{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T20:44:24Z","timestamp":1790196264814,"version":"4.1.0"},"reference-count":27,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T00:00:00Z","timestamp":1750636800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"RSF","doi-asserted-by":"publisher","award":["24-15-00549"],"award-info":[{"award-number":["24-15-00549"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006769","name":"RSF","doi-asserted-by":"publisher","award":["1023022600020-6"],"award-info":[{"award-number":["1023022600020-6"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the government assignment","award":["24-15-00549"],"award-info":[{"award-number":["24-15-00549"]}]},{"name":"the government assignment","award":["1023022600020-6"],"award-info":[{"award-number":["1023022600020-6"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lymphangioleiomyomatosis (LAM) is a rare progressive disease that affects women of reproductive age and is characterized by cystic lung destruction, airflow obstruction, and lymphatic dysfunction. Current diagnostic methods are costly or lack sufficient specificity, highlighting the need for novel non-invasive approaches. Exhaled breath analysis using real-time proton mass spectrometry (PTR-MS) presents a promising strategy for identifying disease-specific volatile organic compounds (VOCs). This cross-sectional study analyzed exhaled breath samples from 51 LAM patients and 51 age- and sex-matched healthy controls. PTR-time-of-flight mass spectrometry (PTR-TOF-MS) was employed to identify VOC signatures associated with LAM. Data preprocessing, feature selection, and statistical analyses were performed using machine learning models, including gradient boosting classifiers (XGBoost), to identify predictive biomarkers of LAM and its complications. We identified several VOCs as potential biomarkers of LAM, including m\/z = 90.06 (lactic acid) and m\/z = 113.13. VOCs predictive of disease complications included m\/z = 49.00 (methanethiol), m\/z = 48.04 (O-methylhydroxylamine), and m\/z = 129.07, which correlated with pneumothorax, obstructive ventilation disorders, and radiological findings of lung cysts and bronchial narrowing. The classifier incorporating these biomarkers demonstrated high diagnostic accuracy (AUC = 0.922). This study provides the first evidence that exhaled breath VOC profiling can serve as a non-invasive additional tool for diagnosing LAM and predicting its complications. These findings warrant further validation in larger cohorts to refine biomarker specificity and explore their clinical applications in disease monitoring and personalized treatment strategies.<\/jats:p>","DOI":"10.3390\/ijms26136005","type":"journal-article","created":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T09:08:44Z","timestamp":1750669724000},"page":"6005","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Exhaled Breath Analysis in Lymphangioleiomyomatosis by Real-Time Proton Mass Spectrometry"],"prefix":"10.3390","volume":"26","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), 119991 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), 119991 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":"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\/0000-0002-2224-0019","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), 119991 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"}]},{"given":"Zhanna","family":"Naumenko","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\/0000-0002-7608-9334","authenticated-orcid":false,"given":"Pavel","family":"Pakhomov","sequence":"additional","affiliation":[{"name":"National Medical Research Center of Otorhinolaryngology, Federal Medical and Biological Agency of Russia, 123182 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3952-6865","authenticated-orcid":false,"given":"Ekaterina","family":"Pershina","sequence":"additional","affiliation":[{"name":"World-Class Research Center \u201cDigital Biodesign and Personalized Healthcare\u201d, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia"},{"name":"First Moscow City Hospital Named After N.I. Pirogov, 119049 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), 119991 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), 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4781-4645","authenticated-orcid":false,"given":"Anastasia","family":"Gordeeva","sequence":"additional","affiliation":[{"name":"Pulmonology Department, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Vergun","sequence":"additional","affiliation":[{"name":"World-Class Research Center \u201cDigital Biodesign and Personalized Healthcare\u201d, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3259-6531","authenticated-orcid":false,"given":"Olesya","family":"Bahankova","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Functional and Ultrasound Diagnostics, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 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), 119991 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), 119991 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), 119991 Moscow, Russia"},{"name":"Research Institute for Systemic Analysis of the Russian Academy of Sciences, 117218 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey","family":"Belevskiy","sequence":"additional","affiliation":[{"name":"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), 119991 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"}]},{"given":"Philipp","family":"Kopylov","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Functional and Ultrasound Diagnostics, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 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), 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"200007","DOI":"10.1183\/20734735.0007-2020","article-title":"Lymphangioleiomyomatosis: A clinical review","volume":"16","author":"Lynn","year":"2020","journal-title":"Breathe"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1183\/09031936.00076209","article-title":"Review Panel of the ERS LAM Task Force. 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