Muscle fiber type IIX atrophy is involved in the loss of fat-free mass in chronic obstructive pulmonary disease.
BACKGROUND
Although the loss of peripheral muscle mass has been shown convincingly in chronic obstructive pulmonary disease (COPD), the underlying pathogenesis remains unclear.


OBJECTIVE
The aim of the present study was to determine the relations between skeletal muscle fiber types, fiber cross-sectional area (CSA), enzyme activities, and fat-free mass (FFM) in patients with COPD and in control subjects.


METHODS
In 15 patients with COPD and 15 healthy, age-matched control subjects, FFM was determined by dual-energy X-ray absorptiometry and bioelectrical impedance analysis. In biopsy specimens from the vastus lateralis fiber types, fiber CSA and activities of cytochrome oxidase (EC 1.9.3.1), succinate dehydrogenase (EC 1.3.99.1), and glycogen phosphorylase (EC 2.4.1.1) were examined immunohistochemically and histochemically.


RESULTS
Compared with control subjects, patients with COPD had less FFM (49 compared with 59 kg, P = 0.030) and lower mean fiber CSA (3839 compared with 4647 microm(2), P = 0.037). A strong correlation (r = 0.87, P < 0.001) was observed between the FFM measured by bioelectrical impedance analysis and mean fiber CSA in patients with COPD. Within fiber-type categories the mean CSA of only the IIA/IIX and IIX fiber types was lower in patients than in control subjects [3358 compared with 4428 microm(2) (P = 0.022) and 2566 compared with 4248 microm(2) (P = 0.003), respectively]. In COPD, 20% of the type IIX fibers lacked stainable activities of cytochrome oxidase, succinate dehydrogenase, and glycogen phosphorylase, and this proportion correlated negatively with type IIX fiber CSA (r = -0.65, P = 0.012).


CONCLUSIONS
Muscle fiber atrophy occurs in the vastus lateralis in patients with COPD and contributes to the loss of muscle mass in COPD. Atrophy is specific to fiber types IIA/IIX and IIX and is associated with a disturbed metabolic capacity.
Gosker
Harry R
HR
Department of Pulmonology, University of Maastricht, Maastricht, Netherlands. h.gosker@pul.unimaas.nl
Engelen
Mariëlle P K J
MP
van Mameren
Henk
H
van Dijk
Paul J
PJ
van der Vusse
Ger J
GJ
Wouters
Emiel F M
EF
Schols
Annemie M W J
AM
D000368:Aged; D001823:Body Composition; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D024981:Glycogen Phosphorylase / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D018656:Muscle Fibers, Fast-Twitch / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D009133:Muscular Atrophy / Q000150:complications* / Q000473:pathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications* / Q000473:pathology; D013385:Succinate Dehydrogenase / Q000378:metabolism; D015431:Weight Loss
D013385:Succinate Dehydrogenase; D003576:Electron Transport Complex IV; D024981:Glycogen Phosphorylase