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.

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 <0.001) than between L3 and pectoralis muscle ( r =0.71, P <0.001). Cox regression analysis revealed that L3 (HR 0.943, 95% CI: 0.92–0.97, P <0.001) and L1 muscle loss (HR 0.954, 95% CI: 0.93–0.98, P <0.001) predicted overall survival, whereas pectoralis muscle loss did not. Conclusion L1 is a better alternative than pectoralis muscle to substitute L3 for analysis of muscle mass from regular chest CT scans.

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 < 0.001), −0.7 ± 3.3 HU (p = 0.026) and −1.9 ± 8.7 cm 2 /m 2 (p = 0.026), while no significant changes in VAT tissue were observed. Longitudinally, median OS was significantly shorter among patients losing SM compared to patients with preserved SM (9.4 versus 14.2 months; HR 1.9, 95% CI: 1.23, 2.79, p = 0.003). Multivariate analyses showed that proportional loss of muscle mass was associated with poor OS (HR 0.949, 95% CI: 0.915, 0.985, p = 0.006) independent from important clinical prognostic factors including WHO-PS, gender, age and Charlson comorbidity index. 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 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.

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.