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Background: Hypermetabolism and muscle wasting frequently occur in patients with severe emphysema. Improving respiratory mechanics by bronchoscopic lung volume reduction (BLVR) might contribute to muscle maintenance by decreasing energy requirements and alleviating eating-related dyspnoea. Objective: The goal was to assess the impact of BLVR on energy balance regulation. Design: Twenty emphysematous subjects participated in a controlled clinical experiment before and 6 months after BLVR. Energy requirements were assessed: basal metabolic rate (BMR) by ventilated hood, total daily energy expenditure (TDEE) by doubly labelled water, whole body fat-free mass (FFM) by deuterium dilution, and physical activity by accelerometry. Oxygen saturation, breathing rate, and heart rate were monitored before, during, and after a standardized meal via pulse oximetry and dyspnoea was rated. Results: Sixteen patients completed follow-up, and among those, 10 patients exceeded the minimal clinically important difference of residual volume (RV) reduction. RV was reduced with median (range) 1,285 mL (−2,430, −540). Before BLVR, 90% of patients was FFM-depleted despite a normal BMI (24.3 ± 4.3 kg/m2). BMR was elevated by 130%. TDEE/BMR was 1.4 ± 0.2 despite a very low median (range) daily step count of 2,188 (739, 7,110). Following BLVR, the components of energy metabolism did not change significantly after intervention compared to before intervention, but BLVR treatment decreased meal-related dyspnoea (4.1 vs. 1.7, p = 0.019). Conclusions: Impaired respiratory mechanics in hyperinflated emphysematous patients did not explain hypermetabolism. Clinical Trial Registry Number: NCT02500004 at www.clinicaltrial.gov.

Background: Patients with COPD are often characterized by disturbed metabolic health which is reflected in altered body composition. Current studies in healthy subjects suggest that resveratrol improves metabolic health by enhancing muscle mitochondrial function and adipose tissue morphology. The primary objective was to investigate the effect of four weeks resveratrol supplementation on muscle mitochondrial function in patients with COPD. Secondary objectives were to investigate the effect of resveratrol on adipose tissue inflammatory and metabolic gene expression, systemic inflammation and body composition in patients with COPD.Methods: In a double-blind randomized placebo-controlled proof-of-concept study, 21 COPD patients (FEVi: 53 +/- 15% predicted; age: 67 +/- 9 years and BMI: 24.5 +/- 3.3 kg/m(2)) received resveratrol (150 mg/day) or placebo for four weeks. Before and after intervention, blood samples, quadriceps muscle and subcutaneous abdominal fat biopsies were obtained for metabolic and inflammatory profiling. Body composition was assessed by dual energy X-ray absorptiometry.Results: Muscle mitochondrial biogenesis regulators AMPK, SIRT1 and PGC-1 alpha as well as mitochondrial respiration, Oxphos complexes, oxidative enzyme activities and kynurenine aminotransferases were not improved by resveratrol. Plasma high-sensitive C-reactive protein and kynurenine did not change after resveratrol supplementation. Adipose tissue inflammatory markers were unaffected by resveratrol, while markers of glycolysis and lipolysis were significantly increased compared to placebo supplementation. Body weight decreased after resveratrol supplementation (resveratrol -0.95 +/- 1.01 kg vs placebo -0.16 +/- 0.66 kg, p = 0.049) due to a reduction in lean mass (resveratrol -1.79 +/- 1.67 kg vs 0.37 +/- 0.86 kg, p = 0.026).Conclusion: We do not confirm previously reported positive effects of resveratrol on skeletal muscle mitochondrial function in patients with COPD, but show an unexpected decline in lean mass. (C) 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

European journal of nuclear medicine and molecular imaging 46(7), 1428-1438 (2019). doi:10.1007/s00259-019-04292-w, Published by Springer-Verl., Heidelberg [u.a.]

Background Assessment of handgrip strength and fat-free mass provides quick and objective information on muscle performance and mass that might complement subjective World Health Organization Performance Status (WHO PS). We investigated to what extent the presence of pre-treatment handgrip weakness and low fat-free mass index (FFMI) provides additional prognostic information on top of well-established prognostic factors (including WHO PS) in non-small cell lung cancer (NSCLC) patients selected for curative-intent (chemo)radiation. Methods Prospectively, patients with early and locally advanced NSCLC (stages I-III) treated with (chemo)radiation were enrolled. Handgrip weakness and low FFMI, derived from bioelectrical impedance analysis, were defined using normative values and were correlated with overall survival (OS). Results We included 936 patients (age 68 +/- 10 years; 64% male; 19% stage I, 9% stage II, and 72% stage III disease; 26% handgrip weakness; 27% low FFMI). In patients with good performance status (WHO PS 0 or 1), handgrip weakness and low FFMI were significant prognostic factors for OS, after adjustment for age, gender, disease stage, and co-morbidities. The combined presence of handgrip weakness and low FFMI was a strong prognostic factor for OS when compared with patients with normal handgrip strength and FFMI (hazard ratio: 1.79, 95% confidence interval: 1.34-2.40, P < 0.0001). In patients with impaired performance status (WHO PS >= 2, 19% of sample), handgrip weakness and low FFMI were not related to OS. Conclusions In early and locally advanced NSCLC patients treated with curative-intent (chemo)radiation who have good WHO PS, patients with combined handgrip weakness and low FFMI have the worst prognosis. This work was supported by Limburg Kankerfonds and a MUMC2020 grant from Maastricht University Medical Centre. The authors of this manuscript certify that they comply with the ethical guidelines for authorship and publishing in the Journal of Cachexia, Sarcopenia and Muscle.36 De Ruysscher, DKM (reprint author), Maastricht Univ, GROW Sch Oncol & Dev Biol, Med Ctr, Dept Radiat Oncol,MAASTRO Clin, Dr Tanslaan 12, NL-6229 ET Maastricht, Netherlands. dirk.deruysscher@maastro.nl

The clinical manifestations of chronic obstructive pulmonary disease (COPD) reflect an aggregate of multiple pulmonary and extrapulmonary processes. It is increasingly clear that full assessment of these processes is essential to characterize disease burden and to tailor therapy. Medical imaging has advanced such that it is now possible to obtain in vivo insight in the presence and severity of lung disease-associated features. In this review, we have assembled data from multiple disciplines of medical imaging research to review the role of imaging in characterization of COPD. Topics include imaging of the lungs, body composition, and extrapulmonary tissue metabolism. The primary focus is on imaging modalities that are widely available in clinical care settings and that potentially contribute to describing COPD heterogeneity and enhance our insight in underlying pathophysiological processes and their structural and functional effects.

Background: Patients with COPD are often characterized by disturbed metabolic health, which is often reflected in altered body composition. Studies in healthy subjects suggest that resveratrol improves metabolic health by enhancing muscle mitochondrial function and adipose tissue morphology. Objective: To investigate the effect of four weeks resveratrol supplementation on muscle mitochondrial function, adipose tissue inflammatory and metabolic gene expression, systemic inflammation and body composition in patients with COPD. Methods: In a double-blind randomized placebo-controlled proof-of-concept study, 21 COPD patients received resveratrol (150 mg/day) or placebo for four weeks. Before and after intervention, blood samples, quadriceps muscle and subcutaneous abdominal fat biopsies were obtained. Body composition was assessed by dual energy X-ray absorptiometry. Results: Muscle mitochondrial biogenesis regulators as well as mitochondrial respiration, Oxphos complexes, oxidative enzyme activities and kynurenine aminotransferases were not improved by resveratrol. Plasma high-sensitive C-reactive protein and kynurenine as well as adipose tissue inflammatory markers were unaffected by resveratrol, while adipose tissue markers of glycolysis and lipolysis were significantly increased compared to placebo supplementation. Body weight decreased after resveratrol supplementation (resveratrol -0.95±1.01 kg vs placebo -0.16±0.66 kg, p=0.049) due to a reduction in lean mass (resveratrol -1.79±1.67 kg vs 0.37±0.86 kg, p=0.026). Conclusion: We do not confirm previously reported positive effects of resveratrol on skeletal muscle mitochondrial function in patients with COPD, but show an unexpected decline in lean mass.

Objectives: To evaluate the relationship between early changes in muscle and adipose tissue during chemotherapy and overall survival (OS) in stage IV non-small cell lung cancer (NSCLC).Materials and methods: In this post-hoc analysis of the first line NVALT12 trial (NCT01171170) in stage IV NSCLC, skeletal muscle (SM), radiation attenuation (RA), subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were assessed at the third lumbar level on CT-images obtained before initiation of chemotherapy and shortly after administration of the second cycle. The contribution of changes in different body compartments to overall survival was assessed.Results: CT scans of 111 patients were included. Analysis of body composition changes between the baseline and the follow-up scan, revealed that overall SM cross sectional area (CSA), radiation attenuation and SAT CSA decreased respectively by -1.2 +/- 2.9 cm(2)/m(2) (p Conclusion: Early loss of SM during first line chemotherapy is a poor prognostic factor in stage IV NSCLC patients. Future studies have to reveal whether early supportive intervention guided by initial CT muscle response to chemotherapy can influence the wasting process and related mortality risk.

Background: Muscle depletion negatively impacts treatment efficacy and survival rates in cancer. Prevention and timely treatment of muscle loss require prediction of patients at risk. We aimed to investigate the potential of skeletal muscle radiomic features to predict future muscle loss.Methods: A total of 116 patients with stage IV non-small cell lung cancer included in a randomised controlled trial (NCT01171170) studying the effect of nitroglycerin added to paclitaxel-carboplatin-bevacizumab were enrolled. In this post hoc analysis, muscle cross-sectional area and radiomic features were extracted from computed tomography images obtained before initiation of chemotherapy and shortly after administration of the second cycle. For internal cross-validation, the cohort was randomly split in a training set and validation set 100 times. We used least absolute shrinkage and selection operator method to select features that were most significantly associated with muscle loss and an area under the curve (AUC) for model performance.Results: Sixty-nine patients (59%) exhibited loss of skeletal muscle. One hundred ninety-three features were used to construct a prediction model for muscle loss. The average AUC was 0.49 (95% confidence interval [CI]: 0.36, 0.62). Differences in intensity and texture radiomic features over time were seen between patients with and without muscle loss.Conclusions: The present study shows that skeletal muscle radiomics did not predict future muscle loss during chemotherapy in non-small cell lung cancer. Differences in radiomic features over time might reflect myosteatosis. Future imaging analysis combined with muscle tissue analysis in patients and in experimental models is needed to unravel the biological processes linked to the radiomic features. (C) 2019 The Authors. Published by Elsevier Ltd.

Muscle wasting frequently occurs in severe emphysema. Improving respiratory mechanics by bronchoscopic lung volume reduction using endobronchial valves (EBV) might prevent further loss or even increase in muscle mass. CT-derived skeletal muscle mass gain was observed in 39/49 patients 6 months after EBV. Multiple linear regression showed that gain in muscle (β=2.4; 95% CI 0.2 to 4.6; p=0.036) and intramuscular fat (β=3.1; 95% CI 0.2 to 5.9; p=0.035) is associated with improved 6 min walk distance independent of the change in residual volume. Skeletal muscle remodelling associates with improved exercise capacity after EBV, independent of hyperinflation reduction.Trial registration numberClinical trial registered with the Dutch trial register www.trialregister.nl (NTR2876), Results.

Karin JC Sanders,1 Juliette HRJ Degens,1 Anne-Marie C Dingemans,2 Annemie MWJ Schols1 1Department of Respiratory Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, Maastricht, the Netherlands; 2Department of Respiratory Medicine, GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands Background: Computed tomography (CT) is increasingly used in clinical research for single-slice assessment of muscle mass to correlate with clinical outcome and evaluate treatment efficacy. The third lumbar level (L3) is considered as reference for muscle, but chest scans generally do not reach beyond the first lumbar level (L1). This study investigates if pectoralis muscle and L1 are appropriate alternatives for L3. Methods: CT scans of 115 stage IV non-small cell lung cancer patients were analyzed before and during tumor therapy. Skeletal muscle assessed at pectoralis and L1 muscle was compared to L3 at baseline. Furthermore, the prognostic significance of changes in muscle mass determined at different locations was investigated. Results: Pearson’s correlation coefficient between skeletal muscle at L3 and L1 was stronger (r=0.90, P

Objectives The aim of this study was to assess the effect of early weight loss before the onset of radiation esophagitis on overall survival (OS) in patients with non–small cell lung cancer treated with concurrent chemoradiotherapy. Methods Characteristics (e.g., patient weight, radiation esophagitis score, sex, World Health Organization performance status, chemotherapy dose, nodal status, and gross tumor volume) of 151 patients who received concurrent chemoradiotherapy (in 2006–2013) were retrospectively correlated with OS. Early weight loss was defined as weight loss of more than 5% between the start and third week of radiotherapy in patients whose weight was stable before treatment initiation. Results In 17% of the patients early weight loss was observed. Median OS (95% confidence interval [CI]) was significantly shorter in the early weight loss group (OS = 13.0 months, 95% CI: 2.0–24.0) versus in the non–early weight loss group (OS = 23.0 months, 95% CI: 14.7–31.3) (hazard ratio [HR] = 1.8, 95% CI: 1.12–2.96, p = 0.017). On multivariate analysis sex (HR = 2.1, 95% CI: 1.33–3.29, p = 0.001), World Health Organization performance status (HR = 1.9, 95% CI: 1.20–2.97, p = 0.006), nodal status (HR = 2.9, 95% CI: 1.38–6.01, p = 0.005), and early weight loss (HR = 1.9, 95% CI: 1.10–3.19, p = 0.022) were associated with OS. Conclusions Early weight loss in patients with non–small cell lung cancer was found to be associated with worse prognosis. These data warrant further investigation into the efficacy of tailored intervention to prevent early weight loss.

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.

Objective: Previously, we reported early weight loss (EWL) during concurrent chemoradiotherapy (CCRT) in advanced stage non-small cell lung cancer (NSCLC) patients that could not be attributed to acute radiation-induced esophagitis (ARIE) or decreased dietary intake. Here, we assessed effect of EWL during CCRT on overall survival (OS). Methods: All advanced stage NSCLC patients treated with CCRT from 2 hospitals between January 906 and December 913 were retrospectively analyzed. Exclusion criteria were weight loss prior to CCRT, no weight recorded or CCRT not completed. EWL was defined as weight loss ≥5% from start of radiotherapy (RT) until the end of the 3 rd week. Compared were EWL versus no EWL for OS, estimated with Kaplan Meier and log-rank test. Cox multivariate analysis was performed including EWL, WHO status, T- and N status, histology, age and BMI. Results: 27 Patients (18%) of in total 152 eligible patients experienced EWL. Groups were comparable regarding disease stage, Charlson comorbidity index score and WHO status. No difference in incidence of ARIE ≥2 in the first 3 weeks of RT was observed between the groups (37% versus 32%, p=0.613). Median OS (95% CI) was 15.2 (2.1-28.4) months in EWL patients and 23.0 (13.1-32.9) months in non-EWL patients (p=0.035). Adjusted HR for EWL is 2.070 (1.202-3.564), p=0.009. Conclusions: EWL in NSCLC patients treated with CCRT is associated with worse OS. These data emphasize the importance of good nutritional status. It warrants further investigation into early nutritional intervention irrespective of onset of ARIE, to combat weight loss during CCRT and to improve treatment outcome.

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.