{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T14:15:22Z","timestamp":1792505722577,"version":"4.5.0"},"reference-count":45,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2018,7,6]],"date-time":"2018-07-06T00:00:00Z","timestamp":1530835200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL102321"],"award-info":[{"award-number":["R01HL102321"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007299","name":"Harvard Catalyst","doi-asserted-by":"publisher","award":["UL1TR001102"],"award-info":[{"award-number":["UL1TR001102"]}],"id":[{"id":"10.13039\/100007299","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":[[2018,9]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>A hypersensitive ventilatory control system or elevated \u201cloop gain\u201d during sleep is a primary phenotypic trait causing obstructive sleep apnoea (OSA).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Despite the multitude of methods available to assess the anatomical contributions to OSA during wakefulness in the clinical setting (e.g. neck circumference, pharyngometry, Mallampati score), it is currently not possible to recognize elevated loop gain in patients in this context.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Loop gain during sleep can now be recognized using simplified testing during wakefulness, specifically in the form of a reduced maximal breath\u2010hold duration, or a larger ventilatory response to voluntary 20\u2010second breath\u2010holds.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We consider that easy breath\u2010holding manoeuvres will enable daytime recognition of a high loop gain in OSA for more personalized intervention.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Increased \u201cloop gain\u201d of the ventilatory control system promotes obstructive sleep apnoea (OSA) in some patients and offers an avenue for more personalized treatment, yet diagnostic tools for directly measuring loop gain in the clinical setting are lacking. Here we test the hypothesis that elevated loop gain during sleep can be recognized using voluntary breath\u2010hold manoeuvres during wakefulness. Twenty individuals (10 OSA, 10 controls) participated in a single overnight study with voluntary breath\u2010holding manoeuvres performed during wakefulness. We assessed (1) maximal breath\u2010hold duration, and (2) the ventilatory response to 20\u00a0s breath\u2010holds. For comparison, gold standard loop gain values were obtained during non\u2010rapid eye movement (non\u2010REM) sleep using the ventilatory response to 20\u00a0s pulses of hypoxic\u2013hypercapnic gas (6% CO<jats:sub>2<\/jats:sub>\u201314% O<jats:sub>2<\/jats:sub>, mimicking apnoea). Continuous positive airway pressure (CPAP) was used to maintain airway patency during sleep. Additional measurements included gold standard loop gain measurement during wakefulness and steady\u2010state loop gain measurement during sleep using CPAP dial\u2010ups. Higher loop gain during sleep was associated with (1) a shorter maximal breath\u2010hold duration (<jats:italic>r<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a00.49, <jats:italic>P\u00a0<\/jats:italic>&lt;\u00a00.001), and (2) a larger ventilatory response to 20\u00a0s breath\u2010holds during wakefulness (second breath; <jats:italic>r<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a00.50, <jats:italic>P\u00a0<\/jats:italic>&lt;\u00a00.001); together these factors combine to predict high loop gain (receiver operating characteristic area\u2010under\u2010curve: 92%). Gold standard loop gain values were remarkably similar during wake and non\u2010REM sleep. The results show that elevated loop gain during sleep can be identified using simple breath\u2010holding manoeuvres performed during wakefulness. This may have implications for personalizing OSA treatment.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp276206","type":"journal-article","created":{"date-parts":[[2018,6,8]],"date-time":"2018-06-08T06:30:38Z","timestamp":1528439438000},"page":"4043-4056","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["Breath\u2010holding as a means to estimate the loop gain contribution to obstructive sleep apnoea"],"prefix":"10.1113","volume":"596","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4142-9124","authenticated-orcid":false,"given":"Ludovico","family":"Messineo","sequence":"first","affiliation":[{"name":"Division of Sleep and Circadian Disorders Departments of Medicine and Neurology Brigham and Women's Hospital and Harvard Medical School  Boston MA USA"},{"name":"Respiratory Medicine and Sleep Laboratory Department of Experimental and Clinical Sciences University of Brescia and Spedali Civili  Brescia 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Brigham and Women's Hospital and Harvard Medical School  Boston MA USA"},{"name":"Pulmonary Division Heart Institute (InCor) Hospital das Cl\u00ednicas University of S\u00e3o Paulo School of Medicine  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Calianese","sequence":"additional","affiliation":[{"name":"Division of Sleep and Circadian Disorders Departments of Medicine and Neurology Brigham and Women's Hospital and Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P.","family":"White","sequence":"additional","affiliation":[{"name":"Division of Sleep and Circadian Disorders Departments of Medicine and Neurology Brigham and Women's Hospital and Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Wellman","sequence":"additional","affiliation":[{"name":"Division of Sleep and Circadian Disorders Departments 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