The Smell of Lung Transplantation

Abstract

<h3>Purpose</h3> Chronic lung allograft dysfunction (CLAD) impairs survival after lung transplantation. CLAD is associated with an inflammatory process in the allograft. Inflammation produces volatile organic compounds (VOC) that can be detected in exhaled breath. This makes VOC a potential biomarker for detection and follow-up of CLAD. The aim of this pilot study is to assess the feasibility of VOC detection in exhaled breath of lung transplant (LTx) patients and to determine whether LTx patients omit a specific VOC pattern or "breathprint". <h3>Methods</h3> In this monocentric, case-control study, multicapillary column-ion mobility spectrometry (MCC-IMS) is used for VOC detection. LTx patients were on average 37 (range: 2-118) months post-transplant. LTx patients were compared to matched healthy controls (HC) and COPD-patients (GOLD III-IV). Alveolar air was sampled from each subject together with a corresponding background sample. The alveolar gradient was calculated for each VOC to minimize external confounders. These were used as independent predictors to build 3 logistic regression models (HC vs. LTx, COPD vs. LTx and non-LTx vs. LTx) , which were internally validated by cross-validation, generating ROC curves. <h3>Results</h3> Thirty-one subjects were included: 14 HC, 9 LTx patients (underlying COPD (n=5), bronchiectasis (n=2), fHP (n=1), IPF (n=1)) and 8 COPD patients (Fig 1A). The VOC alveolar gradients are depicted in a heatmap (Fig 1B). COPD patients were difficult to differentiate from LTx patients with only 65% accuracy (sensitivity 67%, specificity 63%). HC and LTx could be differentiated with 83% accuracy (sensitivity 89%, specificity 79%). LTx patients were discriminated from non-LTx patients with 100% accuracy (sensitivity 100%, specificity 100%) (Fig 1C). <h3>Conclusion</h3> The breathprint of stable LTx patients differs from that of non-LTx-patients. MCC-IMS can be performed in clinic during routine LTx patient follow-up. This opens opportunities for VOC as a clinical biomarker of CLAD. Further research in our lung transplant population is needed.