Investigating the prognostic value of digital mobility outcomes in patients with chronic obstructive pulmonary disease: a systematic literature review and meta-analysis

BACKGROUND: Reduced mobility is a central feature of COPD. Assessment of mobility outcomes that can be measured digitally (digital mobility outcomes (DMOs)) in daily life such as gait speed and steps per day is increasingly possible using devices such as pedometers and accelerometers, but the predictive value of these measures remains unclear in relation to key outcomes such as hospital admission and survival. METHODS: We conducted a systematic review, nested within a larger scoping review by the MOBILISE-D consortium, addressing DMOs in a range of chronic conditions. Qualitative and quantitative analysis considering steps per day and gait speed and their association with clinical outcomes in COPD patients was performed. RESULTS: 21 studies (6076 participants) were included. Nine studies evaluated steps per day and 11 evaluated a measure reflecting gait speed in daily life. Negative associations were demonstrated between mortality risk and steps per day (per 1000 steps) (hazard ratio (HR) 0.81, 95% CI 0.75-0.88, p<0.001), gait speed (<0.80 m·s$^{-1}$) (HR 3.55, 95% CI 1.72-7.36, p<0.001) and gait speed (per 1.0 m·s$^{-1}$) (HR 7.55, 95% CI 1.11-51.3, p=0.04). Fewer steps per day (per 1000) and slow gait speed (<0.80 m·s$^{-1}$) were also associated with increased healthcare utilisation (HR 0.80, 95% CI 0.72-0.88, p<0.001; OR 3.36, 95% CI 1.42-7.94, p=0.01, respectively). Available evidence was of low-moderate quality with few studies eligible for meta-analysis. CONCLUSION: Daily step count and gait speed are negatively associated with mortality risk and other important outcomes in people with COPD and therefore may have value as prognostic indicators in clinical trials, but the quantity and quality of evidence is limited. Larger studies with consistent methodologies are called for

Singing for lung health in COPD: a multicentre randomised controlled trial of online delivery

BACKGROUND: Singing for lung health (SLH) is an arts-based breathing control and movement intervention for people with long-term respiratory conditions, intended to improve symptoms and quality of life. Online, remotely delivered programmes might improve accessibility; however, no previous studies have assessed the effectiveness of this approach. METHODS: We conducted an assessor-blind randomised controlled trial comparing the impact of 12 weeks of once-weekly online SLH sessions against usual care on health-related quality of life, assessed using the RAND 36-Item Short Form Health Survey (SF-36) Mental Health Composite (MHC) and Physical Health Composite (PHC) scores. RESULTS: We enrolled 115 people with stable chronic obstructive pulmonary disease (COPD), median (IQR) age 69 (62-74), 56.5% females, 80% prior pulmonary rehabilitation, Medical Research Council dyspnoea scale 4 (3-4), forced expiratory volume in 1 s % predicted 49 (35-63). 50 participants in each arm completed the study. The intervention arm experienced improvements in physical but not mental health components of RAND SF-36; PHC (regression coefficient (95% CI): 1.77 (95% CI 0.11 to 3.44); p=0.037), but not MHC (0.86 (95% CI -1.68 to 3.40); p=0.504). A prespecified responder analysis based on achieving a 10% improvement from baseline demonstrated a response rate for PHC of 32% in the SLH arm and 12.7% for usual care (p=0.024). A between-group difference in responder rate was not found in relation to the MHC (19.3% vs 25.9%; p=0.403). DISCUSSION AND CONCLUSION: A 12-week online SLH programme can improve the physical component of quality of life for people with COPD, but the overall effect is relatively modest compared with the impact seen in research using face-to-face group sessions. Further work on the content, duration and dose of online interventions may be useful. TRIAL REGISTRATION NUMBER: NCT04034212

Laboratory and free-living gait performance in adults with COPD and healthy controls

BACKGROUND Gait characteristics are important risk factors for falls, hospitalisations and mortality in older adults, but the impact of COPD on gait performance remains unclear. We aimed to identify differences in gait characteristics between adults with COPD and healthy age-matched controls during 1) laboratory tests that included complex movements and obstacles, 2) simulated daily-life activities (supervised) and 3) free-living daily-life activities (unsupervised). METHODS This case-control study used a multi-sensor wearable system (INDIP) to obtain seven gait characteristics for each walking bout performed by adults with mild-to-severe COPD (n=17; forced expiratory volume in 1 s 57±19% predicted) and controls (n=20) during laboratory tests, and during simulated and free-living daily-life activities. Gait characteristics were compared between adults with COPD and healthy controls for all walking bouts combined, and for shorter (≤30 s) and longer (>30 s) walking bouts separately. RESULTS Slower walking speed (-11 cm·s$^{-1}$, 95% CI: -20 to -3) and lower cadence (-6.6 steps·min$^{-1}$, 95% CI: -12.3 to -0.9) were recorded in adults with COPD compared to healthy controls during longer (>30 s) free-living walking bouts, but not during shorter (≤30 s) walking bouts in either laboratory or free-living settings. Double support duration and gait variability measures were generally comparable between the two groups. CONCLUSION Gait impairment of adults with mild-to-severe COPD mainly manifests during relatively long walking bouts (>30 s) in free-living conditions. Future research should determine the underlying mechanism(s) of this impairment to facilitate the development of interventions that can improve free-living gait performance in adults with COPD

Resource limitation drives spatial organization in microbial groups.

Dense microbial groups such as bacterial biofilms commonly contain a diversity of cell types that define their functioning. However, we have a limited understanding of what maintains, or purges, this diversity. Theory suggests that resource levels are key to understanding diversity and the spatial arrangement of genotypes in microbial groups, but we need empirical tests. Here we use theory and experiments to study the effects of nutrient level on spatio-genetic structuring and diversity in bacterial colonies. Well-fed colonies maintain larger well-mixed areas, but they also expand more rapidly compared with poorly-fed ones. Given enough space to expand, therefore, well-fed colonies lose diversity and separate in space over a similar timescale to poorly fed ones. In sum, as long as there is some degree of nutrient limitation, we observe the emergence of structured communities. We conclude that resource-driven structuring is central to understanding both pattern and process in diverse microbial communities

Connecting real-world digital mobility assessment to clinical outcomes for regulatory and clinical endorsement–the Mobilise-D study protocol

Background: The development of optimal strategies to treat impaired mobility related to ageing and chronic disease requires better ways to detect and measure it. Digital health technology, including body worn sensors, has the potential to directly and accurately capture real-world mobility. Mobilise-D consists of 34 partners from 13 countries who are working together to jointly develop and implement a digital mobility assessment solution to demonstrate that real-world digital mobility outcomes have the potential to provide a better, safer, and quicker way to assess, monitor, and predict the efficacy of new interventions on impaired mobility. The overarching objective of the study is to establish the clinical validity of digital outcomes in patient populations impacted by mobility challenges, and to support engagement with regulatory and health technology agencies towards acceptance of digital mobility assessment in regulatory and health technology assessment decisions. Methods/design: The Mobilise-D clinical validation study is a longitudinal observational cohort study that will recruit 2400 participants from four clinical cohorts. The populations of the Innovative Medicine Initiative-Joint Undertaking represent neurodegenerative conditions (Parkinson’s Disease), respiratory disease (Chronic Obstructive Pulmonary Disease), neuro-inflammatory disorder (Multiple Sclerosis), fall-related injuries, osteoporosis, sarcopenia, and frailty (Proximal Femoral Fracture). In total, 17 clinical sites in ten countries will recruit participants who will be evaluated every six months over a period of two years. A wide range of core and cohort specific outcome measures will be collected, spanning patient-reported, observer-reported, and clinician-reported outcomes as well as performance-based outcomes (physical measures and cognitive/mental measures). Daily-living mobility and physical capacity will be assessed directly using a wearable device. These four clinical cohorts were chosen to obtain generalizable clinical findings, including diverse clinical, cultural, geographical, and age representation. The disease cohorts include a broad and heterogeneous range of subject characteristics with varying chronic care needs, and represent different trajectories of mobility disability. Discussion: The results of Mobilise-D will provide longitudinal data on the use of digital mobility outcomes to identify, stratify, and monitor disability. This will support the development of widespread, cost-effective access to optimal clinical mobility management through personalised healthcare. Further, Mobilise-D will provide evidence-based, direct measures which can be endorsed by regulatory agencies and health technology assessment bodies to quantify the impact of disease-modifying interventions on mobility. Trial registration: ISRCTN12051706

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Physiological demands of singing for lung health compared with treadmill walking

Introduction Participating in singing is considered to have a range of social and psychological benefits. However, the physiological demands of singing and its intensity as a physical activity are not well understood.Methods We compared cardiorespiratory parameters while completing components of Singing for Lung Health sessions, with treadmill walking at differing speeds (2, 4 and 6 km/hour).Results Eight healthy adults were included, none of whom reported regular participation in formal singing activities. Singing induced acute physiological responses that were consistent with moderate intensity activity (metabolic equivalents: median 4.12, IQR 2.72–4.78), with oxygen consumption, heart rate and volume per breath above those seen walking at 4 km/hour. Minute ventilation was higher during singing (median 22.42 L/min, IQR 16.83–30.54) than at rest (11 L/min, 9–13), lower than 6 km/hour walking (30.35 L/min, 26.94–41.11), but not statistically different from 2 km/hour (18.77 L/min, 16.89–21.35) or 4 km/hour (23.27 L/min, 20.09–26.37) walking.Conclusions Our findings suggest the acute metabolic demands of singing are comparable with walking at a moderately brisk pace, hence, physical effects may contribute to the health and well-being benefits attributed to singing participation. However, if physical training benefits result remains uncertain. Further research including different singing styles, singers and physical performance impacts when used as a training modality is encouraged.Trial registration number ClinicalTrials.gov registry (NCT04121351)

Eligibility for lung volume reduction in patients with COPD attending pulmonary rehabilitation

Background: lung volume reduction (LVR) therapies are highly effective in appropriately selected patients with COPD. NICE (2018) guidance recommends offering a respiratory review for LVR assessment at the end of pulmonary rehabilitation (PR), if certain criteria apply. Few data exist on likely numbers potentially eligible according to these criteria [1].Methods: data from the 2015 and 2017 UK Royal College of Physicians National Asthma and COPD Audits were used to identify numbers of patients completing PR potentially eligible to be assessed for LVR based on NICE guidelines; FEV1&lt;50%, 6 Minute Walk Distance (6MWD) ≥140m, ex or non smoker and limiting breathlessness [1]. We used a cut off of &gt;80m for the incremental shuttle walk test (ISWT) and breathlessness criteria of either MRC dyspnoea score &gt;3 or ≥3.Results: 8,295 (55.7%) of 14,889 patients in programs using ISWT or 6MWD to assess change in exercise capacity completed PR, and 4,856 (32.6%) had complete data recorded. Of these 310 (6.4%) were eligible to be considered for LVR assessment, at a breathlessness threshold of MRC score &gt;3. Relaxing the criteria to include MRC≥3, meant 881 (18.1%) would be eligible.Conclusions: a systematic approach to identify potential candidates for LVR, during and at the end of PR, is desirable. Approaches for the appropriate evaluation of non-completers also need to be considered

Lung volume reduction eligibility in patients with COPD completing pulmonary rehabilitation: results from the UK National Asthma and COPD Audit Programme

Objectives: to establish what proportion of patients completing a UK pulmonary rehabilitation (PR) programme meet the 2018 National Institute for Health and Care Excellence (NICE) chronic obstructive pulmonary disease (COPD) guideline (NG115) criteria to have a respiratory review to establish whether referral to a lung volume reduction multidisciplinary team would be appropriate. This respiratory review would include evaluation of the presence of hyperinflation and the presence of emphysema on CT scan. The NICE criteria include measures of breathlessness and exercise capacity but these parameters are not completely defined.Design: observational study.Setting: PR programmes across the UK in 2015 (210 centres) and 2017 (184 centres) entering data into the Royal College of Physicians’ National Asthma and COPD Audit Programme.Participants: 8295 (55.7%) of 14 889 patients in programmes using incremental shuttle walk test (ISWT) or 6-minute walk test (6MWT) as an outcome measure completed PR, and 4856 (32.6%) had complete data recorded (6MWT/ISWT, baseline spirometry, Medical Research Council (MRC) dyspnoea score).Results: depending on the walking test safety threshold adopted for the ISWT (≥140 m or ≥ 80 m) and the MRC dyspnoea score threshold used (MRC score ≥3 or ≥4 at the end of PR), between 4.9% and 18.1% of PR completers met the NICE criteria for a lung volume reduction-focused respiratory review.Conclusions: lung volume reduction therapies are beneficial in appropriately selected patients with COPD, but few procedures are performed, and treatment pathways are unclear. These data help to inform the feasibility of the approach recommended by NICE and highlight the need for future systematic pathways to reduce inequalities in patients being considered for effective treatment

Investigating the prognostic value of digital mobility outcomes in patients with chronic obstructive pulmonary disease: a systematic literature review and meta-analysis

Background: Reduced mobility is a central feature of COPD. Assessment of mobility outcomes that can be measured digitally (digital mobility outcomes (DMOs)) in daily life such as gait speed and steps per day is increasingly possible using devices such as pedometers and accelerometers, but the predictive value of these measures remains unclear in relation to key outcomes such as hospital admission and survival. Methods: We conducted a systematic review, nested within a larger scoping review by the MOBILISE-D consortium, addressing DMOs in a range of chronic conditions. Qualitative and quantitative analysis considering steps per day and gait speed and their association with clinical outcomes in COPD patients was performed. Results: 21 studies (6076 participants) were included. Nine studies evaluated steps per day and 11 evaluated a measure reflecting gait speed in daily life. Negative associations were demonstrated between mortality risk and steps per day (per 1000 steps) (hazard ratio (HR) 0.81, 95% CI 0.75-0.88, p<0.001), gait speed (<0.80 m·s-1) (HR 3.55, 95% CI 1.72-7.36, p<0.001) and gait speed (per 1.0 m·s-1) (HR 7.55, 95% CI 1.11-51.3, p=0.04). Fewer steps per day (per 1000) and slow gait speed (<0.80 m·s-1) were also associated with increased healthcare utilisation (HR 0.80, 95% CI 0.72-0.88, p<0.001; OR 3.36, 95% CI 1.42-7.94, p=0.01, respectively). Available evidence was of low-moderate quality with few studies eligible for meta-analysis. Conclusion: Daily step count and gait speed are negatively associated with mortality risk and other important outcomes in people with COPD and therefore may have value as prognostic indicators in clinical trials, but the quantity and quality of evidence is limited. Larger studies with consistent methodologies are called for.This work was supported by the Mobilise-D project; the Mobilise-D project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement no. 820820. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and the European Federation of Pharmaceutical Industries and Associations (EFPIA). This publication reflects the authors’ views and neither IMI nor the European Union, EFPIA or any Associated Partners are responsible for any use that may be made of the information contained herein. H. Demeyer is a postdoctoral research fellow of the FWO-Flanders. ISGlobal acknowledges support from the grant CEX2018–000806-S funded by MCIN/AEI/ 10.13039/501100011033, and the Generalitat de Catalunya through the CERCA Program and L. Delgado-Ortiz is funded by the following grant: Contratos Predoctorales de Formación en Investigación en Salud (PFIS) 2021 of the AES with Exp. FI21/00113 from ISCIII, and the European Social Fund Plus (ESF+). This research was supported by the NIHR Imperial Biomedical Research Centre (BRC). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health and Social Care, the IMI, the European Union, the EFPIA or any Associated Partners. Funding information for this article has been deposited with the Crossref Funder Registry