Muscle dysfunction in chronic obstructive pulmonary disease: update on causes and biological findings

Joaquim Gea, Sergi Pascual, Carme Casadevall, Mauricio Orozco-Levi, Esther Barreiro, Joaquim Gea, Sergi Pascual, Carme Casadevall, Mauricio Orozco-Levi, Esther Barreiro

Abstract

Respiratory and/or limb muscle dysfunction, which are frequently observed in chronic obstructive pulmonary disease (COPD) patients, contribute to their disease prognosis irrespective of the lung function. Muscle dysfunction is caused by the interaction of local and systemic factors. The key deleterious etiologic factors are pulmonary hyperinflation for the respiratory muscles and deconditioning secondary to reduced physical activity for limb muscles. Nonetheless, cigarette smoke, systemic inflammation, nutritional abnormalities, exercise, exacerbations, anabolic insufficiency, drugs and comorbidities also seem to play a relevant role. All these factors modify the phenotype of the muscles, through the induction of several biological phenomena in patients with COPD. While respiratory muscles improve their aerobic phenotype (percentage of oxidative fibers, capillarization, mitochondrial density, enzyme activity in the aerobic pathways, etc.), limb muscles exhibit the opposite phenotype. In addition, both muscle groups show oxidative stress, signs of damage and epigenetic changes. However, fiber atrophy, increased number of inflammatory cells, altered regenerative capacity; signs of apoptosis and autophagy, and an imbalance between protein synthesis and breakdown are rather characteristic features of the limb muscles, mostly in patients with reduced body weight. Despite that significant progress has been achieved in the last decades, full elucidation of the specific roles of the target biological mechanisms involved in COPD muscle dysfunction is still required. Such an achievement will be crucial to adequately tackle with this relevant clinical problem of COPD patients in the near-future.

Keywords: Muscle dysfunction; deconditioning; hyperinflation; proteostasis; systemic inflammation.

Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Schematization of weakness (left) and the process of muscle fatigue (right). (A) The task is carried out by a specific muscle group; (B) when this group comes close to task failure due to muscle fatigue; (C) the workload is shifted to complementary muscles which can also sustain it; (D) finally, they also become fatigued and task failure occurs. However, the duty can be reinitiated following a period of rest.
Figure 2
Figure 2
Consequences of tobacco smoking include local (pulmonary) and systemic inflammation. The former will lead to pulmonary changes characteristic of COPD, whereas the latter appears to be linked to its extrapulmonary manifestations including muscle dysfuntion. However, the key deleterious etiologic factors for muscle dysfunction are pulmonary hyperinflation for respiratory muscles and deconditioning for limb muscles. COPD, chronic obstructive pulmonary disease.
Figure 3
Figure 3
Process of tissue regeneration and remodeling following an insult.
Figure 4
Figure 4
Biological phenomena that have been observed in respiratory and limb muscles of COPD patients (clearly detrimental: black boxes; probably beneficial: white box). COPD, chronic obstructive pulmonary disease.

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