Imperial College London

DrWilliamMan

Faculty of MedicineNational Heart & Lung Institute

Reader in Respiratory Medicine
 
 
 
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Contact

 

+44 (0)1895 828 851w.man

 
 
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Location

 

Harefield HospitalHarefield Hospital

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Summary

 

Publications

Publication Type
Year
to

276 results found

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., Eur Respir Rev, Vol: 32

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., Eur Respir J, Vol: 62

Frailty is a complex, multidimensional syndrome characterised by a loss of physiological reserves that increases a person's susceptibility to adverse health outcomes. Most knowledge regarding frailty originates from geriatric medicine; however, awareness of its importance as a treatable trait for people with chronic respiratory disease (including asthma, COPD and interstitial lung disease) is emerging. A clearer understanding of frailty and its impact in chronic respiratory disease is a prerequisite to optimise clinical management in the future. This unmet need underpins the rationale for undertaking the present work. This European Respiratory Society statement synthesises current evidence and clinical insights from international experts and people affected by chronic respiratory conditions regarding frailty in adults with chronic respiratory disease. The scope includes coverage of frailty within international respiratory guidelines, prevalence and risk factors, review of clinical management options (including comprehensive geriatric care, rehabilitation, nutrition, pharmacological and psychological therapies) and identification of evidence gaps to inform future priority areas of research. Frailty is underrepresented in international respiratory guidelines, despite being common and related to increased hospitalisation and mortality. Validated screening instruments can detect frailty to prompt comprehensive assessment and personalised clinical management. Clinical trials targeting people with chronic respiratory disease and frailty are needed.

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

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

Brighton LJ, Lareau S, Maddocks M, Osadnik C, Lahousse L, Lee A, Allison J, Singer J, Rozenberg D, Man WD, Ferrante L, Spruit MA, Burtin C, Harrison SL, Iyer ASet al., 2023, What is Frailty?, Am J Respir Crit Care Med, Vol: 207, Pages: P5-P6

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., Ann Am Thorac Soc, Vol: 20, Pages: 767-780

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 and

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, Moisés J, Peché 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., Eur Respir J, Vol: 61

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 Res, 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

Patel S, Jones SE, Walsh JA, 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., Ann Am Thorac Soc, Vol: 20, Pages: 476-479

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, 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 (vol 24, 61, 2023), TRIALS, Vol: 24

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

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., Int J Chron Obstruct Pulmon Dis, Vol: 18, Pages: 57-67

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 with matching classifications.

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

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., 2022, Selective androgen receptor modulation for muscle weakness in chronic obstructive pulmonary disease: a randomised control trial, THORAX, ISSN: 0040-6376

Journal article

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

Daynes E, Baldwin MM, Karsanji U, Mcauley H, Man WD, Evans R, Singh SJet al., 2022, The impact of comorbidities on recovery following hospitalisation from COVID-19, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

Plekhanova T, Rowlands A, Evans RA, Edwardson CL, Bishop NC, Bolton CE, Chalmers JD, Davies MJ, Daynes E, Dempsey PC, Docherty AB, Elneima O, Greening NJ, Greenwood SA, Hall AP, Harris VC, Harrison EM, Henson J, Ho L-P, Horsley A, Houchen-Wolloff L, Khunti K, Leavy OC, Lone N, Marks M, Maylor B, McAuley HJC, Nolan CM, Poinasamy K, Quint JK, Raman B, Richardson M, Sargeant JA, Saunders RM, Sereno M, Shikotra A, Singapuri A, Steiner M, Stensel DJ, Wain L, Whitney J, Wootton DG, Brightling CE, Man WD-C, Singh SJ, Yates Tet al., 2022, Device-assessed sleep and physical activity in individuals recovering from a hospital admission for COVID-19: a multicentre study, International Journal of Behavioral Nutrition and Physical Activity, Vol: 19, Pages: 1-13, ISSN: 1479-5868

BackgroundThe number of individuals recovering from severe COVID-19 is increasing rapidly. However, little is known about physical behaviours that make up the 24-h cycle within these individuals. This study aimed to describe physical behaviours following hospital admission for COVID-19 at eight months post-discharge including associations with acute illness severity and ongoing symptoms.MethodsOne thousand seventy-seven patients with COVID-19 discharged from hospital between March and November 2020 were recruited. Using a 14-day wear protocol, wrist-worn accelerometers were sent to participants after a five-month follow-up assessment. Acute illness severity was assessed by the WHO clinical progression scale, and the severity of ongoing symptoms was assessed using four previously reported data-driven clinical recovery clusters. Two existing control populations of office workers and individuals with type 2 diabetes were comparators.ResultsValid accelerometer data from 253 women and 462 men were included. Women engaged in a mean ± SD of 14.9 ± 14.7 min/day of moderate-to-vigorous physical activity (MVPA), with 12.1 ± 1.7 h/day spent inactive and 7.2 ± 1.1 h/day asleep. The values for men were 21.0 ± 22.3 and 12.6 ± 1.7 h /day and 6.9 ± 1.1 h/day, respectively. Over 60% of women and men did not have any days containing a 30-min bout of MVPA. Variability in sleep timing was approximately 2 h in men and women. More severe acute illness was associated with lower total activity and MVPA in recovery. The very severe recovery cluster was associated with fewer days/week containing continuous bouts of MVPA, longer total sleep time, and higher variability in sleep timing. Patients post-hospitalisation with COVID-19 had lower levels of physical activity, greater sleep variability, and lower sleep efficiency than a similarly aged cohort

Journal article

Sharma P, Thomas K, Rogers P, Prendergast C, Banya W, Lane R, Nolan C, Jones S, Canavan J, Kon S, Man W, Dalby Met al., 2022, 4-METRE-GAIT SPEED AS A PREDICTOR OF 5-YEAR SURVIVAL AFTER ACUTE MYOCARDIAL INFARCTION: A PROSPECTIVE COHORT STUDY, Annual Conference of the British-Cardiovascular-Society - 100 Years of Cardiology, Publisher: BMJ PUBLISHING GROUP, Pages: A43-A44, ISSN: 1355-6037

Conference paper

Alqahtani KA, Gerlis C, Nolan CM, Gardiner N, Szczepura A, Man W, Singh SJ, Houchen-Wolloff Let al., 2022, SPACE FOR COPD delivered as a maintenance programme on pulmonary rehabilitation discharge: protocol of a randomised controlled trial evaluating the long-term effects on exercise tolerance and mental well-being, BMJ Open, Vol: 12, Pages: 1-10, ISSN: 2044-6055

Introduction The benefits achieved during pulmonary rehabilitation (PR) are known to be sustained for 6–12 months after the initial programme. Several maintenance trials have been conducted but were heterogeneous in terms of duration, frequency and labour cost. There is no consensus on one best strategy. SPACE FOR COPD (Self-management Programme of Activity, Coping and Education for Chronic Obstructive Pulmonary Disease) is a home-based self-management programme, which has been shown previously to be effective in primary and secondary care settings and is to be tested here as a maintenance programme. The aim is to evaluate the efficacy of the SPACE FOR COPD programme (manual and group sessions), on exercise tolerance and mental well-being, compared with usual care following PR in patients with COPD.Methods and analysis A prospective, multicentre, single-blinded randomised controlled trial requiring 116 participants with a clinical diagnosis of COPD who have finished PR within 4 weeks will be randomised 1:1 to either a usual care group or a SPACE FOR COPD programme group. The intervention comprises a home-based manual and 4, 2-hour group sessions adopting motivational interviewing techniques over 12 months. The primary outcome is endurance capacity measured by the Endurance Shuttle Walking Test at 12 months. Secondary outcomes are: maximal exercise capacity, health-related quality of life, mood, patient activation, physical activity, lung function and healthcare costs. The measures will be taken at baseline, 6 and 12 months. Patient interviews and staff focus groups will be conducted to explore barriers, facilitators and views about the intervention at the end of the study. A framework analysis will be used for the interpretation of qualitative data.Ethics and dissemination The trial was granted ethical approval from Health Research Authority and Health and Care Research Wales (HCRW19/EM/0267 on 10 October 2019). Results will be made availa

Journal article

Nolan CM, Polgar O, Schofield SJ, Patel S, Barker RE, Walsh JA, Ingram KA, George PM, Molyneaux PL, Maher TM, Man WD-Cet al., 2022, Pulmonary rehabilitation in idiopathic pulmonary fibrosis and COPD: a propensity matched real-world study, Chest, Vol: 161, Pages: 728-737, ISSN: 0012-3692

BACKGROUND: The adherence to and clinical efficacy of pulmonary rehabilitation in idiopathic pulmonary fibrosis (IPF), particularly in comparison to people with chronic obstructive pulmonary disease (COPD), remains uncertain. The objectives of this real-world study were to compare the responses of patients with IPF with a matched group of patients with COPD undergoing the same supervised, outpatient pulmonary rehabilitation program, and to determine whether pulmonary rehabilitation is associated with survival in IPF. RESEARCH QUESTION: Do people with IPF improve to the same extent with pulmonary rehabilitation as a matched group of individuals with COPD, and are non-completion of and/or non-response to pulmonary rehabilitation associated with one-year all-cause mortality in IPF? STUDY DESIGN AND METHODS: Using propensity score matching, 163 patients with IPF were matched 1:1 with a control group of 163 patients with COPD referred to pulmonary rehabilitation. We compared between-group pulmonary rehabilitation completion rates and response. Survival status in the IPF cohort was recorded over one-year following pulmonary rehabilitation discharge. Cox proportional-hazards regression explored the association between pulmonary rehabilitation status and all-cause mortality. RESULTS: Similar pulmonary rehabilitation completion rates (IPF: 69%; COPD: 63%; p=0.24) and improvements in exercise response were observed in both groups with no significant mean (95% confidence interval (CI)) between-group differences in incremental shuttle walk (ISW) change (2 (-18 to 22) meters). Pulmonary rehabilitation non-completion (hazard ratio (HR) (95%CI) 5.62 (2.24 to 14.08)) and non-response (HR (95%CI) 3.91 (1.54 to 9.93)) were independently associated with increased one-year all-cause mortality in IPF. INTERPRETATION: Compared with a matched group of patients with COPD, this real-word study demonstrates that patients with IPF have similar completion rates and magnitude of response to pul

Journal article

Polgar O, Patel S, Walsh JA, Barker RE, Ingram KA, Kon SSC, Man WDC, Nolan CMet al., 2022, Digital habits of pulmonary rehabilitation service-users following the COVID-19 pandemic, Chronic Respiratory Disease, Vol: 19, Pages: 1-3, ISSN: 1479-9723

ObjectiveWe previously demonstrated low levels of digital literacy amongst pulmonary rehabilitation service-users prior to the COVID-19 pandemic. We aimed to identify whether the pandemic accelerated digital literacy in this population, resulting in greater acceptance of remote web-based pulmonary rehabilitation programme models.MethodsWe surveyed digital access and behaviours and pulmonary rehabilitation delivery preferences of service-users referred to pulmonary rehabilitation in 2021 (cohort 2021) and propensity score-matched them to a cohort who completed the survey in 2020 (cohort 2020).ResultsThere were indicators that digital access and confidence were better amongst the Cohort 2021 but no difference was seen in the proportion of patients choosing remote web-based pulmonary rehabilitation as an acceptable method of receiving pulmonary rehabilitation.ConclusionIn an unselected cohort of service-users, remote web-based pulmonary rehabilitation was considered acceptable in only a minority of patients which has implications on healthcare commissioning and delivery of pulmonary rehabilitation.

Journal article

Burtin C, Mohan D, Troosters T, Watz H, Hopkinson NS, Garcia-Aymerich J, Moy ML, Vogiatzis I, Rossiter HB, Singh S, Merrill DD, Hamilton A, Rennard S, Fageras M, Petruzzelli S, Tal-Singer R, Tomaszewski E, Corriol-Rohou S, Rochester CL, Sciurba FC, Casaburi R, Man WD-C, Van Lummel RC, Cooper CB, Demeyer H, Spruit MA, Vaes Aet al., 2021, Objectively Measured Physical Activity as a COPD Clinical Trial Outcome, CHEST, Vol: 160, Pages: 2080-2100, ISSN: 0012-3692

Journal article

Walsh JA, Barker RE, Kon SSC, Jones SE, Banya W, Nolan CM, Patel S, Polgar O, Haselden BM, Polkey MI, Cullinan P, Man WD-Cet al., 2021, Reply to: Room for methodological improvement in gait speed study for COPD patients, EUROPEAN RESPIRATORY JOURNAL, Vol: 58, ISSN: 0903-1936

Journal article

Barker RE, Brighton LJ, Bayly J, Walsh JA, Nolan CM, Patel S, Polgar O, Wenneberg J, Kon SSC, Wedzicha JA, Maddocks M, Farquhar M, Man WDCet al., 2021, INTEGRATING HOME-BASED EXERCISE TRAINING WITHIN A HOSPITAL AT HOME SERVICE FOR PATIENTS HOSPITALISED WITH ACUTE EXACERBATIONS OF COPD: A MIXED METHODS FEASIBILITY STUDY, Publisher: BMJ PUBLISHING GROUP, Pages: A18-A19, ISSN: 0040-6376

Conference paper

Demeyer H, Mohan D, Burtin C, Vaes AW, Heasley M, Bowler RP, Casaburi R, Cooper CB, Corriol-Rohou S, Frei A, Hamilton A, Hopkinson NS, Karlsson N, Man WD-C, Moy ML, Pitta F, Polkey MI, Puhan M, Rennard SI, Rochester CL, Rossiter HB, Sciurba F, Singh S, Tal-Singer R, Vogiatzis I, Watz H, Lummel RV, Wyatt J, Merrill DD, Spruit MA, Garcia-Aymerich J, Troosters T, Chronic Lung Disease Biomarker and Clinical Outcome Assessment Qualification Consortium Task Force on Physical Activityet al., 2021, Objectively measured physical activity in patients with COPD: recommendations from an international task force on physical activity., COPD: Journal of Chronic Obstructive Pulmonary Disease, Vol: 8, Pages: 528-550, ISSN: 1541-2555

Physical activity (PA) is of key importance for health among healthy persons and individuals with chronic obstructive pulmonary disease (COPD). PA has multiple dimensions that can be assessed and quantified objectively using activity monitors. Moreover, as shown in the published literature, variable methodologies have been used to date to quantify PA among individuals with COPD, precluding clear comparisons of outcomes across studies. The present paper aims to provide a summary of the available literature for the rationale behind using objectively measured PA and proposes a standardized methodology for assessment, including standard operating procedures for future research. The present paper, therefore, describes the concept of PA, reports on the importance of PA, summarizes the dimensions of PA, provides a standard operating procedure on how to monitor PA using objective assessments, and describes the psychometric properties of objectively measured PA. The present international task force recommends implementation of the standard operating procedure for PA data collection and reporting in the future. This should further clarify the relationship between PA and clinical outcomes, test the impact of treatment interventions on PA in individuals with COPD, and successfully propose a PA endpoint for regulatory qualification in the future.

Journal article

Finney LJ, Doughty R, Lovage S, Spurr L, Mehta B, Kemp SV, Chua F, Price LC, Singh S, Man WDCet al., 2021, Lung function deficits and symptom burden in survivors of COVID-19 requiring mechanical ventilation, Annals of the American Thoracic Society, Vol: 18, Pages: 1740-1743, ISSN: 1546-3222

Journal article

Nolan CM, Walsh JA, Patel S, Barker RE, Polgar O, Maddocks M, Gao W, Wilson R, Fiorentino F, Man Wet al., 2021, Minimal versus specialist equipment in the delivery of pulmonary rehabilitation: protocol for a non-inferiority randomised controlled trial, BMJ Open, Vol: 11, Pages: 1-8, ISSN: 2044-6055

Introduction Pulmonary rehabilitation (PR), an exercise and education programme for people with chronic lung disease, aims to improve exercise capacity, breathlessness and quality of life. Most evidence to support PR is from trials that use specialist exercise equipment, for example, treadmills (PR-gym). However, a significant proportion of programmes do not have access to specialist equipment with training completed with minimal exercise equipment (PR-min). There is a paucity of robust literature examining the efficacy of supervised, centre-based PR-min. We aim to determine whether an 8-week supervised, centre-based PR-min programme is non-inferior to a standard 8-week supervised, centre-based PR-gym programme in terms of exercise capacity and health outcomes for patients with chronic lung disease.Methods and analysis Parallel, two-group, assessor-blinded and statistician-blinded, non-inferiority randomised trial. 436 participants will be randomised using minimisation at the individual level with a 1:1 allocation to PR-min (intervention) or PR-gym (control). Assessment will take place pre-PR (visit 1), post-PR (visit 2) and 12 months following visit 1 (visit 3). Exercise capacity (incremental shuttle walk test), dyspnoea (Chronic Respiratory Questionnaire (CRQ)-Dyspnoea), health-related quality of life (CRQ), frailty (Short Physical Performance Battery), muscle strength (isometric quadriceps maximum voluntary contraction), patient satisfaction (Global Rating of Change Questionnaire), health economic as well as safety and trial process data will be measured. The primary outcome is change in exercise capacity between visit 1 and visit 2. Two sample t-tests on an intention to treat basis will be used to estimate the difference in mean primary and secondary outcomes between patients randomised to PR-gym and PR-min.Ethics and dissemination London-Camden and Kings Cross Research Ethics Committee and Health Research Authority have approved the study (18/LO/0315). Results

Journal article

Barker RE, Kon SS, Clarke SF, Wenneberg J, Nolan CM, Patel S, Walsh JA, Polgar O, Maddocks M, Farquhar M, Hopkinson NS, Bell D, Wedzicha JA, Man WD-Cet al., 2021, COPD discharge bundle and pulmonary rehabilitation referral and uptake following hospitalisation for acute exacerbation of COPD, Thorax, Vol: 76, Pages: 829-831, ISSN: 0040-6376

Pulmonary rehabilitation (PR) following hospitalisations for acute exacerbation of COPD (AECOPD) is associated with improved exercise capacity and quality of life, and reduced readmissions. However, referral for, and uptake of, post-hospitalisation PR are low. In this prospective cohort study of 291 consecutive hospitalisations for AECOPD, COPD discharge bundles delivered by PR practitioners compared with non-PR practitioners were associated with increased PR referral (60% vs 12%, p<0.001; adjusted OR: 14.46, 95% CI: 5.28 to 39.57) and uptake (40% vs 32%, p=0.001; adjusted OR: 8.60, 95% CI: 2.51 to 29.50). Closer integration between hospital and PR services may increase post-hospitalisation PR referral and uptake.

Journal article

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