{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T06:44:14Z","timestamp":1793774654175,"version":"4.6.1"},"reference-count":42,"publisher":"European Respiratory Society (ERS)","issue":"3","license":[{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["ERJ Open Res"],"accepted":{"date-parts":[[2024,11,7]]},"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:sec><jats:title>Rationale<\/jats:title><jats:p>Dysfunctional breathing (DB) is a commonly identified abnormality in post-acute sequelae of SARS-CoV-2 (PASC) patients undergoing cardiopulmonary exercise testing (CPET), and is potentially a contributor to ongoing symptoms. Currently, this oscillating, irregular breathing pattern is identified by visual observation of CPET data by an experienced interpreter, which is subjective. We hypothesise that approximate entropy (ApEn), a regularity statistic that quantifies the unpredictability of time-series data can reliably distinguish DB from normal breathing states.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Breath-by-breath CPET data were obtained for 82 PASC subjects and 25 controls. CPETs were visually analysed for DB prior to analysis. Minute ventilation (<jats:italic>V<\/jats:italic>\u2032<jats:sub>E<\/jats:sub>), tidal volume (<jats:italic>V<\/jats:italic><jats:sub>T<\/jats:sub>) and breathing frequency (BF) over time data were normalised with 100% considered as the ventilation at anaerobic threshold (AT) and detrended before ApEn was calculated. Analysis was initiated at 25\u2005W and ceased at AT.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The ApEn<jats:italic>V<\/jats:italic>\u2032<jats:sub>E<\/jats:sub>of PASC subjects with visualised DB was 0.286\u00b10.128 (mean\u00b1<jats:sc>sd<\/jats:sc>), which was significantly different from control subjects (0.143\u00b10.081) and PASC subjects without visualised DB (0.183\u00b10.104); p&lt;0.05. Receiver operating characteristic curve analysis produced an optimal cut-off value of 0.17 for distinguishing DB, which resulted in a sensitivity of 81% and specificity of 72%. ApEn<jats:italic>V<\/jats:italic><jats:sub>T<\/jats:sub>and ApEn BF were similar among all PASC patients despite visually recognised DB, but significantly greater than controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Identifying DB on CPET requires visual recognition, which has limitations. ApEn<jats:italic>V<\/jats:italic>\u2032<jats:sub>E<\/jats:sub>is an objective metric that can reliably differentiate DB from normal breathing patterns on CPET. This can be a valuable addition to keen visual scrutiny of CPET data.<\/jats:p><\/jats:sec>","DOI":"10.1183\/23120541.00652-2024","type":"journal-article","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T17:00:33Z","timestamp":1739466033000},"page":"00652-2024","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Characterising dysfunctional breathing seen in post-acute sequelae of SARS-CoV-2 using approximate entropy"],"prefix":"10.1183","volume":"11","author":[{"given":"Erin","family":"Eschbach","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin H.","family":"Natelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna M.","family":"Mancini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dane B.","family":"Cook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Rurak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Miranda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beno W.","family":"Oppenheimer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Rapoport","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankit","family":"Parekh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2025,2,13]]},"reference":[{"key":"2025060402100636000_11.3.00652-2024.1","doi-asserted-by":"publisher","DOI":"10.1007\/s42399-022-01167-4"},{"key":"2025060402100636000_11.3.00652-2024.2","doi-asserted-by":"publisher","DOI":"10.1093\/INFDIS\/JIAC136"},{"key":"2025060402100636000_11.3.00652-2024.3","doi-asserted-by":"crossref","first-page":"419","DOI":"10.3390\/medicina58030419","article-title":"Dyspnea in post-COVID syndrome following mild acute COVID-19 infections: potential causes and consequences for a therapeutic approach","volume":"58","author":"Wirth","year":"2022","journal-title":"Medicina (Kaunas)"},{"key":"2025060402100636000_11.3.00652-2024.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2021.10.002"},{"key":"2025060402100636000_11.3.00652-2024.5","doi-asserted-by":"publisher","DOI":"10.1136\/bmjresp-2021-001126"},{"key":"2025060402100636000_11.3.00652-2024.6","doi-asserted-by":"crossref","first-page":"pzac105","DOI":"10.1093\/ptj\/pzac105","article-title":"Persistent exertional dyspnea and perceived exercise intolerance after mild COVID-19: a critical role for breathing dysregulation?","volume":"102","author":"van Voorthuizen","year":"2022","journal-title":"Phys Ther"},{"key":"2025060402100636000_11.3.00652-2024.7","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00629-2023"},{"key":"2025060402100636000_11.3.00652-2024.8","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0088-2015"},{"key":"2025060402100636000_11.3.00652-2024.9","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1513\/AnnalsATS.202004-398FR","article-title":"Residual exertional dyspnea in cardiopulmonary disease","volume":"17","author":"Neder","year":"2020","journal-title":"Ann Am Thorac Soc"},{"key":"2025060402100636000_11.3.00652-2024.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.prrv.2014.10.001"},{"key":"2025060402100636000_11.3.00652-2024.11","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199512073332307"},{"key":"2025060402100636000_11.3.00652-2024.12","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00635.2006"},{"key":"2025060402100636000_11.3.00652-2024.13","doi-asserted-by":"crossref","first-page":"620955","DOI":"10.3389\/fphys.2020.620955","article-title":"Cardiopulmonary exercise testing in the assessment of dysfunctional breathing","volume":"11","author":"Ionescu","year":"2020","journal-title":"Front Physiol"},{"key":"2025060402100636000_11.3.00652-2024.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2011.03.006"},{"key":"2025060402100636000_11.3.00652-2024.15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.resp.2018.05.002","article-title":"Exercise ventilatory irregularity can be quantified by approximate entropy to detect breathing pattern disorder","volume":"255","author":"Bansal","year":"2018","journal-title":"Respir Physiol Neurobiol"},{"key":"2025060402100636000_11.3.00652-2024.16","doi-asserted-by":"publisher","DOI":"10.1007\/BF01619355"},{"key":"2025060402100636000_11.3.00652-2024.17","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.2007.121558"},{"key":"2025060402100636000_11.3.00652-2024.18","doi-asserted-by":"publisher","DOI":"10.1378\/chest.121.5.1572"},{"key":"2025060402100636000_11.3.00652-2024.19","first-page":"959","article-title":"Dynamic and steady-state respiratory responses to bicycle exercise","volume":"42","author":"Pearce","year":"1977","journal-title":"J Appl Physiol Respir Environ Exerc Physiol"},{"key":"2025060402100636000_11.3.00652-2024.20","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1973.35.2.236"},{"key":"2025060402100636000_11.3.00652-2024.21","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.3389\/fphys.2020.614590","article-title":"Hyperventilation: a possible explanation for long-lasting exercise intolerance in mild COVID-19 survivors?","volume":"11","author":"Motiejunaite","year":"2021","journal-title":"Front Physiol"},{"key":"2025060402100636000_11.3.00652-2024.22","doi-asserted-by":"crossref","first-page":"101066.","DOI":"10.1016\/j.eclinm.2021.101066","article-title":"Exercise performance in patients with post-acute sequelae of SARS-CoV-2 infection compared to patients with unexplained dyspnea","volume":"39","author":"Alba","year":"2021","journal-title":"eClinicalMedicine"},{"key":"2025060402100636000_11.3.00652-2024.23","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00063-2023"},{"key":"2025060402100636000_11.3.00652-2024.24","doi-asserted-by":"publisher","DOI":"10.3109\/02770903.2014.922190"},{"key":"2025060402100636000_11.3.00652-2024.25","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00001-2015"},{"key":"2025060402100636000_11.3.00652-2024.26","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00031-2023"},{"key":"2025060402100636000_11.3.00652-2024.27","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.ijosm.2009.04.002","article-title":"The functions of breathing and its dysfunctions and their relationship to breathing therapy","volume":"12","author":"Courtney","year":"2009","journal-title":"Int J Osteopath Med"},{"key":"2025060402100636000_11.3.00652-2024.28","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41533-017-0024-z","article-title":"The breathing, thinking, functioning clinical model: a proposal to facilitate evidence-based breathlessness management in chronic respiratory disease","volume":"27","author":"Spathis","year":"2017","journal-title":"NPJ Prim Care Respir Med"},{"key":"2025060402100636000_11.3.00652-2024.29","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00629-2023"},{"key":"2025060402100636000_11.3.00652-2024.30","doi-asserted-by":"publisher","DOI":"10.1111\/resp.13173"},{"key":"2025060402100636000_11.3.00652-2024.31","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00117-2023"},{"key":"2025060402100636000_11.3.00652-2024.32","doi-asserted-by":"publisher","DOI":"10.1136\/bmjresp-2023-001770"},{"key":"2025060402100636000_11.3.00652-2024.33","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/S2213-2600(22)00125-4","article-title":"An online breathing and wellbeing programme (ENO Breathe) for people with persistent symptoms following COVID-19: a parallel-group, single-blind, randomised controlled trial","volume":"10","author":"Philip","year":"2022","journal-title":"Lancet Respir Med"},{"key":"2025060402100636000_11.3.00652-2024.34","doi-asserted-by":"publisher","DOI":"10.1016\/s1474-4422(20)30308-2"},{"key":"2025060402100636000_11.3.00652-2024.35","doi-asserted-by":"crossref","first-page":"e290","DOI":"10.1016\/S2666-5247(20)30144-0","article-title":"Viral presence and immunopathology in patients with lethal COVID-19: a prospective autopsy cohort study","volume":"1","author":"Schurink","year":"2020","journal-title":"Lancet Microbe"},{"key":"2025060402100636000_11.3.00652-2024.36","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-020-00758-5"},{"key":"2025060402100636000_11.3.00652-2024.37","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04569-5 3"},{"key":"2025060402100636000_11.3.00652-2024.38","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.bbi.2011.06.016","article-title":"Chronic fatigue syndrome, the immune system and viral infection","volume":"26","author":"Bansal","year":"2012","journal-title":"Brain Behav Immun, and"},{"key":"2025060402100636000_11.3.00652-2024.39","doi-asserted-by":"crossref","first-page":"1125208","DOI":"10.3389\/fnins.2023.1125208","article-title":"Brainstem volume changes in myalgic encephalomyelitis\/chronic fatigue syndrome and long COVID patients","volume":"17","author":"Thapaliya","year":"2023","journal-title":"Front Neurosci"},{"key":"2025060402100636000_11.3.00652-2024.40","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26286"},{"key":"2025060402100636000_11.3.00652-2024.41","doi-asserted-by":"crossref","first-page":"1065620","DOI":"10.3389\/fmed.2022.1065620","article-title":"Improvement of long COVID symptoms over one year","volume":"9","author":"Oliveira","year":"2022","journal-title":"Front Med (Lausanne)"},{"key":"2025060402100636000_11.3.00652-2024.42","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00745-2022"}],"container-title":["ERJ Open Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1183\/23120541.00652-2024","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T09:10:17Z","timestamp":1749028217000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.ersnet.org\/lookup\/doi\/10.1183\/23120541.00652-2024"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,13]]},"references-count":42,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,6,4]]},"published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1183\/23120541.00652-2024"],"URL":"https:\/\/doi.org\/10.1183\/23120541.00652-2024","relation":{},"ISSN":["2312-0541"],"issn-type":[{"value":"2312-0541","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,13]]}}}