To Örebro University

This study has examined exercise capacity and muscle morphology in patients with different severities of chronic obstructive pulmonary disease (COPD). Twenty-three patients and 12 healthy matched controls were recruited. Based on the severity of airflow obstruction, patients were divided into two subgroups. Exercise capacity was determined using a 6-min walk test. Muscle fiber composition, fiber area and number of satellite cells/muscle fiber were determined in muscle biopsies using immunohistochemistry. A progressive decline in exercise capacity was noted with ascending disease severity. Furthermore, a correlation between reduction in exercise capacity and changes in muscle fiber composition was observed in COPD. The group with severe and very severe COPD had a lower proportion of type I and a higher proportion of type IIa fibers compared with the other groups. In severe and very severe COPD, a reduction in fiber area of type IIa fibers was also seen. The number of satellite cells/muscle fiber did not differ between the groups. In conclusion, a decline in exercise capacity occurs already in mild and moderate COPD, indicating that the 6-min walk test is a reliable indicator of disease severity. Furthermore, changes in skeletal muscle morphology are associated with disease severity while muscle regenerative capacity is not altered.

Background/aim: A Significant number of patients with chronic obstructive pulmonary disease (COPD) exhibit skeletal muscle wasting and decreased capillary area formation which have been correlated to increased mortality. The current study aimed to determine the molecular mechanisms mediating decreased capillary formation in COPD.

Methods: Twenty-four COPD patients and twelve matching controls were recruited. COPD patients were divided into mild, moderate and severe groups according to GOLD (Global Initiative for Chronic Obstructive Lung Disease) criteria. Skeletal muscle biopsies were obtained from the tibialis anterior muscle. Fibre typing and capillary formation together with messenger RNA (mRNA) expression of hypoxia-inducible factors (HIF-1á and HIF-3á ), vascular endothelial growth factors (VEGF-A, -B and -C isoforms) and von Hippel Lindau (VHL) were determined. VHL expression and localization was further studied by immunohistochemistry.

Results: Skeletal muscle capillary formation was significantly decreased with ascending disease severity. Compared to controls, a tendency to mRNA overexpression of HIF-1á, HIF-3á and VEGF isoforms was observed at mild and moderate COPD that decreased at the severe stage. By contrast, skeletal muscle biopsies from COPD patients exhibited significant overexpression of VHL both on the mRNA and protein levels by immunohistochemistry. VHL protein was further determined to be localized to satellite cells.

Conclusions: Overexpression of VHL was identified in the skeletal muscle of patients with COPD. Increased VHL activity may exert a negative impact on transducing the hypoxic signal and may contribute to decreased capillarization in skeletal muscles of patients with COPD.

Background: It is hypothesized that decreased capillarization of limb skeletal muscle is implicated in the decreased exercise tolerance in COPD patients. We have recently demonstrated decreased number of capillaries per muscle fibre (CAF) but no changes in CAF in relation to fibre area (CAFA), which is based on the diffusion distance between the capillary and muscle fibre. The aim of the current study is to investigate the muscle-to-capillary interface which is an important factor involved in oxygen supply to the muscle that has previously been suggested to be a more sensitive marker for changes in the capillary bed compared to CAF and CAFA.

Methods: 23 COPD patients and 12 age-matched healthy subjects participated in the study. Muscle-to-capillary interface was assessed in muscle biopsies from the tibialis anterior muscle using the following parameters:

1) The capillary-to-fibre ratio (C:F_i) which is defined as the sum of the fractional contributions of all capillary contacts around the fibre

2) The ratio between C:F_i and the fibre perimeter (CFPE-index)

3) The ratio between length of capillary and fibre perimeter (LC/PF) which is also referred to as the index of tortuosity.

Exercise capacity was determined using the 6-min walking test.

Results: A positive correlation was found between CFPE-index and ascending disease severity with CFPE-index for type I fibres being significantly lower in patients with moderate and severe COPD. Furthermore, a positive correlation was observed between exercise capacity and CFPE-index for both type I and type IIa fibres.

Conclusion: It can be concluded that the muscle-to-capillary interface is disturbed in the tibialis anterior muscle in patients with COPD and that interface is strongly correlated to increased disease severity and to decreased exercise capacity in this patient group.

Purpose: It has previously been suggested that exercise capacity is decreased in COPD patients and that it is associated with degree of disease. The reduced exercise capacity may plausibly be due to low levels of physical activity in this patient group. In the present study we aimed to assess exercise capacity and physical activity in different stages of COPD and to examine the associations between exercise capacity, pulmonary function and degree of physical activity.

Methods: 44 COPD patients and 17 healthy subjects participated in the study. Exercise capacity was assessed using the 6 minute walking test and physical activity was assessed using a uniaxial accelerometer worn all waking hours during seven days.

Results: Mean exercise capacity was significantly lower in COPD patients compared to healthy subjects. Mean physical activity level and time spent at least moderately active were significantly lower in patients with moderate and severe COPD compared to healthy subjects while no differences in time spent sedentary were observed between the study groups. Pulmonary function, mean physical activity level and time spent at least moderately physically active were significantly associated with exercise capacity in the patients.

Conclusions: Patients with moderate and severe COPD are significantly less physically active compared to healthy subjects. Furthermore, mean physical activity level as well as physical activity of at least moderate intensity are positively associated with exercise capacity in COPD patients while time spent sedentary is not which stresses an important role of physical activity on exercise capacity in this patient group.