Abstract
Primary graft dysfunction (PGD) is a major determinant of morbidity and mortality following lung transplantation. Delineating basic mechanisms and molecular signatures of PGD remain a fundamental challenge. This pilot study examines if the pulmonary volatile organic compound (VOC) spectrum relate to PGD and postoperative outcomes. The VOC profiles of 58 bronchoalveolar lavage fluid (BALF) and blind bronchial aspirate samples from 35 transplant patients were extracted using solid-phase-microextraction and analyzed with comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry. The support vector machine algorithm was used to identify VOCs that could differentiate patients with severe from lower grade PGD. Using 20 statistically significant VOCs from the sample headspace collected immediately after transplantation (< 6 h), severe PGD was differentiable from low PGD with an AUROC of 0.90 and an accuracy of 0.83 on test set samples. The model was somewhat effective for later time points with an AUROC of 0.80. Three major chemical classes in the model were dominated by alkylated hydrocarbons, linear hydrocarbons, and aldehydes in severe PGD samples. These VOCs may have important clinical and mechanistic implications, therefore large-scale study and potential translation to breath analysis is recommended.
Highlights
Primary graft dysfunction (PGD) is a major determinant of morbidity and mortality following lung transplantation
It suggests that the paradigm that clinical manifestations of severe PGD are preceded by biochemical alterations that can be characterized by a unique pattern of volatile molecular signatures in the headspace of alveolar and bronchial fluids
The development of PGD was associated with poorer clinical outcomes as represented by longer ventilation times and total length of stay in the ICU (Table 1)
Summary
Primary graft dysfunction (PGD) is a major determinant of morbidity and mortality following lung transplantation. Three major chemical classes in the model were dominated by alkylated hydrocarbons, linear hydrocarbons, and aldehydes in severe PGD samples These VOCs may have important clinical and mechanistic implications, large-scale study and potential translation to breath analysis is recommended. Boss and colleagues investigated the breath of patients with acute respiratory distress syndromes (ARDS) in adults, a clinical condition with similarities to PGD. They identified three markers: acetaldehyde, octane, and 3-methyl heptane, as potential ARDS m arkers[18]. These compounds can consider a consequence of lipid peroxidation
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