{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:58:15Z","timestamp":1791845895886,"version":"4.3.4"},"reference-count":83,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2018,5,19]],"date-time":"2018-05-19T00:00:00Z","timestamp":1526688000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["119583"],"award-info":[{"award-number":["119583"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Chronic obstructive pulmonary disease (COPD) is largely caused by smoking, and patient limb muscle exhibits a fast fibre shift and atrophy.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We show that this fast fibre shift is associated with type grouping, suggesting recurring cycles of denervation\u2013reinnervation underlie the type shift.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Compared to patients with normal fat\u2010free mass index (FFMI), patients with low FFMI exhibited an exacerbated fibre type shift, marked accumulation of very small persistently denervated muscle fibres, and a blunted denervation\u2010responsive transcript profile, suggesting failed denervation precipitates muscle atrophy in patients with low FFMI.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Sixteen weeks of passive tobacco smoke exposure in mice caused neuromuscular junction degeneration, consistent with a key role for smoke exposure in initiating denervation in COPD.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>A neurological basis for the fast fibre shift and atrophy seen in limb muscle of patients with chronic obstructive pulmonary disease (COPD) has not been considered previously. The objective of our study was: (1) to determine if denervation contributes to fast fibre shift and muscle atrophy in COPD; and (2) to assess using a preclinical smoking mouse model whether chronic tobacco smoke (TS) exposure could initiate denervation by causing neuromuscular junction (NMJ) degeneration. Vastus lateralis muscle biopsies were obtained from severe COPD patients [<jats:italic>n<\/jats:italic>\u00a0=\u00a010 with low fat\u2010free mass index (FFMI), 65\u00a0years; <jats:italic>n<\/jats:italic>\u00a0=\u00a015 normal FFMI, 65\u00a0years) and healthy age\u2010 and activity\u2010matched non\u2010smoker control subjects (CON; <jats:italic>n<\/jats:italic>\u00a0=\u00a011, 67\u00a0years), to evaluate morphological and transcriptional markers of denervation. To evaluate the potential for chronic TS exposure to initiate these changes, we examined NMJ morphology in male adult mice following 16\u00a0weeks of passive TS exposure. We observed a high proportion of grouped fast fibres and a denervation transcript profile in COPD patients, suggesting that motor unit remodelling drives the fast fibre type shift in COPD patient limb muscle. A further exacerbation of fast fibre grouping in patients with low FFMI, coupled with blunted reinnervation signals, accumulation of very small non\u2010specific esterase hyperactive fibres and neural cell adhesion molecule\u2010positive type I and type II fibres, suggests denervation\u2010induced exhaustion of reinnervation contributes to muscle atrophy in COPD. Evidence from a smoking mouse model showed significant NMJ degeneration, suggesting that recurring denervation in COPD is probably caused by decades of chronic TS exposure.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp275558","type":"journal-article","created":{"date-parts":[[2018,4,17]],"date-time":"2018-04-17T00:12:36Z","timestamp":1523923956000},"page":"2865-2881","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Smoke\u2010induced neuromuscular junction degeneration precedes the fibre type shift and atrophy in chronic obstructive pulmonary disease"],"prefix":"10.1113","volume":"596","author":[{"given":"Sophia","family":"Kapchinsky","sequence":"first","affiliation":[{"name":"Department of Kinesiology and Physical Education McGill University  Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhusudanarao","family":"Vuda","sequence":"additional","affiliation":[{"name":"Meakins Christie Laboratories and Research Institute of the McGill University Health Centre  Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayla","family":"Miguez","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Physical Education McGill University  Montreal QC Canada"},{"name":"Meakins Christie Laboratories and Research Institute of the McGill University Health Centre  Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daren","family":"Elkrief","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Physical Education McGill University  Montreal QC Canada"},{"name":"Meakins Christie Laboratories and Research Institute of the McGill University Health Centre  Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela R.","family":"de Souza","sequence":"additional","affiliation":[{"name":"Meakins Christie Laboratories and Research Institute of the McGill University Health Centre  Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn J.","family":"Baglole","sequence":"additional","affiliation":[{"name":"Meakins Christie Laboratories and Research Institute of the McGill University Health Centre  Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudhakar","family":"Aare","sequence":"additional","affiliation":[{"name":"Meakins Christie Laboratories and Research Institute of the McGill University Health Centre  Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norah J.","family":"MacMillan","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Physical Education McGill University  Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacinthe","family":"Baril","sequence":"additional","affiliation":[{"name":"Montreal Chest Institute  Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Rozakis","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Physical Education McGill University  Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vita","family":"Sonjak","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Physical Education McGill University  Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Pion","sequence":"additional","affiliation":[{"name":"Departement des sciences de l'activite physique; GRAPA, Faculte des Sciences Universite de Quebec a Montreal  Montreal QC Canada"},{"name":"Centre de recherche de l'institut universitaire de geriatrie de Montreal  Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myl\u00e8ne","family":"Aubertin\u2010Leheudre","sequence":"additional","affiliation":[{"name":"Departement des sciences de l'activite physique; GRAPA, Faculte des Sciences Universite de Quebec a Montreal  Montreal QC Canada"},{"name":"Centre de recherche de l'institut universitaire de geriatrie de Montreal  Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose A.","family":"Morais","sequence":"additional","affiliation":[{"name":"Research Institute of the McGill University Health Centre  Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Thomas","family":"Jagoe","sequence":"additional","affiliation":[{"name":"McGill Cancer Nutrition Rehabilitation Program and Peter Brojde Lung Cancer Center, Segal Cancer Centre Jewish General Hospital  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Bourbeau","sequence":"additional","affiliation":[{"name":"Montreal Chest Institute  Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Taivassalo","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Physical Education McGill University  Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3640-486X","authenticated-orcid":false,"given":"Russell T.","family":"Hepple","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Physical Education McGill University  Montreal QC Canada"},{"name":"Meakins Christie Laboratories and Research Institute of the McGill University Health Centre  Montreal QC Canada"},{"name":"Department of Physical Therapy University of Florida  USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,5,19]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.167.2.211"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP270213"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.10-01-00153.1990"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.100879"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.20755"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2016.00006"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1960.sp006395"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmor.1052210207"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.11-191262"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.07.061"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0066433"},{"key":"e_1_2_5_13_1","volume-title":"Pathology of Skeletal Muscle","author":"Carpenter S","year":"2001"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2009.07049.x"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.092361"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.23917"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25001"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kws015"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfu068"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201410-1830PP"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2017.7054"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/60.4.416"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.08.035"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-8966(03)00036-1"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00847.2012"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2013.270207"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.364"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/9781118635469"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/tobaccocontrol-2016-053305"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/76.1.113"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2008-0312OC"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2007.078980"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.13-242750"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1014-17.2017"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP270561"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.2000.0892"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00713495"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.09-146308"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2014-206440"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.10.002"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00004.2014"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00074.2015"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2010.02.011"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.1984.tb07394.x"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00293457"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.02.008"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2015.09.012"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(08)04019-6"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201402-0373ST"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-09-1014"},{"key":"e_1_2_5_51_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.2107031"},{"key":"e_1_2_5_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2010.05.017"},{"key":"e_1_2_5_53_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0b013e32832ffc60"},{"key":"e_1_2_5_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.1979.tb06440.x"},{"key":"e_1_2_5_55_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00013.2006"},{"key":"e_1_2_5_56_1","unstructured":"U.S. Department of Health and Human Service 2010"},{"key":"e_1_2_5_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2012.07.013"},{"key":"e_1_2_5_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10974-010-9200-2"},{"key":"e_1_2_5_59_1","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.1997.0622"},{"key":"e_1_2_5_60_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0029082"},{"key":"e_1_2_5_61_1","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-11-77"},{"key":"e_1_2_5_62_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.13-240390"},{"key":"e_1_2_5_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2015.04.005"},{"key":"e_1_2_5_64_1","doi-asserted-by":"publisher","DOI":"10.1159\/000117421"},{"key":"e_1_2_5_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0802037"},{"key":"e_1_2_5_66_1","first-page":"51812","article-title":"Human skeletal muscle biopsy procedures using the modified Bergstrom technique","volume":"10","author":"Shanely RA","year":"2014","journal-title":"J Vis Exp"},{"key":"e_1_2_5_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25083"},{"key":"e_1_2_5_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2014.04.016"},{"key":"e_1_2_5_69_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP272487"},{"key":"e_1_2_5_70_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2006.062026"},{"key":"e_1_2_5_71_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2992-16.2016"},{"key":"e_1_2_5_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rehab.2009.11.007"},{"key":"e_1_2_5_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2016.02.016"},{"key":"e_1_2_5_74_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1002129"},{"key":"e_1_2_5_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(95)90146-9"},{"key":"e_1_2_5_76_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0128560"},{"key":"e_1_2_5_77_1","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2011-200010"},{"key":"e_1_2_5_78_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1843.2006.00939.x"},{"key":"e_1_2_5_79_1","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.1999.0815"},{"key":"e_1_2_5_80_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.05.00035005"},{"key":"e_1_2_5_81_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.28695"},{"key":"e_1_2_5_82_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005768-199810000-00001"},{"key":"e_1_2_5_83_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1181046"},{"key":"e_1_2_5_84_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.13-228130"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2FJP275558","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP275558","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,17]],"date-time":"2023-09-17T07:28:02Z","timestamp":1694935682000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP275558"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,19]]},"references-count":83,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2018,7]]}},"alternative-id":["10.1113\/JP275558"],"URL":"https:\/\/doi.org\/10.1113\/jp275558","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5,19]]},"assertion":[{"value":"2017-11-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-05-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}