Diagnostic performance of electronic nose technology in chronic lung allograft dysfunction

BACKGROUND: There is a need for reliable biomarkers for the diagnosis of chronic lung allograft dysfunc-tion (CLAD). In this light, we investigated the diagnostic value of exhaled breath analysis using an elec-tronic nose (eNose) for CLAD, CLAD phenotype, and CLAD stage in lung transplant recipients (LTR).METHODS: We performed eNose measurements in LTR with and without CLAD, visiting the outpatient clinic. Through supervised machine learning, the diagnostic value of eNose for CLAD was assessed in a random training and validation set. Next, we investigated the diagnostic value of the eNose measure-ments combined with known risk factors for CLAD. Model performance was evaluated using ROC -analysis.RESULTS: We included 152 LTR (median age 60 years, 49% females), of whom 38 with CLAD. eNose-based classification of patients with and without CLAD provided an AUC of 0.86 in the training set, and 0.82 in the validation set. After adding established risk factors for CLAD (age, gender, type of transplantation, time after transplantation and prior occurrence of acute cellular rejection) to a model with the eNose data, the discriminative ability of the model improved to an AUC of 0.94 (p = 0.02) in the training set and 0.94 (p = 0.04) in the validation set. Discrimination between BOS and RAS was good (AUC 0.95). Discriminative ability for other phenotypes (AUCs ranging 0.50-0.92) or CLAD stages (AUC 0.56) was limited.CONCLUSION: Exhaled breath analysis using eNose is a promising novel biomarker for enabling diag-nosis and phenotyping CLAD. eNose technology could be a valuable addition to the diagnostic arma-mentarium for suspected graft failure in LTR. J Heart Lung Transplant 2023;42:236-245 (c) 2022 The Author(s). Published by Elsevier Inc. on behalf of International Society for Heart and Lung Transplantation. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)