Cytokine profile in quadriceps muscles of patients with severe COPD.

Background: Systemic proinflammatory cytokines and oxidative stress have been described in association with peripheral muscle wasting and weakness of patients with severe chronic obstructive pulmonary disease (COPD), but their expression in skeletal muscle is unknown. The objectives of the present study were to determine muscle protein levels of selected cytokines in patients with COPD and to study their relationships with protein carbonylation as a marker of oxidative stress, quadriceps function and exercise capacity.

Methods: We conducted a cross sectional study in which 36 cytokines were detected using a human antibody array in quadriceps specimens obtained from 19 patients with severe COPD and seven healthy controls.

Systemic inflammation and skeletal muscle dysfunction in chronic obstructive pulmonary disease: state of the art and novel insights in regulation of muscle plasticity.

Systemic inflammation is a recognized hallmark of chronic obstructive pulmonary disease pathogenesis. Although the origin and mechanisms responsible for the persistent chronic inflammatory process remain to be elucidated, it is recognized that it plays an important role in skeletal muscle pathology as observed in chronic obstructive pulmonary disease and several other chronic inflammatory disorders. This article describes state-of-the-art knowledge and novel insights in the role of inflammatory processes on several aspects of inflammation-related skeletal muscle pathology and offers new insights in therapeutic perspectives.

Muscle metabolic modulation by chronic hypoxia.

De Palma et al. published a research paper in which they describe the effect of chronic hypoxia on rat skeletal muscle metabolism by means of a comparative proteomic analysis (J. Proteome Res.

A novel technique for nonvolitional assessment of quadriceps muscle endurance in humans.

Assessment of quadriceps endurance is of interest to investigators studying human disease. We hypothesized that repetitive magnetic stimulation (rMS) of the intramuscular branches of the femoral nerve could be used to induce and quantify quadriceps endurance. To test this hypothesis, we used a novel stimulating coil to compare the quadriceps endurance properties in eight normal humans and, to confirm that the technique could be used in clinical practice, in eight patients with advanced chronic obstructive pulmonary disease (COPD).

Muscle fibre type shifting in the vastus lateralis of patients with COPD is associated with disease severity: a systematic review and meta-analysis.

Background: Skeletal muscle dysfunction is a common feature in chronic obstructive pulmonary disease (COPD) which is associated with intrinsic muscular abnormalities. One of the most consistently reported alterations is a shift from fibre type I to II in the vastus lateralis of these patients. Surprisingly, the relationship between this shift and the severity and phenotype of COPD remains unclear.

Peroxisome proliferator-activated receptor expression is reduced in skeletal muscle in COPD.

Chronic obstructive pulmonary disease (COPD) is a multiorgan systemic disease. The systemic features are skeletal muscle weakness and cachexia, the latter being associated with systemic inflammation. The exact mechanisms underlying skeletal muscle dysfunction in COPD remain obscure.

The functional, metabolic, and anabolic responses to exercise training in renal transplant and hemodialysis patients.

Background: Exercise intolerance is common in hemodialysis (HD) and renal transplant (RTx) patients and is related to muscle weakness. Its pathogenesis may vary between these groups leading to a different response to exercise. The aim of the study was to compare intrinsic muscular parameters between HD and RTx patients and controls, and to assess the response to exercise training on exercise capacity and muscular structure and function in these groups.

Reduced mitochondrial density in the vastus lateralis muscle of patients with COPD.

Skeletal muscle dysfunction is a well-recognised hallmark of chronic obstructive pulmonary disease (COPD) leading to exercise intolerance. The vastus lateralis of COPD patients is characterised by reduced mitochondrial enzyme activity; however, this is not the case in the tibialis anterior. It is, however, unclear whether the compromised oxidative capacity in the vastus is due to reduced mitochondrial volume density.

Supplementation of soy protein with branched-chain amino acids alters protein metabolism in healthy elderly and even more in patients with chronic obstructive pulmonary disease.

Background: It is often suggested that chronic wasting diseases [eg, chronic obstructive pulmonary disease (COPD)] may benefit from branched-chain amino acid (BCAA) administration via improved protein metabolism.

Objective: The aim was to examine whether adding BCAAs to a soy protein meal would enhance protein anabolism in COPD patients and in healthy elderly persons.

Design: Eight normal-weight COPD patients and 8 healthy control subjects were examined on 2 test days.

Recommendations on the use of exercise testing in clinical practice.

Evidence-based recommendations on the clinical use of cardiopulmonary exercise testing (CPET) in lung and heart disease are presented, with reference to the assessment of exercise intolerance, prognostic assessment and the evaluation of therapeutic interventions (e.g. drugs, supplemental oxygen, exercise training).

Myogenic differentiation during regrowth of atrophied skeletal muscle is associated with inactivation of GSK-3beta.

Muscle atrophy contributes to morbidity and mortality in aging and chronic disease, emphasizing the need to gain understanding of the mechanisms involved in muscle atrophy and (re)growth. We hypothesized that the magnitude of muscle regrowth during recovery from atrophy determines whether myonuclear accretion and myogenic differentiation are required and that insulin-like growth factor (IGF)-I/Akt/glycogen synthase kinase (GSK)-3beta signaling differs between regrowth responses. To address this hypothesis we subjected mice to hindlimb suspension (HS) to induce atrophy of soleus (-40%) and plantaris (-27%) muscle.

Cellular protein breakdown and systemic inflammation are unaffected by pulmonary rehabilitation in COPD.

Background: Pulmonary rehabilitation can improve the functional capacity, but has a variable effect on the low fat-free mass (FFM) in patients with chronic obstructive pulmonary disease.

Hypothesis: Pulmonary rehabilitation would not affect catabolic drives such as systemic inflammation and also protein breakdown.

Methods: Patients (n = 40) were studied at the start of an 8-week in-patient pulmonary rehabilitation programme, at the end of the programme and 4 weeks later.

Muscle wasting and impaired muscle regeneration in a murine model of chronic pulmonary inflammation.

Muscle wasting and increased circulating levels of inflammatory cytokines, including TNF-alpha, are common features of chronic obstructive pulmonary disease. To investigate whether inflammation of the lung is responsible for systemic inflammation and muscle wasting, we adopted a mouse model of pulmonary inflammation resulting from directed overexpression of a TNF-alpha transgene controlled by the surfactant protein C (SP-C) promoter. Compared with wild-type mice, SP-C/TNF-alpha mice exhibited increased levels of TNF-alpha in the circulation and increased endogenous TNF-alpha expression in skeletal muscle, potentially reflecting an amplificatory response to circulating TNF-alpha.

ESPEN Guidelines on Enteral Nutrition: Cardiology and pulmonology.

These guidelines are intended to give evidence-based recommendations for the use of enteral nutrition (EN) in patients with chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD). They were developed by an interdisciplinary expert group in accordance with officially accepted standards and are based on all relevant publications since 1985. They have been discussed and accepted in a consensus conference.

Greater whole-body myofibrillar protein breakdown in cachectic patients with chronic obstructive pulmonary disease.

Background: Experimental studies indicate that greater skeletal muscle protein breakdown is a trigger for the cachexia that often is prevalent in chronic obstructive pulmonary disease (COPD).

Objective: We compared myofibrillar protein breakdown (MPB) with whole-body (WB) protein breakdown (PB) in 9 cachectic COPD patients [x +/- SEM forced expiratory volume in 1 s (FEV(1)): 48 +/- 4% of predicted], 7 noncachectic COPD patients (FEV(1): 53 +/- 5% of predicted), and 7 age-matched healthy control subjects, who were matched by body mass index with the noncachectic patients.

Design: After the subjects fasted overnight (10 h) and discontinued the maintenance medication, a primed constant and continuous infusion protocol was used to infuse L-[ring-(2)H(5)]-phenylalanine and L-[ring-(2)H(2)]-tyrosine to measure WB protein turnover and L-[(2)H(3)]-3-methylhistidine to measure WB MPB.

Effect of glutamate ingestion on whole-body glutamate turnover in healthy elderly and patients with chronic obstructive pulmonary disease.

Objective: Decreased whole-body glutamate turnover is found in healthy elderly and in patients with chronic obstructive pulmonary disease (COPD). Glutamate supplementation as an option to increase whole-body glutamate turnover and, hence, glutamate availability has never been investigated. In the present study, we developed a protocol based on repeated glutamate ingestion to increase plasma glutamate concentration to a steady-state level without inducing toxic side effects and to evaluate the effect of repeated glutamate ingestion on whole-body glutamate turnover in patients with COPD and healthy elderly.

Prevalence of nutritional depletion in a large out-patient population of patients with COPD.

Objective: The present study focuses on the prevalence of nutritional depletion in relation to functional performance, airflow limitation, experienced dyspnoea and health status in a large multi-center out-patient population with chronic obstructive pulmonary disease (COPD).

Methods: In 39 out-patient centers in The Netherlands, 389 patients with moderate to severe COPD (217 men) were recruited. The study evaluated on the baseline characteristics of the COSMIC study.

Metabolic effects of glutamine and glutamate ingestion in healthy subjects and in persons with chronic obstructive pulmonary disease.

Background: Because low plasma glutamate and glutamine concentrations are often seen in chronic obstructive pulmonary disease (COPD), glutamine or glutamate supplementation may be a good option for preventing further metabolic disturbances in COPD patients. However, the metabolic effects of glutamate supplementation have never been compared with those of glutamine supplementation.

Objective: We compared the metabolic effects of repeated ingestion of glutamine and glutamate in COPD patients and in age-matched healthy control subjects.

Exercise training restores uncoupling protein-3 content in limb muscles of patients with chronic obstructive pulmonary disease.

Oxidative capacity and uncoupling protein-3 (UCP3) content are reduced in limb muscles of patients with chronic obstructive pulmonary disease (COPD). It has been hypothesized that the physiological role of UCP3 is to protect mitochondria against lipotoxicity in cases where fatty acid influx exceeds the capacity to oxidize them. Exercise training improves oxidative capacity and reduces UCP3 protein content in healthy subjects, but the response of UCP3 to training in COPD is unknown.

Pulmonary cachexia, systemic inflammatory profile, and the interleukin 1beta -511 single nucleotide polymorphism.

Background: Cachexia is common in chronic obstructive pulmonary disease (COPD) and is thought to be linked to an enhanced systemic inflammatory response.

Objective: We investigated differences in the systemic inflammatory profile and polymorphisms in related inflammatory genes in COPD patients.

Design: A cross-sectional study was performed in 99 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease stages II-IV), who were stratified by cachexia based on fat-free mass index (FFMI; in kg/m2: <16 for men and <15 for women) and compared with healthy control subjects (HCs).

Measuring body composition in chronic heart failure: a comparison of methods.

Aims: Fat-free mass (FFM) is increasingly recognized as a systemic marker of disease severity in chronic organ failure and is an important target for physiologic and pharmacologic interventions to improve functional status. The aim of this study was therefore to evaluate two clinical methods to assess FFM in patients with chronic heart failure (CHF) using deuterium dilution (DEU) as reference and bromide dilution to assess the ratio between intracellular (ICW) and extracellular water (ECW) as potential confounder.

Methods: Body composition was measured with dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA) and DEU in 22 stable patients from our heart failure outpatient clinic and 24 healthy age matched controls.

Inhibition of glycogen synthase kinase-3beta activity is sufficient to stimulate myogenic differentiation.

Skeletal muscle atrophy is a prominent and disabling feature of chronic wasting diseases. Prevention or reversal of muscle atrophy by administration of skeletal muscle growth (hypertrophy)-stimulating agents such as insulin-like growth factor I (IGF-I) could be an important therapeutic strategy in these diseases. To elucidate the IGF-I signal transduction responsible for muscle formation (myogenesis) during muscle growth and regeneration, we applied IGF-I to differentiating C(2)C(12) myoblasts and evaluated the effects on phosphatidylinositol 3-kinase (PI3K)/Akt/glycogen synthase kinase-3beta (GSK-3beta) signaling and myogenesis.

Decreased whole-body and splanchnic glutamate metabolism in healthy elderly men and patients with chronic obstructive pulmonary disease in the postabsorptive state and in response to feeding.

Decreased plasma and muscle glutamate concentrations have been observed in patients with chronic obstructive pulmonary disease (COPD), suggesting disturbances in glutamate metabolism. The present study was conducted to further examine glutamate metabolism in 8 male COPD patients (68 +/- 4 y) by measurement of whole-body (WB) glutamate production and splanchnic glutamate extraction in the postabsorptive state as well as in response to feeding. Because COPD is particularly prevalent in the elderly and aging per se may also affect glutamate metabolism, 2 male control groups were included: 8 healthy elderly (63 +/- 3 y) and 8 young (22 +/- 1 y) subjects.