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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. Simultaneous continuous intravenous infusion of L-[[ring-.sup.2][H.sub.5]] phenylalanine (Phe) and L-[[ring-.sup.2][H.sub.2]] tyrosine tracers was done postabsorptively and at 2 h of ingestion of a maltodextrin soy or maltodextrin soy [+ or -]BCAA protein meal (rate of ingestion: 0.02 g protein.kg body [weight.sup.-1]*20 [min.sup.-1]) in a crossover design. Together with the meal, oral ingestion of 1-[[.sup.13]C]Phe was performed to measure first-pass Phe splanchnic extraction (SP[E.sub.Phe]). The endogenous rate of Phe appearance [reflecting whole-body protein breakdown (WbPB)], whole-body protein synthesis (WbPS), and net WbPS (WbPS--WbPB) were calculated. Arterialized venous blood was sampled for amino acid enrichment and concentration analyses. Results: Soy feeding induced a reduction in WbPB and an [+ or -] crease in WbPS. BCAA supplementation of soy protein resulted in a significantly higher (P < 0.05) increase in WbPS than did soy protein alone in COPD patients but not in the healthy elderly. BCAA supplementation did not significantly alter the change in WbPB or net WbPS. Furthermore, BCAA supplementation decreased (absolute) SP[E.sub.Phe] (P < 0.05) but did not change the percentage Phe hydroxylation in the splanchnic area, which indicates a BCAA-relatcd reduction in splanchnic protein synthesis. Conclusion: BCAA supplementation to soy protein enhances WbPS in patients with COPD and alters interorgan protein metabolism in favor of the peripheral (muscle) compartment in healthy elderly and even more in COPD patients. KEY WORDS Chronic obstructive pulmonary disease, protein feeding, branched-chain amino acid supplementation, wholebody protein turnover, interorgan protein metabolism

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 [[bar.x] [+ or -] SEM forced expiratory volume in 1 s ([FEV.sub.1]); 48 [+ or -] 4% of predicted], 7 noncachectic COPD patients ([FEV.sub.1] : 53 [+ or -] 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.sup.-2][H.sub.5]]-phenylalanine and L-[[ring.sup.-2][H.sub.2]]-tyrosine to measure WB protein turnover and L-[[sup.2][H.sub.3]]3-methylhistidine to measure WB MPB. Three arterialized venous blood samples were taken between 80 and 90 min of infusion to measure amino acid concentrations and tracer enrichments. Results: Body composition, WB protein turnover, and WB MPB did not differ significantly between the noncachectic COPD and control subjects. Cachectic COPD patients had lower fat mass and fat-free mass values (both: P < 0.01) than did the noncachectic COPD patients. WB MPB was significantly (P < 0.05) higher in the cachectic COPD group (18 [+ or -] 3 nmol * [kg.sup.-1] * [min.sup.-1]) than in the combined control and noncachectic COPD groups (10 [+ oe -] 1 nmol * [kg.sup.-1] * [min.sup.-1]), but WB protein turnover did not differ significantly between the groups. Correlations with fat-free mass were significant (P < 0.05) for plasma glutamate and branched-chain amino acids, and that for WB MPB trended toward significance (P = 0.07). Conclusion: Cachexia in clinically stable patients with moderate COPD is characterized by increased WB MPB, which indicates that myofibrillar protein wasting is an important target for nutritional and pharmacologic modulation. KEY WORDS Cachexia, myofibrillar protein breakdown, 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. Design: On 3 d separated by intervals of [greater than or equal to] 2 d, a protocol of primed constant and continuous infusion of [[sup.2[H.sub.5]]phenylalanine and [[sup.2[H.sub.2]]tyrosine was performed for 3 h in 8 stable male COPD patients and 8 healthy control subjects. After a 90-min tracer infusion, all subjects ingested a glutamine or glutamate drink or the same amount of water every 20 min for 80 min. Blood samples were taken at the end of the postabsorptive and ingestion periods to test for effects on plasma amino acid and substrate concentrations and whole-body protein turnover. Results: Glutamate but not glutamine ingestion resulted in higher plasma ornithine concentrations than did water ingestion (P < 0.01). The change in plasma arginine, citrulline, and urea concentrations was significantly (P < 0.01) higher after glutamine ingestion than after water or glutamate ingestion. Whole-body protein turnover decreased overall, independent of the drink consumed. Conclusions: Repeated ingestion of glutamine and glutamate resulted in different effects on the plasma amino acid concentration. In both groups, ingestion of glutamine but not of glutamate increased the plasma concentrations of citrulline and arginine, substrates produced in the intestine and the liver. KEY WORDS Glutamine, glutamate, chronic obstructive pulmonary disease, supplementation, amino acids, protein turnover

Background: Previously, we reported increased values for whole-body protein turnover in patients with chronic obstructive pulmonary disease (COPD) in the postabsorptive state. Objective: The objective was to investigate whether intake of a carbohydrate-protein meal influences whole-body protein turnover differently in COPD patients and control subjects. Design: Eight normal-weight patients with moderate COPD and 8 healthy control subjects were examined in the postabsorptive state and after 2 h of repeatedly ingesting a maltodextrin casein-based protein meal (0.02 g x kg body [wt.sup.-1] x 20 [min.sup.-1]). Combined simultaneous, continuous, intravenous infusion of L-[ring-[sup.2][H.sub.5]]-phenylalanine and L-[ring-[sup.2][H.sub.2]]-tyrosine tracer and oral repeated ingestion of 1-[sup.13]C-phenylalanine were performed to measure whole-body protein synthesis (WbPS) and first-pass splanchnic extraction of phenylalanine. Endogenous rate of appearance of phenylalanine as the measure of whole-body protein breakdown (WbPB) and net-WbPS was calculated as WbPS - WbPB. Arterialized venous blood was sampled for amino acid enrichment and concentration analyses. Results: Feeding induced an increase in WbPS and a reduction in WbPB. The reduction in WbPB was larger in the COPD group than in the control group (P < 0.05) and was related to the lower splanchnic extraction of phenylalanine in the patients. Consequently, net-WbPS increased more after feeding in the COPD group than in the control group (P < 0.05). Conclusion: Feeding induces more protein anabolism in normal-weight patients with moderate COPD than in healthy control subjects. This is probably because these COPD patients are characterized by an adaptive interorgan response to feeding to prevent or delay weight loss at this disease stage. KEY WORDS Chronic obstructive pulmonary disease, protein feeding, first-pass splanchnic extraction, whole-body protein turnover, endogenous protein metabolism

Visceral adipose tissue (VAT) was shown to be increased in patients with chronic obstructive pulmonary disease (COPD) compared to control subjects with comparable body mass index (BMI). Our aim was to determine the relation of VAT by dual-energy x-ray absorptiometry (DEXA) in patients with COPD by disease severity, BMI, other indices of body composition and static lung volumes. 294 COPD patients admitted for rehabilitation were studied. Lung function, static lung volumes and body composition (i.e. BMI, waist circumference, fat-free mass, fat mass and fat distribution between android and gynoid fat mass) were assessed before entering pulmonary rehabilitation. VAT was estimated within the android region by using DEXA. Patients were stratified for gender, BMI (cut-off of 25 kg/m2) and GOLD stage. To assess the impact of VAT on lung volumes, patients were also stratified for VAT less and above 50thpercentile. Both male and female patients with more severe airflow limitation had significantly lower VAT values, but these differences disappeared after stratification for BMI. VAT was significantly and strongly correlated with other body composition parameters (all p < 0.001). Patients with moderate to severe airflow limitation and lower VAT had increased static lung hyperinflation and lower diffusing capacity for carbon monoxide. Nevertheless, multivariate stepwise regression models including for BMI, age, gender and forced expiratory volume in 1 s (FEV1) as confounders did not confirm an independent role for VAT on static lung hyperinflation and diffusion capacity. After stratification for BMI, VAT is comparable in moderate to very severe COPD patients. Furthermore, BMI and demographics, but not VAT, were independent predictors of static lung hyperinflation and diffusing capacity in COPD.

Accelerated aging has been proposed as a pathologic mechanism of various chronic diseases, including COPD. This concept has almost exclusively been approached by analyses of individual markers. We investigated whether COPD is associated with accelerated aging using a panel of markers representing various interconnected aspects of the aging process.

COPD is accepted to be a multicomponent disease with various comorbidities. To our knowledge, the contribution of the GI tract to the systemic manifestation of COPD has never been investigated. This metabolically active organ may experience recurring local oxygen deficits during daily life, leading to disturbed intestinal integrity in patients with COPD.

Health status is one of the most important outcome measures to evaluate the effects of integrated care of patients with mild to very severe chronic obstructive pulmonary disease (COPD). Indeed, to improve the health status of patients with COPD has been set as one of the main goals of effective COPD management. Pharmacological treatment has been shown to reduce the deterioration of health status over time in COPD, in comparison with placebo treatment. Nevertheless, health status appears to decrease over time even though COPD patients did receive pharmacological treatments for their respiratory symptoms. Indeed, patients with COPD suffer from multiple extrapulmonary features, which in turn may result in a reduced health status. The present review will summarize the effects of pulmonary rehabilitation, nutritional interventions and of surgical interventions on the health status in the patients with COPD. Based on the present review of the literature, the authors conclude that besides optimal pharmacological interventions, management of COPD has to consist of non-pharmacological treatments, which has been shown to positively influence patients health status. In particular, pulmonary rehabilitation programs have been shown to have positive short-term effects on health status in COPD.

Glutamate is an amino acid of interest because it participates in many metabolic pathways. However, there is evidence that skeletal muscle glutamate metabolism is disturbed in disease. This review presents current knowledge regarding the metabolic function and regulation of glutamate in skeletal muscle under physiological and pathophysiological circumstances. Furthermore, several options for modulating muscle glutamate concentration in order to improve glutamate metabolism are discussed.