Publications
655 results found
Man WD, Maddocks M, Kon SS, et al., 2016, Physical frailty and pulmonary rehabilitation In COPD, International Conference of the American-Thoracic-Society (ATS), Publisher: American Thoracic Society, ISSN: 1073-449X
Coello C, Fisk M, Wilson F, et al., 2016, Quantitative analysis of dynamic 18F-FDG in lungs of HV and COPD subjects, Publisher: SOC NUCLEAR MEDICINE INC, ISSN: 0161-5505
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- Citations: 1
Maddocks M, Nolan C, Man WD, et al., 2016, Neuromuscular electrical stimulation to improve exercise capacity in patients with severe COPD - Authors' reply., Lancet Respiratory Medicine, Vol: 4, Pages: e16-e16, ISSN: 2213-2619
Demeyer H, Gimeno-Santos E, Rabinovich RA, et al., 2016, Physical Activity Characteristics across GOLD Quadrants Depend on the Questionnaire Used, PLOS One, Vol: 11, ISSN: 1932-6203
BackgroundThe GOLD multidimensional classification of COPD severity combines the exacerbationrisk with the symptom experience, for which 3 different questionnaires are permitted. Thisstudy investigated differences in physical activity (PA) in the different GOLD quadrants andpatient’s distribution in relation to the questionnaire used.Methods136 COPD patients (58±21% FEV1 predicted, 34F/102M) completed COPD assessmenttest (CAT), clinical COPD questionnaire (CCQ) and modified Medical Research Council(mMRC) questionnaire. Exacerbation history, spirometry and 6MWD were collected. PAwas objectively measured for 2 periods of 1 week, 6 months apart, in 5 European centres;to minimise seasonal and clinical variation the average of these two periods was used foranalysis.ResultsGOLD quadrants C+D had reduced PA compared with A+B (3824 [2976] vs. 5508 [4671]steps.d-1, p<0.0001). The choice of questionnaire yielded different patient distributions (agreement mMRC-CAT κ = 0.57; CCQ-mMRC κ = 0.71; CCQ-CAT κ = 0.72) with differentclinical characteristics. PA was notably lower in patients with an mMRC score 2 (3430[2537] vs. 5443 [3776] steps.d-1, p <0.001) in both the low and high risk quadrants.ConclusionsUsing different questionnaires changes the patient distribution and results in different clinicalcharacteristics. Therefore, standardization of the questionnaire used for classification iscritical to allow comparison of different studies using this as an entry criterion.
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
Qiu Z-H, Guo H-X, Lu G, et al., 2016, Physiological responses to Tai Chi in stable patients with COPD, RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY, Vol: 221, Pages: 30-34, ISSN: 1569-9048
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- Citations: 12
Hopkinson NS, Polkey, Shah PL, et al., 2016, Effective Bronchoscopic Lung Volume Reduction Accelerates Exercise Oxygen Uptake Kinetics in Emphysema, Chest, Vol: 149, Pages: 435-446, ISSN: 1931-3543
The impact of bronchoscopic lung volume reduction (BLVR) on physiologic responses to exercise in patients with advanced emphysema remains incompletely understood. We hypothesized that effective BLVR (e-BLVR), defined as a reduction in residual volume > 350 mL, would improve cardiovascular responses to exercise and accelerate oxygen uptake (View the MathML sourceo2) kinetics.MethodsThirty-one patients (FEV1, 36% ± 9% predicted; residual volume, 219% ± 57% predicted) underwent a constant intensity exercise test at 70% peak work rate to the limit of tolerance before and after treatment bronchoscopy (n = 24) or sham bronchoscopy (n = 7). Physiologic responses in patients who had e-BLVR (n = 16) were compared with control subjects (ineffective BLVR or sham bronchoscopy; n = 15).Resultse-BLVR reduced residual volume (−1.1 ± 0.5 L, P = .001), improved lung diffusing capacity by 12% ± 13% (P = .001), and increased exercise tolerance by 181 ± 214 s (P = .004). View the MathML sourceo2 kinetics were accelerated in the e-BLVR group but remained unchanged in control subjects (Δ mean response time, −20% ± 29% vs 1% ± 25%, P = .04). Acceleration of View the MathML sourceo2 kinetics was associated with reductions in heart rate and oxygen pulse response half-times by 8% (84 ± 14 to 76 ± 15 s, P = .04) and 20% (49 ± 16 to 34 ± 16 s, P = .01), respectively. There were also increases in heart rate and oxygen pulse amplitudes during the cardiodynamic phase post e-BLVR. Faster View the MathML sourceo2 kinetics in the e-BLVR group were significantly correlated with reductions in residual volume (r = 0.66, P = .005) and improvements in inspiratory reserve volume (r = 0.56, P = .024) and exercise tolerance (r = 0.63, P = .008).ConclusionsLung deflation induced by e-BLVR accelerated exercise View the MathML sourceo2 kinetics in patients with emphysema. This beneficial effect appears to be
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
Buttery SC, Mohan D, Fisk M, et al., 2016, Longitudinal Follow-Up Of A Chronic Obstructive Pulmonary Disease Cohort After 3 Years: Changes In Quadriceps Strength, Aortic Pulse Wave Velocity And Blood Biomarkers, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
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
Boutou AK, Polkey MI, Hopkinson NS, 2016, Erratum: Non-anaemic iron deficiency in COPD: A potential therapeutic target? (Respirology (2015) 20 (1004-1005)), Respirology, Vol: 21, Pages: 196-196, ISSN: 1323-7799
Harvey-Dunstan TC, Edwards SE, Houchen-Wolloff L, et al., 2016, Correlation Between Five Exercise Tests To The COPD Assessment Test (cat) In Stable COPD, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Mohan D, Polkey MI, Forman JR, et al., 2016, Fibrinogen Is Not Associated With Cardiovascular And Muscular Co-Morbidities In Chronic Obstructive Pulmonary Disease: The Erica Study, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
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- Citations: 2
Fisk M, Mohan D, Cheriyan J, et al., 2016, Effects Of Losmapimod, A Novel P38 Mitogen-Activated Protein Kinase (mapk) Inhibitor On Vascular Inflammation In Chronic Obstructive Pulmonary Disease (COPD) Subjects Stratified By Fibrinogen: Evolution Trial, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
He B, Zhou L, Xiao S, et al., 2016, Increased Neural Respiratory Drive Due To Upper Airway Resistance; A Possible Protective Mechanism In COPD?, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Luo Y-M, Qiu Z, He B, et al., 2016, The Inspiratory Capacity (ic) Maneuver May Underestimate Dynamic Hyperinflation In Patients With COPD During Exhaustive Exercise, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Polkey MI, Rooks D, Franssen F, et al., 2016, Anabolic Treatment Of COPD-Associated Skeletal Muscle Wasting With Bimagrumab; Results Of A Phase Iia Double-Blind Rct, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Luo Y, Qin H, He B, et al., 2016, Neural Respiratory Drive Generated By Inspiratory Capacity Maneuver Could Be Further Increased By Inhalation Of Co2, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
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.
Hopkinson NS, Polkey MI, Curtis K, et al., 2015, Acute dietary nitrate supplementation and exercise performance in COPD: a double-blind, placebo-controlled, randomised controlled pilot study, PLOS One, Vol: 10, ISSN: 1932-6203
BackgroundDietary nitrate supplementation can enhance exercise performance in healthy people, but it is not clear if it is beneficial in COPD. We investigated the hypotheses that acute nitrate dosing would improve exercise performance and reduce the oxygen cost of submaximal exercise in people with COPD.MethodsWe performed a double-blind, placebo-controlled, cross-over single dose study. Subjects were randomised to consume either nitrate-rich beetroot juice (containing 12.9mmoles nitrate) or placebo (nitrate-depleted beetroot juice) 3 hours prior to endurance cycle ergometry, performed at 70% of maximal workload assessed by a prior incremental exercise test. After a minimum washout period of 7 days the protocol was repeated with the crossover beverage.Results21 subjects successfully completed the study (age 68±7years; BMI 25.2±5.5kg/m2; FEV1 percentage predicted 50.1±21.6%; peak VO2 18.0±5.9ml/min/kg). Resting diastolic blood pressure fell significantly with nitrate supplementation compared to placebo (-7±8mmHg nitrate vs. -1±8mmHg placebo; p = 0.008). Median endurance time did not differ significantly; nitrate 5.65 (3.90–10.40) minutes vs. placebo 6.40 (4.01–9.67) minutes (p = 0.50). However, isotime oxygen consumption (VO2) was lower following nitrate supplementation (16.6±6.0ml/min/kg nitrate vs. 17.2±6.0ml/min/kg placebo; p = 0.043), and consequently nitrate supplementation caused a significant lowering of the amplitude of the VO2-percentage isotime curve.ConclusionsAcute administration of oral nitrate did not enhance endurance exercise performance; however the observation that beetroot juice caused reduced oxygen consumption at isotime suggests that further investigation of this treatment approach is warranted, perhaps targeting a more hypoxic phenotype.
Wells CE, Polkey MI, Baker EH, 2015, Insulin resistance is associated with skeletal muscle weakness in COPD, Respirology, Vol: 21, Pages: 689-696, ISSN: 1440-1843
Suh E-S, Mandal S, Harding R, et al., 2015, Neural respiratory drive predicts clinical deterioration and safe discharge in exacerbations of COPD, Thorax, Vol: 70, Pages: 1123-1130, ISSN: 0040-6376
Rationale Hospitalised patients with acuteexacerbation of COPD may deteriorate despite treatment,with early readmission being common.Objectives To investigate whether neural respiratorydrive, measured using second intercostal space parasternalmuscle electromyography (EMGpara), would identifyworsening dyspnoea and physician-defined inpatientclinical deterioration, and predict early readmission.Methods Patients admitted to a single-site universityhospital with exacerbation of COPD were enrolled.Spirometry, inspiratory capacity (IC), EMGpara, routinephysiological parameters, modified early warning score(MEWS), modified Borg scale for dyspnoea and physiciandefinedepisodes of deterioration were recorded daily untildischarge. Readmissions at 14 and 28 days post dischargewere recorded.Measurements and main results 120 patients wererecruited (age 70±9 years, forced expiratory volume in 1 s(FEV1) of 30.5±11.2%). Worsening dyspnoea, defined asat least one-point increase in Borg scale, was associatedwith increases in EMGpara%max and MEWS, whereas anincrease in EMGpara%max alone was associated withphysician-defined inpatient clinical deterioration.Admission-to-discharge change (Δ) in the normalised valueof EMGpara (ΔEMGpara%max) was inversely correlated withΔFEV1 (r=−0.38, p<0.001) and ΔIC (r=−0.44, p<0.001).ΔEMGpara%max predicted 14-day readmission (OR 1.13,95% 1.03 to 1.23) in the whole cohort and 28-dayreadmission in patients under 85 years (OR 1.09, 95% CI1.01 to 1.18). Age (OR 1.08, 95% CI 1.03 to 1.14) and12-month admission frequency (OR 1.29, 1.01 to 1.66),also predicted 28-day readmission in the whole cohort.Conclusions Measurement of neural respiratory drive byEMGpara represents a novel physiological biomarker thatmay be helpful in detecting inpatient clinical deteriorationand identifying the risk of early readmission amongpatients with exacerbations of COPD.
Bansal T, Haji GS, Rossiter HB, et al., 2015, VENTILATORY IRREGULARITY QUANTIFIED BY APPROXIMATE ENTROPY IDENTIFIES DISORDERED BREATHING IN PATIENTS WITH UNEXPLAINED DYSPNOEA, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A31-A31, ISSN: 0040-6376
Bloch SAA, Donaldson AVJ, Lewis A, et al., 2015, MiR-181a: a potential biomarker of acute muscle wasting following elective high-risk cardiothoracic surgery, Critical Care, Vol: 19, ISSN: 1364-8535
Paul RG, Polkey MI, Kemp PR, et al., 2015, GDF-15, THE MIR-542 CLUSTER AND MIR-422A ARE ASSOCIATED WITH MUSCLE WASTING IN INTENSIVE CARE UNIT ACQUIRED PARESIS, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A66-A67, ISSN: 0040-6376
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- Citations: 2
Fisk M, Gale NS, Mohan D, et al., 2015, THE BODE INDEX IS AN INDEPENDENT DETERMINANT OF ARTERIAL STIFFNESS IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD), Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A70-A71, ISSN: 0040-6376
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Garfield B, Shao D, Crosby A, et al., 2015, THE ROLE OF GROWTH AND DIFFERENTIATION FACTOR 15 IN SMOOTH MUSCLE CELL PROLIFERATION IN PULMONARY HYPERTENSION, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A213-A214, ISSN: 0040-6376
Mandal S, Suh ES, Harding R, et al., 2015, NUTRITION AND EXERCISE REHABILITATION IN OBESITY HYPOVENTILATION SYNDROME (NERO): A PILOT RANDOMISED CONTROLLED TRIAL, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A21-A22, ISSN: 0040-6376
Fearon KCH, Argiles JM, Baracos VE, et al., 2015, Request for regulatory guidance for cancer cachexia intervention trials, Journal of Cachexia Sarcopenia and Muscle, Vol: 6, Pages: 272-274, ISSN: 2190-5991
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