objective was item reduction and initial validation of two instruments to measure physical activity in COPD. Physical activity was assessed in a 6-week, randomised, two-way cross-over, multicentre study using PROactive draft questionnaires (daily and clinical visit versions) and two activity monitors. Item reduction followed an iterative process including classical and Rasch model analyses, and input from patients and clinical experts. 236 COPD patients from five European centres were included. Results indicated the concept of physical activity in COPD had two domains, labelled “amount” and “difficulty”. After item reduction, the daily PROactive instrument comprised nine items and the clinical visit contained 14. Both demonstrated good model fit (person separation index >0.7). Confirmatory factor analysis supported the bidimensional structure. Both instruments had good internal consistency (Cronbach's α>0.8), test–retest reliability (intraclass correlation coefficient ≥0.9) and exhibited moderate-to-high correlations (r>0.6) with related constructs and very low correlations (r, Both PROactive hybrid tools are simple, valid, and reliable measures of physical activity in COPD patients http://ow.ly/LJqP8