{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T15:46:03Z","timestamp":1792856763063,"version":"4.5.0"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,1,25]],"date-time":"2019-01-25T00:00:00Z","timestamp":1548374400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["CR23I2_149617"],"award-info":[{"award-number":["CR23I2_149617"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Respirology"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and objective<\/jats:title>\n                    <jats:p>Diagnosis of idiopathic pulmonary fibrosis (IPF) is complex and its pathogenesis is poorly understood. Recent findings indicate elevated levels of proline and other amino acids in lung tissue of IPF patients which may also be of diagnostic value. Following these findings, we hypothesized that such altered metabolic profiles would be mirrored in exhaled breath and could therefore be captured non\u2010invasively in real time.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We aimed to validate these results using real\u2010time exhaled breath analysis by secondary electrospray ionization\u2010mass spectrometry, which can provide a non\u2010invasive, painless and fast insight into the metabolism. Breath analysis was performed in a matched 1:1 case\u2013control study involving 21 patients with IPF and 21 control subjects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found significantly (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;\u20090.05) elevated levels of proline, 4\u2010hydroxyproline, alanine, valine, leucine\/isoleucine and allysine in breath of IPF patients, whereas pyroglutamic acid and phenylalanine did not show significant differences. This coincides with the amino acid's abundance in pulmonary tissue indicating that our observations reflect progressing fibrosis. In addition, amino acid levels correlated across subjects, further supporting a common underlying pathway. We were able to obtain a cross\u2010validated area under the curve of 0.86, suggesting that these increased amino acid levels in exhaled breath have the potential to be used as biomarkers for IPF.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We could validate previous findings of elevated lung tissue amino acid levels in IPF and show that online breath analysis might be a practical tool for a rapid screening for IPF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/resp.13465","type":"journal-article","created":{"date-parts":[[2019,1,25]],"date-time":"2019-01-25T06:32:19Z","timestamp":1548397939000},"page":"437-444","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":77,"title":["Molecular breath analysis supports altered amino acid metabolism in idiopathic pulmonary fibrosis"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4956-9532","authenticated-orcid":false,"given":"Martin Thomas","family":"Gaugg","sequence":"first","affiliation":[{"name":"Department of Chemistry and Applied Biosciences Swiss Federal Institute of Technology  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Engler","sequence":"additional","affiliation":[{"name":"Department of Pulmonology University Hospital of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Bregy","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Applied Biosciences Swiss Federal Institute of Technology  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Nussbaumer\u2010Ochsner","sequence":"additional","affiliation":[{"name":"Department of Pulmonology University Hospital of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Eiffert","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Applied Biosciences Swiss Federal Institute of Technology  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Bruderer","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Applied Biosciences Swiss Federal Institute of Technology  Zurich Switzerland"},{"name":"Division of Respiratory Medicine, Children's Research Center University Children's Hospital Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato","family":"Zenobi","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Applied Biosciences Swiss Federal Institute of Technology  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5602-2880","authenticated-orcid":false,"given":"Pablo","family":"Sinues","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Applied Biosciences Swiss Federal Institute of Technology  Zurich Switzerland"},{"name":"University Children's Hospital Basel  Basel Switzerland"},{"name":"Department of Biomedical Engineering University of Basel  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malcolm","family":"Kohler","sequence":"additional","affiliation":[{"name":"Department of Pulmonology University Hospital of Zurich  Zurich Switzerland"},{"name":"Centre for Integrative Human Physiology University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,1,25]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"RaghuG CollardHR EganJJ MartinezFJ BehrJ BrownKK ColbyTV CordierJF FlahertyKR LaskyJAet al.;ATS\/ERS\/JRS\/ALAT Committee on Idiopathic Pulmonary Fibrosis. 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