{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T10:43:26Z","timestamp":1790073806852,"version":"4.0.1"},"reference-count":32,"publisher":"European Respiratory Society (ERS)","issue":"1","license":[{"start":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:00:00Z","timestamp":1759363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/publications.ersnet.org\/user-licence"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL102321"],"award-info":[{"award-number":["R01HL102321"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL146697"],"award-info":[{"award-number":["R01HL146697"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL168067"],"award-info":[{"award-number":["R01HL168067"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["15SDG25890059"],"award-info":[{"award-number":["15SDG25890059"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001030","name":"National Heart Foundation of Australia","doi-asserted-by":"publisher","award":["101167"],"award-info":[{"award-number":["101167"]}],"id":[{"id":"10.13039\/501100001030","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Monash Lung and Sleep Institute","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2025,9,14]]},"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Treatment for obstructive sleep apnoea (OSA) is limited by intolerance to continuous positive airway pressure. While OSA manifests due to both increased pharyngeal collapsibility and ventilatory control instability, randomised trials targeting both components are lacking. We tested whether combining a ventilatory control intervention (supplemental oxygen) with an upper airway mechanical intervention (mandibular advancement device (MAD)) improves treatment efficacy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In a multicentre randomised crossover trial, 41 patients with moderate-to-severe OSA (apnoea\u2013hypopnoea index (AHI) &gt;20\u2005events\u00b7h\n                      <jats:sup>\u22121<\/jats:sup>\n                      , scored without desaturation criteria) underwent polysomnography with four single-night interventions: oxygen (4\u2005L\u00b7min\n                      <jats:sup>\u22121<\/jats:sup>\n                      ), MAD, combination therapy and sham (air). Primary analysis compared percent change in AHI from baseline between combination therapy and MAD monotherapy. Secondary outcomes included arousal index and visual analogue scale for sleep quality (VASSQ). Gold standard baseline pathophysiological traits facilitated mechanistic subgroup analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 41 randomised patients (14 females:27 males, median (interquartile range) baseline AHI 49 (29, 62)\u2005events\u00b7h\n                      <jats:sup>\u22121<\/jats:sup>\n                      ), 38 completed all interventions. Compared with sham, AHI was lowered with oxygen (estimate: \u221233 (95% CI \u221246, \u221217)%), MAD (\u221254 (95% CI \u221264, \u221241)%) and the combination (\u221268 (95% CI \u221277, \u221257)%); the combination provided a greater reduction than MAD monotherapy (\u221214 (95% CI \u221223, \u22124)%; p=0.009). The combination also improved AHI per 3% desaturation\/arousal criteria (\u221273 (95% CI \u221281, \u221262)%\n                      <jats:italic>versus<\/jats:italic>\n                      sham and \u221217 (95% CI \u221225, \u22127)%\n                      <jats:italic>versus<\/jats:italic>\n                      MAD). The combination improved arousal index (\u221236 (95% CI \u221243, \u221227)%\n                      <jats:italic>versus<\/jats:italic>\n                      sham) and VASSQ (+0.98 (95% CI 0.39, 1.58)\n                      <jats:italic>versus<\/jats:italic>\n                      sham), albeit not significantly beyond MAD alone. Effects were greatest in those with higher loop gain and collapsibility.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Combining a ventilatory control intervention (supplemental oxygen) with an upper airway intervention (MAD) is a promising approach to markedly attenuate OSA severity beyond that offered by each intervention alone.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1183\/13993003.01320-2025","type":"journal-article","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T13:45:13Z","timestamp":1759412713000},"page":"2501320","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Combined supplemental oxygen and mandibular advancement device therapy for obstructive sleep apnoea: a randomised controlled trial"],"prefix":"10.1183","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9383-1644","authenticated-orcid":false,"given":"Bradley A.","family":"Edwards","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5568-775X","authenticated-orcid":false,"given":"Luke D.J.","family":"Thomson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1740-8777","authenticated-orcid":false,"given":"Daniel","family":"Vena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Gikas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Radmand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Calianese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren B.","family":"Hess","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinny","family":"Collet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dillon","family":"Gilbertson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie V.","family":"Lawrence","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9041-3655","authenticated-orcid":false,"given":"Shane A.","family":"Landry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7909-8025","authenticated-orcid":false,"given":"Simon A.","family":"Joosten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1744-2839","authenticated-orcid":false,"given":"Garun S.","family":"Hamilton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Wellman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3752-0328","authenticated-orcid":false,"given":"Scott A.","family":"Sands","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2025,10,2]]},"reference":[{"key":"2026010801350624000_67.1.2501320.1","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1513\/AnnalsATS.201903-190OC","article-title":"Polysomnographic endotyping to select patients with obstructive sleep apnea for oral appliances","volume":"16","author":"Bamagoos","year":"2019","journal-title":"Ann Am Thorac Soc"},{"key":"2026010801350624000_67.1.2501320.2","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1164\/rccm.201601-0099OC","article-title":"Upper-airway collapsibility and loop gain predict the response to oral appliance therapy in patients with obstructive sleep apnea","volume":"194","author":"Edwards","year":"2016","journal-title":"Am J Respir Crit Care Med"},{"key":"2026010801350624000_67.1.2501320.3","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1513\/AnnalsATS.202003-220OC","article-title":"Mandibular advancement device treatment efficacy is associated with polysomnographic endotypes","volume":"18","author":"Op de Beeck","year":"2021","journal-title":"Ann Am Thorac Soc"},{"key":"2026010801350624000_67.1.2501320.4","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2021-217756"},{"key":"2026010801350624000_67.1.2501320.5","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.5664\/jcsm.8556","article-title":"The effect of gradually increased mandibular advancement on the efficacy of an oral appliance in the treatment of obstructive sleep apnea","volume":"16","author":"Ma","year":"2020","journal-title":"J Clin Sleep Med"},{"key":"2026010801350624000_67.1.2501320.6","unstructured":"American Academy of Sleep Medicine . The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications, Version 2.6. Darien, AASM, 2020."},{"key":"2026010801350624000_67.1.2501320.7","doi-asserted-by":"crossref","first-page":"zsx183","DOI":"10.1093\/sleep\/zsx183","article-title":"Quantifying the arousal threshold using polysomnography in obstructive sleep apnea","volume":"41","author":"Sands","year":"2018","journal-title":"Sleep"},{"key":"2026010801350624000_67.1.2501320.8","doi-asserted-by":"publisher","DOI":"10.1136\/thorax-2023-220184"},{"key":"2026010801350624000_67.1.2501320.9","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.chest.2025.03.013","article-title":"Effects of the combination of pimavanserin and atomoxetine on OSA severity: a randomized crossover trial","volume":"168","author":"Messineo","year":"2025","journal-title":"Chest"},{"key":"2026010801350624000_67.1.2501320.10","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1164\/rccm.202403-0501OC","article-title":"Hypnotics on obstructive sleep apnea severity and endotypes: a systematic review and meta-analysis","volume":"210","author":"Messineo","year":"2024","journal-title":"Am J Respir Crit Care Med"},{"key":"2026010801350624000_67.1.2501320.11","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201303-0448OC"},{"key":"2026010801350624000_67.1.2501320.12","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2011.223925"},{"key":"2026010801350624000_67.1.2501320.13","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00282.2006"},{"key":"2026010801350624000_67.1.2501320.14","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1046\/j.1440-1819.1999.00551.x","article-title":"Clinical efficacy and indication of acetazolamide treatment on sleep apnea syndrome","volume":"53","author":"Inoue","year":"1999","journal-title":"Psychiatry Clin Neurosci"},{"key":"2026010801350624000_67.1.2501320.15","doi-asserted-by":"crossref","first-page":"963","DOI":"10.3390\/life14080963","article-title":"Acetazolamide as an add-on therapy following barbed reposition pharyngoplasty in obstructive sleep apnea: a randomized controlled trial","volume":"14","author":"Hellemans","year":"2024","journal-title":"Life"},{"key":"2026010801350624000_67.1.2501320.16","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1513\/AnnalsATS.202210-892OC","article-title":"Stepwise add-on and endotype-informed targeted combination therapy to treat obstructive sleep apnea: a proof-of-concept study","volume":"20","author":"Aishah","year":"2023","journal-title":"Ann Am Thorac Soc"},{"key":"2026010801350624000_67.1.2501320.17","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2014.277210"},{"key":"2026010801350624000_67.1.2501320.18","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00674-2018"},{"key":"2026010801350624000_67.1.2501320.19","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1164\/rccm.202101-0237OC","article-title":"Ventilatory drive withdrawal rather than reduced genioglossus compensation as a mechanism of obstructive sleep apnea in REM","volume":"205","author":"Messineo","year":"2021","journal-title":"Am J Respir Crit Care Med"},{"key":"2026010801350624000_67.1.2501320.20","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1016\/j.chest.2020.10.080","article-title":"Assessing the physiologic endotypes responsible for REM- and NREM-based OSA","volume":"159","author":"Joosten","year":"2021","journal-title":"Chest"},{"key":"2026010801350624000_67.1.2501320.21","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00625.2004"},{"key":"2026010801350624000_67.1.2501320.22","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD007160.pub4"},{"key":"2026010801350624000_67.1.2501320.23","doi-asserted-by":"crossref","first-page":"215","DOI":"10.5664\/jcsm.3460","article-title":"Oral appliance treatment for obstructive sleep apnea: an update","volume":"10","author":"Sutherland","year":"2014","journal-title":"J Clin Sleep Med"},{"key":"2026010801350624000_67.1.2501320.24","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1306766"},{"key":"2026010801350624000_67.1.2501320.25","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.5664\/jcsm.11272","article-title":"Gefapixant as a P2X3 receptor antagonist treatment for obstructive sleep apnea: a randomized controlled trial","volume":"20","author":"Robbins","year":"2024","journal-title":"J Clin Sleep Med"},{"key":"2026010801350624000_67.1.2501320.26","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1164\/rccm.202109-2043OC","article-title":"A randomized controlled clinical trial exploring safety and tolerability of sulthiame in sleep apnea","volume":"205","author":"Hedner","year":"2022","journal-title":"Am J Respir Crit Care Med"},{"key":"2026010801350624000_67.1.2501320.27","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1007\/s11325-014-1068-8","article-title":"A promising concept of combination therapy for positional obstructive sleep apnea","volume":"19","author":"Dieltjens","year":"2015","journal-title":"Sleep Breath"},{"key":"2026010801350624000_67.1.2501320.28","doi-asserted-by":"crossref","first-page":"403","DOI":"10.5664\/jcsm.10296","article-title":"Personalized multimodal management for severe obstructive sleep apnea in a patient intolerant of positive airway pressure with hypoglossal nerve stimulator and mandibular advancement device","volume":"19","author":"Lowery","year":"2023","journal-title":"J Clin Sleep Med"},{"key":"2026010801350624000_67.1.2501320.29","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00076.2021"},{"key":"2026010801350624000_67.1.2501320.30","first-page":"958","article-title":"The effects of oxygen in patients with sleep apnea","volume":"130","author":"Smith","year":"1984","journal-title":"Am Rev Respir Dis"},{"key":"2026010801350624000_67.1.2501320.31","first-page":"e48280","article-title":"Appliances therapy in obstructive sleep apnoea: a systematic review and meta-analysis","volume":"15","author":"Beri","year":"2023","journal-title":"Cureus"},{"key":"2026010801350624000_67.1.2501320.32","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0173-2023"}],"container-title":["European Respiratory Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1183\/13993003.01320-2025","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T09:35:17Z","timestamp":1767864917000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.ersnet.org\/lookup\/doi\/10.1183\/13993003.01320-2025"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,2]]},"references-count":32,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1,8]]},"published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1183\/13993003.01320-2025"],"URL":"https:\/\/doi.org\/10.1183\/13993003.01320-2025","relation":{},"ISSN":["0903-1936","1399-3003"],"issn-type":[{"value":"0903-1936","type":"print"},{"value":"1399-3003","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,2]]}}}