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The Journal of Heart and Lung Transplantation
International Society for Heart and Lung Transplantation.

Triaging donor lungs based on a microaspiration signature that predicts adverse recipient outcome

  • Rayoun Ramendra
    Affiliations
    Toronto Lung Transplant Program, Ajmera Transplant Center, University Health Network, Toronto, Ontario, Canada

    Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada
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  • Andrew T. Sage
    Affiliations
    Toronto Lung Transplant Program, Ajmera Transplant Center, University Health Network, Toronto, Ontario, Canada

    Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada
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  • Jonathan Yeung
    Affiliations
    Toronto Lung Transplant Program, Ajmera Transplant Center, University Health Network, Toronto, Ontario, Canada

    Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada

    Division of Thoracic Surgery, Faculty of Surgery, University of Toronto, Toronto, Ontario, Canada
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  • Juan C. Fernandez-Castillo
    Affiliations
    Toronto Lung Transplant Program, Ajmera Transplant Center, University Health Network, Toronto, Ontario, Canada

    Division of Respirology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
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  • Marcelo Cuesta
    Affiliations
    Toronto Lung Transplant Program, Ajmera Transplant Center, University Health Network, Toronto, Ontario, Canada

    Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada
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  • Meghan Aversa
    Affiliations
    Toronto Lung Transplant Program, Ajmera Transplant Center, University Health Network, Toronto, Ontario, Canada

    Division of Respirology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
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  • Mingyao Liu
    Affiliations
    Toronto Lung Transplant Program, Ajmera Transplant Center, University Health Network, Toronto, Ontario, Canada

    Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada
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  • Marcelo Cypel
    Affiliations
    Toronto Lung Transplant Program, Ajmera Transplant Center, University Health Network, Toronto, Ontario, Canada

    Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada

    Division of Thoracic Surgery, Faculty of Surgery, University of Toronto, Toronto, Ontario, Canada
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  • Shaf Keshavjee
    Affiliations
    Toronto Lung Transplant Program, Ajmera Transplant Center, University Health Network, Toronto, Ontario, Canada

    Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada

    Division of Thoracic Surgery, Faculty of Surgery, University of Toronto, Toronto, Ontario, Canada
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  • Tereza Martinu
    Correspondence
    Reprint requests: Tereza Martinu, MD MHS, Toronto Lung Transplant Program, Ajmera Transplant Center, University Health Network, 585 University Ave, 11-128, Peter Munk Building, Toronto, ON, M5G 2N2. Telephone: 416-340-4800.
    Affiliations
    Toronto Lung Transplant Program, Ajmera Transplant Center, University Health Network, Toronto, Ontario, Canada

    Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada

    Division of Respirology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
    Search for articles by this author
Published:January 05, 2023DOI:https://doi.org/10.1016/j.healun.2022.12.024

      BACKGROUND

      Aspiration is a relative contraindication to accepting donor lungs for transplant and is currently assessed by visual inspection of the airways via bronchoscopy. However, this method is limited as it does not assess for microaspiration. Bile acids measured in large airway bronchial wash (LABW) samples have been shown to be a marker of aspiration in lung transplant recipients. Herein, we investigate the utility of measuring total bile acids (TBA) in donor LABW to predict performance of donor lungs and recipient outcomes.

      METHODS

      TBA was measured in 605 consecutive lung donors at the Toronto Lung Transplant Program. TBA levels were compared in donor lungs deemed unsuitable for transplant, requiring further assessment on ex vivo lung perfusion (EVLP), and those suitable for direct transplantation using Mann-Whitney-U tests. Relationships between LABW TBA concentrations and recipient outcomes were evaluated using multivariable Cox-PH models and log-rank analysis.

      RESULTS

      Donor TBA was highest in lungs deemed unsuitable for transplant and correlated with clinical assessment of aspiration. LABW TBA concentration correlated with calcium, decreased pH, and increased pro-inflammatory mediators in EVLP perfusate. TBA cut-off of 1245 nM was able to differentiate donor lungs directly declined from those suitable for direct transplantation with a 91% specificity (AUROC: 73%). High donor TBA status was associated with the increased rate of primary graft dysfunction, longer time to extubation, and shorter time to chronic lung allograft dysfunction.

      CONCLUSIONS

      In a large retrospective cohort, we observed that donor LABW TBA was associated with suitability of donor lungs for transplant, performance of the organ on EVLP, and adverse recipient outcomes.

      KEYWORDS

      Abbreviations:

      TBA (total bile acids), LABW (large airway bronchial wash), EVLP (ex vivo lung perfusion), AUROC (area under the receiver operating characteristic curve)
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