{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:19:03Z","timestamp":1791325143231,"version":"4.3.1"},"reference-count":62,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2007,6,1]],"date-time":"2007-06-01T00:00:00Z","timestamp":1180656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Inspiratory muscle weakness in patients with chronic obstructive pulmonary disease (COPD) is of major clinical relevance; 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 of pathologic nature. Although the fiber-type shift toward oxidative type I fibers in COPD diaphragm is regarded as 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. Moreover, the diaphragm in COPD is exposed to oxidative stress and sarcomeric injury. The current Pulmonary Perspective 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 do not appear to be limited in their daily-life activities. Therefore, investigating in vivo diaphragm function in mild to moderate COPD should be the focus of future research. Treatment of diaphragm dysfunction in COPD is complex because its etiology is unclear, but recent findings show promise for the use of proteasome inhibitors in syndromes associated with muscle wasting, such as the diaphragm in COPD.<\/jats:p>","DOI":"10.1164\/rccm.200701-020pp","type":"journal-article","created":{"date-parts":[[2007,4,5]],"date-time":"2007-04-05T21:21:02Z","timestamp":1175808062000},"page":"1233-1240","source":"Crossref","is-referenced-by-count":114,"title":["Diaphragm Muscle Fiber Dysfunction in Chronic Obstructive Pulmonary Disease"],"prefix":"10.1093","volume":"175","author":[{"given":"Coen A. C.","family":"Ottenheijm","sequence":"first","affiliation":[{"name":"Department of Pulmonary Diseases and"},{"name":"Institute for Fundamental and Clinical Human Movement Sciences, Radboud University, Nijmegen Medical Centre, Nijmegen, The Netherlands"},{"name":"Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, Washington State University, Pullman, Washington; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo M. A.","family":"Heunks","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases and"},{"name":"Institute for Fundamental and Clinical Human Movement Sciences, Radboud University, Nijmegen Medical Centre, Nijmegen, The Netherlands"},{"name":"Department of Intensive Care Medicine, Radboud University, Nijmegen Medical Centre, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. N. 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