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Sceletal muscle characteristics and physical activity patterns in COPD
Örebro University, School of Health and Medical Sciences.
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality worldwide. Besides abnormities within the respiratory system COPD is also associated with effects outside the lungs, so called systemic effects. One systemic effect that has been highlighted is skeletal muscle dysfunction which has also been associated with reduced exercise capacity. Apart from changes in muscle morphology, low levels of physical activity have also been suggested as a plausible mediator of reduced exercise capacity in COPD. The aim of this thesis was to study muscle morphology and physical activity patterns in patients with different degrees of COPD and to examine the associations between muscle morphology, physical activity and exercise capacity in these patients. Skeletal muscle morphology was found to shift towards a more glycolytic muscle profile in COPD patients and changes in muscle morphology were found to be correlated to disease severity and to exercise capacity. Muscle capillarization was also found to be lower in COPD compared with healthy subjects and to be correlated to disease severity and exercise capacity. When studying signalling pathways involved in muscle capillarization, an overexpression of VHL was found in patients with mild and moderate COPD compared with healthy subjects. Furthermore, COPD patients were found to be less physically active compared with healthy subjects and the level of physical activity was associated with exercise capacity.In conclusion, changes in skeletal muscle morphology and low levels of physical activity are present in COPD patients and may partly explain the lower exercise capacity observed in these patients. The more glycolytic muscle profile in COPD is suggested to be mediated by hypoxia and low levels of physical activity in this patient group. Furthermore, increased levels of VHL may lead to impaired transduction of the hypoxic signalling pathway, which may contribute to the decreased muscle capillarization observed in COPD.

Place, publisher, year, edition, pages
Örebro: Örebro universitet , 2010. , 65 p.
Series
Örebro Studies in Sport Sciences, ISSN 1654-7535 ; 10
Keyword [en]
COPD, muscle morphology, muscle fibre distribution, muscle capillarization, physical activity, von Hippel-Lindau protein, exercise capacity
National Category
Social Sciences Interdisciplinary Sport and Fitness Sciences
Research subject
Sports Science
Identifiers
URN: urn:nbn:se:oru:diva-12341ISBN: 978-91-7668-768-0 (print)OAI: oai:DiVA.org:oru-12341DiVA: diva2:359331
Public defence
2011-01-14, Hörsal P2, Fakutetsgatan 1, Örebro universitet, Örebro, 13:00
Opponent
Supervisors
Available from: 2010-10-27 Created: 2010-10-27 Last updated: 2011-04-21Bibliographically approved
List of papers
1. Physical performance and muscular characteristics in different stages of COPD
Open this publication in new window or tab >>Physical performance and muscular characteristics in different stages of COPD
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2009 (English)In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 19, no 6, 865-870 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Wiley-Blackwell Publishing Inc., 2009
Keyword
Activities of Daily Living/*psychology, Adaptation; Psychological, Aged, Aged; 80 and over, Attitude to Health, Body Image, Dependency (Psychology), Female, Health Services Needs and Demand, Humans, Interpersonal Relations, Male, Middle Aged, Models; Psychological, Neoplasms/psychology, Nursing Methodology Research, Palliative Care/methods/*psychology, Power (Psychology), Quality of Life/psychology, Questionnaires, Respite Care/psychology, Self Concept, Social Support, Sweden
National Category
Medical and Health Sciences Physiology Respiratory Medicine and Allergy Sport and Fitness Sciences
Research subject
Physiology; Sports Science
Identifiers
urn:nbn:se:oru:diva-3417 (URN)10.1111/j.1600-0838.2008.00858.x (DOI)000272132200014 ()18980606 (PubMedID)2-s2.0-70450260481 (Scopus ID)
Available from: 2008-12-04 Created: 2008-12-04 Last updated: 2017-02-17Bibliographically approved
2. Overexpression of von Hippel-Lindau protein in skeletal muscles of patients with chronic obstructive pulmonary disease
Open this publication in new window or tab >>Overexpression of von Hippel-Lindau protein in skeletal muscles of patients with chronic obstructive pulmonary disease
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2009 (English)In: Journal of Clinical Pathology, ISSN 0021-9746, E-ISSN 1472-4146, Vol. 62, no 1, 70-76 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
London: BMJ Publishing Group Ltd, 2009
National Category
Medical and Health Sciences Cell and Molecular Biology
Research subject
Pathology; Medicine
Identifiers
urn:nbn:se:oru:diva-3418 (URN)10.1136/jcp.2008.057190 (DOI)000262420400018 ()18818266 (PubMedID)2-s2.0-58349102711 (Scopus ID)
Available from: 2008-12-04 Created: 2008-12-04 Last updated: 2017-03-15Bibliographically approved
3. Alterations in the muscle-to-capillary interface in patients with different degrees of chronic obstructive pulmonary disease
Open this publication in new window or tab >>Alterations in the muscle-to-capillary interface in patients with different degrees of chronic obstructive pulmonary disease
2010 (English)In: Respiratory research (Online), ISSN 1465-9921, E-ISSN 1465-993X, Vol. 11, 97Article in journal (Refereed) Published
Abstract [en]

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:Fi) which is defined as the sum of the fractional contributions of all capillary contacts around the fibre

2) The ratio between C:Fi 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.

 

Place, publisher, year, edition, pages
London, United Kingdom: BioMed Central, 2010
Keyword
COPD, muscle-capillary interface, CFPE-index, LC/PF, tortuosity
National Category
Physiology Medical and Health Sciences
Research subject
Physiology; Medicine
Identifiers
urn:nbn:se:oru:diva-12493 (URN)10.1186/1465-9921-11-97 (DOI)000282550500002 ()20633289 (PubMedID)2-s2.0-77956692758 (Scopus ID)
Available from: 2010-11-19 Created: 2010-11-18 Last updated: 2017-02-14Bibliographically approved
4. Physical activity patterns in patients with different degrees of chronic obstructive pulmonary disease
Open this publication in new window or tab >>Physical activity patterns in patients with different degrees of chronic obstructive pulmonary disease
(English)Manuscript (preprint) (Other academic)
Abstract [en]

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. 

National Category
Physiology Medical and Health Sciences
Research subject
Physiology; Medicine
Identifiers
urn:nbn:se:oru:diva-12495 (URN)
Available from: 2010-11-18 Created: 2010-11-18 Last updated: 2016-12-12Bibliographically approved

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