Publications
297 results found
Nolan CM, Longworth L, Lord J, et al., 2016, The EQ-5D-5L health status questionnaire in COPD: validity, responsiveness and minimum important difference, Thorax, Vol: 71, Pages: 493-500, ISSN: 1468-3296
Background The EQ-5D, a generic health status questionnaire that is widely used in health economic evaluation, was recently expanded to the EQ-5D-5L to address criticisms of unresponsiveness and ceiling effect.Aims To describe the validity, responsiveness and minimum important difference of the EQ-5D-5L in COPD.Methods Study 1: The validity of the EQ-5D-5L utility index and visual analogue scale (EQ-VAS) was compared with four established disease-specific health status questionnaires and other measures of disease severity in 616 stable outpatients with COPD. Study 2: The EQ-5D-5L utility index and EQ-VAS were measured in 324 patients with COPD before and after 8 weeks of pulmonary rehabilitation. Distribution and anchor-based approaches were used to estimate the minimum important difference.Results There were moderate-to-strong correlations between utility index and EQ-VAS with disease-specific questionnaires (Pearson's r=0.47–0.72). A ceiling effect was seen in 7% and 2.6% of utility index and EQ-VAS. Utility index decreased (worsening health status) with indices of worsening disease severity. With rehabilitation, mean (95% CI) changes in utility index and EQ-VAS were 0.065 (0.047 to 0.083) and 8.6 (6.5 to 10.7), respectively, with standardised response means of 0.39 and 0.44. The mean (range) anchor estimates of the minimum important difference for utility index and EQ-VAS were 0.051 (0.037 to 0.063) and 6.9 (6.5 to 8.0), respectively.Conclusions The EQ-5D-5L is a valid and responsive measure of health status in COPD and may provide useful additional cost-effectiveness data in clinical trials.
Patel MS, Donaldson AV, Lewis A, et al., 2016, Klotho and smoking – An interplay influencing the skeletal muscle function deficits that occur in COPD, Respiratory Medicine, Vol: 113, Pages: 50-56, ISSN: 0954-6111
BackgroundKlotho is an ‘anti-ageing’ hormone and transmembrane protein; Klotho deficient mice develop a similar ageing phenotype to smokers including emphysema and muscle wasting. The objective of this study was to evaluate skeletal muscle and circulating Klotho protein in smokers and COPD patients and to relate Klotho levels to relevant skeletal muscle parameters. We sought to validate our findings by undertaking complimentary murine studies.MethodsFat free mass, quadriceps strength and spirometry were measured in 87 participants (61 COPD, 13 ‘healthy smokers’ and 13 never smoking controls) in whom serum and quadriceps Klotho protein levels were also measured. Immunohistochemistry was performed to demonstrate the location of Klotho protein in human skeletal muscle and in mouse skeletal muscle in which regeneration was occurring following injury induced by electroporation. In a separate study, gastrocnemius Klotho protein was measured in mice exposed to 77 weeks of smoke or sham air.ResultsQuadriceps Klotho levels were lower in those currently smoking (p = 0.01), irrespective of spirometry, but were not lower in patients with COPD. A regression analysis identified current smoking status as the only independent variable associated with human quadriceps Klotho levels, an observation supported by the finding that smoke exposed mice had lower gastrocnemius Klotho levels than sham exposed mice (p = 0.005). Quadriceps Klotho levels related to local oxidative stress but were paradoxically higher in patients with established muscle wasting or weakness; the unexpected relationship with low fat free mass was the only independent association. Within locomotor muscle, Klotho localized to the plasma membrane and to centralized nuclei in humans and in mice with induced muscle damage. Serum Klotho had an independent association with quadriceps strength but did not relate to quadriceps Klotho levels or to spirometric parameters.ConclusionsKlotho is expressed
Lewis A, Donaldson AV, Natanek SA, et al., 2016, Increased expression of H19/miR-675 is associated with a low fat free mass index in patients with COPD, Journal of Cachexia, Sarcopenia and Muscle, Vol: 7, Pages: 330-344, ISSN: 2190-6009
BackgroundLoss of muscle mass and strength is a significant comorbidity in patients with chronic obstructive pulmonary disease (COPD) that limits their quality of life and has prognostic implications but does not affect everyone equally. To identify mechanisms that may contribute to the susceptibility to a low muscle mass, we investigated microRNA (miRNA) expression, methylation status, and regeneration in quadriceps muscle from COPD patients and the effect of miRNAs on myoblast proliferation in vitro. The relationships of miRNA expression with muscle mass and strength was also determined in a group of healthy older men.MethodsWe identified miRNAs associated with a low fat-free mass (FFM) phenotype in a small group of patients with COPD using a PCR screen of 750 miRNAs. The expression of two differentially expressed miRNAs (miR-675 and miR-519a) was determined in an expanded group of COPD patients and their associations with FFM and strength identified. The association of these miRNAs with FFM and strength was also explored in a group of healthy community-dwelling older men. As the expression of the miRNAs associated with FFM could be regulated by methylation, the relative methylation of the H19 ICR was determined. Furthermore, the proportion of myofibres with centralized nuclei, as a marker of muscle regeneration, in the muscle of COPD patients was identified by immunofluorescence.ResultsImprinted miRNAs (miR-675 and from a cluster, C19MC which includes miR-519a) were differentially expressed in the quadriceps of patients with a low fat-free mass index (FFMI) compared to those with a normal FFMI. In larger cohorts, miR-675 and its host gene (H19) were higher in patients with a low FFMI and strength. The association of miR-519a expression with FFMI was present in male patients with severe COPD. Similar associations of miR expression with lean mass and strength were not observed in healthy community dwelling older men participating in the Hertfordshire Sarcopenia Stu
Curtis KJ, Meyrick VM, Mehta B, et al., 2016, Angiotensin-Converting Enzyme Inhibition As An Adjunct To Pulmonary Rehabilitation: A Randomised Controlled Trial, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Maddocks M, Nolan CM, Man WD, et al., 2016, Neuromuscular electrical stimulation to improve exercise capacity in patients with severe COPD: a randomised double-blind, placebo-controlled trial., The Lancet Respiratory Medicine, Vol: 4, Pages: 27-36, ISSN: 2213-2600
BACKGROUND: Skeletal muscle dysfunction and exercise intolerance are common in severe chronic obstructive pulmonary disease (COPD). We assessed the effectiveness of neuromuscular electrical stimulation (NMES) as a home-based exercise therapy. METHODS: In this double-blind, placebo-controlled trial, undertaken across three UK National Health Service sites, we randomly assigned (1:1) adults with COPD, a forced expiratory volume in 1 s (FEV1) less than 50% predicted, and incapacitating breathlessness (Medical Research Council dyspnoea scale ≥4) to receive active or placebo NMES, daily over a 6-week period. Randomisation was by an independent system using minimisation to balance age, GOLD stage, and quadriceps strength. Participants and outcome assessors were masked to group allocation. The primary endpoint was change in 6-min walk test (6MWT) distance at 6 weeks. Analysis was by intention to treat. The trial was registered as ISRCTN15985261 and is now closed. FINDINGS: Between June 29, 2012, and July 4, 2014, we enrolled 73 participants, of whom 52 participants were randomly assigned; 25 to receive active NMES and 27 to placebo NMES. Change in 6MWT distance was greater in the active NMES group (mean 29·9 [95% CI 8·9 to 51·0]) compared with in the placebo group (-5·7 [-19·9 to 8·4]; mean difference at 6 weeks 35·7 m [95% CI 10·5 to 60·9]; p=0·005). Sensitivity analyses for complete-cases and adjustment for baseline values showed similar results. 6 weeks after stopping the intervention the effect waned (7·3 m [95% CI -32·5 to 47·0]; p=0·50). The proportion of participants who had adverse events was similar between groups (five [20%] in the active NMES group and nine [33%] in the placebo group). Two participants, one from each group, reported persistent erythema, which was considered to be possibly related to NMES and the use of adhesive electrodes. INTERPRETATION: NMES im
Jones S, Man WD-C, Gao W, et al., 2016, Neuromuscular electrical stimulation for muscle weakness in adults with advanced disease, COCHRANE DATABASE OF SYSTEMATIC REVIEWS, ISSN: 1469-493X
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- Citations: 58
Patel MS, Lee J, Baz M, et al., 2015, Growth differentiation factor-15 is associated with muscle mass in chronic obstructive pulmonary disease and promotes muscle wasting in vivo, Journal of Cachexia, Sarcopenia and Muscle, Vol: 7, Pages: 436-448, ISSN: 2190-6009
BackgroundLoss of muscle mass is a co-morbidity common to a range of chronic diseases including chronic obstructive pulmonary disease (COPD). Several systemic features of COPD including increased inflammatory signalling, oxidative stress, and hypoxia are known to increase the expression of growth differentiation factor-15 (GDF-15), a protein associated with muscle wasting in other diseases. We therefore hypothesized that GDF-15 may contribute to muscle wasting in COPD.MethodsWe determined the expression of GDF-15 in the serum and muscle of patients with COPD and analysed the association of GDF-15 expression with muscle mass and exercise performance. To determine whether GDF-15 had a direct effect on muscle, we also determined the effect of increased GDF-15 expression on the tibialis anterior of mice by electroporation.ResultsGrowth differentiation factor-15 was increased in the circulation and muscle of COPD patients compared with controls. Circulating GDF-15 was inversely correlated with rectus femoris cross-sectional area (P < 0.001) and exercise capacity (P < 0.001) in two separate cohorts of patients but was not associated with body mass index. GDF-15 levels were associated with 8-oxo-dG in the circulation of patients consistent with a role for oxidative stress in the production of this protein. Local over-expression of GDF-15 in mice caused wasting of the tibialis anterior muscle that expressed it but not in the contralateral muscle suggesting a direct effect of GDF-15 on muscle mass (P < 0.001).ConclusionsTogether, the data suggest that GDF-15 contributes to the loss of muscle mass in COPD.
Man W, Puhan M, Harrison SL, et al., 2015, Pulmonary rehabilitation and severe exacerbations of COPD: Solution or white elephant?, ERJ Open Research, Vol: 1, ISSN: 2312-0541
Hospitalisations for severe exacerbations of chronic obstructive pulmonary disease are associated with significant physical and psychological consequences including an increase in symptom severity, severe reductions in physical activity, a deleterious effect on skeletal muscle, impaired exercise tolerance/ability to self-care, decline in quality of life, and increased anxiety and depression. As these consequences are potentially amenable to exercise training, there is a clear rationale for pulmonary rehabilitation in the peri/post-exacerbation setting. Although a 2011 Cochrane review was overwhelmingly positive, subsequent trials have shown less benefit and real-life observational studies have revealed poor acceptability. Qualitative studies have demonstrated that the patient experience is a determining factor while the presence of comorbidities may influence referral, adherence and response to pulmonary rehabilitation. Systematic reviews of less supervised interventions, such as self-management, have shown limited benefits in the post-exacerbation setting. The recent update of the Cochrane review of peri-exacerbation pulmonary rehabilitation showed that benefits were associated with the “comprehensive” nature of the intervention (the number of sessions received, the intensity of exercise training and education delivered, and the degree of supervision) but implementation is demanding. The challenge is to develop interventions that are deliverable and acceptable around the time of an acute exacerbation but also deliver the desired clinical impact.
Nolan CM, Canavan JL, Jones SE, et al., 2015, Response of the King's brief interstitial lung disease (KBILD) questionnaire to pulmonary rehabilitation (PR), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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Kon S, Canavan J, Schofield S, et al., 2015, Gait Speed as a predictor of mortality in COPD, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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- Citations: 3
Kon S, Jones S, Canavan J, et al., 2015, Sit-to-stand ability in patients hospitalised for acute exacerbation of COPD: Clinical characteristics and short-term outcomes, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Carrington D, Jones S, Canavan J, et al., 2015, Responsiveness of the short physical performance battery (SPPB) in severely dyspnoeic patients with COPD, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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- Citations: 2
Jones SE, Canavan JL, Nolan CM, et al., 2015, Sit to stand performance and physical activity levels in COPD, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Moghal M, Goburdhun R, Hopkinson N, et al., 2015, An auto-titrating intelligent oxygen therapy (iO<sub>2</sub>T) system in COPD patients: A randomised cross-over trial, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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Canavan JL, Jones SE, Nolan CM, et al., 2015, Multi-frequency bioelectric impedance ratio and physical performance in stable COPD:, European Respiratory Society Conference, Pages: PA4598-PA4598, ISSN: 0903-1936
Kon SSC, Jones SE, Schofield SJ, et al., 2015, Gait speed and readmission following hospitalisation for acute exacerbations of COPD: a prospective study, Thorax, Vol: 70, Pages: 1131-1137, ISSN: 1468-3296
Canavan JL, Maddocks M, Nolan CM, et al., 2015, Functionally relevant cut point for isometric quadriceps muscle strength in chronic respiratory disease, American Journal of Respiratory and Critical Care Medicine, Vol: 192, Pages: 395-397, ISSN: 1535-4970
Canavan JL, Kaliaraju D, Nolan CM, et al., 2015, Does pulmonary rehabilitation reduce peripheral blood pressure in patients with chronic obstructive pulmonary disease?, Chronic Respiratory Disease, Vol: 12, Pages: 256-263, ISSN: 1479-9731
Pulmonary rehabilitation (PR) can improve aerobic exercise capacity, health-related quality of life and dyspnoea in patients with chronic obstructive pulmonary disease (COPD). Recent studies have suggested that exercise training may improve blood pressure and arterial stiffness, albeit in small highly selected cohorts. The aim of the study was to establish whether supervised outpatient or unsupervised home PR can reduce peripheral blood pressure. Resting blood pressure was measured in 418 patients with COPD before and after outpatient PR, supervised by a hospital-based team (HOSP). Seventy-four patients with COPD undergoing an unsupervised home-based programme acted as a comparator group (HOME). Despite significant improvements in mean (95% confidence interval) exercise capacity in the HOSP group (56 (50–60) m, p < 0.001) and HOME group (30 (17–42) m, p < 0.001) systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MAP) did not change in either the HOSP (SBP: p = 0.47; DBP: p = 0.06; MAP: p = 0.38) or HOME group (SBP: p = 0.67; DBP: p = 0.38; MAP: p = 0.76). Planned subgroup analysis of HOSP patients with known hypertension and/or cardiovascular disease showed no impact of PR upon blood pressure. PR is unlikely to reduce blood pressure, and by implication, makes a mechanism of action in which arterial stiffness is reduced, less likely.
Nikoletou D, Man WD, Mustfa N, et al., 2015, Evaluation of the effectiveness of a home-based inspiratory muscle training programme in patients with chronic obstructive pulmonary disease using multiple inspiratory muscle tests, Disability and Rehabilitation, Vol: 38, Pages: 250-259, ISSN: 1464-5165
PURPOSE: To evaluate the effectiveness of a home-based inspiratory muscle training (IMT) programme using multiple inspiratory muscle tests. METHOD: Sixty-eight patients (37 M) with moderate to severe chronic obstructive pulmonary disease (COPD) (Mean [SD], FEV1 36.1 [13.6]% pred.; FEV1/FVC 35.7 [11.2]%) were randomised into an experimental or control group and trained with a threshold loading device at intensity >30% maximum inspiratory pressure (PImax) or <15% PImax, respectively, for 7 weeks. Thirty-nine patients (23 M) completed the study. The following measures were assessed pre- and post-IMT: PImax, sniff inspiratory nasal pressure (SNIP), diaphragm contractility (Pdi,tw), incremental shuttle walk test (ISWT), respiratory muscle endurance (RME), chronic respiratory disease questionnaire (CRDQ), the hospital anxiety and depression scale (HADS) and the SF-36. Between-group changes were assessed using one-way analysis of variance (ANOVA). RESULTS: PImax and perception of well-being improved significantly post-IMT [p = 0.04 and <0.05 in four domains, respectively]. This was not reflected in SNIP [p = 0.7], Pdi,tw [p = 0.8], RME [p = 0.9] or ISWT [p = 0.5]. CONCLUSIONS: A seven-week, community-based IMT programme, with realistic use of health-care resources, improves PImax and perception of well-being but a different design may be required for improvement in other measures. Multiple tests provide a more comprehensive evaluation of changes in muscle function post-IMT. IMPLICATIONS FOR REHABILITATION: A seven-week, home-based inspiratory muscle training programme improves maximal inspiratory pressure and perception of well-being in patients with moderate to severe COPD but not sniff nasal inspiratory pressure or diaphragm contractility, respiratory muscle endurance and exercise capacity. Multiple tests are recommended for a more comprehensive assessment of changes in muscle fu
Maddocks M, Jones SE, Kon SSC, et al., 2015, Sarcopenia definitions: where to draw the line? Response to Scarlata et al, Thorax, Vol: 70, Pages: 694-694, ISSN: 1468-3296
Maddocks M, Kon SSC, Singh SJ, et al., 2015, Rehabilitation following hospitalization in patients with COPD: Can it reduce readmissions?, Respirology, Vol: 20, Pages: 395-404, ISSN: 1323-7799
Exacerbations of chronic obstructive pulmonary disease (COPD) are one of the commonest causes of emergency hospital admission and are associated with high rates of readmission. Rehabilitation in the peri- and early post-hospitalization setting may counteract the deleterious consequences of an acute hospital admission and target modifiable risk factors for readmission such as physical inactivity, reduced exercise capacity and impaired physical function. Pulmonary rehabilitation in the peri-hospitalization period can improve exercise capacity and health-related quality of life and can also reduce rates of readmission. Consequently, guidelines have recommended the provision of pulmonary rehabilitation in the acute setting. However, recent trials showing less positive results and observational data questioning acceptability may challenge prevailing enthusiasm. This review examines the role of pulmonary rehabilitation in the peri- and early post-hospitalization setting, considering the modifiable risk factors for readmission, the latest evidence regarding rehabilitation in the acute setting, issues around acceptability and uptake, and alternative strategies to help deliver rehabilitation to more patients. The acceptability and effectiveness of pulmonary rehabilitation offered that post-exacerbation could be improved by overcoming issues around the setting, timing and format of rehabilitation approaches, including their integration with self-management interventions.
Maddocks M, Kon SSC, Singh SJ, et al., 2015, Rehabilitation following hospitalization in patients with COPD: Can it reduce readmissions?, RESPIROLOGY, Vol: 20, Pages: 395-404, ISSN: 1323-7799
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- Citations: 35
Jones SE, Maddocks M, Kon SSC, et al., 2015, Sarcopenia in COPD: prevalence, clinical correlates and response to pulmonary rehabilitation, THORAX, Vol: 70, Pages: 213-218, ISSN: 0040-6376
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- Citations: 257
Jolley C, Luo Y, Steier J, et al., 2015, Neural respiratory drive and symptoms that limit exercise in chronic obstructive pulmonary disease, LANCET, Vol: 385, Pages: 51-51, ISSN: 0140-6736
Maddocks M, Kon SSC, Jones SE, et al., 2015, Bioelectrical impedance phase angle relates to function, disease severity and prognosis in stable chronic obstructive pulmonary disease, Clinical Nutrition, Vol: 34, Pages: 1245-1250, ISSN: 1532-1983
Kon SSC, Jones SE, Schofield SJ, et al., 2014, GAIT SPEED IS A PREDICTOR OF MORTALITY FOLLOWING HOSPITALISATION FOR ACUTE EXACERBATIONS OF COPD, Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A45-A45, ISSN: 0040-6376
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Jolley CJ, Luo YM, Steier J, et al., 2014, NEURAL RESPIRATORY DRIVE AND SYMPTOMS LIMITING EXERCISE CAPACITY IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE, Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A29-A30, ISSN: 0040-6376
Canavan JL, Kon SSC, Nolan CM, et al., 2014, STATIC BALANCE DEFICIT IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE: PREVALENCE, CLINICAL CHARACTERISTICS AND RISK OF SIGNIFICANT FALLS, Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A103-A103, ISSN: 0040-6376
Jones SE, Maddocks M, Kon SSC, et al., 2014, SARCOPENIA IN COPD: PREVALENCE, CLINICAL CORRELATES AND RESPONSE TO PULMONARY REHABILITATION, Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A104-A104, ISSN: 0040-6376
Lord VM, Hume VJ, Kelly JL, et al., 2014, Singing classes for chronic obstructive pulmonary disease: a randomized controlled trial (vol 12, 69, 2012), BMC PULMONARY MEDICINE, Vol: 14, ISSN: 1471-2466
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- Citations: 3
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