Martin Thomas Gaugg1, Anna Engler2, Lukas Bregy1, Yvonne Nussbaumer-Ochsner2, Lara Eiffert1, Tobias Bruderer1,3, Renato Zenobi1, Pablo Sinues1,4,5, Malcolm Kohler2,6. 1. Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, Zurich, Switzerland. 2. Department of Pulmonology, University Hospital of Zurich, Zurich, Switzerland. 3. Division of Respiratory Medicine, Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland. 4. University Children's Hospital Basel, Basel, Switzerland. 5. Department of Biomedical Engineering, University of Basel, Basel, Switzerland. 6. Centre for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
Abstract
BACKGROUND AND OBJECTIVE: 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-invasively in real time. METHODS: We aimed to validate these results using real-time exhaled breath analysis by secondary electrospray ionization-mass spectrometry, which can provide a non-invasive, painless and fast insight into the metabolism. Breath analysis was performed in a matched 1:1 case-control study involving 21 patients with IPF and 21 control subjects. RESULTS: We found significantly (P < 0.05) elevated levels of proline, 4-hydroxyproline, 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-validated 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. CONCLUSION: 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.
BACKGROUND AND OBJECTIVE: 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-invasively in real time. METHODS: We aimed to validate these results using real-time exhaled breath analysis by secondary electrospray ionization-mass spectrometry, which can provide a non-invasive, painless and fast insight into the metabolism. Breath analysis was performed in a matched 1:1 case-control study involving 21 patients with IPF and 21 control subjects. RESULTS: We found significantly (P < 0.05) elevated levels of proline, 4-hydroxyproline, alanine, valine, leucine/isoleucine and allysine in breath of IPFpatients, 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-validated 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. CONCLUSION: 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.
Authors: C Meier; K Freiburghaus; C Bovet; J Schniering; Y Allanore; O Distler; C Nakas; B Maurer Journal: Sci Rep Date: 2020-12-14 Impact factor: 4.379
Authors: Josep Mercader-Barceló; Joan Truyols-Vives; Carlos Río; Nora López-Safont; Ernest Sala-Llinàs; Alice Chaplin Journal: Int J Mol Sci Date: 2020-08-22 Impact factor: 5.923
Authors: L Plantier; A Smolinska; R Fijten; M Flamant; J Dallinga; J J Mercadier; D Pachen; M P d'Ortho; F J van Schooten; B Crestani; A W Boots Journal: Respir Res Date: 2022-01-20