Clinical outcome and cost-effectiveness of a 1-year nutritional intervention programme in COPD patients with low muscle mass: The randomized controlled NUTRAIN trial.

BACKGROUND AND AIMS: The efficacy of nutritional intervention to enhance short- and long-term outcomes of pulmonary rehabilitation in COPD is still unclear, hence this paper aims to investigate the clinical outcome and cost-effectiveness of a 12-month nutritional intervention strategy in muscle-wasted COPD patients. METHODS: Prior to a 4-month pulmonary rehabilitation programme, 81 muscle-wasted COPD patients (51% males, aged 62.5 ± 0.9 years) with moderate airflow obstruction (FEV1 55.1 ± 2.2% predicted) and impaired exercise capacity (Wmax 63.5 ± 2.4% predicted) were randomized to 3 portions of nutritional supplementation per day (enriched with leucine, vitamin D and polyunsaturated fatty acids) [NUTRITION] or PLACEBO (phase 1). In the unblinded 8-month maintenance phase (phase 2), both groups received structured feedback on their physical activity level assessed by accelerometry. NUTRITION additionally received 1 portion of supplemental nutrition per day and motivational interviewing-based nutritional counselling. A 3-month follow-up (phase 3) was included. RESULTS: After 12 months, physical capacity measured by quadriceps muscle strength and cycle endurance time were not different, but physical activity was higher in NUTRITION than in PLACEBO (Δ1030 steps/day, p = 0.025). Plasma levels of the enriched nutrients (p < 0.001) were higher in NUTRITION than PLACEBO. Trends towards weight gain in NUTRITION and weight loss in PLACEBO led to a significant between-group difference after 12 months (Δ1.54 kg, p = 0.041). The HADS anxiety and depression scores improved in NUTRITION only (Δ-1.92 points, p = 0.037). Generic quality of life (EQ-5D) was decreased in PLACEBO but not in NUTRITION (between-group difference after 15 months 0.072 points, p = 0.009). Overall motivation towards exercising and healthy eating was high and did not change significantly after 12 months; only amotivation towards healthy eating yielded a significant between-group difference (Δ1.022 points, p = 0.015). The cost per quality-adjusted life-year after 15 months was EUR 16,750. CONCLUSIONS: Nutritional intervention in muscle-wasted patients with moderate COPD does not enhance long-term outcome of exercise training on physical capacity but ameliorates plasma levels of the supplemented nutrients, total body weight, physical activity and generic health status, at an acceptable increase of costs for patients with high disease burden.

The effect of acute and 7-days dietary nitrate on mechanical efficiency, exercise performance and cardiac biomarkers in patients with chronic obstructive pulmonary disease.

BACKGROUND & AIMS: Many COPD patients have a reduced exercise capacity and mechanical efficiency and are at increased cardiometabolic risk. This study aimed to assess acute and 7-days effects of dietary nitrate on mechanical efficiency, exercise performance and cardiac biomarkers in patients with COPD. METHODS: This double-blind, randomized cross-over placebo controlled trial included 20 mild-to-moderate COPD patients (66.6 ± 7.5 years) with moderate exercise impairments and decreased mechanical efficiency, normal BMI (26 ± 3 kg/m2) but high prevalence of abdominal obesity (83.3%). Subjects were randomly allocated to the treatment order of 7 days sodium nitrate ingestion (∼8 mmol/day) and 7 days placebo (NaCl solution) or vice versa, separated by a washout period. Before (Day-1) and after (Day-7) both intervention periods resting metabolic rate and the metabolic response during submaximal cycle ergometry, cycling endurance time, plasma nitrate and nitrite levels, cardiac plasma biomarkers (e.g. cardiac troponin T, Nt-proBNP and creatinine kinase) and blood pressure were measured. Subsequently, gross, net and delta mechanical efficiency were calculated. RESULTS: Plasma nitrate and nitrite concentrations increased at Day-1 and Day-7 after sodium nitrate but not after placebo ingestion. Systolic and diastolic blood pressure did not change following nitrate ingestion. Furthermore, no differences were observed in gross, net, and delta mechanical efficiency during submaximal exercise, cycling endurance time and cardiac biomarkers between nitrate and placebo on Day-1 and Day-7. Meta-analysis of all available studies in COPD also showed no beneficial effect of beetroot juice on systolic and diastolic blood pressure. CONCLUSION: Acute as well as 7-days sodium nitrate supplementation does not modulate mechanical efficiency, blood pressure or cardiac biomarkers in mild-to-moderate 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.

Normal Weight but Low Muscle Mass and Abdominally Obese: Implications for the Cardiometabolic Risk Profile in Chronic Obstructive Pulmonary Disease.

BACKGROUND: It is well established that low muscle mass affects physical performance in chronic obstructive pulmonary disease (COPD). We hypothesize that combined low muscle mass and abdominal obesity may also adversely influence the cardiometabolic risk profile in COPD, even in those with normal weight. The cardiometabolic risk profile and the responsiveness to 4 months high-intensity exercise training was assessed in normal-weight patients with COPD with low muscle mass stratified by abdominal obesity. METHODS: This is a cross-sectional study including 81 clinically stable patients with COPD (age 62.5 ± 8.2 years; 50.6% males; forced expiratory volume in 1 second 55.1 ± 19.5 percentage predicted) with fat-free mass index <25th percentile eligible for outpatient pulmonary rehabilitation. Body composition, blood biomarkers, blood pressure, physical activity level, dietary intake, and physical performance were assessed at baseline and in a subgroup after 4 months of exercise training. RESULTS: Mean body mass index was 22.7 ± 2.7 kg/m2, and 75% of patients had abdominal obesity. Abdominally obese patients had higher glucose, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), branched chain amino acids and a higher prevalence of metabolic syndrome compared with those without abdominal obesity. Exercise training improved cycling endurance time and quadriceps strength, but did not yield a clinically meaningful improvement of the cardiometabolic risk profile. Triglycerides showed a significant decrease, while the HOMA-IR increased. CONCLUSION: Abdominal obesity is highly prevalent in normal-weight patients with COPD with low muscle mass who showed an increased cardiometabolic risk compared with patients without abdominal obesity. This cardiometabolic risk profile was not altered after 4 months of exercise training.

Cachexia in chronic obstructive pulmonary disease: new insights and therapeutic perspective.

Cachexia and muscle wasting are well recognized as common and partly reversible features of chronic obstructive pulmonary disease (COPD), adversely affecting disease progression and prognosis. This argues for integration of weight and muscle maintenance in patient care. In this review, recent insights are presented in the diagnosis of muscle wasting in COPD, the pathophysiology of muscle wasting, and putative mechanisms involved in a disturbed energy balance as cachexia driver. We discuss the therapeutic implications of these new insights for optimizing and personalizing management of COPD-induced cachexia.

Muscle Quality is More Impaired in Sarcopenic Patients With Chronic Obstructive Pulmonary Disease.

BACKGROUND: Quadriceps muscle fiber atrophy and a loss of oxidative type I muscle fibers and mitochondrial content often occur in chronic obstructive pulmonary disease (COPD), which adversely affects exercise performance. Sarcopenia is an age-related syndrome characterized by wasting and weakness of muscle mass. We recently showed in a large cohort of patients that COPD-related sarcopenia, in particular in male patients, was not only associated with impaired quadriceps muscle strength but also with decreased exercise performance endurance, which could imply involvement of altered muscle fiber type composition. Hence, we hypothesized that both the fiber atrophy and loss of oxidative muscle fibers are more pronounced in sarcopenic compared with nonsarcopenic patients with COPD. OBJECTIVE: The objective of this study was to investigate quadriceps muscle fiber-type characteristics in relation to presence of sarcopenia in patients with COPD and in healthy age-matched controls. DESIGN: For this retrospective cross-sectional study, body composition (assessed by dual-energy x-ray absorptiometry) and quadriceps muscle biopsy (fiber type distribution and sizes) data were collected from 45 patients with COPDs (aged 42-77 years) and 52 healthy controls (aged 50-77 years). Sarcopenia was based on assessment of appendicular skeletal muscle mass index. RESULTS: Sarcopenia was found in 5.8% of healthy controls and in 31.1% of patients with COPD (P < .01). The proportion of oxidative type I fibers and size of type IIx muscle fibers were decreased in patients with COPD, and the sarcopenic subgroup showed a further decreased proportion as well as a lower size of type I fibers. CONCLUSIONS: Type I muscle fiber proportion is lower in sarcopenic compared with nonsarcopenic patients with COPD. Longitudinal studies may elucidate if the loss of muscle oxidative phenotype drives or accelerates the process of muscle wasting.

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.

Maintenance of a physically active lifestyle after pulmonary rehabilitation in patients with COPD: a qualitative study toward motivational factors.

OBJECTIVES: To explore determinants of behavior change maintenance of a physically active lifestyle in patients with chronic obstructive pulmonary disease (COPD) 8-11 months after completion of a 4-month outpatient pulmonary rehabilitation program. DESIGN: A qualitative descriptive study of semistructured interviews. SETTING: Pulmonary rehabilitation assessment center. PARTICIPANTS: Patients with COPD. MEASUREMENTS: Semistructured interviews until data saturation, coded by 2 independent researchers. Patients were classified as responder (maintenance or improvement) or nonresponder (relapse or decrease), based on 3 quantitative variables reflecting exercise capacity (Constant Work Rate Test), health-related quality of life (Short-Form health survey [SF-36]), and self-management abilities (Self-Management Ability Scale [SMAS-30/Version 2]). RESULTS: Mean (SD) forced expiratory volume in the first second (FEV1) among interviewees was 52.5% (14.4%) predicted and the mean age was 63.5 years (range: 45-78). The group consisted of 15 responders and 7 nonresponders. Physical limitations reduced competence to engage in an active lifestyle and responders appeared to experience higher levels of perceived competence. Social support was found important and the experienced understanding from fellow patients made exercising together enjoyable. Particularly, responders expressed autonomous motivation and said they exercised because of the benefits they gain from it. Unexpectedly, only responders also experienced controlled motivation. CONCLUSION: Perceived competence and autonomous motivation are important determinants for maintenance of an active lifestyle in patients with COPD. In contrast to common theoretical assumptions, a certain threshold level of controlled motivation may remain important in maintaining a physically active lifestyle after a pulmonary rehabilitation program.

Nutritional targets to enhance exercise performance in chronic obstructive pulmonary disease.

PURPOSE OF REVIEW: This review presents current knowledge regarding the rationale and efficacy of nutrition as an ergogenic aid to enhance the effects of exercise and training in chronic obstructive pulmonary disease (COPD). RECENT FINDINGS: Altered body composition and skeletal muscle dysfunction in COPD suggest that exercise capacity can be targeted via several metabolic routes. Muscle metabolic alterations in COPD include a reduced oxidative metabolism and enhanced susceptibility for oxidative stress. Muscle wasting may be associated with deficiencies of vitamin D and low branched-chain amino acid levels. Exercise training is of established benefit in COPD but clear-cut clinical trial evidence to support the performance enhancing effect of nutritional intervention is lacking. One randomized controlled trial suggested that augmentation of training with polyunsaturated fatty acids may improve exercise capacity. Conflicting results are reported on dietary creatine supplementation in patients with COPD receiving pulmonary rehabilitation and results from acute intervention studies do not directly imply long-term effects of glutamate or glutamine supplementation as an ergogenic aid in COPD. Recent data indicate that not only muscle but also visceral fat may be an important additional target for combined nutrition and exercise intervention in COPD to improve physical performance and decrease cardiometabolic risk. SUMMARY: There is a clear need for adequately powered and controlled intervention and maintenance trials to establish the role of nutritional supplementation in the enhancement of exercise performance and training and the wider management of the systemic features of the disease.

Differences in walking pattern during 6-min walk test between patients with COPD and healthy subjects.

BACKGROUND: To date, detailed analyses of walking patterns using accelerometers during the 6-min walk test (6MWT) have not been performed in patients with chronic obstructive pulmonary disease (COPD). Therefore, it remains unclear whether and to what extent COPD patients have an altered walking pattern during the 6MWT compared to healthy elderly subjects. METHODOLOGY/PRINCIPAL FINDINGS: 79 COPD patients and 24 healthy elderly subjects performed the 6MWT wearing an accelerometer attached to the trunk. The accelerometer features (walking intensity, cadence, and walking variability) and subject characteristics were assessed and compared between groups. Moreover, associations were sought with 6-min walk distance (6MWD) using multiple ordinary least squares (OLS) regression models. COPD patients walked with a significantly lower walking intensity, lower cadence and increased walking variability compared to healthy subjects. Walking intensity and height were the only two significant determinants of 6MWD in healthy subjects, explaining 85% of the variance in 6MWD. In COPD patients also age, cadence, walking variability measures and their interactions were included were significant determinants of 6MWD (total variance in 6MWD explained: 88%). CONCLUSIONS/SIGNIFICANCE: COPD patients have an altered walking pattern during 6MWT compared to healthy subjects. These differences in walking pattern partially explain the lower 6MWD in patients with COPD.