Persistent Link:
http://hdl.handle.net/10150/610242
Title:
Diaphragm adaptations in patients with COPD
Author:
Ottenheijm, Coen; Heunks, Leo; Dekhuijzen, Richard
Affiliation:
Dept. of Pulmonary Diseases, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; Dept. of Intensive Care Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; Institute for Fundamental and Clinical Human Movement Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; Dept. of Molecular and Cellular Biology, University of Arizona, Tucson, USA
Issue Date:
2008
Publisher:
BioMed Central
Citation:
Respiratory Research 2008, 9:12 doi:10.1186/1465-9921-9-12
Journal:
Respiratory Research
Rights:
© 2008 Ottenheijm et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)
Collection Information:
This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.
Abstract:
Inspiratory muscle weakness in patients with COPD is of major clinical relevance. For instance, maximum inspiratory pressure generation is an independent determinant of survival in severe COPD. Traditionally, inspiratory muscle weakness has been ascribed to hyperinflation-induced diaphragm shortening. However, more recently, invasive evaluation of diaphragm contractile function, structure, and biochemistry demonstrated that cellular and molecular alterations occur, of which several can be considered pathologic of nature. Whereas the fiber type shift towards oxidative type I fibers in COPD diaphragm is regarded beneficial, rendering the overloaded diaphragm more resistant to fatigue, the reduction of diaphragm fiber force generation in vitro likely contributes to diaphragm weakness. The reduced diaphragm force generation at single fiber level is associated with loss of myosin content in these fibers. Moreover, the diaphragm in COPD is exposed to oxidative stress and sarcomeric injury. This review postulates that the oxidative stress and sarcomeric injury activate proteolytic machinery, leading to contractile protein wasting and, consequently, loss of force generating capacity of diaphragm fibers in patients with COPD. Interestingly, several of these presumed pathologic alterations are already present early in the course of the disease (GOLD I/II), although these patients appear not limited in their daily life activities. Treatment of diaphragm dysfunction in COPD is complex since its etiology is unclear, but recent findings indicate the ubiquitin-proteasome pathway as a prime target to attenuate diaphragm wasting in COPD.
EISSN:
1465-993X
DOI:
10.1186/1465-9921-9-12
Version:
Final published version
Additional Links:
http://respiratory-research.com/content/9/1/12

Full metadata record

DC FieldValue Language
dc.contributor.authorOttenheijm, Coenen
dc.contributor.authorHeunks, Leoen
dc.contributor.authorDekhuijzen, Richarden
dc.date.accessioned2016-05-20T09:02:00Z-
dc.date.available2016-05-20T09:02:00Z-
dc.date.issued2008en
dc.identifier.citationRespiratory Research 2008, 9:12 doi:10.1186/1465-9921-9-12en
dc.identifier.doi10.1186/1465-9921-9-12en
dc.identifier.urihttp://hdl.handle.net/10150/610242-
dc.description.abstractInspiratory muscle weakness in patients with COPD is of major clinical relevance. For instance, maximum inspiratory pressure generation is an independent determinant of survival in severe COPD. Traditionally, inspiratory muscle weakness has been ascribed to hyperinflation-induced diaphragm shortening. However, more recently, invasive evaluation of diaphragm contractile function, structure, and biochemistry demonstrated that cellular and molecular alterations occur, of which several can be considered pathologic of nature. Whereas the fiber type shift towards oxidative type I fibers in COPD diaphragm is regarded beneficial, rendering the overloaded diaphragm more resistant to fatigue, the reduction of diaphragm fiber force generation in vitro likely contributes to diaphragm weakness. The reduced diaphragm force generation at single fiber level is associated with loss of myosin content in these fibers. Moreover, the diaphragm in COPD is exposed to oxidative stress and sarcomeric injury. This review postulates that the oxidative stress and sarcomeric injury activate proteolytic machinery, leading to contractile protein wasting and, consequently, loss of force generating capacity of diaphragm fibers in patients with COPD. Interestingly, several of these presumed pathologic alterations are already present early in the course of the disease (GOLD I/II), although these patients appear not limited in their daily life activities. Treatment of diaphragm dysfunction in COPD is complex since its etiology is unclear, but recent findings indicate the ubiquitin-proteasome pathway as a prime target to attenuate diaphragm wasting in COPD.en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.relation.urlhttp://respiratory-research.com/content/9/1/12en
dc.rights© 2008 Ottenheijm et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)en
dc.titleDiaphragm adaptations in patients with COPDen
dc.typeArticleen
dc.identifier.eissn1465-993Xen
dc.contributor.departmentDept. of Pulmonary Diseases, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlandsen
dc.contributor.departmentDept. of Intensive Care Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlandsen
dc.contributor.departmentInstitute for Fundamental and Clinical Human Movement Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlandsen
dc.contributor.departmentDept. of Molecular and Cellular Biology, University of Arizona, Tucson, USAen
dc.identifier.journalRespiratory Researchen
dc.description.collectioninformationThis item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
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