BACKGROUND: In most patients with COPD, rehabilitative exercise training partially reverses the morphologic and structural abnormalities of peripheral muscle fibers. However, whether the degree of improvement in muscle fiber morphology and typology with exercise training varies depending on disease severity remains unknown. METHODS: Forty-six clinically stable patients with COPD classified by GOLD (Global Initiative for Obstructive Lung Disease) as stage II (n = 14), III (n = 18), and IV (n = 14) completed a 10-week comprehensive pulmonary rehabilitation program consisting of high-intensity exercise three times weekly. RESULTS: At baseline, muscle fiber mean cross-sectional area and capillary density did not significantly differ between patients with COPD and healthy control subjects, whereas muscle fiber type I and II proportion was respectively lower (P < .001) and higher (P < .002) in patients with GOLD stage IV compared with healthy subjects and patients with GOLD stages II and III. Exercise training improved, to a comparable degree, functional capacity and the St. George Respiratory Questionnaire health-related quality of life score across all three GOLD stages. Vastus lateralis muscle fiber mean cross-sectional area was increased (P < .001) in all patient groups (stage II: from 4,507 ± 280 μm² to 5,091 ± 271 μm² [14% ± 3%]; stage III: from 3,753 ± 258 μm² to 4,212 ± 268 μm² [14% ± 3%]; stage IV: from 3,961 ± 266 μm² to 4,551 ± 262 μm² [17% ± 5%]), whereas all groups exhibited a comparable reduction (P < .001) in type IIb fiber proportion (stage II: by 6% ± 2%; stage III: by 6% ± 1%; stage IV: by 7% ± 1%) and an increase (P < .001) in capillary to fiber ratio (stage II: from 1.48 ± 0.10 to 1.81 ± 0.10 [23% ± 5%]; stage III: from 1.29 ± 0.06 to 1.56 ± 0.09 [21% ± 5%]; stage IV: from 1.43 ± 0.10 to 1.71 ± 0.13 [18 ± 3%]). The magnitude of changes in the aforementioned variables did not differ across GOLD stages. CONCLUSIONS: Functional capacity and morphologic and typologic adaptations to rehabilitation in peripheral muscle fibers were similar across GOLD stages II to IV. Pulmonary rehabilitation should be implemented in patients at all COPD stages.

Pompe disease is an inherited metabolic disorder caused by α-glycosidase deficiency. The adult onset form is mainly characterized by progressive proximal muscle weakness and respiratory dysfunction. The aim of the present study is to evaluate body composition in adult patients before and after enzyme replacement therapy (ERT). Body composition was examined at baseline by means of dual x-ray absorptiometry (DXA) in nine adult patients and after different time periods in six of them who received ERT. Total BMD (bone mineral density) was initially mildly decreased in two patients, while femoral neck BMD was decreased in five patients. On the other hand fat mass was increased in the majority of patients, while body mass index (BMI) was high in four. ERT administration did not seem to induce obvious BMD changes in any patient. Conclusively, the greater femoral neck BMD involvement may be attributed to the lower mechanical load applied by the selectively weakened muscles, whereas the increased fat mass may be the result of metabolic and nutritional derangement.

Pompe disease is a rare autosomal recessive disorder characterized by the deficiency of acid α-glycosidase resulting in lysosomal accumulation of glycogen. The late-onset disease form is characterized by progressive skeletal and respiratory muscle dysfunction. In addition to the recently introduced enzyme replacement therapy (ERT), treatments such as protein-enriched diet and exercise training have been proposed, although little is known about their effectiveness on the physical condition of such patients. Aim of the present study was to investigate the effect of exercise training on muscular strength and body composition in five patients with late-onset Pompe disease receiving ERT. All subjects followed a 20 week lasting program of supervised aerobic and progressive resistance exercise training. Before and after the training period, body composition was determined with dual X-ray absorptiometry and isometric muscular strength was measured with a specialized load transducer. Functional capacity was assessed using the 6-min shuttle walk test. A significant increase in muscular strength (15-50% at various body parts, p<0.05) and 6-minute walking distance (203.8 ± 177 m before vs. 248.2 ± 184 m after, p<0.01) was observed after training, whereas total and lower extremities lean body mass did not change significantly. These results suggest that exercise training has a positive effect on muscular strength and functional capacity in patients on ERT with late-onset Pompe disease.

8-Oxo-7,8-dihydroguanine (8-oxoG) accumulates in the genome over time and is believed to contribute to the development of aging characteristics of skeletal muscle and various aging-related diseases. Here, we show a significantly increased level of intrahelical 8-oxoG and 8-oxoguanine-DNA glycosylase (OGG1) expression in aged human skeletal muscle compared to that of young individuals. In response to exercise, the 8-oxoG level was lastingly elevated in sedentary young and old subjects, but returned rapidly to preexercise levels in the DNA of physically active individuals independent of age. 8-OxoG levels in DNA were inversely correlated with the abundance of acetylated OGG1 (Ac-OGG1), but not with total OGG1, apurinic/apyrimidinic endonuclease 1 (APE1), or Ac-APE1. The actual Ac-OGG1 level was linked to exercise-induced oxidative stress, as shown by changes in lipid peroxide levels and expression of Cu,Zn-SOD, Mn-SOD, and SIRT3, as well as the balance between acetyltransferase p300/CBP and deacetylase SIRT1, but not SIRT6 expression. Together these data suggest that that acetylated form of OGG1, and not OGG1 itself, correlates inversely with the 8-oxoG level in the DNA of human skeletal muscle, and the Ac-OGG1 level is dependent on adaptive cellular responses to physical activity, but is age independent.