{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:02:50Z","timestamp":1790744570549,"version":"4.1.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"\n Background<\/jats:title>\n \n Controlled voluntary hyperventilation is widely used to study the ventilatory control of end-tidal CO\n 2<\/jats:sub>\n (PetCO\n 2<\/jats:sub>\n ), but the breath-by-breath determinants of PetCO\n 2<\/jats:sub>\n during an externally paced maneuver remain incompletely characterized. This repeated-measures pilot study aimed to describe PetCO\n 2<\/jats:sub>\n changes and to quantify associations with ventilatory timing and expired gas output during paced voluntary hyperventilation.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Thirty healthy males (age range 19.2\u201339.8) performed a metronome-paced voluntary hyperventilation maneuver at 30 breaths\/min intended to last up to 3\u00a0min. Breath-by-breath data were recorded with a COSMED K5 (COSMED, Rome, Italy). After excluding breaths with implausible respiratory frequency, 2,298 breaths from 30 participants were analyzed with a linear mixed model (LMM) using a cubic B-spline for elapsed time, participant-specific random intercepts and random slopes, and fixed effects of minute ventilation (VE), expired CO\n 2<\/jats:sub>\n output (VCO\n 2<\/jats:sub>\n ), and expiratory time (Te). A generalized estimating equation (GEE) with AR(1) working correlation was a sensitivity analysis, and participant-level cluster-bootstrap CIs provided the primary inferential intervals.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Participant-level mean PetCO\n 2<\/jats:sub>\n during the maneuver was 17.1 \u00b1 1.8 mmHg (range 13.3\u201321.2 mmHg) and declined over time. In the primary LMM, VE \u03b2 = \u22120.144, VCO\n 2<\/jats:sub>\n \u03b2 = 0.009, and Te \u03b2 = 4.18. Because residual diagnostics showed non-normality, heteroscedasticity, and strong serial autocorrelation (GEE AR(1) alpha approximately 0.79 for the spline model and 0.86 for the linear-time model), cluster-bootstrap CIs are reported as the primary inferential intervals: VE \u22120.174 to \u22120.110, VCO2 0.005 to 0.012, Te 2.330 to 6.164, and a predicted PetCO2 change from 0 to 180 s of \u22128.58 mmHg (95% CI \u221210.30 to \u22126.92 mmHg). Marginal R\n 2<\/jats:sup>\n \u00a0=\u00a00.775 and conditional R\n 2<\/jats:sup>\n \u00a0=\u00a00.828; leave-one-participant-out cross-validation yielded R\n 2<\/jats:sup>\n \u00a0=\u00a00.737 and RMSE\u00a0=\u00a02.52 mmHg.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n PetCO\n 2<\/jats:sub>\n during paced hyperventilation was associated with elapsed time, VE, VCO\n 2<\/jats:sub>\n , and Te. Because VE and VCO\n 2<\/jats:sub>\n are algebraically coupled, and VCO\n 2<\/jats:sub>\n and PetCO\n 2<\/jats:sub>\n also share information from the expired-CO\n 2<\/jats:sub>\n signal, they should not be interpreted as independent physiological determinants; the principal contribution is the within-participant expiratory-time association. The findings are exploratory and require confirmation in clinical populations.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fphys.2026.1890190","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:53:15Z","timestamp":1790743995000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["End-tidal CO2 responses and ventilatory correlates during voluntary hyperventilation: a repeated-measures pilot study"],"prefix":"10.3389","volume":"17","author":[{"given":"Liping","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Research, People\u2019s Liberation Army Air Force Special Medical Center","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihao","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Research, People\u2019s Liberation Army Air Force Special Medical Center","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenglin","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Research, People\u2019s Liberation Army Air Force Special Medical Center","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huibian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Research, People\u2019s Liberation Army Air Force Special Medical Center","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihua","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Research, People\u2019s Liberation Army Air Force Special Medical Center","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"GuiYou","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Research, People\u2019s Liberation Army Air Force Special Medical Center","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Research, People\u2019s Liberation Army Air Force Special Medical Center","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/children12070938","article-title":"Non-invasive capnography versus pulse oximetry for early detection of respiratory depression during pediatric procedural sedation: a prospective observational study","volume":"12","author":"Altarriba","year":"2025","journal-title":"Children (Basel)"},{"key":"B2","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1016\/j.jml.2007.12.005","article-title":"Mixed-effects modeling with crossed random effects for subjects and items","volume":"59","author":"Baayen","year":"2008","journal-title":"J. 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