{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T11:41:53Z","timestamp":1792582913766,"version":"4.5.0"},"reference-count":66,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000222","name":"Heart and Stroke Foundation of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000222","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"abstract":"\n Abstract<\/jats:title>\n \n Stable breathing depends on the integrated action of central and peripheral chemoreceptors, but the nature of this interaction in humans and its physiological importance remain controversial. Previous studies reported additive, hypo\u2010additive and hyper\u2010additive responses across species, preparations and protocols. Here, we used a novel method to quantify peripheral chemoreflex sensitivity across graded levels of central chemoreceptor activation to test whether central\u2013peripheral chemoreceptor interaction in awake humans is fixed or state dependent. At low altitude, the form of interaction varied across individuals, with most showing additive responses (12\/17) and a substantial subset showing hypo\u2010additivity (5\/17). After 7\u201310\u00a0days of acclimatization to 3500\u00a0m, all five hypo\u2010additive individuals became additive, and four additive participants became hyper\u2010additive. This shift in interaction towards hyper\u2010additivity provides the first evidence that central\u2010peripheral chemoreceptor integration is plastic. Plasticity during wakefulness was not associated with individual differences in central sleep apnoea severity at high altitude. Thus, our findings confirm that central\u2013peripheral chemoreceptor interaction differs among individuals and suggest that the form of interaction can be reshaped by hypobaric hypoxic stress.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n How central and peripheral chemoreceptor drives to breathe interact in humans and whether this process is plastic remains uncertain.<\/jats:p>\n <\/jats:list-item>\n \n We quantified peripheral chemoreflex sensitivity to hypoxia (PChS) across graded levels of central chemoreceptor activation at low altitude and after 7\u201310\u00a0days of high\u2010altitude exposure (3500 m).<\/jats:p>\n <\/jats:list-item>\n \n \n Seventeen participants performed repeated modified rebreathing tests with end\u2010tidal fixed at 150 (hyperoxia), 60 and 45\u00a0mmHg (hypoxia). PChS was computed at 1 mmHg intervals of end\u2010tidal () from linear regression of the difference in ventilation between hypoxic and hyperoxic conditions\n vs<\/jats:italic>\n . calculated arterial oxygen saturation (ScO\n 2<\/jats:sub>\n ) (L\u00b7min\n \u22121<\/jats:sup>\n \u00b7mmHg\n \u22121<\/jats:sup>\n \u00b7%ScO\n 2<\/jats:sub>\n \u22121<\/jats:sup>\n ).\n <\/jats:p>\n <\/jats:list-item>\n \n At low altitude, PChS increased with in all individuals; the relationship was linear (no interaction) in 12 participants, and 5 showed hypo\u2010additivity.<\/jats:p>\n <\/jats:list-item>\n \n After acclimatization, central and peripheral chemoreflex sensitivities increased. All hypo\u2010additive individuals became additive; four additive individuals became hyper\u2010additive.<\/jats:p>\n <\/jats:list-item>\n \n Central\u2013peripheral chemoreceptor interaction is plastic in humans and can shift towards hyper\u2010additivity with sustained hypobaric hypoxia.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp291920","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T11:01:11Z","timestamp":1792580471000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Altitude\u2010induced plasticity of respiratory central\u2013peripheral chemoreflex interaction"],"prefix":"10.1113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5830-6481","authenticated-orcid":false,"given":"Nasimi A.","family":"Guluzade","sequence":"first","affiliation":[{"name":"School of Kinesiology The University of Western Ontario London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin W.L.","family":"MacKenzie","sequence":"additional","affiliation":[{"name":"Department of Biology Faculty of Science and Technology Mount Royal University Calgary Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7102-4235","authenticated-orcid":false,"given":"Trevor A.","family":"Day","sequence":"additional","affiliation":[{"name":"Department of Biology Faculty of Science and Technology Mount Royal University Calgary Canada"},{"name":"Department of Physiology and Pharmacology Cumming School of Medicine University of Calgary Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9942-4775","authenticated-orcid":false,"given":"Richard J.A.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Cumming School of Medicine University of Calgary Calgary Alberta Canada"},{"name":"Hotchkiss Brain Institute University of Calgary Calgary Alberta Canada"},{"name":"Alberta Children's Hospital Research Institute for Child and Maternal Health University of Calgary Calgary Alberta Canada"},{"name":"Libin Cardiovascular Institute University of Calgary Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5656-373X","authenticated-orcid":false,"given":"Daniel A.","family":"Keir","sequence":"additional","affiliation":[{"name":"School of Kinesiology The University of Western Ontario London Ontario Canada"},{"name":"Lawson Health Research Institute London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.91008.2008.\u2010Cerebral"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2013.05.020"},{"issue":"12","key":"e_1_2_7_4_1","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.abm1444","article-title":"Novel oxygen sensing mechanism in the spinal cord involved in cardiorespiratory responses to hypoxia","volume":"8","author":"Barioni N. 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