Chronic obstructive pulmonary disease,
COPD is a highly prevalent disorder of increasing medical and socio-economical importance. It is characterized by irreversible airflow obstruction. Besides airflow obstruction also other features are present. One of these is respiratory muscle weakness. Inspiratory
muscle weakness is caused by hyperinflation and by generalized
muscle weakness causing both respiratory and peripheral muscle dysfunction. The expiratory muscles partake in this generalized
muscle weakness. Hyperinflation shortens the inspiratory muscles although in chronic hyperinflation sarcomere adaptation occurs. Generalized
muscle weakness is caused by deconditioning,
malnutrition,
electrolyte disturbances,
cardiac failure, systemic
inflammation and treatment with
corticosteroids causing
steroid-induced
myopathy. The latter disease was studied intensively both in patients and in animal models of disease. The major findings were that microscopically a myopathic pattern was present associated with generalized fiber
atrophy. This is in contrast to classical belief that the
atrophy would be confined to type IIx fibers. We noted severe down-regulation of the
IGF-I mRNA expression, without important changes in the expression of the
binding proteins. This may be responsible for the observed
muscle atrophy and the
myopathy. The latter is likely to be caused by a simultaneous upregulation of the
ubiquitin protease pathway attacking structural
proteins. Presently, we study the relationship between local and systemic
cytokine expression and respiratory and peripheral muscle dysfunction in
COPD patients. Respiratory and peripheral muscle dysfunction have significant consequences for
COPD patients. Both respiratory and peripheral muscle dysfunction are associated with reduced exercise tolerance and reduced quality of life. Both are independent determinants of survival, in addition to the degree of airflow obstruction as measured by FEV1. Finally, also the utilization of health care resources appeared to be related to respiratory and peripheral
muscle weakness. Treatment of respiratory and peripheral
muscle weakness in
COPD patients is possible. Respiratory and peripheral muscle training have been shown to produce beneficial effects. Nutritional intervention and
anabolic steroids are only useful in combination with muscle training. Systemic administration of
growth hormone and
IGF-I only produces small effects. In animal models, local administration of
IGF-I and transfer of the
IGF-I gene transfer appear more promising for the future.
Lung volume reduction surgery, LVRS, improves the force-generating capacity of the inspiratory muscles, presumably because of the geometrical alterations it causes in these muscles. It does not appear to improve intrinsic inspiratory muscle function.