Imperial College London

DrWilliamMan

Faculty of MedicineNational Heart & Lung Institute

Reader in Respiratory Medicine
 
 
 
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+44 (0)1895 828 851w.man

 
 
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Location

 

Harefield HospitalHarefield Hospital

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Summary

 

Publications

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297 results found

Trivedi P, Patel S, Edwards G, Jenkins T, Man WD-C, Nolan CMet al., 2024, Five-Repetition Sit-to-Stand Test: Responsiveness and Minimal Important Difference in Idiopathic Pulmonary Fibrosis., Ann Am Thorac Soc, Vol: 21, Pages: 577-584

Rationale: Standing from a sitting position is an important activity of daily living. The five-repetition sit-to-stand test (5STS) is a simple physical performance test that measures the fastest time taken to stand five times from a chair with arms folded. It can be measured in most healthcare settings and at home, where traditional field walking tests may not be possible. The 5STS has been validated in community-dwelling older adults and people with chronic obstructive pulmonary disease, but data in idiopathic pulmonary fibrosis (IPF) are limited.Objectives: The aims of this cohort study were to establish the construct validity, responsiveness to pulmonary rehabilitation (PR), and minimal important difference (MID) of the 5STS in IPF.Methods: In 149 people with IPF, we compared the 5STS with measures of lung function, exercise capacity, quadriceps strength, breathlessness, and health-related quality of life. Responsiveness and effect sizes were determined by measuring the 5STS before and after PR. The MID was estimated using anchor- and distribution-based methods.Results: The 5STS correlated significantly with incremental shuttle walk test (ISW) (r = -0.55), isometric quadriceps maximum voluntary contraction (QMVC) (r = -0.45), Medical Research Council dyspnea scale score (r = 0.40), Chronic Respiratory Questionnaire-Total (r = -0.21), and King's Brief Interstitial Lung Disease Questionnaire-Total (r = -0.21) but not forced vital capacity percentage predicted or quadriceps one-repetition maximum (1RM). There was a significant but very weak correlation between change in 5STS and changes in Medical Research Council (r = 0.18), ISW (r = -0.21), and Chronic Respiratory Questionnaire-Total (r = -0.26) but no significant correlation with change in 1RM (r = -0.12) or QMVC (r = -0.18). 5STS time improved with PR (median [25th percentil

Journal article

C-MOREPHOSP-COVID Collaborative Group, 2023, Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study, The Lancet Respiratory Medicine, Vol: 11, Pages: 1003-1019, ISSN: 2213-2600

INTRODUCTION: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. METHODS: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. FINDINGS: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2-6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MR

Journal article

Doe G, Taylor SJC, Topalovic M, Russell R, Evans RA, Maes J, Van Orshovon K, Sunjaya A, Scott D, Prevost AT, El-Emir E, Harvey J, Hopkinson NS, Kon SS, Patel S, Jarrold I, Spain N, Man WD-C, Hutchinson Aet al., 2023, Spirometry services in England post-pandemic and the potential role of AI support software: a qualitative study of challenges and opportunities, BRITISH JOURNAL OF GENERAL PRACTICE, ISSN: 0960-1643

Journal article

Man W, Chaplin E, Daynes E, Drummond A, Evans RA, Greening NJ, Nolan C, Pavitt MJ, Roberts NJ, Vogiatzis I, Singh SJet al., 2023, British Thoracic Society Clinical Statement on pulmonary rehabilitation., Thorax, Vol: 78, Pages: s2-s15

Journal article

Anand R, McLeese R, Busby J, Stewart J, Clarke M, Man WD-C, Bradley Jet al., 2023, Unsupervised home spirometry versus supervised clinic spirometry for respiratory disease: a systematic methodology review and meta-analysis, European Respiratory Review, Vol: 32, ISSN: 0905-9180

BACKGROUND: The number of patients completing unsupervised home spirometry has recently increased due to more widely available portable technology and the COVID-19 pandemic, despite a lack of solid evidence to support it. This systematic methodology review and meta-analysis explores quantitative differences in unsupervised spirometry compared with spirometry completed under professional supervision. METHODS: We searched four databases to find studies that directly compared unsupervised home spirometry with supervised clinic spirometry using a quantitative comparison (e.g. Bland-Altman). There were no restrictions on clinical condition. The primary outcome was measurement differences in common lung function parameters (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC)), which were pooled to calculate overall mean differences with associated limits of agreement (LoA) and confidence intervals (CI). We used the I2 statistic to assess heterogeneity, the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool to assess risk of bias and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess evidence certainty for the meta-analyses. The review has been registered with PROSPERO (CRD42021272816). RESULTS: 3607 records were identified and screened, with 155 full texts assessed for eligibility. We included 28 studies that quantitatively compared spirometry measurements, 17 of which reported a Bland-Altman analysis for FEV1 and FVC. Overall, unsupervised spirometry produced lower values than supervised spirometry for both FEV1 with wide variability (mean difference -107 mL; LoA= -509, 296; I2=95.8%; p<0.001; very low certainty) and FVC (mean difference -184 mL, LoA= -1028, 660; I2=96%; p<0.001; very low certainty). CONCLUSIONS: Analysis under the conditions of the included studies indicated that unsupervised spirometry is not interchangeable with supervised spirometry for individual patients owing to var

Journal article

Osadnik CR, Brighton LJ, Burtin C, Cesari M, Lahousse L, Man WDC, Marengoni A, Sajnic A, Singer JP, ter Beek L, Tsiligianni I, Varga JT, Pavanello S, Maddocks Met al., 2023, European Respiratory Society statement on frailty in adults with chronic lung disease, EUROPEAN RESPIRATORY JOURNAL, Vol: 62, ISSN: 0903-1936

Journal article

Jackson C, Stewart ID, Plekhanova T, Cunningham PS, Hazel AL, Al-Sheklly B, Aul R, Bolton CE, Chalder T, Chalmers JD, Chaudhuri N, Docherty AB, Donaldson G, Edwardson CL, Elneima O, Greening NJ, Hanley NA, Harris VC, Harrison EM, Ho L-P, Houchen-Wolloff L, Howard LS, Jolley CJ, Jones MG, Leavy OC, Lewis KE, Lone NI, Marks M, McAuley HJC, McNarry MA, Patel BV, Piper-Hanley K, Poinasamy K, Raman B, Richardson M, Rivera-Ortega P, Rowland-Jones SL, Rowlands AV, Saunders RM, Scott JT, Sereno M, Shah AM, Shikotra A, Singapuri A, Stanel SC, Thorpe M, Wootton DG, Yates T, Gisli Jenkins R, Singh SJ, Man WD-C, Brightling CE, Wain LV, Porter JC, Thompson AAR, Horsley A, Molyneaux PL, Evans RA, Jones SE, Rutter MK, Blaikley JF, PHOSP-COVID Study Collaborative Groupet al., 2023, Effects of sleep disturbance on dyspnoea and impaired lung function following hospital admission due to COVID-19 in the UK: a prospective multicentre cohort study, The Lancet Respiratory Medicine, Vol: 11, Pages: 673-684, ISSN: 2213-2600

BACKGROUND: Sleep disturbance is common following hospital admission both for COVID-19 and other causes. The clinical associations of this for recovery after hospital admission are poorly understood despite sleep disturbance contributing to morbidity in other scenarios. We aimed to investigate the prevalence and nature of sleep disturbance after discharge following hospital admission for COVID-19 and to assess whether this was associated with dyspnoea. METHODS: CircCOVID was a prospective multicentre cohort substudy designed to investigate the effects of circadian disruption and sleep disturbance on recovery after COVID-19 in a cohort of participants aged 18 years or older, admitted to hospital for COVID-19 in the UK, and discharged between March, 2020, and October, 2021. Participants were recruited from the Post-hospitalisation COVID-19 study (PHOSP-COVID). Follow-up data were collected at two timepoints: an early time point 2-7 months after hospital discharge and a later time point 10-14 months after hospital discharge. Sleep quality was assessed subjectively using the Pittsburgh Sleep Quality Index questionnaire and a numerical rating scale. Sleep quality was also assessed with an accelerometer worn on the wrist (actigraphy) for 14 days. Participants were also clinically phenotyped, including assessment of symptoms (ie, anxiety [Generalised Anxiety Disorder 7-item scale questionnaire], muscle function [SARC-F questionnaire], dyspnoea [Dyspnoea-12 questionnaire] and measurement of lung function), at the early timepoint after discharge. Actigraphy results were also compared to a matched UK Biobank cohort (non-hospitalised individuals and recently hospitalised individuals). Multivariable linear regression was used to define associations of sleep disturbance with the primary outcome of breathlessness and the other clinical symptoms. PHOSP-COVID is registered on the ISRCTN Registry (ISRCTN10980107). FINDINGS: 2320 of 2468 participants in the PHOSP-COVID study attended

Journal article

Dawson C, Clunie G, Evison F, Duncan S, Whitney J, Houchen-Wolloff L, Bolton CE, Leavy OC, Richardson M, Omer E, McAuley H, Shikotra A, Singapuri A, Sereno M, Saunders RM, Harris VC, Greening NJ, Nolan CM, Wootton DG, Daynes E, Donaldson G, Sargent J, Scott J, Pimm J, Bishop L, McNarry M, Hart N, Evans RA, Singh S, Yates T, Chalder T, Man W, Harrison E, Docherty A, Lone NI, Quint JK, Chalmers J, Ho L-P, Horsley AR, Marks M, Poinasamy K, Raman B, Wain LV, Brightling C, PHOSP-COVID collaborative Group, Sharma N, Coffey M, Kulkarni A, Wallace Set al., 2023, Prevalence of swallow, communication, voice and cognitive compromise following hospitalisation for COVID-19: the PHOSP-COVID analysis, BMJ Open Respiratory Research, Vol: 10, ISSN: 2052-4439

Objective: Identify prevalence of self-reported swallow, communication, voice and cognitive compromise following hospitalisation for COVID-19.Design: Multicentre prospective observational cohort study using questionnaire data at visit 1 (2–7 months post discharge) and visit 2 (10–14 months post discharge) from hospitalised patients in the UK. Lasso logistic regression analysis was undertaken to identify associations.Setting: 64 UK acute hospital Trusts.Participants: Adults aged >18 years, discharged from an admissions unit or ward at a UK hospital with COVID-19.Main outcome measures: Self-reported swallow, communication, voice and cognitive compromise.Results: Compromised swallowing post intensive care unit (post-ICU) admission was reported in 20% (188/955); 60% with swallow problems received invasive mechanical ventilation and were more likely to have undergone proning (p=0.039). Voice problems were reported in 34% (319/946) post-ICU admission who were more likely to have received invasive (p<0.001) or non-invasive ventilation (p=0.001) and to have been proned (p<0.001). Communication compromise was reported in 23% (527/2275) univariable analysis identified associations with younger age (p<0.001), female sex (p<0.001), social deprivation (p<0.001) and being a healthcare worker (p=0.010). Cognitive issues were reported by 70% (1598/2275), consistent at both visits, at visit 1 respondents were more likely to have higher baseline comorbidities and at visit 2 were associated with greater social deprivation (p<0.001).Conclusion: Swallow, communication, voice and cognitive problems were prevalent post hospitalisation for COVID-19, alongside whole system compromise including reduced mobility and overall health scores. Research and testing of rehabilitation interventions are required at pace to explore these issues.

Journal article

Nolan CM, Schofield SJ, Maddocks M, Patel S, Barker RE, Walsh JA, Polgar O, George PM, Molyneaux PL, Maher TM, Cullinan P, Man WD-Cet al., 2023, Change in gait speed and adverse outcomes in patients with idiopathic pulmonary fibrosis: a prospective cohort study, Respirology, Vol: 28, Pages: 649-658, ISSN: 1323-7799

BACKGROUND AND OBJECTIVE: Gait speed is associated with survival in individuals with idiopathic pulmonary fibrosis (IPF). The extent to which four-metre gait speed (4MGS) decline predicts adverse outcome in IPF remains unclear. We aimed to examine longitudinal 4MGS change and identify a cut-point associated with adverse outcome. METHODS: In a prospective cohort study, we recruited 132 individuals newly diagnosed with IPF and measured 4MGS change over 6 months. Death/first hospitalization at 6 months were composite outcome events. Complete data (paired 4MGS plus index event) were available in 85 participants; missing 4MGS data were addressed using multiple imputation. Receiver-Operating Curve plots identified a 4MGS change cut-point. Cox proportional-hazard regression assessed the relationship between 4MGS change and time to event. RESULTS: 4MGS declined over 6 months (mean [95% CI] change: -0.05 [-0.09 to -0.01] m/s; p = 0.02). A decline of 0.07 m/s or more in 4MGS over 6 months had better discrimination for the index event than change in 6-minute walk distance, forced vital capacity, Composite Physiologic Index or Gender Age Physiology index. Kaplan-Meier curves demonstrated a significant difference in time to event between 4MGS groups (substantial decline: >-0.07 m/s versus minor decline/improvers: ≤-0.07 m/s; p = 0.007). Those with substantial decline had an increased risk of hospitalization/death (adjusted hazard ratio [95% CI] 4.61 [1.23-15.83]). Similar results were observed in multiple imputation analysis. CONCLUSION: In newly diagnosed IPF, a substantial 4MGS decline over 6 months is associated with shorter time to hospitalization/death at 6 months. 4MGS change has potential as a surrogate endpoint for interventions aimed at modifying hospitalization/death.

Journal article

Nolan CM, Brighton LJ, Mo Y, Bayly J, Higginson IJ, Man WD-C, Maddocks Met al., 2023, Meditative movement for breathlessness in advanced COPD or cancer: a systematic review and meta-analysis, European Respiratory Review, Vol: 32, ISSN: 0905-9180

The effect of meditative movement, which includes yoga, tai chi and qi gong, on breathlessness in advanced disease is unknown. This systematic review aims to comprehensively assess the evidence on the effect of meditative movement on breathlessness (primary outcome), health-related quality of life, exercise capacity, functional performance and psychological symptoms (secondary outcomes) in advanced disease. 11 English and Chinese language databases were searched for relevant trials. Risk of bias was assessed using the Cochrane tool. Standardised mean differences (SMDs) with 95% confidence intervals were computed. 17 trials with 1125 participants (n=815 COPD, n=310 cancer), all with unclear or high risk of bias, were included. Pooled estimates (14 studies, n=671) showed no statistically significant difference in breathlessness between meditative movement and control interventions (SMD (95% CI) 0.10 (-0.15-0.34); Chi2=30.11; I2=57%; p=0.45), irrespective of comparator, intervention or disease category. Similar results were observed for health-related quality of life and exercise capacity. It was not possible to perform a meta-analysis for functional performance and psychological symptoms. In conclusion, in people with advanced COPD or cancer, meditative movement does not improve breathlessness, health-related quality of life or exercise capacity. Methodological limitations lead to low levels of certainty in the results.

Journal article

Brighton LJ, Lareau S, Maddocks M, Osadnik C, Lahousse L, Lee A, Allison J, Singer J, Rozenberg D, Man WDC, Ferrante L, Spruit MA, Burtin C, Harrison SL, Iyer ASet al., 2023, What is frailty?, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 207, Pages: P5-P6, ISSN: 1073-449X

Journal article

Maddocks M, Brighton LJ, Alison JA, ter Beek L, Bhatt SP, Brummel NE, Burtin C, Cesari M, Evans RA, Ferrante LE, Flores-Flores O, Franssen FME, Garvey C, Harrison SL, Iyer AS, Lahouse L, Lareau S, Lee AL, Man WD-C, Marengoni A, McAuley HJC, Rozenberg D, Singer JP, Spruit MA, Osadnik CRet al., 2023, Rehabilitation for people with respiratory disease and frailty an official American Thoracic Society workshop report, Annals of the American Thoracic Society, Vol: 20, Pages: 767-780, ISSN: 1546-3222

People with respiratory disease have increased risk of developing frailty, which is associated with worse health outcomes. There is growing evidence of the role of rehabilitation in managing frailty in people with respiratory disease. However, several challenges remain regarding optimal methods of identifying frailty and delivering rehabilitation for this population. The aims of this American Thoracic Society workshop were to outline key definitions and concepts around rehabilitation for people with respiratory disease and frailty, synthesize available evidence, and explore how programs may be adapted to align to the needs and experiences of this population. Across two half-day virtual workshops, 20 professionals from diverse disciplines, professions, and countries discussed key developments and identified opportunities for future research, with additional input via online correspondence. Participants highlighted a “frailty rehabilitation paradox” whereby pulmonary rehabilitation can effectively reduce frailty, but programs are challenging for some individuals with frailty to complete. Frailty should not limit access to rehabilitation; instead, the identification of frailty should prompt comprehensive assessment and tailored support, including onward referral for additional specialist input. Exercise prescriptions that explicitly consider symptom burden and comorbidities, integration of additional geriatric or palliative care expertise, and/or preemptive planning for disruptions to participation may support engagement and outcomes. To identify and measure frailty in people with respiratory disease, tools should be selected on the basis of sensitivity, specificity, responsiveness, and feasibility for their intended purpose. Research is required to expand understanding beyond the physical dimensions of frailty and to explore the merits and limitations of telerehabilitation or home-based pulmonary rehabilitation for people with chronic respiratory disease a

Journal article

Das N, Happaerts S, Gyselinck I, Staes M, Derom E, Brusselle G, Burgos F, Contoli M, Dinh-Xuan AT, Franssen FME, Gonem S, Greening N, Haenebalcke C, Man WD-C, Moises J, Peche R, Poberezhets V, Quint JK, Steiner MC, Vanderhelst E, Abdo M, Topalovic M, Janssens Wet al., 2023, Collaboration between explainable artificial intelligence and pulmonologists improves the accuracy of pulmonary function test interpretation, European Respiratory Journal, Vol: 61, ISSN: 0903-1936

Background Few studies have investigated the collaborative potential between artificial intelligence (AI) and pulmonologists for diagnosing pulmonary disease. We hypothesised that the collaboration between a pulmonologist and AI with explanations (explainable AI (XAI)) is superior in diagnostic interpretation of pulmonary function tests (PFTs) than the pulmonologist without support.Methods The study was conducted in two phases, a monocentre study (phase 1) and a multicentre intervention study (phase 2). Each phase utilised two different sets of 24 PFT reports of patients with a clinically validated gold standard diagnosis. Each PFT was interpreted without (control) and with XAI's suggestions (intervention). Pulmonologists provided a differential diagnosis consisting of a preferential diagnosis and optionally up to three additional diagnoses. The primary end-point compared accuracy of preferential and additional diagnoses between control and intervention. Secondary end-points were the number of diagnoses in differential diagnosis, diagnostic confidence and inter-rater agreement. We also analysed how XAI influenced pulmonologists’ decisions.Results In phase 1 (n=16 pulmonologists), mean preferential and differential diagnostic accuracy significantly increased by 10.4% and 9.4%, respectively, between control and intervention (p<0.001). Improvements were somewhat lower but highly significant (p<0.0001) in phase 2 (5.4% and 8.7%, respectively; n=62 pulmonologists). In both phases, the number of diagnoses in the differential diagnosis did not reduce, but diagnostic confidence and inter-rater agreement significantly increased during intervention. Pulmonologists updated their decisions with XAI's feedback and consistently improved their baseline performance if AI provided correct predictions.Conclusion A collaboration between a pulmonologist and XAI is better at interpreting PFTs than individual pulmonologists reading without XAI support or XAI alone.

Journal article

Edwards GD, Polgar O, Patel S, Barker RE, Walsh JA, Harvey J, Man WD-C, Nolan CMet al., 2023, Mood disorder in idiopathic pulmonary fibrosis: response to pulmonary rehabilitation, ERJ Open Research, Vol: 9, ISSN: 2312-0541

Background Pulmonary rehabilitation improves mood disorder in COPD, but there are limited data in idiopathic pulmonary fibrosis (IPF). The aims of this cohort study were to investigate whether pulmonary rehabilitation reduces mood disorder in IPF, and estimate the minimal important difference (MID) of the Hospital Anxiety and Depression Scale (HADS).Methods HADS and core pulmonary rehabilitation outcomes were measured in 166 participants before and after an 8-week, in-person, outpatient pulmonary rehabilitation programme. Anchor- and distribution-based methods were used to calculate the MID of HADS-Anxiety (A) and HADS-Depression (D).Results Suggestive or probable anxiety and depression (HADS ≥8) were present in 35% and 37% of participants, respectively, at baseline, and this reduced significantly following pulmonary rehabilitation (post-pulmonary rehabilitation: HADS-A 23%, HADS-D 26%). Overall, there was a significant reduction in HADS-D (mean change −1.1, 95% CI −1.6– −0.5), but not HADS-A (−0.6, −1.3–0.15) with pulmonary rehabilitation. Subgroup analysis of those with HADS ≥8 revealed significant improvements in HADS domains (mean change: HADS-A −4.5, 95% CI −5.7– −3.4; median change: HADS-D −4.0, interquartile range −6.0– −1.0). The mean (range) MID estimates for HADS-A and HADS-D were −2 (−2.3– −1.7) and −1.2 (−1.9– −0.5), respectively.Conclusion In people with IPF and suggestive or probable mood disorder, pulmonary rehabilitation reduces anxiety and depression.

Journal article

Man W, Littlemore H, Patel S, Harvey J, Ingram K, Jenkins TO, Nolan CMet al., 2023, Video Telerehabilitation Versus Centre-based Pulmonary Rehabilitation: A Real-World Propensity Matched Analysis, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Patel S, Harvey JL, Jenkins T, Nolan CM, Man Wet al., 2023, Screening for Clinically Relevant Thresholds of the Incremental Shuttle Walk in People With COPD Using the One-minute Sit to Stand, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Mohan D, Rossiter H, Watz H, Fogarty C, Evans RA, Man W, Tabberer M, Beerahee M, Kumar S, Millns H, Thomas S, Tal-Singer R, Russell AJ, Holland MC, Akinseye C, Neil D, Polkey Met al., 2023, Selective androgen receptor modulation for muscle weakness in chronic obstructive pulmonary disease: a randomised control trial, Thorax, Vol: 78, Pages: 258-266, ISSN: 0040-6376

Background Selective androgen receptor modulators (SARMs) increase muscle mass via the androgen receptor. This phase 2A trial investigated the effects of a SARM, GSK2881078, in conjunction with exercise, on leg strength in patients with chronic obstructive pulmonary disease (COPD) and impaired physical function.Methods 47 postmenopausal women and 50 men with COPD (forced expiratory volume in 1 s 30%–65% predicted; short physical performance battery score: 3–11) were enrolled into a randomised double-blind, placebo control trial. Patients were randomised 1:1 to once daily placebo or oral GSK2881078 (females: 1.0 mg; males: 2.0 mg) for 13 weeks with a concurrent home-exercise programme, involving strength training and physical activity. Primary endpoints were change from baseline in leg strength at 90 days (one-repetition maximum; absolute (kg) and relative (% change)) and multiple safety outcomes. Secondary endpoints included lean body mass, physical function and patient-reported outcomes.Results GSK2881078 increased leg strength in men. The difference in adjusted mean change from baseline and adjusted mean percentage change from baseline between treatment and placebo were: for women, 8.0 kg (90% CI −2.5 to 18.4) and 5.2% (90% CI −4.7 to 15.0), respectively; for men, 11.8 kg (90% CI −0.5 to 24.0) and 7.0% (90% CI 0.5 to 13.6), respectively. Lean body mass increased, but no changes in patient-reported outcomes were observed. Reversible reductions in high-density lipoprotein-cholesterol and transient elevations in hepatic transaminases were the main treatment-related safety findings.Conclusions GSK2881078 was well tolerated and short-term treatment increased leg strength, when expressed as per cent predicted, in men with COPD more than physical training alone.

Journal article

Patel S, Jones SE, Barker RE, Polgar O, Maddocks M, Hopkinson NS, Nolan CM, Man WD-Cet al., 2023, The six-minute step test as an exercise outcome in chronic obstructive pulmonary disease, Annals of the American Thoracic Society, Vol: 20, Pages: 476-479, ISSN: 1546-3222

Journal article

McAuley HJC, Evans RA, Bolton CE, Brightling CE, Chalmers JD, Docherty AB, Elneima O, Greenhaff PL, Gupta A, Harris VC, Harrison EM, Ho L-P, Horsley A, Houchen-Wolloff L, Jolley CJ, Leavy OC, Lone NI, Man WD-C, Marks M, Parekh D, Poinasamy K, Quint JK, Raman B, Richardson M, Saunders RM, Sereno M, Shikotra A, Singapuri A, Singh SJ, Steiner M, Tan AL, Wain LV, Welch C, Whitney J, Witham MD, Lord J, Greening NJ, PHOSP-COVID Study Collaborative Groupet al., 2023, Prevalence of physical frailty, including risk factors, up to 1 year after hospitalisation for COVID-19 in the UK: a multicentre, longitudinal cohort study., EClinicalMedicine, Vol: 57, Pages: 1-13, ISSN: 2589-5370

BACKGROUND: The scale of COVID-19 and its well documented long-term sequelae support a need to understand long-term outcomes including frailty. METHODS: This prospective cohort study recruited adults who had survived hospitalisation with clinically diagnosed COVID-19 across 35 sites in the UK (PHOSP-COVID). The burden of frailty was objectively measured using Fried's Frailty Phenotype (FFP). The primary outcome was the prevalence of each FFP group-robust (no FFP criteria), pre-frail (one or two FFP criteria) and frail (three or more FFP criteria)-at 5 months and 1 year after discharge from hospital. For inclusion in the primary analysis, participants required complete outcome data for three of the five FFP criteria. Longitudinal changes across frailty domains are reported at 5 months and 1 year post-hospitalisation, along with risk factors for frailty status. Patient-perceived recovery and health-related quality of life (HRQoL) were retrospectively rated for pre-COVID-19 and prospectively rated at the 5 month and 1 year visits. This study is registered with ISRCTN, number ISRCTN10980107. FINDINGS: Between March 5, 2020, and March 31, 2021, 2419 participants were enrolled with FFP data. Mean age was 57.9 (SD 12.6) years, 933 (38.6%) were female, and 429 (17.7%) had received invasive mechanical ventilation. 1785 had measures at both timepoints, of which 240 (13.4%), 1138 (63.8%) and 407 (22.8%) were frail, pre-frail and robust, respectively, at 5 months compared with 123 (6.9%), 1046 (58.6%) and 616 (34.5%) at 1 year. Factors associated with pre-frailty or frailty were invasive mechanical ventilation, older age, female sex, and greater social deprivation. Frail participants had a larger reduction in HRQoL compared with before their COVID-19 illness and were less likely to describe themselves as recovered. INTERPRETATION: Physical frailty and pre-frailty are common following hospitalisation with COVID-19. Improvement in frailty was seen between 5 and 12 months although

Journal article

Daynes E, Baldwin M, Greening NJ, Yates T, Bishop NC, Mills G, Roberts M, Hamrouni M, Plekhanova T, Vogiatzis I, Echevarria C, Nathu R, McAuley HJC, Latimer L, Glennie J, Chambers F, Penfold R, Hume E, Megaritis D, Alexiou C, Potthof S, Hogg MJ, Haighton C, Nichol B, Leavy OC, Richardson M, Elneima O, Singapuri A, Sereno M, Saunders RM, Harris VC, Nolan CM, Bolton C, Houchen-Wolloff L, Harrison EM, Lone N, Quint J, Chalmers JD, Ho L-P, Horsley A, Marks M, Poinasamy K, Ramen B, Wain LV, Brightling C, Man WD-C, Evans R, Singh SJet al., 2023, Correction: The effect of COVID rehabilitation for ongoing symptoms Post HOSPitalisation with COVID-19 (PHOSP-R): protocol for a randomised parallel group controlled trial on behalf of the PHOSP consortium, Trials, Vol: 24, ISSN: 1745-6215

Journal article

Philip K, 2023, Digital delivery and assessment of holistic interventions for breathlessness

Breathlessness is a common and important symptom, resulting from the interaction between multiple physical, psychological and social factors, and causes substantial negative impacts to health-related quality of life. Interest has grown in therapeutic potential of holistic participatory arts-in-health activities using singing and dance for people with breathlessness, within the broader context of social prescribing. A small body of research has indicated such interventions might be effective, however properly conducted studies investigating impact, and mechanisms of impact, are lacking. Additionally, advances in digital health have expanded remote healthcare delivery, a trend accelerated by the COVID-19 pandemic, creating novel opportunities and challenges.This thesis aims to assess the impact, potential mechanisms, and possible future approaches, of digitally delivered holistic arts-in-health interventions for people with breathlessness. I present six results chapters addressing current research gaps. First, an observational study comparing the physiological demands of Singing for Lung Health (SLH) with treadmill walking, to investigate potential mechanisms of impact. Second, I present data from the first group of a planned larger randomised controlled trial (RCT) investigating the impact of face-to-face SLH. This group transferred to online SLH halfway through the intervention due to the COVID-19 pandemic, but viewed as a convenience pilot study, the findings provide valuable insights into digital adaptation of complex interventions. Third, a digitally delivered, remotely assessed, RCT comparing online SLH to usual care in COPD. Fourth, a digitally delivered and assessed RCT comparing the English National Opera’s Breathe programme to usual care in people with Long COVID and breathlessness. The fifth and sixth results chapters are qualitative studies investigating the experience of dance group participants for people with breathlessness in England and Uganda.T

Thesis dissertation

Daynes E, Baldwin M, Greening NJ, Yates T, Bishop NC, Mills G, Roberts M, Hamrouni M, Plekhanova T, Vogiatzis I, Echevarria C, Nathu R, McAuley HJC, Latimer L, Glennie J, Chambers F, Penfold R, Hume E, Magaritis D, Alexiou C, Potthoff S, Hogg MJ, Haighton C, Nichol B, Leavy OC, Richardson M, Elneima O, Singapuri A, Sereno M, Saunders RM, Harris VC, Nolan CM, Bolton C, Houchen-Wolloff L, Harrison EM, Lone N, Quint J, Chalmers JD, Ho L-P, Horsley A, Marks M, Poinasamy K, Ramen B, Wain LV, Brightling C, Man WD-C, Evans R, Singh SJet al., 2023, The effect of COVID rehabilitation for ongoing symptoms Post HOSPitalisation with COVID-19 (PHOSP-R): protocol for a randomised parallel group controlled trial on behalf of the PHOSP consortium, Trials, Vol: 24, ISSN: 1745-6215

IntroductionMany adults hospitalised with COVID-19 have persistent symptoms such as fatigue, breathlessness and brain fog that limit day-to-day activities. These symptoms can last over 2 years. Whilst there is limited controlled studies on interventions that can support those with ongoing symptoms, there has been some promise in rehabilitation interventions in improving function and symptoms either using face-to-face or digital methods, but evidence remains limited and these studies often lack a control group.Methods and analysisThis is a nested single-blind, parallel group, randomised control trial with embedded qualitative evaluation comparing rehabilitation (face-to-face or digital) to usual care and conducted within the PHOSP-COVID study. The aim of this study is to determine the effectiveness of rehabilitation interventions on exercise capacity, quality of life and symptoms such as breathlessness and fatigue. The primary outcome is the Incremental Shuttle Walking Test following the eight week intervention phase. Secondary outcomes include measures of function, strength and subjective assessment of symptoms. Blood inflammatory markers and muscle biopsies are an exploratory outcome. The interventions last eight weeks and combine symptom-titrated exercise therapy, symptom management and education delivered either in a face-to-face setting or through a digital platform (www.yourcovidrecovery.nhs.uk). The proposed sample size is 159 participants, and data will be intention-to-treat analyses comparing rehabilitation (face-to-face or digital) to usual care.Ethics and disseminationEthical approval was gained as part of the PHOSP-COVID study by Yorkshire and the Humber Leeds West Research NHS Ethics Committee, and the study was prospectively registered on the ISRCTN trial registry (ISRCTN13293865). Results will be disseminated to stakeholders, including patients and members of the public, and published in appropriate journals.

Journal article

Brighton LJ, Nolan CM, Barker RE, Patel S, Walsh JA, Polgar O, Kon SSC, Gao W, Evans CJ, Maddocks M, Man WDCet al., 2023, Frailty and mortality risk in COPD: a cohort study comparing the fried frailty phenotype and short physical performance battery, The International Journal of Chronic Obstructive Pulmonary Disease, Vol: 18, Pages: 57-67, ISSN: 1176-9106

Background: Identifying frailty in people with chronic obstructive pulmonary disease (COPD) is deemed important, yet comparative characteristics of the most commonly used frailty measures in COPD are unknown. This study aimed to compare how the Fried Frailty Phenotype (FFP) and Short Physical Performance Battery (SPPB) characterise frailty in people with stable COPD, including prevalence of and overlap in identification of frailty, disease and health characteristics of those identified as living with frailty, and predictive value in relation to survival time.Methods: Cohort study of people with stable COPD attending outpatient clinics. Agreement between frailty classifications was described using Cohen’s Kappa. Disease and health characteristics of frail versus not frail participants were compared using t-, Mann–Whitney U and Chi-Square tests. Predictive value for mortality was examined with multivariable Cox regression.Results: Of 714 participants, 421 (59%) were male, mean age 69.9 years (SD 9.7), mean survival time 2270 days (95% CI 2185– 2355). Similar proportions were identified as frail using the FFP (26.2%) and SPPB (23.7%) measures; classifications as frail or not frail matched in 572 (80.1%) cases, showing moderate agreement (Kappa = 0.469, SE = 0.038, p < 0.001). Discrepancies seemed driven by FFP exhaustion and weight loss criteria and the SPPB balance component. People with frailty by either measure had worse exercise capacity, health-related quality of life, breathlessness, depression and dependence in activities of daily living. In multivariable analysis controlling for the Age Dyspnoea Obstruction index, sex, BMI, comorbidities and exercise capacity, both the FFP and SPPB had predictive value in relation to mortality (FFP aHR = 1.31 [95% CI 1.03– 1.66]; SPPB aHR = 1.29 [95% CI 0.99– 1.68]).Conclusion: In stable COPD, both the FFP and SPPB identify similar proportions of people living with/without frailty, the majority

Journal article

George PM, Reed A, Desai SR, Devaraj A, Faiez TS, Laverty S, Kanwal A, Esneau C, Liu MKC, Kamal F, Man WD-C, Kaul S, Singh S, Lamb G, Faizi FK, Schuliga M, Read J, Burgoyne T, Pinto AL, Micallef J, Bauwens E, Candiracci J, Bougoussa M, Herzog M, Raman L, Ahmetaj-Shala B, Turville S, Aggarwal A, Farne HA, Dalla Pria A, Aswani AD, Patella F, Borek WE, Mitchell JA, Bartlett NW, Dokal A, Xu X-N, Kelleher P, Shah A, Singanayagam Aet al., 2022, A persistent neutrophil-associated immune signature characterizes post-COVID-19 pulmonary sequelae., Science Translational Medicine, Vol: 14, Pages: 1-16, ISSN: 1946-6234

Interstitial lung disease and associated fibrosis occur in a proportion of individuals who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through unknown mechanisms. We studied individuals with severe coronavirus disease 2019 (COVID-19) after recovery from acute illness. Individuals with evidence of interstitial lung changes at 3 to 6 months after recovery had an up-regulated neutrophil-associated immune signature including increased chemokines, proteases, and markers of neutrophil extracellular traps that were detectable in the blood. Similar pathways were enriched in the upper airway with a concomitant increase in antiviral type I interferon signaling. Interaction analysis of the peripheral phosphoproteome identified enriched kinases critical for neutrophil inflammatory pathways. Evaluation of these individuals at 12 months after recovery indicated that a subset of the individuals had not yet achieved full normalization of radiological and functional changes. These data provide insight into mechanisms driving development of pulmonary sequelae during and after COVID-19 and provide a rational basis for development of targeted approaches to prevent long-term complications.

Journal article

Philip KEJ, Buttery SC, Bowen S, Lewis A, Alghamdi SM, Williams PJ, Alasmari AM, Alsulayyim AS, Orton CM, Conway F, Chan L, Vijayakurnar B, Tana A, Tonkin J, Perkins A, Garner J, Srikanthan K, Sadaka A, Pavitt M, Banya W, Lound A, Elkin S, Polkey MI, Man W, Lewis K, Fancourt D, Hopkinson NSet al., 2022, A SINGLE-BLIND, MULTICENTRE, MULTINATIONAL, RANDOMISED CONTROLLED TRIAL OF ONLINE SINGING FOR LUNG HEALTH (SLH) VS USUAL CARE FOR PEOPLE WITH COPD: THE SINGING FOR HEALTH, IMPROVING EXPERIENCES OF LUNG DISEASE (SHIELD) TRIAL, Winter Meeting of the British-Thoracic-Society (BTS), Publisher: BMJ PUBLISHING GROUP, Pages: A53-A53, ISSN: 0040-6376

Conference paper

Price LC, Garfield B, Bloom C, Jeyin N, Nissan D, Hull JH, Patel B, Jenkins G, Padley S, Man W, Singh S, Ridge CAet al., 2022, Persistent isolated impairment of gas transfer following COVID-19 pneumonitis relates to perfusion defects on dual-energy computed tomography, ERJ Open Research, Vol: 8, Pages: 1-5, ISSN: 2312-0541

Journal article

Trivedi P, Polgar O, Patel S, Barker R, Man W, Nolan Cet al., 2022, The minimal important difference (MID) of the five-repetition sit to stand test (5STS) in IPF, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

Edwards GD, Polgar O, Patel S, Barker RE, Walsh J, Harvey J, Man WD-C, Nolan CMet al., 2022, Anxiety and Depression in IPF and response to pulmonary rehabilitation (PR), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

Patel S, Sylvester K, Wu Z, Nolan C, Maher T, Molyneaux P, Man Wet al., 2022, Validity and symptom burden of impulse oscillometry (iOS) in idiopathic pulmonary fibrosis (IPF), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

Baldwin MM, Daynes E, Karsanji U, Mcauley H, Man WD, Evans RA, Singh SJet al., 2022, Exercise tolerance and limiting symptoms 5 and 12 months after hospital discharge from COVID-19, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

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