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We developed a volatile biomarker signature to predict sputum eosinophilia in asthma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>VOCs emitted into the space above sputum samples (headspace) from patients with severe asthma (n\u2009=\u200936) were collected onto sorbent tubes and analyzed using thermal desorption gas chromatography\u2013mass spectrometry (GC-MS). Elastic net regression identified stable VOCs associated with sputum eosinophilia\u2009\u2a7e\u20093% and generated a volatile biomarker signature. This VOC signature was validated in breath samples from: 1) patients with acute asthma according to blood eosinophilia \u2a7e0.3\u2009\u00d7\u2009109cells\/L or sputum eosinophilia of \u2a7e3% in the UK EMBER (East Midlands Breathomics Pathology Node) consortium (n\u2009=\u200965) and 2) U-BIOPRED-IMI (Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes Innovative Medicines Initiative) consortium (n\u2009=\u200942). Breath samples were collected onto sorbent tubes (EMBER) or Tedlar bags (U-BIOPRED) and analyzed by GC-MS (GC\u2009\u00d7\u2009GC-MS for EMBER or GC-MS for U-BIOPRED).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>The in vitro headspace identified 19 VOCs associated with sputum eosinophilia, and the derived VOC signature yielded good diagnostic accuracy for sputum eosinophilia \u2a7e3% in headspace (area under the receiver operating characteristic curve [AUROC] 0.90; 95% confidence interval [CI], 0.80\u20130.99; P\u2009&amp;lt;\u20090.0001), correlated inversely with sputum eosinophil percentage (r \u00a0s\u2009=\u2009\u22120.71; P\u2009&amp;lt;\u20090.0001), and outperformed fractional exhaled nitric oxide (AUROC 0.61; 95% CI, 0.35\u20130.86). Analysis of exhaled breath in replication cohorts yielded a VOC signature AUROC (95% CI) for acute asthma exacerbations of 0.89 (0.76\u20131.0) (EMBER cohort) with sputum eosinophilia and 0.90 (0.75\u20131.0) in U-BIOPRED, again outperforming fractional exhaled nitric oxide in U-BIOPRED (0.62 [0.33\u20130.90]).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We have discovered and provided early-stage clinical validation of a volatile biomarker signature associated with eosinophilic airway inflammation. Further work is needed to translate our discovery using point-of-care clinical sensors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202310-1759oc","type":"journal-article","created":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T13:38:01Z","timestamp":1717162681000},"page":"1101-1112","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":25,"title":["Discovery and Validation of a Volatile Signature of Eosinophilic Airway Inflammation in Asthma"],"prefix":"10.1093","volume":"210","author":[{"given":"Rosa","family":"Peltrini","sequence":"first","affiliation":[{"name":"Department of Respiratory Sciences and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca L.","family":"Cordell","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Leicester, Leicester, United 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