Epigenetic mechanisms regulate muscle mass and function in models of muscle dysfunction and atrophy. We assessed whether quadriceps muscle weakness and atrophy are associated with a differential expression profile of epigenetic events in patients with advanced COPD (chronic obstructive pulmonary disease). In vastus lateralis (VL) of sedentary severe COPD patients (n=41), who were further subdivided into those with (n=25) and without (n=16) muscle weakness and healthy controls (n=19), expression of muscle-enriched miRNAs, histone acetyltransferases (HATs) and deacetylases (HDACs), growth and atrophy signalling markers, total protein and histone acetylation, transcription factors, small ubiquitin-related modifier (SUMO) ligases and muscle structure were explored. All subjects were clinically evaluated. Compared with controls, in VL of all COPD together and in muscle-weakness patients, expression of miR-1, miR-206 and miR-27a, levels of lysine-acetylated proteins and histones and acetylated histone 3 were increased, whereas expression of HDAC3, HDAC4, sirtuin-1 (SIRT-1), IGF-1 (insulin-like growth factor-1) were decreased, Akt (v-akt murine thymoma viral oncogene homologue 1) expression did not differ, follistatin expression was greater, whereas myostatin expression was lower, serum reponse factor (SRF) expression was increased and fibre size of fast-twitch fibres was significantly reduced. In VL of severe COPD patients with muscle weakness and atrophy, epigenetic events regulate muscle differentiation rather than proliferation and muscle growth and atrophy signalling, probably as feedback mechanisms to prevent those muscles from undergoing further atrophy. Lysine-hyperacetylation of histones may drive enhanced protein catabolism in those muscles. These findings may help design novel therapeutic strategies (enhancers of miRNAs promoting myogenesis and acetylation inhibitors) to selectively target muscle weakness and atrophy in severe COPD.

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Muscle dysfunction, adjusted by GOLD stage, is associated with an increased risk of hospital admissions due to acute episodes of exacerbation of the disease. Current exacerbations further deteriorate muscle dysfunction.

Adolescent idiopathic scoliosis (AIS) can lead to ventilatory restriction, respiratory muscle weakness and exercise limitation. However, both the causes and the extent of muscle dysfunction remain unclear. The aim of our study is to describe muscle weakness and its relationship to lung function and tolerance to exercise in AIS patients.Lung and muscle function, together with exercise capacity, were assessed in 60 patients with pronounced spinal deformity (.40u) and in 25 healthy volunteers.Patients with AIS had only mild to moderate abnormal ventilatory patterns, the most frequent of which were restrictive abnormalities. The function of respiratory and limb muscles and exercise capacity were below normal limits in AIS patients, and were significantly lower than in controls. Exercise capacity was found to correlate with the function of inspiratory, expiratory, upper limb and lower limb muscles which, in addition, were reciprocally interrelated. Multivariate analysis showed that lower limb muscle function is the main contributor to exercise intolerance. There appeared to be no connection between spinal deformity and lung function, muscle function or exercise capacity.We conclude that AIS patients show generalised muscle dysfunction which contributes to the reduction in their exercise capacity, even in the absence of severe ventilatory impairment.

Discrepancies exist regarding the involvement of cellular inflammation and apoptosis in the muscle dysfunction of chronic obstructive pulmonary disease (COPD) patients with preserved body composition. We explored whether levels of inflammatory cells and apoptosis were increased in both respiratory and limb muscles of COPD patients without nutritional abnormalities. In the vastus lateralis, external intercostals, and diaphragms of severe and moderate COPD patients with normal body composition, and in healthy subjects, intramuscular leukocytes and macrophage levels were determined (immunohistochemistry). Muscle structure was also evaluated. In the diaphragm and vastus lateralis of severe and moderate COPD patients and controls, apoptotic nuclei were explored using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, electron microscopy, and caspase-3 expression. In COPD patients compared with controls, diaphragm and intercostal levels of inflammatory cells were extremely low and not significantly different. However, in the vastus lateralis of the severe patients, inflammatory cell counts, although also very low, were significantly greater. In those patients, TUNEL-positive nuclei levels were also significantly greater in diaphragms and vastus lateralis. A significant inverse relationship was found between quadriceps TUNEL-positive nuclei levels and muscle force. Ultrastructural apoptotic nuclei revealed no differences in respiratory or limb muscles between COPD patients and controls. Muscle caspase-3 expression did not differ between patients and controls. In severe COPD patients with preserved body composition, while increased apoptotic nuclei seems to be a contributor to their muscle dysfunction, cellular inflammation does not. The increased numbers of TUNEL-positive nuclei in their muscles suggest that they may also be exposed to a continuous repair/remodeling process.

Study design A controlled prospective cross-sectional case study. Objective To investigate body mass index (BMI) and corporal composition in girls with adolescent idiopathic scoliosis (AIS) and compare them with a normal population matched by sex and age. Summary and background data There is controversy as to whether there are real anthropometric alterations in patients with AIS. Relative to the weight or the BMI, some studies find differences and other studies do not detect them. AIS and anorexia nervosa (AN) make their debut during adolescence and both may be associated with an alteration of their subjective physical perception. Some authors propose a link between AIS and AN supported both by an alteration of physical perception and lower BMI. No studies on body composition in AIS have been published. Methods Adolescent idiopathic scoliosis patient surgery candidates during 2008 were studied. Body composition was evaluated using the bioelectrical impedance analysis (Bodystat, Isle of Man, UK). A study population of more than 5,000 patients that was published by Kyle et al. (Nutrition 17:534-541, 2001) was chosen as a control (group 1). Another control group (group 2) of healthy volunteers matched by sex and age was selected among a school age and university population in Barcelona, Spain. A variance analysis was used to analyze differences between the mean values of the control group 1, the European control group, and the AIS patient surgery candidates (Epiinfo 6.2001). Comparisons between the AIS patients and control group 2 were performed with the T Student test of unpaired samples using the SPSS 15.0 (Statistical Package Social Science) software. Results Twenty-seven women with a mean age of 17.4 years. BMI was 18.9 kg/m 2 (SD 1.7; 95 % CI 18.31-19.73). In the variance analysis, a significant difference between AIS and group 1 in BMI was observed (21.0 vs. 18.9, p = 0.000004); fat-free mass (FFM = 42.6 vs. 38.9, p = 0.0000009) and fat mass (FM = 15.6 vs. 13.7, p = 0.03). Significant differences in BMI (22.13 vs. 18.9, p = 0.001; 95 % CI difference 1.85-4.60), fat mass index (FMi = 7.17 vs. 4.97, p = 0.000; 95 % CI difference 1.36-3.05) and fat-free mass index (FFMi = 14.95 vs. 13.09, p = 0.001; 95 % CI difference 0.26-1.86) between AIS and group 2 were also seen. Conclusion The conclusion is that there is a real alteration of body composition in AIS. The BMI, FFMi and FMi are lower than in the general population in the series under study.

Epigenetic events are differentially expressed in the lungs and airways of patients with chronic obstructive pulmonary disease (COPD). Moreover, epigenetic mechanisms are involved in the skeletal (peripheral) muscle dysfunction of COPD patients. Whether epigenetic events may also regulate respiratory muscle dysfunction in COPD remains unknown. We hypothesized that epigenetic mechanisms would be differentially expressed in the main inspiratory muscle (diaphragm) of patients with COPD of a wide range of disease severity compared to healthy controls. In diaphragm muscle specimens (thoracotomy due to lung localized neoplasms) of sedentary patients with mild-to-moderate and severe COPD, with preserved body composition, and sedentary healthy controls, expression of muscle-enriched microRNAs, histone acetyltransferases (HATs) and deacetylases (HDACs), total DNA methylation and protein acetylation, small ubiquitin-related modifier (SUMO) ligases, muscle-specific transcription factors, and muscle structure were explored. All subjects were also clinically evaluated: lung and muscle functions and exercise capacity. Compared to healthy controls, patients exhibited moderate airflow limitation and diffusion capacity, and reduced exercise tolerance and transdiaphragmatic strength. Moreover, in the diaphragm of the COPD patients, muscle-specific microRNA expression was downregulated, while HDAC4 and myocyte enhancer factor (MEF)2C protein levels were higher, and DNA methylation levels, muscle fiber types and sizes did not differ between patients and controls. In the main respiratory muscle of COPD patients with a wide range of disease severity and normal body composition, muscle-specific microRNAs were downregulated, while HDAC4 and MEF2C levels were upregulated. It is likely that these epigenetic events act as biological adaptive mechanisms to better overcome the continuous inspiratory loads of the respiratory system in COPD. These findings may offer novel therapeutic strategies to specifically target respiratory muscle dysfunction in patients with COPD.

In patients with chronic obstructive pulmonary disease (COPD), skeletal muscle dysfunction is a major comorbidity that negatively impacts their exercise capacity and quality of life. In the current guidelines, the most recent literature on the various aspects of COPD muscle dysfunction has been included. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) scale has been used to make evidence-based recommendations on the different features. Compared to a control population, one third of COPD patients exhibited a 25% decline in quadriceps muscle strength, even at early stages of their disease. Although both respiratory and limb muscles are altered, the latter are usually more severely affected. Numerous factors and biological mechanisms are involved in the etiology of COPD muscle dysfunction. Several tests are proposed in order to diagnose and evaluate the degree of muscle dysfunction of both respiratory and limb muscles (peripheral), as well as to identify the patients' exercise capacity (six-minute walking test and cycloergometry). Currently available therapeutic strategies including the different training modalities and pharmacological and nutritional support are also described.