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Original Article|Articles in Press

Exhaled breath profiles to detect lung infection with Staphylococcus aureus in children with cystic fibrosis

  • Author Footnotes
    1 Equal contribution
    Johann-Christoph Licht
    Footnotes
    1 Equal contribution
    Affiliations
    Division of Respiratory Medicine, Department of Pediatrics, Hospital for Sick Children, Toronto, ON M5G 1 X 8, Canada and University of Toronto

    Translational Medicine, Research Institute, Hospital for Sick Children, Toronto, ON M5G 1 × 8, Canada
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  • Author Footnotes
    1 Equal contribution
    Elias Seidl
    Footnotes
    1 Equal contribution
    Affiliations
    Division of Respiratory Medicine, Department of Pediatrics, Hospital for Sick Children, Toronto, ON M5G 1 X 8, Canada and University of Toronto
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  • Gitte Slingers
    Affiliations
    Breathomix BV, Bargelaan 200, 2333 CW Leiden, the Netherlands
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  • Valerie Waters
    Affiliations
    Translational Medicine, Research Institute, Hospital for Sick Children, Toronto, ON M5G 1 × 8, Canada

    Division of Infectious Diseases, Department of Pediatrics, Hospital for Sick Children, Toronto, ON M5G 1 X 8, Canada and University of Toronto
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  • Rianne de Vries
    Affiliations
    Breathomix BV, Bargelaan 200, 2333 CW Leiden, the Netherlands
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  • Martin Post
    Affiliations
    Translational Medicine, Research Institute, Hospital for Sick Children, Toronto, ON M5G 1 × 8, Canada
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  • Felix Ratjen
    Affiliations
    Division of Respiratory Medicine, Department of Pediatrics, Hospital for Sick Children, Toronto, ON M5G 1 X 8, Canada and University of Toronto

    Translational Medicine, Research Institute, Hospital for Sick Children, Toronto, ON M5G 1 × 8, Canada
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  • Hartmut Grasemann
    Correspondence
    Correspondence and reprints: Hartmut Grasemann, Division of Respiratory Medicine, Department of Pediatrics, The Hospital for Sick Children, Toronto, ON M5G 1 X 8, Canada.
    Affiliations
    Division of Respiratory Medicine, Department of Pediatrics, Hospital for Sick Children, Toronto, ON M5G 1 X 8, Canada and University of Toronto

    Translational Medicine, Research Institute, Hospital for Sick Children, Toronto, ON M5G 1 × 8, Canada
    Search for articles by this author
  • Author Footnotes
    1 Equal contribution
Published:February 25, 2023DOI:https://doi.org/10.1016/j.jcf.2023.02.010

      Highlights

      • Cystic fibrosis lung infection with Staphylococcus aureus can be detected in breath by electronic nose.
      • The electronic nose can distinguish between Staphylococcus aureus and Pseudomonas aeruginosa lung infection.
      • Breath profiles of children with cystic fibrosis and no infection of the lung are different from those of healthy children.
      • CFTR modulator therapy may not normalize the breath profile of treated individuals with cystic fibrosis.

      Abstract

      Background

      An electronic nose (eNose) can be used to detect volatile organic compounds (VOCs). Exhaled breath contains numerous VOCs and individuals’ VOCs mixtures create distinct breath profiles. Previous reports have shown that eNose can detect lung infections. Whether eNose can detect Staphylococcus aureus airway infections in breath of children with cystic fibrosis (CF) is currently unclear.

      Methods

      In this cross-sectional observational study, a cloud-connected eNose was used for breath profile analysis of clinically stable paediatric CF patients with airway microbiology cultures positive or negative for CF pathogens. Data-analysis involved advanced signal processing, ambient correction and statistics based on linear discriminant and receiver operating characteristics (ROC) analyses.

      Results

      Breath profiles from 100 children with CF (median predicted FEV1 91%) were obtained and analysed. CF patients with positive airway cultures for any CF pathogen were distinguishable from no CF pathogens (no growth or usual respiratory flora) with accuracy of 79.0% (AUC-ROC 0.791; 95% CI: 0.669–0.913) and between patients positive for Staphylococcus aureus (SA) only and no CF pathogen with accuracy of 74.0% (AUC-ROC 0.797; 95% CI: 0.698–0.896). Similar differences were seen for Pseudomonas aeruginosa (PA) infection vs no CF pathogens (78.0% accuracy, AUC-ROC 0.876, 95% CI: 0.794–0.958). SA- and PA-specific signatures were driven by different sensors in the SpiroNose suggesting pathogen-specific breath signatures.

      Conclusions

      Breath profiles of CF patients with SA in airway cultures are distinct from those with no infection or PA infection, suggesting the utility of eNose technology in the detection of this early CF pathogen in children with CF.

      Keywords

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