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Biological Mechanisms Involved in Muscle Dysfunction in COPD: An Integrative Damage-Regeneration-Remodeling

Joaquim Gea1,2, Mauricio Orozco-Levi1,3, Sergi Pascual-Guàrdia1

  • 1Respiratory Medicine Department, Hospital del Mar Research Institute, Área de Enfermedades Respiratorias, CIBER, ISCIII, 08003 Barcelona, Spain.

Cells
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Summary
This summary is machine-generated.

Skeletal muscle dysfunction in Chronic Obstructive Pulmonary Disease (COPD) involves damage, regeneration, and remodeling. Interventions targeting these processes can improve respiratory muscle function and overall patient outcomes.

Keywords:
deconditioninghyperinflationinflammationinjurymuscle dysfunctionoxidative stress

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Area of Science:

  • Pulmonary Medicine
  • Muscle Physiology
  • Translational Research

Background:

  • Skeletal muscle dysfunction is a key systemic feature of Chronic Obstructive Pulmonary Disease (COPD), significantly impacting patient symptoms, exercise capacity, and survival.
  • COPD-related mechanical changes (hyperinflation, chest wall loading) and disuse (inactivity, exacerbations) affect respiratory and limb muscles differently.
  • Muscle quality degradation in COPD stems from oxidative stress, proteolytic pathway activation, cellular stress (mitochondrial, ER), microvascular issues, neuromuscular junction instability, and myosteatosis.

Purpose of the Study:

  • To integrate current evidence on skeletal muscle dysfunction in COPD within a Damage-Regeneration-Remodeling framework.
  • To link the mechanical and biological mechanisms of muscle dysfunction to clinical phenotypes in COPD.
  • To identify and categorize translational interventions targeting muscle dysfunction in COPD.

Main Methods:

  • Literature review and evidence synthesis to establish a Damage-Regeneration-Remodeling framework.
  • Analysis of physiological changes in diaphragm and limb muscles in COPD patients.
  • Categorization of interventions based on their role in reducing damage, enabling regeneration, or steering remodeling.

Main Results:

  • The diaphragm adapts to chronic loading with a shift towards oxidative fibers and improved endurance, while limb muscles exhibit atrophy, reduced oxidative capacity, and fat infiltration.
  • A comprehensive framework identifies specific mechanisms contributing to muscle dysfunction across different muscle groups in COPD.
  • Interventions are categorized into three tiers: reducing damage (e.g., bronchodilation, ventilation), enabling regeneration (e.g., exercise, nutrition), and steering remodeling (e.g., physical activity, monitoring).

Conclusions:

  • The Damage-Regeneration-Remodeling framework provides a unified view of skeletal muscle dysfunction in COPD.
  • Lung deflation strategies primarily benefit inspiratory muscle mechanics.
  • Limb muscle recovery necessitates a combination of behavioral, metabolic, and systemic optimization interventions.