{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T20:39:19Z","timestamp":1793479159276,"version":"4.5.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2001,4,1]],"date-time":"2001-04-01T00:00:00Z","timestamp":986083200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The role of chemical control instability in the pathogenesis of obstructive sleep apnea (OSA) is not clear. We studied 32 patients with OSA during sleep while their upper airway was stabilized with continuous positive airway pressure. Twelve patients had repetitive OSA whenever they were asleep, regardless of body position or sleep stage, and were classified as having severe OSA (apnea\u2013hypopnea index [AHI] = 88 \u00b1 19). The remaining 20 patients had sporadic OSA or repetitive OSA for only part of the time (mild\/moderate OSA; AHI = 27 \u00b1 16). Susceptibility to periodic breathing (PB) was assessed by gradually increasing controller gain, using proportional assist ventilation. The increase in loop gain (LG) at each assist level was quantified from the ratio of assisted tidal volume (Vt) to the Vt obtained during single-breath reloading tests (Vt amplification factor [VtAF]). Nine of 12 patients with severe OSA developed PB, with recurrent central apneas, whereas only six of 20 patients in the mild\/moderate group developed PB (p &amp;lt; 0.02). This difference was observed despite the subjection of the mild\/moderate group to greater amplification of LG; the highest values of VtAF in the mild\/moderate and severe groups were 2.7 \u00b1 1.0 and 1.9 \u00b1 0.7, respectively (p &amp;lt; 0.01). We conclude that the chemical control system is more unstable in patients with severe OSA than in patients with milder OSA. We speculate that this may contribute to the severity of OSA, at least in some patients.<\/jats:p>","DOI":"10.1164\/ajrccm.163.5.2007013","type":"journal-article","created":{"date-parts":[[2013,4,4]],"date-time":"2013-04-04T14:37:03Z","timestamp":1365086223000},"page":"1181-1190","source":"Crossref","is-referenced-by-count":356,"title":["Chemical Control Stability in Patients with Obstructive Sleep Apnea"],"prefix":"10.1093","volume":"163","author":[{"given":"MAGDY","family":"YOUNES","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MICHELE","family":"OSTROWSKI","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"WAYNE","family":"THOMPSON","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"COLLEEN","family":"LESLIE","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"WARREN","family":"SHEWCHUK","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2001,4,1]]},"reference":[{"key":"2026032708195281400_B1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0272-5231(05)70428-7","article-title":"Recognition and consequences of obstructive sleep apnea hypopnea syndrome.","volume":"19","author":"Redline","year":"1998","journal-title":"Clin Chest Med"},{"key":"2026032708195281400_B2","first-page":"909","article-title":"Control of breathing during sleep.","volume":"118","author":"Phillipson","year":"1978","journal-title":"Am Rev Respir Dis"},{"key":"2026032708195281400_B3"},{"key":"2026032708195281400_B4","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1093\/sleep\/3.3-4.407","article-title":"Quantitative analysis of sleep and sleep apnea before and after tracheostomy in patients with the hypersomnia sleep apnea syndrome.","volume":"3","author":"Weitzman","year":"1980","journal-title":"Sleep"},{"key":"2026032708195281400_B5","first-page":"676","article-title":"Periodic breathing and the pathogenesis of occlusive sleep apnea.","volume":"126","author":"Onal","year":"1982","journal-title":"Am Rev Respir Dis"},{"key":"2026032708195281400_B6","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1152\/jappl.1998.85.5.1929","article-title":"Susceptibility to periodic breathing with assisted ventilation during sleep in normal subjects.","volume":"85","author":"Meza","year":"1998","journal-title":"J Appl Physiol"},{"key":"2026032708195281400_B7","doi-asserted-by":"crossref","first-page":"S164","DOI":"10.1093\/sleep\/19.suppl_10.164","article-title":"Ventilatory stability during sleep studied with proportional assist ventilation.","volume":"19","author":"Meza","year":"1998","journal-title":"Sleep"},{"key":"2026032708195281400_B8","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1164\/ajrccm\/145.1.114","article-title":"Proportional assist ventilation: a new approach to ventilatory support theory.","volume":"145","author":"Younes","year":"1992","journal-title":"Am Rev Respir Dis"},{"key":"2026032708195281400_B9","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/0034-5687(79)90070-7","article-title":"Experimentally induced Cheyne-Stokes breathing.","volume":"37","author":"Cherniack","year":"1979","journal-title":"Respir Physiol"},{"key":"2026032708195281400_B10","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1056\/NEJM197305032881810","article-title":"Cheyne-Stokes breathing\u2014an instability in physiologic control.","volume":"288","author":"Cherniack","year":"1973","journal-title":"N Eng J Med"},{"key":"2026032708195281400_B11","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1152\/jappl.1982.53.3.644","article-title":"Factors inducing periodic breathing in humans: a general model.","volume":"53","author":"Khoo","year":"1982","journal-title":"J Appl Physiol"},{"key":"2026032708195281400_B12","first-page":"265","article-title":"The physiologic basis of central apnea and periodic breathing.","volume":"10","author":"Younes","year":"1989","journal-title":"Curr Pulmonol"},{"key":"2026032708195281400_B13"},{"key":"2026032708195281400_B14"},{"key":"2026032708195281400_B15","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1152\/jappl.1998.84.1.3","article-title":"Control of breathing during sleep assessed by proportional assist ventilation (PAV).","volume":"84","author":"Meza","year":"1998","journal-title":"J Appl Physiol"},{"key":"2026032708195281400_B16","first-page":"A525","article-title":"A method for determining the pressure-flow (P-V) relation during proportional assist ventilation [abstract].","volume":"155","author":"Younes","year":"1997","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032708195281400_B17"},{"key":"2026032708195281400_B18"},{"key":"2026032708195281400_B19","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1152\/jappl.1990.68.3.1195","article-title":"Effect of mechanical loading on inspiratory and expiratory muscle activity during NREM sleep.","volume":"68","author":"Badr","year":"1990","journal-title":"J Appl Physiol"},{"key":"2026032708195281400_B20","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1152\/jappl.1987.63.2.603","article-title":"Neuromuscular and mechanical responses to inspiratory resistive loading during sleep.","volume":"63","author":"Hudgel","year":"1987","journal-title":"J Appl Physiol"},{"key":"2026032708195281400_B21","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1152\/jappl.1988.64.1.347","article-title":"Response of genioglossus muscle activity to nasal airway occlusion in normal sleeping adults.","volume":"64","author":"Kuna","year":"1988","journal-title":"J Appl Physiol"},{"key":"2026032708195281400_B22","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.1164\/ajrccm.159.6.9704025","article-title":"Responses of ventilator dependent patients to different levels of pressure support and proportional assist.","volume":"159","author":"Giannouli","year":"1999","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032708195281400_B23","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1152\/jappl.1996.80.2.397","article-title":"Response of ventilator dependent patients to different levels of proportional assist (PAV).","volume":"80","author":"Marantz","year":"1996","journal-title":"J Appl Physiol"},{"key":"2026032708195281400_B24"},{"key":"2026032708195281400_B25","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1097\/00003246-198207000-00001","article-title":"Hemodynamic response to changes in ventilatory pattern in patients with normal and poor left ventricular reserve.","volume":"10","author":"Mathru","year":"1982","journal-title":"Crit Care Med"},{"key":"2026032708195281400_B26","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1161\/01.CIR.66.1.108","article-title":". The effects of airway pressure on cardiac function in intact dogs and man.","volume":"66","author":"Rankin","year":"1982","journal-title":"Circulation"},{"key":"2026032708195281400_B27","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1164\/ajrccm\/140.5.1257","article-title":"Mechanism of reduced cardiac output during positive end-expiratory pressure in the dog.","volume":"140","author":"Johnston","year":"1989","journal-title":"Am Rev Respir Dis"},{"key":"2026032708195281400_B28","doi-asserted-by":"crossref","first-page":"2014","DOI":"10.1152\/jappl.1991.70.5.2014","article-title":"Sleep-induced periodic breathing and apnea: a theoretical study.","volume":"70","author":"Khoo","year":"1991","journal-title":"J Appl Physiol"},{"key":"2026032708195281400_B29","first-page":"A365","article-title":"Mechanism of downregulation of inspiratory muscle pressure with unloading during sleep [abstract].","volume":"155","author":"Mendez","year":"1997","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032708195281400_B30","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1164\/ajrccm.158.4.9712105","article-title":"Instability of ventilatory control in patients with obstructive sleep apnea.","volume":"158","author":"Hudgel","year":"1998","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032708195281400_B31","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1164\/ajrccm\/146.5_Pt_1.1250","article-title":"Respiratory short-term poststimulus potentiation (after-discharge) in patients with obstructive sleep apnea.","volume":"146","author":"Georgopoulos","year":"1992","journal-title":"Am Rev Respir Dis"},{"key":"2026032708195281400_B32","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1152\/jappl.1977.43.2.312","article-title":"Relationship of thoracic volume and airway occlusion pressure: muscular effects.","volume":"43","author":"Eldridge","year":"1997","journal-title":"J Appl Physiol"},{"key":"2026032708195281400_B33","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1152\/jappl.1981.51.4.963","article-title":"A model for the relationship between respiratory neural and mechanical outputs: I. Theory.","volume":"51","author":"Younes","year":"1981","journal-title":"J Appl Physiol"},{"key":"2026032708195281400_B34","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1152\/jappl.1990.69.2.617","article-title":"Effects of sleep-induced increases in upper airway resistance on ventilation.","volume":"69","author":"Henke","year":"1990","journal-title":"J Appl Physiol"},{"key":"2026032708195281400_B35"},{"key":"2026032708195281400_B36","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1164\/ajrccm.149.3.8118640","article-title":"Mechanisms of apnea termination in obstructive sleep apnea: role of chemoreceptor versus mechanoreceptor stimuli.","volume":"149","author":"Kimoff","year":"1994","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032708195281400_B37","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1152\/jappl.1992.72.4.1221","article-title":"Load compensation and respiratory muscle function during sleep.","volume":"72","author":"Henke","year":"1992","journal-title":"J Appl Physiol"},{"key":"2026032708195281400_B38","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1152\/jappl.1978.44.6.931","article-title":"Pathogenesis of upper airway occlusion during sleep.","volume":"44","author":"Remmers","year":"1978","journal-title":"J Appl Physiol"},{"key":"2026032708195281400_B39","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1152\/jappl.1986.61.4.1438","article-title":"Induction of periodic breathing during sleep causes upper airway obstruction in humans.","volume":"61","author":"Onal","year":"1986","journal-title":"J Appl Physiol"},{"key":"2026032708195281400_B40","doi-asserted-by":"crossref","first-page":"2201","DOI":"10.1152\/jappl.1987.62.6.2201","article-title":"Effect of hypoxia-induced periodic breathing on upper airway obstruction during sleep.","volume":"62","author":"Warner","year":"1987","journal-title":"J Appl Physiol"},{"key":"2026032708195281400_B41","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1164\/arrd.1987.135.4.899","article-title":"Changes in inspiratory muscle electrical activity and upper airway resistance during periodic breathing induced by hypoxia during sleep.","volume":"135","author":"Hudgel","year":"1987","journal-title":"Am Rev Respir Dis"},{"key":"2026032708195281400_B42","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1164\/ajrccm\/144.2.406","article-title":"Effect of hypercapnia on total pulmonary resistance during wakefulness and during NREM sleep.","volume":"144","author":"Badr","year":"1991","journal-title":"Am Rev Respir Dis"},{"key":"2026032708195281400_B43","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1152\/jappl.1994.76.4.1682","article-title":"Effect of chemoreceptor stimulation and inhibition on total pulmonary resistance in humans during NREM sleep.","volume":"76","author":"Badr","year":"1994","journal-title":"J Appl Physiol"},{"key":"2026032708195281400_B44","doi-asserted-by":"crossref","first-page":"2198","DOI":"10.1152\/jappl.1993.74.5.2198","article-title":"Pattern of breathing and upper airway mechanics during wakefulness and sleep in healthy elderly humans.","volume":"74","author":"Hudgel","year":"1993","journal-title":"J Appl Physiol"},{"key":"2026032708195281400_B45","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1152\/jappl.1983.55.3.813","article-title":"Interaction of sleep state and chemical stimuli in sustaining rhythmic ventilation.","volume":"55","author":"Skatrud","year":"1983","journal-title":"J Appl Physiol"}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/163\/5\/1181\/67548268\/ajrccm_163_5_1181.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/163\/5\/1181\/67548268\/ajrccm_163_5_1181.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T12:20:14Z","timestamp":1774614014000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/163\/5\/1181\/8541290"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,4,1]]},"references-count":45,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2001,4,1]]},"published-print":{"date-parts":[[2001,4,1]]}},"URL":"https:\/\/doi.org\/10.1164\/ajrccm.163.5.2007013","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2001,4]]},"published":{"date-parts":[[2001,4,1]]}}}