Donor Airway Bile Acid as a Biomarker of Aspiration and Predictor of Post Lung Transplant Outcomes

Abstract

<h3>Purpose</h3> Emesis and aspiration contribute to donor lung damage and may promote allograft dysfunction. Currently, there is no clinical tool to detect occult aspiration and objectively assess its severity in donor lungs. A previous study by our group identified that aspirated total bile acids (TBA) in donor bronchial wash (BW) was associated with acceptability of donor lungs for transplant. Herein, we seek to validate this finding in a large retrospective cohort and assess the association between donor TBA and recipient outcomes. <h3>Methods</h3> TBA was measured in available BW samples of 605 consecutive lung donors from 2012 to 2018. 90% specificity threshold was used to derive a TBA cut-off that identified donor lungs unsuitable for transplant. We further assessed associations between BW TBA concentrations and performance of donor lungs undergoing ex vivo lung perfusion (EVLP), as well as post-transplant recipient outcomes. <h3>Results</h3> Donor TBA was higher in lungs deemed unsuitable for transplant compared to those suitable for direct transplant and those requiring further assessment on EVLP (Figure A; Mann-Whitney U test). In lungs assessed on EVLP, higher TBA concentration in donor BW correlated with lower pH, higher lactate levels, and higher pro-inflammatory cytokines in EVLP perfusate. In lungs not assessed on EVLP, TBA cut-off of 1245nM was able to differentiate donor lungs suitable for transplantation vs declined with 90% specificity. Based on this cut-off, high donor TBA was associated with worse post-transplant recipient outcomes: longer time to extubation (p<0.001) (Figure B; log-rank test) and shorter time to chronic lung allograft dysfunction (p=0.01). <h3>Conclusion</h3> In a large retrospective cohort we observed that high TBA in donor bronchial wash was associated with suitability of donor lungs for transplant, performance on EVLP, and adverse recipient outcomes. TBA measurement may be useful to triage donor lungs for further assessment on EVLP and potential pre-transplant therapeutic interventions.