{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T00:21:54Z","timestamp":1778890914902,"version":"3.51.4"},"reference-count":43,"publisher":"IOP Publishing","issue":"4","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/iopscience.iop.org\/page\/copyright"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/iopscience.iop.org\/info\/page\/text-and-data-mining"}],"content-domain":{"domain":["iopscience.iop.org"],"crossmark-restriction":false},"short-container-title":["J. Breath Res."],"published-print":{"date-parts":[[2025,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>There is an unmet need for breath-based markers for pulmonary vascular disease (PVD). We developed a fully-automatic algorithm to analyze expiratory CO<jats:sub>2<\/jats:sub> flow from resting ventilation and evaluated the clinical associations of our readouts. We enrolled patients with chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), pulmonary arterial hypertension (PAH) and healthy controls and evaluated fractionated volumes for dead space, mixed space (MSV) and alveolar space, their respective CO<jats:sub>2<\/jats:sub> volumes and ventilatory equivalents for CO<jats:sub>2<\/jats:sub> (EqCO<jats:sub>2<\/jats:sub>) and the maximum slope of the first derivative of the cumulative expiratory CO<jats:sub>2<\/jats:sub> volume over expired volume (MSV-slope) as primary readouts. Differences between groups were analyzed using non-parametric tests. Associations were analyzed by Spearman correlation. The discriminatory power was determined with receiver operating characteristic analysis. Eleven COPD (median (IQR) age 64 (63\u201369) years), 10 ILD (61 (54\u201377) years), 10 PAH (64 (61\u201373) years) and 21 healthy controls (56 (52\u201361) years) were investigated. Patients vs healthy controls showed increased MSV and mixed space CO<jats:sub>2<\/jats:sub> (221 (164\u2013270) ml vs 144 (131\u2013167) ml, and 3.9 (3.2\u20134.9) ml vs 3.0 (2.7\u20133.4) ml, <jats:italic>p<\/jats:italic> &lt; 0.001 and <jats:italic>p<\/jats:italic> = 0.002) and EqCO<jats:sub>2<\/jats:sub> (38 (34\u201342) vs 30 (29\u201335), <jats:italic>p<\/jats:italic> &lt; 0.001), and decreased MSV-slopes (0.16 (0.12\u20130.21) vs 0.27 (0.23\u20130.32) l CO<jats:sub>2<\/jats:sub> l<jats:sup>\u22122<\/jats:sup>, <jats:italic>p<\/jats:italic> &lt; 0.001). Area under the curve (AUC) for MSV and MSV-slope for disease prediction was 0.81 (95% CI 0.69\u20130.93) and 0.84 (0.73\u20130.95), respectively. MSV and mixed space CO<jats:sub>2<\/jats:sub> were only strongly increased in COPD and ILD but not PAH, resulting in a significant difference between PAH and COPD&amp;ILD (AUC 0.74 (95% CI: 0.56\u20130.92). MSV and MSV-slope were significantly correlated with DLCO (<jats:italic>\u03c1<\/jats:italic>=\u22120.69 and <jats:italic>\u03c1<\/jats:italic>= 0.72, respectively; both <jats:italic>p<\/jats:italic> &lt; 0.001). Fully-automatic high-fidelity expiratory CO<jats:sub>2<\/jats:sub> flow analysis is technically feasible, easy and safe to perform, and may represent a novel approach to detect PVD with or without structural changes of the airways and lung parenchyma. Prospective studies with larger sample size are needed to validate these findings.<\/jats:p>","DOI":"10.1088\/1752-7163\/adf253","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T22:51:57Z","timestamp":1753138317000},"page":"046002","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Detection of structural pulmonary changes with real-time high-fidelity analysis of expiratory CO<sub>2<\/sub>"],"prefix":"10.1088","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5864-785X","authenticated-orcid":true,"given":"Teresa","family":"John","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabor","family":"Kovacs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philipp","family":"Douschan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8863-0298","authenticated-orcid":true,"given":"Vasile","family":"Foris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maximilian","family":"Gumpoldsberger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikolaus","family":"John","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8415-727X","authenticated-orcid":true,"given":"Katarina","family":"Zeder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6290-3297","authenticated-orcid":true,"given":"Andreas","family":"Zirlik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2834-7466","authenticated-orcid":true,"given":"Horst","family":"Olschewski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5542-7069","authenticated-orcid":true,"given":"Michael","family":"Pienn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"266","published-online":{"date-parts":[[2025,8,1]]},"reference":[{"key":"jbradf253bib1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00879-2022","article-title":"ESC\/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension","volume":"2022","author":"Humbert","year":"2022","journal-title":"Eur. Respir. J."},{"key":"jbradf253bib2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00016-2016","article-title":"ERS\/ATS standards for single-breath carbon monoxide uptake in the lung","volume":"49","author":"Graham","year":"2017","journal-title":"Eur. Respir. J."},{"key":"jbradf253bib3","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00164-2019","article-title":"Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease: the GOLD science committee report 2019","volume":"53","author":"Singh","year":"2019","journal-title":"Eur. Respir. J."},{"key":"jbradf253bib4","doi-asserted-by":"publisher","first-page":"e44","DOI":"10.1164\/rccm.201807-1255ST","article-title":"Diagnosis of idiopathic pulmonary fibrosis. An official ATS\/ERS\/JRS\/ALAT clinical practice guideline","volume":"198","author":"Raghu","year":"2018","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"jbradf253bib5","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1136\/heartjnl-2016-309981","article-title":"Cardiopulmonary exercise testing for detecting pulmonary arterial hypertension in systemic sclerosis","volume":"103","author":"Dumitrescu","year":"2017","journal-title":"Heart"},{"key":"jbradf253bib6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0014293","article-title":"Developing pulmonary vasculopathy in systemic sclerosis, detected with non-invasive cardiopulmonary exercise testing","volume":"5","author":"Dumitrescu","year":"2010","journal-title":"PLoS One"},{"key":"jbradf253bib7","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1093\/eurheartj\/ehz405","article-title":"ESC guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS)","volume":"41","author":"Konstantinides","year":"2019","journal-title":"Eur. Heart J."},{"key":"jbradf253bib8","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1034\/j.1399-3003.2000.16d16.x","article-title":"Partitioning of dead space \u2010 a method and reference values in the awake human","volume":"16","author":"\u00c5str\u00f6m","year":"2000","journal-title":"Eur. Respir. J."},{"key":"jbradf253bib9","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1111\/j.1475-097X.2008.00815.x","article-title":"Capnovolumetry: a new tool for lung function testing in children with asthma","volume":"28","author":"Stei\u00df","year":"2008","journal-title":"Clin. Physiol. Funct. Imaging"},{"key":"jbradf253bib10","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1186\/s12931-019-1067-1","article-title":"Diagnostic accuracy of capnovolumetry for the identification of airway obstruction\u2014results of a diagnostic study in ambulatory care","volume":"20","author":"Kellerer","year":"2019","journal-title":"Respir. Res."},{"key":"jbradf253bib11","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1183\/09031936.00109710","article-title":"Diagnosis of CTEPH versus IPAH using capillary to end-tidal carbon dioxide gradients","volume":"39","author":"Scheidl","year":"2012","journal-title":"Eur. Respir. J."},{"key":"jbradf253bib12","doi-asserted-by":"publisher","first-page":"00099","DOI":"10.1183\/23120541.00099-2018","article-title":"Retrospective validation of a new volumetric capnography parameter for the exclusion of pulmonary embolism at the emergency department","volume":"4","author":"Fabius","year":"2018","journal-title":"ERJ Open Res."},{"key":"jbradf253bib13","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1183\/09031936.00084709","article-title":"Bedside end-tidal CO2 tension as a screening tool to exclude pulmonary embolism","volume":"35","author":"Hemnes","year":"2010","journal-title":"Eur. Respir. J."},{"key":"jbradf253bib14","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1111\/j.1748-1716.1891.tb00581.x","article-title":"Ueber die Lungenathmung","volume":"2","author":"Bohr","year":"1891","journal-title":"Skand. Arch. Physiol."},{"key":"jbradf253bib15","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1113\/jphysiol.1928.sp002485","article-title":"On the fluctuation in the composition of the alveolar air during the respiratory cycle in muscular exercise","volume":"65","author":"Aitken","year":"1928","journal-title":"J. Physiol."},{"key":"jbradf253bib16","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1152\/ajplegacy.1948.154.3.405","article-title":"LUNG FUNCTION STUDIES. II. THE RESPIRATORY DEAD SPACE","volume":"154","author":"Fowler","year":"1948","journal-title":"Am. J. Physiol. Legacy Content"},{"key":"jbradf253bib17","first-page":"209","article-title":"Ventilatory consequences of unilateral pulmonary artery occlusion","volume":"51","author":"Langley","year":"1976","journal-title":"Les colloques de L\u2019Institut National de la Sant\u00e9 et de la Recherche Medicale"},{"key":"jbradf253bib18","doi-asserted-by":"publisher","first-page":"v1","DOI":"10.1136\/thx.2008.101691","article-title":"Interstitial lung disease guideline: the British Thoracic Society in collaboration with the Thoracic Society of Australia and New Zealand and the Irish Thoracic Society","volume":"63","author":"Wells","year":"2008","journal-title":"Thorax"},{"key":"jbradf253bib19","doi-asserted-by":"publisher","DOI":"10.1055\/a-2017-8971","article-title":"S1 Leitlinie Interdisziplin\u00e4re Diagnostik interstitieller Lungenerkrankungen im Erwachsenenalter","author":"Kreuter","year":"2023"},{"key":"jbradf253bib20","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1007\/BF03008330","article-title":"Capnometry and anaesthesia","volume":"39","author":"Bhavani-Shankar","year":"1992","journal-title":"Can. J. Anaesth."},{"key":"jbradf253bib21","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1007\/BF01617719","article-title":"Terminology and the current limitations of time capnography: a brief review","volume":"11","author":"Bhavani-Shankar","year":"1995","journal-title":"J. Clin. Monit."},{"key":"jbradf253bib22","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1093\/bja\/56.2.109","article-title":"Deadspace and the single breath test for carbon dioxide during anaesthesia and artificial ventilation. Effects of tidal volume and frequency of respiration","volume":"56","author":"Fletcher","year":"1984","journal-title":"Br. J. Anaesth."},{"key":"jbradf253bib23","doi-asserted-by":"publisher","first-page":"2882","DOI":"10.1109\/TBME.2014.2332954","article-title":"Automated quantitative analysis of capnogram shape for COPD-normal and COPD-CHF classification","volume":"61","author":"Mieloszyk","year":"2014","journal-title":"IEEE Trans. Biomed. Eng."},{"key":"jbradf253bib24","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1111\/j.1365-2044.2011.06793.x","article-title":"Time for capnography\u2014everywhere","volume":"66","author":"Whitaker","year":"2011","journal-title":"Anaesthesia"},{"key":"jbradf253bib25","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1378\/chest.15-1369","article-title":"Capnography during critical illness","volume":"149","author":"Nassar","year":"2016","journal-title":"Chest"},{"key":"jbradf253bib26","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1186\/s13054-016-1377-3","article-title":"Volumetric capnography: lessons from the past and current clinical applications","volume":"20","author":"Verscheure","year":"2016","journal-title":"Crit. care"},{"key":"jbradf253bib27","doi-asserted-by":"publisher","first-page":"785","DOI":"10.3233\/THC-181288","article-title":"Assessment of newly developed real-time human respiration carbon dioxide measurement device for management of asthma outside of hospital","volume":"26","author":"Singh","year":"2018","journal-title":"Technol. Health Care"},{"key":"jbradf253bib28","doi-asserted-by":"publisher","first-page":"18","DOI":"10.37934\/scbtrj.1.1.1839","article-title":"A narrative review of capnography usage in clinical medicine","volume":"1","author":"Vijayam","year":"2024","journal-title":"SCBTRJ"},{"key":"jbradf253bib29","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1007\/s10877-009-9182-z","article-title":"Model fitting of volumetric capnograms improves calculations of airway dead space and slope of phase III","volume":"23","author":"Tusman","year":"2009","journal-title":"J. Clin. Monit. Comput."},{"key":"jbradf253bib30","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1007\/s00134-023-07050-7","article-title":"ESICM guidelines on acute respiratory distress syndrome: definition, phenotyping and respiratory support strategies","volume":"49","author":"Grasselli","year":"2023","journal-title":"Intensive Care Med."},{"key":"jbradf253bib31","doi-asserted-by":"publisher","DOI":"10.1080\/15412555.2024.2321379","article-title":"Diagnosis and severity assessment of COPD using a novel fast-response capnometer and interpretable machine learning","volume":"21","author":"Talker","year":"2024","journal-title":"COPD"},{"key":"jbradf253bib32","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1183\/09031936.97.10061309","article-title":"Physiologically based indices of volumetric capnography in patients receiving mechanical ventilation","volume":"10","author":"Romero","year":"1997","journal-title":"Eur. Respir. J."},{"key":"jbradf253bib33","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1378\/chest.07-0935","article-title":"Prognostic value of different dead space indices in mechanically ventilated patients with acute lung injury and ARDS","volume":"133","author":"Lucangelo","year":"2008","journal-title":"Chest"},{"key":"jbradf253bib34","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1097\/00000542-199501000-00010","article-title":"Volumetric capnography in children. Influence of growth on the alveolar plateau slope","volume":"82","author":"Ream","year":"1995","journal-title":"Anesthesiology"},{"key":"jbradf253bib35","author":"Wasserman","year":"2005","edition":"(ed)"},{"key":"jbradf253bib36","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02036-2016","article-title":"Physiological and clinical relevance of exercise ventilatory efficiency in COPD","volume":"49","author":"Neder","year":"2017","journal-title":"Eur. Respir. J."},{"key":"jbradf253bib37","doi-asserted-by":"publisher","first-page":"659","DOI":"10.3389\/fphys.2020.00659","article-title":"Measurement and interpretation of exercise ventilatory efficiency","volume":"11","author":"Phillips","year":"2020","journal-title":"Front. Physiol."},{"key":"jbradf253bib38","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0101-2018","article-title":"ERS statement on standardisation of cardiopulmonary exercise testing in chronic lung diseases","volume":"28","author":"Radtke","year":"2019","journal-title":"Eur. Respir. Rev."},{"key":"jbradf253bib39","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/1471-2466-12-23","article-title":"Ventilatory efficiency testing as prognostic value in patients with pulmonary hypertension","volume":"12","author":"Schwaiblmair","year":"2012","journal-title":"BMC Pulm. Med."},{"key":"jbradf253bib40","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1161\/01.cir.0000022687.18568.2a","article-title":"Assessment of survival in patients with primary pulmonary hypertension: importance of cardiopulmonary exercise testing","volume":"106","author":"Wensel","year":"2002","journal-title":"Circulation"},{"key":"jbradf253bib41","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1161\/hc3101.093699","article-title":"Peripheral chemoreceptor hypersensitivity: an ominous sign in patients with chronic heart failure","volume":"104","author":"Ponikowski","year":"2001","journal-title":"Circulation"},{"key":"jbradf253bib42","doi-asserted-by":"publisher","first-page":"1410","DOI":"10.1183\/09031936.00217911","article-title":"Exercise testing to predict outcome in idiopathic versus associated pulmonary arterial hypertension","volume":"40","author":"Deboeck","year":"2012","journal-title":"Eur. Respir. J."},{"key":"jbradf253bib43","doi-asserted-by":"publisher","first-page":"1284","DOI":"10.1378\/chest.10-3357","article-title":"Differences in ventilatory inefficiency between pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension","volume":"140","author":"Zhai","year":"2011","journal-title":"Chest"}],"container-title":["Journal of Breath Research"],"original-title":[],"link":[{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1752-7163\/adf253","content-type":"text\/html","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1752-7163\/adf253\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1752-7163\/adf253","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1752-7163\/adf253\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1752-7163\/adf253\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1752-7163\/adf253\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1752-7163\/adf253\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"similarity-checking"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1752-7163\/adf253\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T12:11:48Z","timestamp":1754050308000},"score":1,"resource":{"primary":{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1752-7163\/adf253"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,1]]},"references-count":43,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,8,1]]},"published-print":{"date-parts":[[2025,10,1]]}},"URL":"https:\/\/doi.org\/10.1088\/1752-7163\/adf253","relation":{},"ISSN":["1752-7155","1752-7163"],"issn-type":[{"value":"1752-7155","type":"print"},{"value":"1752-7163","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,1]]},"assertion":[{"value":"Detection of structural pulmonary changes with real-time high-fidelity analysis of expiratory CO2","name":"article_title","label":"Article Title"},{"value":"Journal of Breath Research","name":"journal_title","label":"Journal Title"},{"value":"paper","name":"article_type","label":"Article Type"},{"value":"\u00a9 2025 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.","name":"copyright_information","label":"Copyright Information"},{"value":"2024-08-07","name":"date_received","label":"Date Received","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2025-07-21","name":"date_accepted","label":"Date Accepted","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2025-08-01","name":"date_epub","label":"Online publication date","group":{"name":"publication_dates","label":"Publication dates"}}]}}