{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T18:30:59Z","timestamp":1786473059984,"version":"build-2736575974"},"reference-count":33,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006109","name":"VEGA","doi-asserted-by":"crossref","award":["1\/0425\/26"],"award-info":[{"award-number":["1\/0425\/26"]}],"id":[{"id":"10.13039\/501100006109","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100006453","name":"Charles R. Drew University of Medicine and Science","doi-asserted-by":"publisher","award":["Cooperatio Program, research area INDI"],"award-info":[{"award-number":["Cooperatio Program, research area INDI"]}],"id":[{"id":"10.13039\/100006453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005357","name":"Slovak Research and Development Agency","doi-asserted-by":"crossref","award":["APVV-25-0558"],"award-info":[{"award-number":["APVV-25-0558"]}],"id":[{"id":"10.13039\/501100005357","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosdigitalhealth.org"],"crossmark-restriction":false},"short-container-title":["PLOS Digit Health"],"abstract":"<jats:p>\n                    Based on the principle that increased airway resistance prolongs the expiratory time constant (TC), we investigated whether TC patterns could serve as a signature for obstruction. In this cross-sectional multicenter study of 19,937 validated spirometry records, we divided the descending expiratory flow-volume curve into five equal volume segments and derived consecutive TCs for each. A K-means algorithm trained on the normal subset defined data-driven patterns, which were then used to classify the entire cohort. We quantified pattern prevalence and used propensity score matching to assess spirometric differences between patterns within each spirometric category. Two distinct patterns were identified: a \u2018normal\u2019 pattern (stable consecutive TCs) and an \u2018obstructive\u2019 pattern (progressively prolonging TCs). The obstructive pattern was present in 7% of normal spirometry, 13% of possible restriction, and 33% of nonspecific FEV\n                    <jats:sub>1<\/jats:sub>\n                    reduction, while 9% of patients meeting obstruction criteria had a normal TC pattern. In normal spirometry group, the obstructive pattern group showed lower forced expiratory volume in 1 second (FEV\n                    <jats:sub>1<\/jats:sub>\n                    ) (males: 2.7 vs 3.0 L; females: 1.8 vs 2.0 L), reduced FEV\n                    <jats:sub>1<\/jats:sub>\n                    \/forced vital capacity (FVC) (males: 67% vs 76%; females: 68% vs 78%), and impaired small airway metrics, including maximal mid-expiratory flow (MMEF\n                    <jats:sub>25\u201375<\/jats:sub>\n                    ) (males: 1.6 vs 2.6 L\/s; females: 1.0 vs 1.8 L\/s) and FEV\n                    <jats:sub>3<\/jats:sub>\n                    \/FEV\n                    <jats:sub>6<\/jats:sub>\n                    (males: 91% vs 94%; females: 91% vs 95%), all p\u2009&lt;\u20090.001. Other spirometric groups mirrored these findings. The obstructive TC pattern represents a distinct physiological phenotype suggestive of obstructive lung mechanics and is highly prevalent across common spirometric categories.\n                  <\/jats:p>","DOI":"10.1371\/journal.pdig.0001653","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T17:36:10Z","timestamp":1786469770000},"page":"e0001653","update-policy":"https:\/\/doi.org\/10.1371\/journal.pdig.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Expiratory time constant patterns reveal obstructive lung mechanics in non-obstructive spirometry"],"prefix":"10.1371","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2854-0450","authenticated-orcid":true,"given":"Filip","family":"Depta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Surya P.","family":"Bhatt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Heinz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radek","family":"\u010cern\u00fd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladim\u00edr","family":"Kobl\u00ed\u017eek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavol","family":"Pobeha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"pdig.0001653.ref001","doi-asserted-by":"crossref","DOI":"10.1016\/S2213-2600(24)00413-2","article-title":"GOLD COPD report: 2025 update","volume":"13","author":"P Venkatesan","year":"2025","journal-title":"Lancet Respir Med"},{"issue":"5","key":"pdig.0001653.ref002","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/S2213-2600(21)00511-7","article-title":"Global, regional, and national prevalence of, and risk factors for, chronic obstructive pulmonary disease (COPD) in 2019: A systematic review and modelling analysis","volume":"10","author":"D Adeloye","year":"2022","journal-title":"Lancet Respir Med"},{"key":"pdig.0001653.ref003","unstructured":"European Respiratory Society. European Lung White Book. Sheffield, UK: European Respiratory Society; 2013 [cited 2025 Oct 8]. https:\/\/www.erswhitebook.org\/"},{"issue":"2","key":"pdig.0001653.ref004","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1378\/chest.06-1349","article-title":"Spirometric criteria for airway obstruction: Use percentage of FEV1\/FVC ratio below the fifth percentile, not < 70%","volume":"131","author":"JE Hansen","year":"2007","journal-title":"Chest"},{"issue":"2","key":"pdig.0001653.ref005","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1183\/09031936.05.00034805","article-title":"Standardisation of spirometry","volume":"26","author":"MR Miller","year":"2005","journal-title":"Eur Respir J"},{"issue":"6","key":"pdig.0001653.ref006","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1183\/09031936.00080312","article-title":"Multi-ethnic reference values for spirometry for the 3-95-yr age range: The global lung function 2012 equations","volume":"40","author":"PH Quanjer","year":"2012","journal-title":"Eur Respir J"},{"key":"pdig.0001653.ref007","first-page":"801","article-title":"The role of small airways in the development of chronic obstructive pulmonary disease: A state-of-the-art review","volume":"162","author":"IZ Barjaktarevic","year":"2022","journal-title":"Chest"},{"issue":"1","key":"pdig.0001653.ref008","article-title":"Isolated small airways obstruction predicts future chronic airflow obstruction: A multinational longitudinal study","volume":"10","author":"B Knox-Brown","year":"2023","journal-title":"BMJ Open Respir Res"},{"issue":"6","key":"pdig.0001653.ref009","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/0002-9343(72)90078-2","article-title":"A reduction in maximum mid-expiratory flow rate. A spirographic manifestation of small airway disease","volume":"52","author":"ER McFadden","year":"1972","journal-title":"Am J Med"},{"key":"pdig.0001653.ref010","doi-asserted-by":"crossref","DOI":"10.1164\/rccm.201908-1590ST","article-title":"Standardization of spirometry 2019 update. An Official American Thoracic Society and European Respiratory Society Technical Statement","volume":"200","author":"BL Graham","year":"2019","journal-title":"Am J Respir Crit Care Med"},{"issue":"4","key":"pdig.0001653.ref011","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1378\/chest.117.4.1146","article-title":"Office spirometry for lung health assessment in adults: A consensus statement from the National Lung Health Education Program","volume":"117","author":"GT Ferguson","year":"2000","journal-title":"Chest"},{"key":"pdig.0001653.ref012","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/j.chest.2021.10.046","article-title":"Significance of FEV3\/FEV6 in recognition of early airway disease in smokers at risk of development of COPD: Analysis of the SPIROMICS Cohort","volume":"161","author":"N Yee","year":"2022","journal-title":"Chest"},{"issue":"4","key":"pdig.0001653.ref013","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1378\/chest.12-2816","article-title":"An isolated reduction of the FEV3\/FVC ratio is an indicator of mild lung injury","volume":"144","author":"ZQ Morris","year":"2013","journal-title":"Chest"},{"issue":"2","key":"pdig.0001653.ref014","first-page":"00624","article-title":"Optimal spirometry thresholds for the prediction of chronic airflow obstruction: A multinational longitudinal study","volume":"11","author":"AHS Lam","year":"2025","journal-title":"ERJ Open Res"},{"key":"pdig.0001653.ref015","first-page":"355","article-title":"The shape of the expiratory flow-volume curve in smokers with and without COPD","volume":"177","author":"MT Dransfield","year":"2008","journal-title":"Am J Respir Crit Care Med"},{"issue":"1","key":"pdig.0001653.ref016","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1148\/radiol.11110173","article-title":"Chronic obstructive pulmonary disease exacerbations in the COPDGene study: Associated radiologic phenotypes","volume":"261","author":"MK Han","year":"2011","journal-title":"Radiology"},{"issue":"1","key":"pdig.0001653.ref017","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s40635-024-00612-z","article-title":"Six methods to determine expiratory time constants in mechanically ventilated patients: A prospective observational physiology study","volume":"12","author":"F Depta","year":"2024","journal-title":"Intensive Care Med Exp"},{"issue":"1","key":"pdig.0001653.ref018","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s40635-025-00745-9","article-title":"Expiratory time constants in mechanically ventilated patients: Rethinking the old concept-a narrative review","volume":"13","author":"F Depta","year":"2025","journal-title":"Intensive Care Med Exp"},{"key":"pdig.0001653.ref019","article-title":"Spirometric time constant for detection of early and mild airflow obstruction","volume":"209","author":"S Bodduluri","year":"2024","journal-title":"Am J Respir Crit Care Med"},{"issue":"1","key":"pdig.0001653.ref020","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1183\/09031936.95.08010114","article-title":"Time constant\/volume relationship of passive expiration in mechanically ventilated ARDS patients","volume":"8","author":"J Guttmann","year":"1995","journal-title":"Eur Respir J"},{"issue":"11","key":"pdig.0001653.ref021","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1007\/s001340000632","article-title":"Expiratory time constants in mechanically ventilated patients with and without COPD","volume":"26","author":"MS Lourens","year":"2000","journal-title":"Intensive Care Med"},{"issue":"1","key":"pdig.0001653.ref022","doi-asserted-by":"crossref","first-page":"2101499","DOI":"10.1183\/13993003.01499-2021","article-title":"ERS\/ATS technical standard on interpretive strategies for routine lung function tests","volume":"60","author":"S Stanojevic","year":"2022","journal-title":"Eur Respir J"},{"issue":"3","key":"pdig.0001653.ref023","doi-asserted-by":"crossref","first-page":"100181","DOI":"10.1016\/j.chpulm.2025.100181","article-title":"Expiratory time constants in patients undergoing routine spirometry","volume":"3","author":"F Depta","year":"2025","journal-title":"CHEST Pulmonary"},{"key":"pdig.0001653.ref024","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s00408-025-00866-8","article-title":"Four methods to determine expiratory time constants from spirometry and their sensitivity to detect airway obstruction","volume":"204","author":"F Depta","year":"2026","journal-title":"Lung"},{"issue":"6","key":"pdig.0001653.ref025","doi-asserted-by":"crossref","first-page":"615740","DOI":"10.1155\/2015\/615740","article-title":"An enhanced k-means clustering algorithm for pattern discovery in healthcare data","volume":"11","author":"RA Haraty","year":"2015","journal-title":"International Journal of Distributed Sensor Networks"},{"issue":"1","key":"pdig.0001653.ref026","first-page":"96","article-title":"Studies of free collapse in the intact human lung","volume":"54","author":"JA Pierce","year":"1959","journal-title":"J Lab Clin Med"},{"issue":"1","key":"pdig.0001653.ref027","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1186\/s12890-019-0976-6","article-title":"Reference value for expiratory time constant calculated from the maximal expiratory flow-volume curve","volume":"19","author":"T Ikeda","year":"2019","journal-title":"BMC Pulm Med"},{"key":"pdig.0001653.ref028","article-title":"A reduced FEV1\/FVC ratio in combination with a low FVC is a common finding in patients with a restrictive spirometric pattern","volume":"100","author":"JD Leuppi","year":"2006","journal-title":"Respir Med"},{"key":"pdig.0001653.ref029","first-page":"1589","article-title":"The mixed ventilatory defect: Is it a distinct clinical entity?","volume":"60","author":"DL Balfe","year":"2015","journal-title":"Respir Care"},{"issue":"2","key":"pdig.0001653.ref030","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1056\/NEJMoa1411532","article-title":"Lung-function trajectories leading to chronic obstructive pulmonary disease","volume":"373","author":"P Lange","year":"2015","journal-title":"N Engl J Med"},{"issue":"22","key":"pdig.0001653.ref031","doi-asserted-by":"crossref","first-page":"2268","DOI":"10.1001\/jama.2020.6918","article-title":"Association of dysanapsis with chronic obstructive pulmonary disease among older adults","volume":"323","author":"BM Smith","year":"2020","journal-title":"JAMA"},{"key":"pdig.0001653.ref032","first-page":"16441","article-title":"Standalone electrical impedance tomography predicts spirometry indicators and enables regional lung assessment","volume":"12","author":"AD Waldmann","year":"2022","journal-title":"Scientific Reports"},{"issue":"1","key":"pdig.0001653.ref033","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1038\/s41467-024-55505-2","article-title":"Early screening of lung function by electrical impedance tomography in people with normal spirometry reveals unrecognized pathological features","volume":"16","author":"S Qu","year":"2025","journal-title":"Nat Commun"}],"container-title":["PLOS Digital Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pdig.0001653","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T17:36:19Z","timestamp":1786469779000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pdig.0001653"}},"subtitle":[],"editor":[{"given":"Jie-Zhi","family":"Cheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,8,11]]},"references-count":33,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8,11]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pdig.0001653","relation":{},"ISSN":["2767-3170"],"issn-type":[{"value":"2767-3170","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,11]]}}}