Publications
516 results found
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
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
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
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
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