Different Training-Induced Skeletal Muscle Adaptations in COPD Patients with and without Alpha-1 Antitrypsin Deficiency.
BACKGROUND
Pulmonary rehabilitation (PR) improves oxidative capacity of peripheral muscles in patients with chronic obstructive pulmonary disease (COPD). The exercise-induced oxidative skeletal muscle adaptation in COPD patients with inherited alpha-1 antitrypsin deficiency (A1ATD) has not been studied.


OBJECTIVE
To compare PR effects on skeletal muscle adaptation in COPD patients with and without A1ATD.


METHODS
Nine COPD patients with A1ATD (genotype PiZZ, 6 receiving A1AT augmentation therapy), and 10 'usual' COPD patients (genotype PiMM) performed an incremental cycling test and underwent musculus vastus lateralis biopsies before and after a 3-week PR program including exercise training.


RESULTS
PiZZ and PiMM patients improved peak work rate following PR (+9 ± 11 W, p < 0.05, and +18 ± 9 W, p < 0.001, between-group difference p < 0.05). PiMM patients increased fibre type I (+8.1%), reduced fibre type IIA (-2.1%) and hybrid fibre type IIA/IIX proportion (-3.9%). Following PR, PiMM patients also raised mitochondrial signalling proteins PGC-1α (4.5-fold), and TFAM (6.4-fold). PiZZ patients had no change in fibre type I but showed a shift of type IIA/IIX (-8.8%) towards fibre type IIA distribution (+8.9%). The capillary to fibre ratio increased by 28% (p < 0.05) in PiZZ, whereas no change was observed in PiMM patients. Linear regression analysis revealed that diffusion capacity and A1AT therapy are predictor variables for myofibre type I response to PR (r2 = 0.684, p < 0.01).


CONCLUSIONS
Following a 3-week PR with comparable training modalities, PiMM but not PiZZ patients increased the oxidative myofibre type I proportion. This skeletal muscle adaptation pattern suggests better improvement of exercise capacity in PiMM than in PiZZ patients with COPD.
Department of Respiratory Medicine, Schön Klinik Berchtesgadener Land, Schönau am Königssee, Germany.
Inga
I
Jarosch
Sebastian
S
Gehlert
Daniel
D
Jacko
Rembert Andreas
RA
Koczulla
Marion
M
Wencker
Tobias
T
Welte
Wilhelm
W
Bloch
Sabina
S
Janciauskiene
Klaus
K
Kenn
D000222:Adaptation, Physiological; D000368:Aged; D015153:Blotting, Western; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000378:metabolism; D005080:Exercise Test; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000378:metabolism; D018656:Muscle Fibers, Fast-Twitch / Q000473:pathology; D018657:Muscle Fibers, Slow-Twitch / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000378:metabolism; D011446:Prospective Studies; D011653:Pulmonary Diffusing Capacity; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000378:metabolism / Q000503:physiopathology / Q000534:rehabilitation*; D052097:Quadriceps Muscle / Q000378:metabolism / Q000473:pathology*; D012138:Respiratory Therapy; D014157:Transcription Factors / Q000378:metabolism; D019896:alpha 1-Antitrypsin Deficiency / Q000150:complications / Q000378:metabolism / Q000503:physiopathology / Q000534:rehabilitation*
D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C499631:TFAM protein, human; D014157:Transcription Factors