Publications
515 results found
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.
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.
Savi D, Simmonds N, Di Paolo M, et al., 2015, Relationship between pulmonary exacerbations and daily physical activity in adults with cystic fibrosis, BMC Pulmonary Medicine, Vol: 15, ISSN: 1471-2466
Background: The aim of this study was to examine the relationship between pulmonary exacerbations andphysical activity (PA) in adults with cystic fibrosis (CF).Methods: We grouped adults with CF according to their exacerbation status in the year before study enrolment:(1) <1 exacerbation/year; (2) 1–2 exacerbations/year; and (3) >2 exacerbations/year. PA was assessed objectively bymeans of an accelerometer at the time of study enrolment.Results: Patients with >2 exacerbations/year spent less time in PA; specifically, fewer activities of mild intensity [>3metabolic equivalents (METs)], and lower active energy expenditure (P = 0.01 and P = 0.03, respectively). Aftercorrecting for relevant confounders, PA levels were not related to the exacerbation frequency in the preceding year.PA at moderate intensity (4.8–7.2 METs) or greater (>7.2 METs) was independently associated with gender and FEV1% predicted (P = 0.007 and P = 0.04, respectively). Compared with men, women had reduced vigorous activities(P = 0.01) and active energy expenditure (P = 0.01).Conclusions: Adult CF patients with more pulmonary exacerbations in the preceding year have more advanceddisease and are less active than their peers. PA was independently associated with gender and airflow obstruction.Gender differences in PA are evident in CF adults
Hopkinson NS, Hart N, Jenkins G, et al., 2015, Embracing social media., Thorax, Vol: 70, ISSN: 0040-6376
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