Skeletal muscle dysfunction in COPD: clinical and laboratory observations

2009 ◽  
Vol 117 (7) ◽  
pp. 251-264 ◽  
Author(s):  
William D.-C. Man ◽  
Paul Kemp ◽  
John Moxham ◽  
Michael I. Polkey
Keyword(s):  
Skeletal Muscle ◽  
Skeletal Muscles ◽  
Current Knowledge ◽  
Clinical Importance ◽  
Chronic Obstructive ◽  
Muscle Dysfunction ◽  
Obstructive Pulmonary Disease ◽  
Skeletal Muscle Dysfunction ◽  
Skeletal Muscle Weakness ◽  
Systemic Manifestations

COPD (chronic obstructive pulmonary disease), although primarily a disease of the lungs, exhibits secondary systemic manifestations. The skeletal muscles are of particular interest because their function (or dysfunction) not only influences the symptoms that limit exercise, but may contribute directly to poor exercise performance. Furthermore, skeletal muscle weakness is of great clinical importance in COPD as it is recognized to contribute independently to poor health status, increased healthcare utilization and even mortality. The present review describes the current knowledge of the structural and functional abnormalities of skeletal muscles in COPD and the possible aetiological factors. Increasing knowledge of the molecular pathways of muscle wasting will lead to the development of new therapeutic agents and strategies to combat COPD muscle dysfunction.

scholarly journals Muscle-Bone Crosstalk in Chronic Obstructive Pulmonary Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Lijiao Zhang ◽  
Yongchang Sun
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Skeletal Muscle ◽  
Bone Metabolism ◽  
Pulmonary Disease ◽  
Skeletal Muscles ◽  
Chronic Obstructive ◽  
Muscle Dysfunction ◽  
Obstructive Pulmonary Disease ◽  
Skeletal Muscle Dysfunction ◽  
Endocrine Organs

Sarcopenia and osteoporosis are common musculoskeletal comorbidities of chronic obstructive pulmonary disease (COPD) that seriously affect the quality of life and prognosis of the patient. In addition to spatially mechanical interactions, muscle and bone can also serve as endocrine organs by producing myokines and osteokines to regulate muscle and bone functions, respectively. As positive and negative regulators of skeletal muscles, the myokines irisin and myostatin not only promote/inhibit the differentiation and growth of skeletal muscles, but also regulate bone metabolism. Both irisin and myostatin have been shown to be dysregulated and associated with exercise and skeletal muscle dysfunction in COPD. During exercise, skeletal muscles produce a large amount of IL-6 which acts as a myokine, exerting at least two different conflicting functions depending on physiological or pathological conditions. Remarkably, IL-6 is highly expressed in COPD, and considered to be a biomarker of systemic inflammation, which is associated with both sarcopenia and bone loss. For osteokines, receptor activator of nuclear factor kappa-B ligand (RANKL), a classical regulator of bone metabolism, was recently found to play a critical role in skeletal muscle atrophy induced by chronic cigarette smoke (CS) exposure. In this focused review, we described evidence for myokines and osteokines in the pathogenesis of skeletal muscle dysfunction/sarcopenia and osteoporosis in COPD, and proposed muscle-bone crosstalk as an important mechanism underlying the coexistence of muscle and bone diseases in COPD.

scholarly journals IL-13-driven pulmonary emphysema leads to skeletal muscle dysfunction attenuated by endurance exercise

2020 ◽  
Vol 128 (1) ◽  
pp. 134-148 ◽  
Author(s):  
Joseph Balnis ◽  
Tanner C. Korponay ◽  
Catherine E. Vincent ◽  
Diane V. Singer ◽  
Alejandro P. Adam ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Animal Model ◽  
Pulmonary Emphysema ◽  
Skeletal Muscles ◽  
Force Generation ◽  
Chronic Obstructive ◽  
Muscle Dysfunction ◽  
Obstructive Pulmonary Disease ◽  
Skeletal Muscle Dysfunction ◽  
Generation Capacity

Patients with chronic obstructive pulmonary disease (COPD) usually develop skeletal muscle dysfunction, which represents a major comorbidity in these patients and is strongly associated with mortality and other poor outcomes. Although clinical data indicates that accelerated protein degradation and metabolic disruption are common associations of muscle dysfunction in COPD, there is very limited data on the mechanisms regulating the process, in part, due to the lack of research performed on a validated animal model of pulmonary emphysema. This model deficiency complicates the translational value of data generated with highly reductionist settings. Here, we use an established transgenic animal model of COPD based on inducible IL-13-driven pulmonary emphysema (IL-13TG) to interrogate the mechanisms of skeletal muscle dysfunction. Skeletal muscles from these emphysematous mice develop most features present in COPD patients, including atrophy, decreased oxygen consumption, and reduced force-generation capacity. Analysis of muscle proteome indicates downregulation of succinate dehydrogenase C (SDH-C), which correlates with reduced enzymatic activity, also consistent with previous clinical observations. Ontology terms identified with human data, such as ATP binding/bioenergetics are also downregulated in this animal’s skeletal muscles. Moreover, chronic exercise can partially restore muscle mass, metabolic and force-generation capacity, and SDH activity in COPD mice. We conclude that this animal model of COPD/emphysema is an adequate platform to further investigate mechanisms of muscle dysfunction in this setting and demonstrates multiple approaches that can be used to address specific mechanisms regulating this process. NEW & NOTEWORTHY Skeletal muscle dysfunction is a relevant comorbidity in patients with chronic obstructive pulmonary disease (COPD). Mechanistic research in the area has so far been accomplished with models based on specific exposures to otherwise healthy animals, and no investigation using an established and validated animal model of COPD has been accomplished. We present an animal model of COPD that was previously shown to recapitulate pulmonary functional and histologic features present in patients with COPD, and demonstrates most of the features present in patients with pulmonary emphysema-associated muscle dysfunction, which we proposed as an adequate tool to develop mechanistic research in the area.

scholarly journals Ultrasonic Elastography of the Rectus Femoris, a Potential Tool to Predict Sarcopenia in Patients With Chronic Obstructive Pulmonary Disease

2022 ◽  
Vol 12 ◽  
Author(s):  
Mingming Deng ◽  
Xiaoming Zhou ◽  
Yanxia Li ◽  
Yan Yin ◽  
Chaonan Liang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Physical Function ◽  
Muscle Function ◽  
Rectus Femoris ◽  
Chronic Obstructive ◽  
Muscle Dysfunction ◽  
Obstructive Pulmonary Disease ◽  
Skeletal Muscle Dysfunction ◽  
Tnf Α ◽  
Potential Tool

Purpose: Skeletal muscle dysfunction is common in patients with chronic obstructive pulmonary disease (COPD) and is associated with a poor prognosis. Abnormal muscle quantity of the lower limbs is a manifestation of skeletal muscle dysfunction in patients with COPD. Shear wave ultrasound elastography (SWE) is a novel and possible tool to evaluate qualitative muscle parameters. This study explores the feasibility of SWE to measure the stiffness of the rectus femoris and evaluates its value in predicting sarcopenia in patients with COPD.Methods: Ultrasound examination of the rectus femoris was performed to determine the mean elasticity index (SWEmean), cross-sectional area (RFcsa), and thickness (RFthick) using grayscale ultrasonography (US) and SWE in 53 patients with COPD and 23 age-matched non-COPD healthy controls. The serum levels of circulating biomarkers (GDF15, resistin, and TNF-α) were measured using ELISA. The definition of sarcopenia followed the guidelines from the Asian Working Group for Sarcopenia. Receiver operating characteristic (ROC) curve analysis of the SWEmean, RFthick, and RFcsa was used to evaluate their predictive ability for sarcopenia.Results: The intraobserver and interobserver repeatability of SWE performance was excellent (all correlation coefficients > 0.95; p < 0.05). The SWEmean of the rectus femoris in patients with COPD (8.98 ± 3.12 kPa) was decreased compared with that in healthy controls (17.00 ± 5.14 kPa) and decreased with advanced global initiative for chronic obstructive lung disease (GOLD) stage. Furthermore, SWEmean was found to be independent of sex, height, and body mass, and a lower SWEmean in patients with COPD was positively associated with reduced pulmonary function, worse physical function, poor exercise tolerance, decreased muscle strength, and worse dyspnea index score. The correlation between physical function [five-repetition sit-to-stand test (5STST)], muscle function, and SWEmean was higher than those of RFthick and RFcsa. In addition, SWEmean was negatively correlated with serum GDF15 levels (r = −0.472, p < 0.001), serum resistin levels (r = −0.291, p = 0.035), and serum TNF-α levels (r = −0.433, p = 0.001). Finally, the predictive power of SWEmean [area under the curve (AUC): 0.863] in the diagnosis of sarcopenia was higher than that of RFthick (AUC: 0.802) and RFcsa (AUC: 0.816).Conclusion: Compared with grayscale US, SWE was not affected by the patient’s height, weight, or BMI and better represented skeletal muscle function and physical function. Furthermore, SWE is a promising potential tool to predict sarcopenia in patients with COPD.

scholarly journals AMP-Activated Protein Kinase (AMPK) at the Crossroads Between CO2 Retention and Skeletal Muscle Dysfunction in Chronic Obstructive Pulmonary Disease (COPD)

2020 ◽  
Vol 21 (3) ◽  
pp. 955 ◽  
Author(s):  
Joseph Balnis ◽  
Tanner C. Korponay ◽  
Ariel Jaitovich
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Skeletal Muscle ◽  
Pulmonary Disease ◽  
Future Research ◽  
Chronic Obstructive ◽  
Muscle Dysfunction ◽  
Ribosomal Biogenesis ◽  
Obstructive Pulmonary Disease ◽  
Skeletal Muscle Dysfunction ◽  
Amp Activated Protein Kinase

Skeletal muscle dysfunction is a major comorbidity in chronic obstructive pulmonary disease (COPD) and other pulmonary conditions. Chronic CO2 retention, or hypercapnia, also occur in some of these patients. Both muscle dysfunction and hypercapnia associate with higher mortality in these populations. Over the last years, we have established a mechanistic link between hypercapnia and skeletal muscle dysfunction, which is regulated by AMPK and causes depressed anabolism via reduced ribosomal biogenesis and accelerated catabolism via proteasomal degradation. In this review, we discuss the main findings linking AMPK with hypercapnic pulmonary disease both in the lungs and skeletal muscles, and also outline potential avenues for future research in the area based on knowledge gaps and opportunities to expand mechanistic research with translational implications.

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