{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T14:24:07Z","timestamp":1787408647016,"version":"build-2736575974"},"reference-count":25,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["R126087"],"award-info":[{"award-number":["R126087"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Scalable, non\u2010invasive tools are critically needed to improve early lung cancer detection and optimize primary care referral pathways. We evaluated Inflammacheck, a point\u2010of\u2010care device utilizing exhaled breath condensate (EBC) H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    and physiological parameters with machine learning for non\u2010invasive lung cancer detection in a real\u2010world screening population. Exhaled Hydrogen Peroxide for Early Lung Cancer Detection (ExPeL) study participants, from the UK Targeted Lung Health Check (TLHC) programme, included individuals with suspected lung cancer and low\u2010risk ever\u2010smoker controls. EBC was collected via Inflammacheck, measuring H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    , end\u2010tidal CO\n                    <jats:sub>2<\/jats:sub>\n                    , humidity, temperature, and exhalation flow rate. Multivariate analyses (PCA, LDA and Mahalanobis distance) assessed intrinsic group separation. SMOTE\u2010balanced data trained supervised machine learning models (stacked and voting ensembles), which were then evaluated on held\u2010out test sets. In parallel, untargeted LC\u2013MS metabolomics was performed to identify discriminatory molecular features. Analyzing 34 participants with valid EBC data, 83% of cancer cases were early\u2010stage (I\u2013II), reflecting a screening population. Multivariate analysis clearly separated lung cancer and controls across PCA, LDA, and Mahalanobis mapping. The voting ensemble model achieved: Accuracy 85.7%, Sensitivity 80%, Specificity 100%, Precision (PPV) 100%, ROC\u2013AUC 0.90 and MCC 0.73. Crucially, no false positives were identified. EBC variables revealed greater dispersion in cancer patients, reflecting physiological heterogeneity missed by univariate analysis. Untargeted metabolomics identified 2132 features, with four key metabolites yielding an AUC of 0.969 for cancer discrimination. Inflammacheck effectively distinguishes early\u2010stage lung cancer via a rapid, non\u2010invasive breath test, findings which are highly relevant for primary care and screening triage, where non\u2010specific symptoms and low prevalence pose challenges.\n                  <\/jats:p>","DOI":"10.1111\/cts.70687","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T04:10:34Z","timestamp":1785384634000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Harnessing Exhaled Breath for Lung Cancer Early Detection\u2014Results From the\n                    <scp>ExPeL<\/scp>\n                    Study"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8946-9221","authenticated-orcid":false,"given":"Danita Kasi","family":"Patel","sequence":"first","affiliation":[{"name":"Manchester Institute of Biotechnology (MIB), Department of Chemistry University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8684-6231","authenticated-orcid":false,"given":"Leon","family":"D'Cruz","sequence":"additional","affiliation":[{"name":"School of Medicine, Pharmacy and Biomedical Sciences, Faculty of Science and Health University of Portsmouth  Portsmouth UK"},{"name":"Research and Innovation Department Portsmouth Hospitals University NHS Trust  Portsmouth UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waqar","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Division of Immunology, Immunity to Infection and Respiratory Medicine; School of Biological Sciences; Faculty of Biology, Medicine and Health University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4044-6114","authenticated-orcid":false,"given":"Anoop","family":"Chauhan","sequence":"additional","affiliation":[{"name":"School of Medicine, Pharmacy and Biomedical Sciences, Faculty of Science and Health University of Portsmouth  Portsmouth UK"},{"name":"Research and Innovation Department Portsmouth Hospitals University NHS Trust  Portsmouth UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2102-1997","authenticated-orcid":false,"given":"Nawar Diar","family":"Bakerly","sequence":"additional","affiliation":[{"name":"Respiratory Department, Salford Care Organisation Northern Care Alliance Foundation Trust  Salford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7213-2055","authenticated-orcid":false,"given":"Seamus","family":"Grundy","sequence":"additional","affiliation":[{"name":"Respiratory Department, Salford Care Organisation Northern Care Alliance Foundation Trust  Salford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7969-0195","authenticated-orcid":false,"given":"Drupad K.","family":"Trivedi","sequence":"additional","affiliation":[{"name":"Manchester Institute of Biotechnology (MIB), Department of Chemistry University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4773-6843","authenticated-orcid":false,"given":"Sean","family":"Knight","sequence":"additional","affiliation":[{"name":"Division of Immunology, Immunity to Infection and Respiratory Medicine; School of Biological Sciences; Faculty of Biology, Medicine and Health University of Manchester  Manchester UK"},{"name":"Respiratory Department, Salford Care Organisation Northern Care Alliance Foundation Trust  Salford UK"},{"name":"Lydia Becker Institute of Immunology and Inflammation University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02221\u20102018"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1088\/1752\u20107155\/10\/1\/016011"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1088\/1752\u20107155\/10\/2\/026002"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/CANCERS11081191"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0b013e3181949eb9"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.HELIYON.2020.E04303"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/J.1752\u20108062.2009.00093.X;SUBPAGE:STRING:ABSTRACT;REQUESTEDJOURNAL:JOURNAL:17528062;JOURNAL:JOURNAL:17528062;WGROUP:STRING:PUBLICATION"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1088\/1752\u20107163\/ADD17C"},{"key":"e_1_2_9_10_1","unstructured":"NHS England \u201cStandard Protocol and Quality Assurance Standards for the Lung Cancer Screening Programme \u201d 2026 https:\/\/www.england.nhs.uk\/publication\/targeted\u2010screening\u2010for\u2010lung\u2010cancer\/?utm_source=chatgpt.com."},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1613\/JAIR.953"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/JOURNAL.PCBI.1003123"},{"key":"e_1_2_9_13_1","first-page":"49","article-title":"On the Generalized Distance in Statistics on JSTOR","volume":"2","author":"Mahalanobis P. 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