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Volatile organic compound breath signatures of children with cystic fibrosis by real-time SESI-HRMS

Ronja Weber, Naemi Haas, Astghik Baghdasaryan, Tobias Bruderer, Demet Inci, Srdjan Micic, Nathan Perkins, Renate Spinas, Renato Zenobi, Alexander Moeller for the Paediatric Exhalomics Group at the University Children's Hospital Zurich
ERJ Open Research 2020 6: 00171-2019; DOI: 10.1183/23120541.00171-2019
Ronja Weber
1Division of Respiratory Medicine and Childhood Research Center, University Children's Hospital Zürich, Zürich, Switzerland
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Naemi Haas
1Division of Respiratory Medicine and Childhood Research Center, University Children's Hospital Zürich, Zürich, Switzerland
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Astghik Baghdasaryan
1Division of Respiratory Medicine and Childhood Research Center, University Children's Hospital Zürich, Zürich, Switzerland
2Joint Medical Center Arabkir, Division of Pulmonology, Yerevan, Armenia
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Tobias Bruderer
1Division of Respiratory Medicine and Childhood Research Center, University Children's Hospital Zürich, Zürich, Switzerland
3ETH Zürich, Dept of Chemistry and Applied Bioscience, Zürich, Switzerland
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  • ORCID record for Tobias Bruderer
Demet Inci
1Division of Respiratory Medicine and Childhood Research Center, University Children's Hospital Zürich, Zürich, Switzerland
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Srdjan Micic
1Division of Respiratory Medicine and Childhood Research Center, University Children's Hospital Zürich, Zürich, Switzerland
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Nathan Perkins
4Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zürich, Zürich, Switzerland
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Renate Spinas
1Division of Respiratory Medicine and Childhood Research Center, University Children's Hospital Zürich, Zürich, Switzerland
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Renato Zenobi
3ETH Zürich, Dept of Chemistry and Applied Bioscience, Zürich, Switzerland
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Alexander Moeller
1Division of Respiratory Medicine and Childhood Research Center, University Children's Hospital Zürich, Zürich, Switzerland
5A list of the members of the Paediatric Exhalomics Group can be found at the end of this article
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  • For correspondence: alexander.moeller@kispi.uzh.ch
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Abstract

Early pulmonary infection and inflammation result in irreversible lung damage and are major contributors to cystic fibrosis (CF)-related morbidity. An easy to apply and noninvasive assessment for the timely detection of disease-associated complications would be of high value. We aimed to detect volatile organic compound (VOC) breath signatures of children with CF by real-time secondary electrospray ionisation high-resolution mass spectrometry (SESI-HRMS).

A total of 101 children, aged 4–18 years (CF=52; healthy controls=49) and comparable for sex, body mass index and lung function were included in this prospective cross-sectional study. Exhaled air was analysed by a SESI-source linked to a high-resolution time-of-flight mass spectrometer. Mass spectra ranging from m/z 50 to 500 were recorded.

Out of 3468 m/z features, 171 were significantly different in children with CF (false discovery rate adjusted p-value of 0.05). The predictive ability (CF versus healthy) was assessed by using a support-vector machine classifier and showed an average accuracy (repeated cross-validation) of 72.1% (sensitivity of 77.2% and specificity of 67.7%).

This is the first study to assess entire breath profiles of children with SESI-HRMS and to extract sets of VOCs that are associated with CF. We have detected a large set of exhaled molecules that are potentially related to CF, indicating that the molecular breath of children with CF is diverse and informative.

Abstract

This is the first study to assess entire breath profiles of 101 children with SESI-HRMS. 171 molecules that are potentially related to CF were detected, indicating that the molecular breath profile of children with CF is diverse and informative. http://bit.ly/33nIeML

Footnotes

  • This article has supplementary material available from openres.ersjournals.com

  • This work is part of the Zürich Exhalomics project under the umbrella of “Hochschulmedizin Zürich”.

  • Paediatric Exhalomics Group: Astghik Baghdasaryan, Christoph Berger, Christian Bieli, Tobias Bruderer, Naemi Haas, Martin Hersberger, Katharina Heschl, Demet Inci, Andreas Jung, Malcolm Kohler, Srdjan Micic, Alexander Moeller, Simona Müller, Nathan Perkins, Tina Schürmann, Florian Singer, Renate Spinas, Bettina Streckenbach, Jakob Usemann, Ronja Weber and Renato Zenobi.

  • Support statement: This study was supported by grants from the Swiss National Science Foundation (326030_177101) and the Uniscientia foundation. This study is part of the HMZ flagship project Zürich Exhalomics. Funding information for this article has been deposited with the Crossref Funder Registry.

  • Conflict of interest: Ronja Weber has nothing to disclose.

  • Conflict of interest: N. Haas has nothing to disclose.

  • Conflict of interest: A. Baghdasaryan has nothing to disclose.

  • Conflict of interest: T. Bruderer has nothing to disclose.

  • Conflict of interest: D. Inci has nothing to disclose.

  • Conflict of interest: S. Micic has nothing to disclose.

  • Conflict of interest: N. Perkins has nothing to disclose.

  • Conflict of interest: R. Spinas has nothing to disclose.

  • Conflict of interest: R. Zenobi has nothing to disclose.

  • Conflict of interest: A. Moeller has nothing to disclose.

  • Received July 7, 2019.
  • Accepted November 5, 2019.
  • Copyright ©ERS 2020
http://creativecommons.org/licenses/by-nc/4.0/

This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.

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Volatile organic compound breath signatures of children with cystic fibrosis by real-time SESI-HRMS
Ronja Weber, Naemi Haas, Astghik Baghdasaryan, Tobias Bruderer, Demet Inci, Srdjan Micic, Nathan Perkins, Renate Spinas, Renato Zenobi, Alexander Moeller
ERJ Open Research Jan 2020, 6 (1) 00171-2019; DOI: 10.1183/23120541.00171-2019

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Volatile organic compound breath signatures of children with cystic fibrosis by real-time SESI-HRMS
Ronja Weber, Naemi Haas, Astghik Baghdasaryan, Tobias Bruderer, Demet Inci, Srdjan Micic, Nathan Perkins, Renate Spinas, Renato Zenobi, Alexander Moeller
ERJ Open Research Jan 2020, 6 (1) 00171-2019; DOI: 10.1183/23120541.00171-2019
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