{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T17:28:41Z","timestamp":1789925321437,"version":"4.0.1"},"reference-count":54,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,1,18]],"date-time":"2019-01-18T00:00:00Z","timestamp":1547769600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Pulmonary rehabilitation (PR) is a cornerstone in the management of chronic obstructive pulmonary disease (COPD), targeting skeletal muscle to improve functional performance. However, there is substantial inter\u2010individual variability in the effect of PR on functional performance, which cannot be fully accounted for by generic phenotypic factors. We performed an unbiased integrative analysis of the skeletal muscle molecular responses to PR in COPD patients and comprehensively characterized their baseline pulmonary and physical function, body composition, blood profile, comorbidities, and medication use.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:italic>Musculus vastus lateralis<\/jats:italic> biopsies were obtained from 51 COPD patients (age 64\u00a0\u00b1\u00a01\u00a0years, sex 73% men, FEV<jats:sub>1<\/jats:sub>, 34 (26\u201341) %pred.) before and after 4\u00a0weeks high\u2010intensity supervised in\u2010patient PR. Muscle molecular markers were grouped by network\u2010constrained clustering, and their relative changes in expression values\u2014assessed by qPCR and western blot\u2014were reduced to process scores by principal component analysis. Patients were subsequently clustered based on these process scores. Pre\u2010PR and post\u2010PR functional performance was assessed by incremental cycle ergometry and 6\u00a0min walking test (6MWT).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Eight molecular processes were discerned by network\u2010constrained hierarchical clustering of the skeletal muscle molecular rehabilitation responses. Based on the resulting process scores, four clusters of patients were identified by hierarchical cluster analysis. Two major patient clusters differed in PR\u2010induced autophagy (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001), myogenesis (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.014), glucocorticoid signalling (<jats:italic>P\u00a0&lt;<\/jats:italic>\u00a00.001), and oxidative metabolism regulation (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001), with Cluster 1 (C1; <jats:italic>n<\/jats:italic>\u00a0=\u00a029) overall displaying a more pronounced change in marker expression than Cluster 2 (C2; <jats:italic>n<\/jats:italic>\u00a0=\u00a016). General baseline characteristics did not differ between clusters. Following PR, both 6\u00a0min walking distance (+26.5\u00a0\u00b1\u00a08.3\u00a0m, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.003) and peak load on the cycle ergometer test (+9.7\u00a0\u00b1\u00a01.9\u00a0W, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001) were improved. However, the functional improvement was more pronounced in C1, as a higher percentage of patients exceeded the minimal clinically important difference in peak workload (61 vs. 21%, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.022) and both peak workload and 6\u00a0min walking test (52 vs. 8%, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.008) upon PR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We identified patient groups with distinct skeletal muscle molecular responses to rehabilitation, associated with differences in functional improvements upon PR.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12370","type":"journal-article","created":{"date-parts":[[2019,1,18]],"date-time":"2019-01-18T14:06:51Z","timestamp":1547820411000},"page":"311-322","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Distinct skeletal muscle molecular responses to pulmonary rehabilitation in chronic obstructive pulmonary disease: a cluster analysis"],"prefix":"10.1002","volume":"10","author":[{"given":"Anita E.M.","family":"Kneppers","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism Maastricht University Medical Centre+  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy A.M.","family":"Haast","sequence":"additional","affiliation":[{"name":"Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience Maastricht University  Maastricht The Netherlands"},{"name":"Maastricht Centre for Systems Biology Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramon C.J.","family":"Langen","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism Maastricht University Medical Centre+  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lex B.","family":"Verdijk","sequence":"additional","affiliation":[{"name":"Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism Maastricht University Medical Centre+  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter A.","family":"Leermakers","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism Maastricht University Medical Centre+  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry R.","family":"Gosker","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism Maastricht University Medical Centre+  Maastricht The 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