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J Appl Physiol (1985). 2013 May;114(9):1291-9. doi: 10.1152/japplphysiol.00847.2012. Epub 2013 Jan 31.

Mechanisms of striated muscle dysfunction during acute exacerbations of COPD.

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Respiratory Muscle Research Unit, Laboratory of Pneumology and Respiratory Division, Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.


During acute exacerbations of chronic obstructive pulmonary disease (COPD), limb and respiratory muscle dysfunction develops rapidly and functional recovery is partial and slow. The mechanisms leading to this muscle dysfunction are not yet fully established. However, recent evidence has shown that several pathways involved in muscle catabolism, apoptosis, and oxidative stress are activated in the vastus lateralis muscle of patients during acute exacerbations of COPD, while those implicated in mitochondrial function are downregulated. These pathways may be targeted in different ways by factors related to exacerbations. These factors include enhanced systemic inflammation, oxidative stress, impaired energy balance, hypoxia, hypercapnia and acidosis, corticosteroid treatment, and physical inactivity. Data on the respiratory muscles are limited, but these muscles are undoubtedly overloaded during exacerbations. While they are also subjected to the same systemic elements as the limb muscles (except for inactivity), they also face a specific mechanical disadvantage caused by changes in lung volume during exacerbation. The latter will affect the ability to generate force by the foreshortening of the muscle (especially for the diaphragm), but also by altering rib orientation and motion (especially for the parasternal intercostals and the external intercostals). Because acute exacerbations of COPD are associated with an increase in both prevalence and severity of generalized muscle dysfunction, and both remain present even during recovery, early interventions to minimize muscle dysfunction during exacerbation are warranted. Although rehabilitation may be promising, other therapeutic strategies such as counterbalancing the adverse effects of exacerbations on skeletal muscle pathways may also be used.


limb muscles; mitochondria; oxidative stress; proteolysis; respiratory muscles; striated muscles

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