ORCID Profile
0000-0002-9578-2249
Current Organisation
University of Nottingham
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Publisher: Elsevier BV
Date: 08-2022
Publisher: BMJ
Date: 11-01-2017
Publisher: Springer Science and Business Media LLC
Date: 26-01-2023
DOI: 10.1186/S13063-023-07093-7
Abstract: Many 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. This 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 s le size is 159 participants, and data will be intention-to-treat analyses comparing rehabilitation (face-to-face or digital) to usual care. Ethical 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. Strengths and limitations of this study • This protocol utilises two interventions to support those with ongoing symptoms of COVID-19 • This is a two-centre parallel-group randomised controlled trial • The protocol has been supported by patient and public involvement groups who identified treatments of symptoms and activity limitation as a top priority
Publisher: BMJ
Date: 23-07-2013
Publisher: Elsevier BV
Date: 08-2023
Publisher: Springer Science and Business Media LLC
Date: 28-07-2022
DOI: 10.1186/S12966-022-01333-W
Abstract: The number of in iduals recovering from severe COVID-19 is increasing rapidly. However, little is known about physical behaviours that make up the 24-h cycle within these in iduals. 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. One 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 in iduals with type 2 diabetes were comparators. Valid 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 of office workers or those with type 2 diabetes. Those recovering from a hospital admission for COVID-19 have low levels of physical activity and disrupted patterns of sleep several months after discharge. Our comparative cohorts indicate that the long-term impact of COVID-19 on physical behaviours is significant.
Publisher: Informa UK Limited
Date: 09-2017
DOI: 10.2147/COPD.S141620
Publisher: BMJ
Date: 30-03-2022
DOI: 10.1136/THORAXJNL-2021-218582
Abstract: Given the large numbers of people infected and high rates of ongoing morbidity, research is clearly required to address the needs of adult survivors of COVID-19 living with ongoing symptoms (long COVID). To help direct resource and research efforts, we completed a research prioritisation process incorporating views from adults with ongoing symptoms of COVID-19, carers, clinicians and clinical researchers. The final top 10 research questions were agreed at an independently mediated workshop and included: identifying underlying mechanisms of long COVID, establishing diagnostic tools, understanding trajectory of recovery and evaluating the role of interventions both during the acute and persistent phases of the illness.
Publisher: Springer Science and Business Media LLC
Date: 19-01-2022
DOI: 10.1186/S12890-022-01835-0
Abstract: Respiratory medicine (RM) and palliative care (PC) physicians’ management of chronic breathlessness in advanced chronic obstructive pulmonary disease (COPD), fibrotic interstitial lung disease (fILD) and lung cancer (LC), and the influence of practice guidelines was explored via an online survey. A voluntary, online survey was distributed to RM and PC physicians via society newsletter mailing lists. 450 evaluable questionnaires (348 (77%) RM and 102 (23%) PC) were analysed. Significantly more PC physicians indicated routine use (often/always) of opioids across conditions (COPD: 92% vs. 39%, fILD: 83% vs. 36%, LC: 95% vs. 76% all p 0.001) and significantly more PC physicians indicated routine use of benzodiazepines for COPD (33% vs. 10%) and fILD (25% vs. 12%) (both p 0.001). Significantly more RM physicians reported routine use of a breathlessness score (62% vs. 13%, p 0.001) and prioritised exercise training/rehabilitation for COPD (49% vs. 7%) and fILD (30% vs. 18%) (both p 0.001). Overall, 40% of all respondents reported reading non-cancer palliative care guidelines (either carefully or looked at them briefly). Respondents who reported reading these guidelines were more likely to: routinely use a breathlessness score ( χ 2 = 13.8 p 0.001), use opioids ( χ 2 = 12.58, p 0.001) and refer to pulmonary rehabilitation ( χ 2 = 6.41, p = 0.011) in COPD use antidepressants ( χ 2 = 6.25 p = 0.044) and refer to PC ( χ 2 = 5.83 p = 0.016) in fILD and use a handheld fan in COPD ( χ 2 = 8.75, p = 0.003), fILD ( χ 2 = 4.85, p = 0.028) and LC ( χ 2 = 5.63 p = 0.018). These findings suggest a need for improved dissemination and uptake of jointly developed breathlessness management guidelines in order to encourage appropriate use of existing, evidence-based therapies. The lack of opioid use by RM, and continued benzodiazepine use in PC, suggest that a wider range of acceptable therapies need to be developed and trialled.
Publisher: Cold Spring Harbor Laboratory
Date: 14-12-2022
DOI: 10.1101/2022.12.13.22283391
Abstract: Sleep disturbance is common following hospitalisation both for COVID-19 and other causes. The clinical associations are poorly understood, despite it altering pathophysiology in other scenarios. We, therefore, investigated whether sleep disturbance is associated with dyspnoea along with relevant mediation pathways. Sleep parameters were assessed in a prospective cohort of patients (n=2,468) hospitalised for COVID-19 in the United Kingdom in 39 centres using both subjective and device-based measures. Results were compared to a matched UK biobank cohort and associations were evaluated using multivariable linear regression. 64% (456/714) of participants reported poor sleep quality 56% felt their sleep quality had deteriorated for at least 1-year following hospitalisation. Compared to the matched cohort, both sleep regularity (44.5 vs 59.2, p .001) and sleep efficiency (85.4% vs 88.5%, p .001) were lower whilst sleep period duration was longer (8.25h vs 7.32h, p .001). Overall sleep quality (effect estimate 4.2 (3.0–5.5)), deterioration in sleep quality following hospitalisation (effect estimate 3.2 (2.0–4.5)), and sleep regularity (effect estimate 5.9 (3.7–8.1)) were associated with both dyspnoea and impaired lung function (FEV 1 and FVC). Depending on the sleep metric, anxiety mediated 13–42% of the effect of sleep disturbance on dyspnoea and muscle weakness mediated 29-43% of this effect. Sleep disturbance is associated with dyspnoea, anxiety and muscle weakness following COVID-19 hospitalisation. It could have similar effects for other causes of hospitalisation where sleep disturbance is prevalent. UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council.
Publisher: Elsevier BV
Date: 11-2021
Publisher: American Physiological Society
Date: 12-2018
DOI: 10.1152/AJPLUNG.00175.2018
Abstract: Dysregulated protease activity is thought to cause parenchymal and airway damage in chronic obstructive pulmonary disease (COPD). Multiple proteases have been implicated in COPD, and identifying their substrates may reveal new disease mechanisms and treatments. However, as proteases interact with many substrates that may be protease inhibitors or proteases themselves, these webs of protease interactions make the wider consequences of therapeutically targeting proteases difficult to predict. We therefore used a systems approach to determine protease substrates and protease activity in COPD airways. Protease substrates were determined by proteomics using the terminal amine isotopic labeling of substrates (TAILS) methodology in paired sputum s les during stable COPD and exacerbations. Protease activity and specific protein degradation in airway s les were assessed using Western blotting, substrate assays, and ex vivo cleavage assays. Two hundred ninety-nine proteins were identified in human COPD sputum, 125 of which were proteolytically processed, including proteases, protease inhibitors, mucins, defensins, and complement and other innate immune proteins. During exacerbations, airway neutrophils and neutrophil proteases increased and more proteins were cleaved, particularly at multiple sites, consistent with degradation and inactivation. During exacerbations, different substrates were processed, including protease inhibitors, mucins, and complement proteins. Exacerbations were associated with increasing airway elastase activity and increased processing of specific elastase substrates, including secretory leukocyte protease inhibitor. Proteolysis regulates multiple processes including elastase activity and innate immune proteins in COPD airways and differs during stable disease and exacerbations. The complexity of protease, inhibitor, and substrate networks makes the effect of protease inhibitors hard to predict which should be used cautiously.
Publisher: Elsevier BV
Date: 03-2021
Publisher: Elsevier BV
Date: 2023
Publisher: Informa UK Limited
Date: 29-09-2015
DOI: 10.3109/15412555.2015.1043522
Abstract: Matrix metalloproteinases (MMPs) are elevated in the airways and blood of COPD patients, contributing to disease pathogenesis and tissue remodelling. However, it is not clear if MMP levels in airways, blood and urine are related or if MMP levels are related to disease severity or presence of exacerbations requiring hospitalisation. Seventy-two patients requiring hospitalisation for COPD exacerbations had serum, urine and sputum MMP-8, -9 and active MMP-9 measured by ELISA and gelatin zymography on day one, five and four weeks later (recovery). Clinical history, spirometry, COPD Assessment Test and MRC dyspnoea score were obtained. Twenty-two stable COPD patients had MMP measurements one week apart. During exacerbations, serum and urine MMP-9 were slightly elevated by 17% and 30% compared with recovery values respectively (p = 0.001 and p = 0.026). MMP-8 was not significantly changed. These MMP levels related to serum neutrophil numbers but not to outcome of exacerbations, disease severity measures or smoking status. In clinically stable patients, serum MMP levels did not vary significantly over 7 days, whereas urine MMPs varied by up to nine fold for MMP-8 (p = 0.003). Sputum, serum and urine contained different MMP species and complexes. Median values for sputum active MMP-9 were significantly different from serum (p = 0.035) and urine (p = 0.024). Serum and urine MMPs are only modestly elevated during exacerbations of COPD and unlikely to be useful biomarkers in this clinical setting. Airway, serum and urine MMP levels are independent of each other in COPD patients. Further, MMP levels are variable between patients and do not reflect airflow obstruction.
Publisher: Elsevier BV
Date: 03-2011
DOI: 10.1016/J.JCF.2010.12.001
Abstract: Adult patients with cystic fibrosis (CF) have resting abnormal large artery haemodynamics. Here, we obtain further insight in patients with CF by evaluating haemodynamic response to physiological stress. Thirty-six stable CF patients mean (SD) age 28.9 (9.0)years and 25 controls matched for age, gender and body mass index were studied. Central haemodynamic parameters including augmentation index (AIx) and wasted left ventricular pressure energy (∆E(W)) were determined pre, during and post light intensity cycle ergometry. During exercise, despite a similar heart rate and blood pressure, patients had comparatively greater ∆E(W) (P=0.03) and trend towards greater AIx (P=0.07) than controls. Exercise ∆E(W) was greatest in patients with CF related diabetes (n=11). In all subjects, exercise ∆E(W) was related to age (r=0.54, P<0.001) and FEV(1)% predicted (r=-0.32, P=0.01). Adults with CF have an abnormal haemodynamic response to exercise. This finding has deleterious implications for myocardial performance.
Publisher: Wiley
Date: 15-02-2021
DOI: 10.1002/HSR2.250
Publisher: Cold Spring Harbor Laboratory
Date: 11-05-2023
DOI: 10.1101/2023.05.08.23289442
Abstract: PHOSP-COVID is a national UK multi-centre cohort study of patients who were hospitalised for COVID-19 and subsequently discharged. PHOSP-COVID was established to investigate the medium- and long-term sequelae of severe COVID-19 requiring hospitalisation, understand the underlying mechanisms of these sequelae, evaluate the medium- and long-term effects of COVID-19 treatments, and to serve as a platform to enable future studies, including clinical trials. Data collected covered a wide range of physical measures, biological s les, and Patient Reported Outcome Measures (PROMs). Participants could join the cohort either in Tier 1 only with remote data collection using hospital records, a PROMs app and postal saliva s le for DNA, or in Tier 2 where they were invited to attend two specific research visits for further data collection and biological research s ling. These research visits occurred at five (range 2-7) months and 12 (range 10-14) months post-discharge. Participants could also participate in specific nested studies (Tier 3) at selected sites. All participants were asked to consent to further follow-up for 25 years via linkage to their electronic healthcare records and to be re-contacted for further research. In total, 7935 participants were recruited from 83 UK sites: 5238 to Tier 1 and 2697 to Tier 2, between August 2020 and March 2022. Cohort data are held in a Trusted Research Environment and s les stored in a central biobank. Data and s les can be accessed upon request and subject to approvals.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Charlotte Bolton.