{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T20:44:23Z","timestamp":1790196263721,"version":"4.1.0"},"reference-count":32,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"crossref","award":["No. 24-15-00549"],"award-info":[{"award-number":["No. 24-15-00549"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"crossref"}]},{"award":["No. 24-15-00549"],"award-info":[{"award-number":["No. 24-15-00549"]}],"id":[{"id":"https:\/\/ror.org\/03y2gwe85","id-type":"ROR","asserted-by":"publisher"}]},{"name":"government assignment","award":["1023022600020-6"],"award-info":[{"award-number":["1023022600020-6"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic obstructive and inflammatory lung diseases share overlapping clinical manifestations and spirometric features, complicating differential diagnosis and monitoring. In this study, we performed an integrative real-time proton-transfer-reaction time-of-flight mass spectrometry (PTR-TOF-MS) breathomics analysis to assess whether exhaled volatile organic compound (VOC) profiles enable multiclass discrimination among bronchial asthma (BA), chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and lymphangioleiomyomatosis (LAM), with healthy individuals as controls. Breath VOC data from 843 subjects were analyzed using a stratified 70\/30 train\/test split. An ensemble feature selection strategy based on gradient boosting (XGBoost with SMOTE within cross-validation) identified stable VOC panels (top 25% selection probability), yielding 29 VOCs and 31 features including clinical covariates. On the independent test set, the VOC-only model achieved a macro-averaged one-vs-one (OvO) AUC of 0.866 (95% CI 0.829\u20130.903), while the combined model improved to 0.888 (95% CI 0.853\u20130.919), indicating modest value of clinical variables. Pairwise analysis demonstrated highest discrimination for CF (AUC up to 0.988), whereas BA and LAM showed lower sensitivity (&lt;0.60), likely reflecting heterogeneity and limited sample size. Given differences in age, sex, BMI, and smoking status across cohorts, confounding effects were assessed, confirming that VOC signatures retain independent diagnostic information. Disease-specific VOC interaction networks revealed distinct remodeling patterns, with central metabolites not captured by univariate analysis. Overall, PTR-TOF-MS breathomics demonstrates proof-of-concept multiclass discrimination across chronic lung diseases.<\/jats:p>","DOI":"10.3390\/ijms27083483","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T13:12:26Z","timestamp":1776085946000},"page":"3483","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cross-Disease Breathomics by PTR-TOF-MS: Multiclass Machine Learning and Network Remodeling Across Asthma, COPD, Cystic Fibrosis, and Lymphangioleiomyomatosis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0250-9949","authenticated-orcid":false,"given":"Malika","family":"Mustafina","sequence":"first","affiliation":[{"name":"Department of Cardiology, Functional and Ultrasound Diagnostics, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119048 Moscow, Russia"},{"name":"Pulmonology Research Institute under the Federal Medical and Biological Agency of Russia, 115682 Moscow, Russia"},{"name":"Research Institute for Systemic Analysis of the Russian Academy of Sciences, 117218 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artemiy","family":"Silantyev","sequence":"additional","affiliation":[{"name":"World-Class Research Center \u201cDigital Biodesign and Personalized Healthcare\u201d, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119048 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2224-0019","authenticated-orcid":false,"given":"Aleksandr","family":"Suvorov","sequence":"additional","affiliation":[{"name":"World-Class Research Center \u201cDigital Biodesign and Personalized Healthcare\u201d, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119048 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanislav","family":"Krasovskiy","sequence":"additional","affiliation":[{"name":"Pulmonology Research Institute under the Federal Medical and Biological Agency of Russia, 115682 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4913-087X","authenticated-orcid":false,"given":"Marina","family":"Makarova","sequence":"additional","affiliation":[{"name":"Pulmonology Research Institute under the Federal Medical and Biological Agency of Russia, 115682 Moscow, Russia"},{"name":"Federal State Autonomous Educational Institution of Higher Education, N.I. Pirogov Russian National Research Medical University, 1 Ostrovityanova str., Bldg. 6, 117513 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2001-5504","authenticated-orcid":false,"given":"Alexander","family":"Chernyak","sequence":"additional","affiliation":[{"name":"Pulmonology Research Institute under the Federal Medical and Biological Agency of Russia, 115682 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9661-7213","authenticated-orcid":false,"given":"Olga","family":"Suvorova","sequence":"additional","affiliation":[{"name":"Pulmonology Department, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119048 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1314-0091","authenticated-orcid":false,"given":"Anna","family":"Shmidt","sequence":"additional","affiliation":[{"name":"Pulmonology Department, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119048 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"Gognieva","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Functional and Ultrasound Diagnostics, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119048 Moscow, Russia"},{"name":"Research Institute for Systemic Analysis of the Russian Academy of Sciences, 117218 Moscow, Russia"},{"name":"World-Class Research Center \u201cDigital Biodesign and Personalized Healthcare\u201d, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119048 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2035-2340","authenticated-orcid":false,"given":"Aleksandra","family":"Bykova","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Functional and Ultrasound Diagnostics, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119048 Moscow, Russia"},{"name":"Research Institute for Systemic Analysis of the Russian Academy of Sciences, 117218 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0243-6724","authenticated-orcid":false,"given":"Nana","family":"Gogiberidze","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Functional and Ultrasound Diagnostics, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119048 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1946-6965","authenticated-orcid":false,"given":"Andrei","family":"Akselrod","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Functional and Ultrasound Diagnostics, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119048 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey","family":"Belevskiy","sequence":"additional","affiliation":[{"name":"Federal State Autonomous Educational Institution of Higher Education, N.I. Pirogov Russian National Research Medical University, 1 Ostrovityanova str., Bldg. 6, 117513 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey","family":"Avdeev","sequence":"additional","affiliation":[{"name":"Pulmonology Research Institute under the Federal Medical and Biological Agency of Russia, 115682 Moscow, Russia"},{"name":"Pulmonology Department, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119048 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Betelin","sequence":"additional","affiliation":[{"name":"Research Institute for Systemic Analysis of the Russian Academy of Sciences, 117218 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6452-1222","authenticated-orcid":false,"given":"Abram","family":"Syrkin","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Functional and Ultrasound Diagnostics, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119048 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Kopylov","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Functional and Ultrasound Diagnostics, I.M. 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