Effects of obesity on weight-bearing versus weight-supported exercise testing in patients with COPD.

BACKGROUND AND OBJECTIVE: Obesity is associated with increased dyspnoea and reduced health status in patients with chronic obstructive pulmonary disease (COPD). Studies on the effects of obesity on exercise capacity showed divergent results. The objective of this study is to investigate the impact of obesity on weight-bearing versus weight-supported exercise tolerance in obese and normal weight patients, matched for age, gender and degree of airflow limitation. METHODS: Retrospective analyses of data obtained during pre-pulmonary rehabilitation assessment in 108 obese COPD patients (OB) (age: 61.2 ± 5.3y, FEV1 : 43.2 ± 7.4%, BMI: 34.1 ± 3.9 kg/m(2) ,) and 108 age and FEV1 -matched normal weight COPD patients (NW) (age: 61.7 ± 3.6y, FEV1 : 41.5 ± 8.4%, BMI: 22.9 ± 1.2 kg/m(2) ,). Cardiopulmonary exercise test (CPET) and 6 min walk test (6MWT) were performed, Borg scores for dyspnoea and leg fatigue were recorded, before and after the tests. RESULTS: Six-minute walk distance differed between OB (398 ± 107 m) and NW patients (446 ± 109 m, P < 0.05), while peak cycling exercise load was comparable (OB: 75 ± 29 W, NW: 70 ± 25 W, ns). Dyspnoea (OB 3.2 ± 2.0 vs NW 3.1 ± 1.7, ns) and leg fatigue (OB 2.4 ± 2.3 vs NW 1.9 ± 1.7, ns) were not significantly different in OB compared with NW after 6MWT, or after CPET (dyspnoea: OB 5.1 ± 2.4 vs NW 5.4 ± 2.2, ns; leg fatigue: OB 4.0 ± 2.3 vs NW 4.0 ± 2.7, ns). CONCLUSION: In contrast to weight-supported exercise, obesity has a negative impact on weight-bearing exercise capacity, despite comparable exercise-related symptoms. The results of this study enhance the understanding of the impact of obesity on physical performance in COPD.

Antagonistic implications of sarcopenia and abdominal obesity on physical performance in COPD.

Decreased physical performance due to loss of muscle mass (i.e. sarcopenia) is prevalent in ageing and appears more pronounced in chronic disease. A comprehensive profile of the sarcopenic phenotype in chronic obstructive pulmonary disease (COPD) is not yet available. The aim of the present study was to characterise prevalence, functional implications and predictive value of sarcopenia with or without abdominal obesity in Dutch COPD patients eligible for pulmonary rehabilitation.505 COPD patients (aged 37-87 years; 57% male) underwent assessment of lung function, body composition and physical functioning, before entering pulmonary rehabilitation. Sarcopenia was assessed by appendicular skeletal muscle index (ASMI) and abdominal obesity by android/gynoid percentage fat mass (A/G%FM) using dual energy X-ray absorptiometry.86.5% of patients were sarcopenic and showed lower physical functioning, while coexistent abdominal obesity (78.0%) resulted in higher physical functioning. Implications on endurance were less pronounced in women. The predictive value for physical functioning was higher for the "three-compartment" model (ASMI, bone mineral content and A/G%FM) than the "two-compartment" model (fat-free mass index and fat mass index) or "one-compartment" model (body mass index).In patients eligible for pulmonary rehabilitation, sarcopenia is highly prevalent in all body mass index categories and associated with impaired strength, and in men also with decreased endurance. Abdominal obesity seems to have protective effects on physical functioning. ASMI is a better predictor for physical functioning than fat-free mass index.

Differential response to pulmonary rehabilitation in COPD: multidimensional profiling.

The aim of the present study was to profile a multidimensional response to pulmonary rehabilitation in patients with chronic obstructive pulmonary disease (COPD).Dyspnoea, exercise performance, health status, mood status and problematic activities of daily life were assessed before and after a 40-session pulmonary rehabilitation programme in 2068 patients with COPD (mean forced expiratory volume in 1 s of 49% predicted). Patients were ordered by their overall similarity concerning their multidimensional response profile, which comprises the overall response on MRC dyspnoea grade, 6MWD, cycle endurance time, Canadian Occupational Performance Measure performance and satisfaction scores, Hospital Anxiety and Depression Scale anxiety and depression, and St George's Respiratory Questionnaire total score, using a novel non-parametric regression technique.Patients were clustered into four groups with distinct multidimensional response profiles: n=378 (18.3%; "very good responder"), n=742 (35.9%; "good responder"), n=731 (35.4%; "moderate responder"), and n=217 (10.5%; "poor responder"). Patients in the "very good responder" cluster had higher symptoms of dyspnoea, number of hospitalisations <12 months, worse exercise performance, worse performance and satisfaction scores for problematic activities of daily life, more symptoms of anxiety and depression, worse health status, and a higher proportion of patients following an inpatient PR programme compared to the other three clusters.A multidimensional response outcome needs to be considered to study the efficacy of pulmonary rehabilitation services in patients with COPD, as responses to regular outcomes are differential within patients with COPD.

Vitamin D deficiency and airflow limitation in the Baltimore Longitudinal Study of Ageing.

BACKGROUND: Vitamin D deficiency is common in patients with chronic obstructive pulmonary disease (COPD) and has also been linked to comorbidities often present in COPD. AIM: The aim of this study was to investigate whether vitamin D deficiency was related specifically to airflow limitation or whether vitamin D deficiency was determined by conditions that frequently coexist with COPD: insulin resistance, hypertension, anaemia, obesity and hypercholesterolaemia. METHODS: For this cross-sectional analysis, we included 897 subjects from the Baltimore Longitudinal Study of Aging. Subjects taking vitamin D supplements were excluded. Airflow limitation was defined as FEV1 /FVC < lower limit of normal. Logistic regression was used to assess the association between vitamin D deficiency (25-hydroxy vitamin D < 20 ng/mL) and possible determinants. RESULTS: Vitamin D deficiency was not specific for subjects with airflow limitation. Body mass index (BMI) (OR: 1.05, P < 0.03) and obesity (BMI > 30 kg/m(2)) (OR: 1.9, P < 0.002) were significantly associated with vitamin D deficiency in the adjusted multivariate regression analysis. Physical activity was associated with a decreased risk of vitamin D deficiency. CONCLUSIONS: Airflow limitation was not an independent determinant of vitamin D deficiency. The effect of weight loss and increased physical activity on vitamin D levels should be investigated further in intervention studies.

Fracture prevention in COPD patients; a clinical 5-step approach.

Although osteoporosis and its related fractures are common in patients with COPD, patients at high risk of fracture are poorly identified, and consequently, undertreated. Since there are no fracture prevention guidelines available that focus on COPD patients, we developed a clinical approach to improve the identification and treatment of COPD patients at high risk of fracture. We organised a round-table discussion with 8 clinical experts in the field of COPD and fracture prevention in the Netherlands in December 2013. The clinical experts presented a review of the literature on COPD, osteoporosis and fracture prevention. Based on the Dutch fracture prevention guideline, they developed a 5-step clinical approach for fracture prevention in COPD. Thereby, they took into account both classical risk factors for fracture (low body mass index, older age, personal and family history of fracture, immobility, smoking, alcohol intake, use of glucocorticoids and increased fall risk) and COPD-specific risk factors for fracture (severe airflow obstruction, pulmonary exacerbations and oxygen therapy). Severe COPD (defined as postbronchodilator FEV1 < 50% predicted) was added as COPD-specific risk factor to the list of classical risk factors for fracture. The 5-step clinical approach starts with case finding using clinical risk factors, followed by risk evaluation (dual energy X-ray absorptiometry and imaging of the spine), differential diagnosis, treatment and follow-up. This systematic clinical approach, which is evidence-based and easy-to-use in daily practice by pulmonologists, should contribute to optimise fracture prevention in COPD patients at high risk of fracture.

Plasma advanced glycation end-products and skin autofluorescence are increased in COPD.

Chronic obstructive pulmonary disease (COPD) is associated with systemic inflammation and oxidative stress. These conditions may lead to the formation of advanced glycation end-products (AGEs). In this study we investigated in 88 COPD patients and 55 control subjects (80% ex-smokers) the association of the plasma protein-bound AGEs N(ε)-(carboxymethyl)lysine (CML), pentosidine, N(ε)-(carboxyethyl)lysine (CEL), and AGE accumulation in skin by skin autofluorescence (AFR), with lung function. Mean ± sd plasma CML was decreased (COPD 61.6 ± 15.6 nmol · mmol(-1) lysine, never-smokers 80.7 ± 19.8 nmol · mmol(-1) lysine and ex-smokers 82.9 ± 19.3 nmol · mmol(-1) lysine) and CEL (COPD 39.1 ± 10.9 nmol · mmol(-1) lysine, never-smokers 30.4 ± 5.0 nmol · mmol(-1) lysine and ex-smokers 27.7 ± 6.4 nmol · mmol(-1) lysine) and AFR (COPD 3.33 ± 0.67 arbitrary units (AU), never-smokers 2.24 ± 0.45 AU and ex-smokers 2.31 ± 0.47 AU) were increased in COPD patients compared to controls. Disease state was inversely associated with CML, and linearly associated with CEL and AFR. Performing regression analyses in the total group, CEL and AFR showed a negative association and CML a positive association with lung function, even after correction for potential confounders. In conclusion, CEL and AFR were negatively and CML was positively associated with disease state. In the total group only the AGEs showed an association with forced expiratory volume in 1 s. Our data suggest that AGEs are involved in the pathophysiology of COPD, although their exact role remains to be determined.

Arterial stiffness in patients with COPD: the role of systemic inflammation and the effects of pulmonary rehabilitation.

Clear evidence for an association between systemic inflammation and increased arterial stiffness in patients with chronic obstructive pulmonary disease (COPD) is lacking. Moreover, the effects of pulmonary rehabilitation on arterial stiffness are not well studied. We aimed to 1) confirm increased arterial stiffness in COPD; 2) evaluate its correlates including systemic inflammation; and 3) study whether or not it is influenced by pulmonary rehabilitation. Aortic pulse-wave velocity (APWV) was determined in 168 healthy volunteers, and APWV and inflammatory markers were determined in 162 COPD patients during baseline evaluation of a pulmonary rehabilitation programme. A complete post-pulmonary rehabilitation dataset was collected in 129 patients. It was found that APWV was increased in COPD patients when compared with controls, blood pressure and age predicted baseline APWV, and systemic inflammatory markers were not independently related to APWV. Although baseline APWV was predictive for the change in APWV after pulmonary rehabilitation (r= -0.77), on average APWV did not change (10.7 ± 2.7 versus 10.9 ± 2.5 m·s(-1); p=0.339). Arterial stiffness in COPD is not related to systemic inflammation and does not respond to state-of-the-art pulmonary rehabilitation. These results emphasise the complexity of cardiovascular risk and its management in COPD.

Association of plasma sRAGE, but not esRAGE with lung function impairment in COPD.

RATIONALE: Plasma soluble Receptor for Advanced Glycation End Product (sRAGE) is considered as a biomarker in COPD. The contribution of endogenous sRAGE (esRAGE) to the pool of plasma sRAGE and the implication of both markers in COPD pathogenesis is however not clear yet. The aim of the current study was therefore to measure plasma levels of esRAGE comparative to total sRAGE in patients with COPD and a control group. Further, we established the relations of esRAGE and total sRAGE with disease specific characteristics such as lung function and DLCO, and with different circulating AGEs. METHODS: Plasma levels of esRAGE and sRAGE were measured in an 88 patients with COPD and in 55 healthy controls. FEV1 (%predicted) and FEV1/VC (%) were measured in both groups; DLCO (%predicted) was measured in patients only. In this study population we previously reported that the AGE Nϵ-(carboxymethyl) lysine (CML) was decreased, Nϵ-(carboxyethyl) lysine (CEL) increased and pentosidine was not different in plasma of COPD patients compared to controls. RESULTS: Plasma esRAGE (COPD: 533.9 ± 412.4, CONTROLS: 848.7 ± 690.3 pg/ml; p = 0.000) was decreased in COPD compared to controls. No significant correlations were observed between plasma esRAGE levels and lung function parameters or plasma AGEs. A positive correlation was present between esRAGE and total sRAGE levels in the circulation. Confirming previous findings, total sRAGE (COPD: 512.6 ± 403.8, CONTROLS: 1834 ± 804.2 pg/ml; p < 0.001) was lower in patients compared to controls and was positively correlated FEV1 (r = 0.235, p = 0.032), FEV1/VC (r = 0.218, p = 0.047), and DLCO (r = 0.308, p = 0.006). sRAGE furthermore did show a significant positive association with CML (r = 0.321, p = 0.003). CONCLUSION: Although plasma esRAGE is decreased in COPD patients compared to controls, only total sRAGE showed a significant and independent association with FEV1, FEV1/VC and DLCO, indicating that total sRAGE but not esRAGE may serve as marker of COPD disease state and severity.

Clusters of comorbidities based on validated objective measurements and systemic inflammation in patients with chronic obstructive pulmonary disease.

RATIONALE: Comorbidities contribute to disease severity and mortality in patients with chronic obstructive pulmonary disease (COPD). Comorbidities have been studied individually and were mostly based on self-reports. The coexistence of objectively identified comorbidities and the role of low-grade systemic inflammation in the pathophysiology of COPD remain to be elucidated. OBJECTIVES: To cluster 13 clinically important objectively identified comorbidities, and to characterize the comorbidity clusters in terms of clinical outcomes and systemic inflammation. METHODS: A total of 213 patients with COPD (FEV1, 51 ± 17% predicted; men, 59%; age, 64 ± 7 yr) were included prospectively. Comorbidities were based on well-known cut-offs identified in the peer-reviewed English literature. Systemic inflammatory biomarkers were determined in all patients. Self-organizing maps were used to generate comorbidity clusters. MEASUREMENTS AND MAIN RESULTS: A total of 97.7% of all patients had one or more comorbidities and 53.5% had four or more comorbidities. Five comorbidity clusters were identified: (1) less comorbidity, (2) cardiovascular, (3) cachectic, (4) metabolic, and (5) psychological. Comorbidity clusters differed in health status but were comparable with respect to disease severity. An increased inflammatory state was observed only for tumor necrosis factor (TNF) receptors in the metabolic cluster (geometric mean [lower and upper limit]; TNF-R1, 2,377 [1,850, 3,055] pg/ml, confidence, 98.5%; TNF-R2, 4,080 [3,115, 5,344] pg/ml, confidence, 98.8%) and only for IL-6 in the cardiovascular cluster (IL-6, 3.4 [1.8, 6.6] pg/ml; confidence, 99.8%). CONCLUSIONS: Multimorbidity is common in patients with COPD, and different comorbidity clusters can be identified. Low-grade systemic inflammation is mostly comparable among comorbidity clusters. Increasing knowledge on the interactions between comorbidities increases the understanding of their development and contributes to strategies for prevention or improved treatment.

Associations between COPD related manifestations: a cross-sectional study.

BACKGROUND: Cardiovascular disease, osteoporosis and emphysema are associated with COPD. Associations between these factors and whether they predict all-cause mortality in COPD patients are not well understood. Therefore, we examined associations between markers of cardiovascular disease (coronary artery calcification [CAC], thoracic aortic calcification [TAC] and arterial stiffness), bone density (bone attenuation of the thoracic vertebrae), emphysema (PI-950 and 15th percentile) and all-cause mortality in a COPD cohort. METHODS: We assessed CAC, TAC, bone attenuation of the thoracic vertebrae, PI-950 and 15th percentile on low-dose chest computed tomography in COPD subjects. We measured arterial stiffness as carotid-radial pulse wave velocity (PWV), and identified deaths from the national register. RESULTS: We studied 119 COPD subjects; aged 67.8 ±7.3, 66% were males and mean FEV1% predicted was 46.0 ±17.5. Subjects were classified into three pre-specificed groups: CAC = 0 (n = 14), 0 < CAC ≤ 400 (n = 41) and CAC > 400 (n = 64). Subjects with higher CAC were more likely to be older (p < 0.001) and male (p = 0.03), and more likely to have higher systolic blood pressure (p = 0.001) and a history of hypertension (p = 0.002) or ischemic heart disease (p = 0.003). Higher CAC was associated with higher PWV (OR 1.62, p = 0.04) and lower bone attenuation (OR 0.32, p = 0.02), but not with 15th percentile, after adjustment for age, sex and pack-years of smoking. In a Cox proportional hazards model, CAC, TAC and 15th percentile predicted all-cause mortality (HR 2.01, 2.09 and 0.66, respectively). CONCLUSIONS: Increased CAC was associated with increased arterial stiffness and lower bone density in a COPD cohort. In addition, CAC, TAC and extent of emphysema predicted all-cause mortality. TRIAL REGISTRATION: Lothian NHS Board, Lothian Research Ethics Committee, LREC/2003/8/28.

Changes in body composition in patients with chronic obstructive pulmonary disease: do they influence patient-related outcomes?

AIMS: The follow-up of the ECLIPSE study, a prospective longitudinal study to identify and define parameters that predict disease progression over 3 years in chronic obstructive pulmonary disease (COPD), allows the examination of the effect of body composition changes on COPD-related outcomes. METHODS: Body composition and health status were established in 2,115 COPD patients, 327 smoking and 239 nonsmoking controls at baseline and 3 years, while mortality was recorded in year 2 and 3 in the COPD patients. Associations between fat free mass index (FFMI) and fat mass index (FMI) changes to deterioration in health status and mortality were determined. RESULTS: Change in FFMI and FMI over 3 years was small and comparable between the groups. Underweight and obese patients had the worst health status. Worsening health status was associated with FFMI decrease in underweight patients and FMI increase in overweight/obese patients. While overweight patients had the lowest mortality, FFMI or FMI decrease was associated with a higher mortality. CONCLUSION: Changes in body composition over 3 years were small and comparable in COPD patients and control subjects. Nevertheless, muscle mass decline in underweight and fat mass increase in overweight/obese patients is associated with worsening health status. Overweight is associated with decreased mortality, but muscle mass and fat mass decline are detrimental for mortality.

Anemia is associated with bone mineral density in chronic obstructive pulmonary disease.

OBJECTIVE: Patients with chronic obstructive pulmonary disease (COPD) often suffer from systemic co-morbidities, including anemia. However, anemia is related to multiple outcomes in COPD and in other chronic diseases, but it's impact is underestimated in COPD. The objective of the present study was to relate anemia in patients with COPD with disease-related outcomes, systemic inflammation and COPD related co-morbidities. METHODS: Data of 321 patients with COPD admitted for pulmonary rehabilitation were analysed. Besides general characteristics, lung function, body composition, arterial gases and plasma haemoglobin concentration, disease-related outcomes (health-related quality of life by St. George's Respiratory Questionnaire, 6-minute walking distance, mMRC dyspnea scale, and BODE index), systemic inflammation (C-reactive protein (CRP)) and self-reported and objectified co-morbidities (low muscle mass, osteoporosis, renal failure, risk for undernutrition) were taken into account. RESULTS: First, 20% of the patients were anemic, and 8% was polycythemic. Polycythemic patients had a lower proportion of men and a lower proportion of low muscle mass compared to the other groups. Anemic patients had higher plasma CRP levels and lower total body bone mineral density compared to the other groups. There was no difference in disease-related outcomes or other co-morbidities in the patients with and without anemia. Even after adjustment for confounders, anemia was an independent determinant for higher CRP levels and lower bone mineral density. CONCLUSION: Anemia is frequently present in patients with COPD and there is evidence that it is associated with lower whole body bone mineral density.

Decreased plasma sRAGE levels in COPD: influence of oxygen therapy.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with systemic inflammation and oxidative stress. N(ε) -(carboxymethyl) lysine (CML), an advanced glycation end product (AGE) and the soluble decoy receptor, sRAGE, are exciting new molecules linked to oxidative stress and inflammation. Here the levels of plasma sRAGE and CML were determined and their variation in relation to lung function, external long-term oxygen therapy (LTOT) and plasma levels of inflammatory molecules in COPD evaluated. METHODS: Plasma sRAGE and CML levels were measured by ELISA in 146 patients with stable COPD and 81 healthy subjects, subgrouped from a larger case-control study and matched for age, gender and pack-years smoked. RESULTS: Decreased levels of plasma sRAGE and no significant difference in levels of plasma CML were found in patients with COPD in comparison with controls. In the total group, plasma sRAGE was positively associated with FEV(1) and forced vital capacity and negatively with pack-years smoked. In patients receiving LTOT, levels of plasma sRAGE were lower compared with those without LTOT. Only in controls, a weak correlation was found between plasma sRAGE and CML. sRAGE did not correlate with measured inflammatory markers, whereas CML was negatively correlated with fibrinogen. CONCLUSION: Plasma sRAGE levels are lower in patients with COPD compared with healthy control subjects, and even lower levels in patients receiving LTOT. Because sRAGE correlated with lung function only in the whole group, sRAGE can be considered a marker of COPD, but not of disease severity. A lack of clear association between sRAGE, CML and systemic inflammation is furthermore evident.

Dysregulated adipokine metabolism in chronic obstructive pulmonary disease.

BACKGROUND: Research concerning the involvement of body composition and systemic inflammatory markers in adipokine metabolism in chronic obstructive pulmonary disease (COPD) is still limited. Therefore, we primarily aimed to investigate the adipokine metabolism in relation to these systemic inflammatory biomarkers and to evaluate possible gender-related differences in the adipokine metabolism in patients with COPD. MATERIALS AND METHODS: One hundred and eighty-six subjects with COPD [mean (SD) FEV(1) %pred: 50 (±16)] and 113 controls, matched for age, gender and body composition were selected from the ECLIPSE cohort. The following serological data were collected: serum levels of leptin, adiponectin and systemic inflammatory biomarkers such as C-reactive protein (CRP), Interleukin-6 (IL-6) and fibrinogen. RESULTS: Compared with controls, patients with COPD had higher levels of CRP, IL-6, fibrinogen and adiponectin. After stratification for gender, men with COPD had higher CRP, IL6 and fibrinogen levels compared with male controls, while women with COPD had higher levels of CRP and fibrinogen compared with the female controls. Moreover, in both female controls and patients with COPD, leptin correlated with CRP and fibrinogen, while leptin only correlated with CRP in male controls. Adiponectin correlated negatively with CRP, only in patients with COPD. Body mass index and gender were the strongest determinants for both leptin and adiponectin. CONCLUSIONS: This study shows a gender-dependent dysregulation of adipokine metabolism in patients with COPD compared with BMI-matched controls. Furthermore, results from this study suggest a more prominent role of adiponectin in the systemic response to COPD.

Disease-Specific Comorbidity Clusters in COPD and Accelerated Aging.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often suffer from multiple morbidities, which occur in clusters and are sometimes related to accelerated aging. This study aimed to assess the disease specificity of comorbidity clusters in COPD and their association with a biomarker of accelerated aging as a potential mechanistic factor. METHODS: Body composition, metabolic, cardiovascular, musculoskeletal, and psychological morbidities were objectively evaluated in 208 COPD patients (age 62 ± 7 years, 58% males, FEV1 50 ± 16% predicted) and 200 non-COPD controls (age 61 ± 7 years, 45% males). Based on their presence and severity, the morbidities were clustered to generate distinct clusters in COPD and controls. Telomere length in circulating leukocytes was compared across the clusters. RESULTS: (co)morbidities were more prevalent in COPD patients compared to controls (3.9 ± 1.7 vs. 2.4 ± 1.5, p < 0.05). A "Psychologic" and "Cachectic" cluster were only present in the COPD population. "Less (co)morbidity", "Cardiovascular", and "Metabolic" clusters were also observed in controls, although with less complexity. Telomere length was reduced in COPD patients, but did not differ between the (co)morbidity clusters in both populations. CONCLUSIONS: Two COPD-specific comorbidity clusters, a "Cachectic" and "Psychologic" cluster, were identified and warrant further studies regarding their development. Accelerated aging was present across various multimorbidity clusters in COPD.

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. Simultaneous continuous intravenous infusion of l-[ring-(2)H(5)]phenylalanine (Phe) and l-[ring-(2)H(2)]tyrosine tracers was done postabsorptively and at 2 h of ingestion of a maltodextrin soy or maltodextrin soy + BCAA protein meal (rate of ingestion: 0.02 g protein.kg body weight(-1).20 min(-1)) in a crossover design. Together with the meal, oral ingestion of 1-[(13)C]Phe was performed to measure first-pass Phe splanchnic extraction (SPE(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 increase 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) SPE(Phe) (P < 0.05) but did not change the percentage Phe hydroxylation in the splanchnic area, which indicates a BCAA-related 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.

A randomized clinical trial investigating the efficacy of targeted nutrition as adjunct to exercise training in COPD.

BACKGROUND: Evidence regarding the efficacy of nutritional supplementation to enhance exercise training responses in COPD patients with low muscle mass is limited. The objective was to study if nutritional supplementation targeting muscle derangements enhances outcome of exercise training in COPD patients with low muscle mass. METHODS: Eighty-one COPD patients with low muscle mass, admitted to out-patient pulmonary rehabilitation, randomly received oral nutritional supplementation, enriched with leucine, vitamin D, and omega-3 fatty acids (NUTRITION) or PLACEBO as adjunct to 4 months supervised high intensity exercise training. RESULTS: The study population (51% males, aged 43-80) showed moderate airflow limitation, low diffusion capacity, normal protein intake, low plasma vitamin D, and docosahexaenoic acid. Intention-to-treat analysis revealed significant differences after 4 months favouring NUTRITION for body mass (mean difference ± SEM) (+1.5 ± 0.6 kg, P = 0.01), plasma vitamin D (+24%, P = 0.004), eicosapentaenoic acid (+91%,P < 0.001), docosahexaenoic acid (+31%, P < 0.001), and steps/day (+24%, P = 0.048). After 4 months, both groups improved skeletal muscle mass (+0.4 ± 0.1 kg, P < 0.001), quadriceps muscle strength (+12.3 ± 2.3 Nm,P < 0.001), and cycle endurance time (+191.4 ± 34.3 s, P < 0.001). Inspiratory muscle strength only improved in NUTRITION (+0.5 ± 0.1 kPa, P = 0.001) and steps/day declined in PLACEBO (-18%,P = 0.005). CONCLUSIONS: High intensity exercise training is effective in improving lower limb muscle strength and exercise performance in COPD patients with low muscle mass and moderate airflow obstruction. Specific nutritional supplementation had additional effects on nutritional status, inspiratory muscle strength, and physical activity compared with placebo.

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. DESIGN: On 3 d separated by intervals of > or = 2 d, a protocol of primed constant and continuous infusion of [2H5]phenylalanine and [2H2]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.