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Molecular breath analysis supports altered amino acid metabolism in idiopathic pulmonary fibrosis


Gaugg, Martin Thomas; Engler, Anna; Bregy, Lukas; Nussbaumer-Ochsner, Yvonne; Eiffert, Lara; Bruderer, Tobias; Zenobi, Renato; Sinues, Pablo; Kohler, Malcolm (2019). Molecular breath analysis supports altered amino acid metabolism in idiopathic pulmonary fibrosis. Respirology, 24(5):437-444.

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Pneumology
Dewey Decimal Classification:610 Medicine & health
Uncontrolled Keywords:Pulmonary and Respiratory Medicine
Language:English
Date:1 May 2019
Deposited On:14 Mar 2019 16:26
Last Modified:18 Apr 2019 01:04
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:1323-7799
OA Status:Closed
Publisher DOI:https://doi.org/10.1111/resp.13465
PubMed ID:30681243
Project Information:
  • : FunderSNSF
  • : Grant IDCR23I2_149617
  • : Project TitlePhenotyping Lung Diseases and Monitoring of Drugs via Mass Spectral Fingerprinting of Exhaled Breath
  • : FunderFP7
  • : Grant ID276860
  • : Project TitleCMPTIMSMS - Cancer metabolic profiling through ion mobility and mass spectrometric-based methods

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