Integrative Omics of Aspiration in Lung Transplantation

Abstract

<h3>Purpose</h3> Prior studies have defined lung biomarkers associated with graft injury in lung transplant. We have developed a lung metabolomic profile of bile acid aspiration. We correlated the metabolites of aspiration to other omic measures of lung injury. <h3>Methods and Materials</h3> We performed metabolomic profiling on 29 recipients who had episodic bile detected in lung lavages. Each patient contributed a lung lavage specimen that was positive and negative for bile acid resulting in 58 total samples. Lavages were tested using C18 liquid chromatography coupled to mass spectroscopy. We used three approaches: Principle component analysis, Principle component regression, and Hierarchical clustering analysis. 252 Bile acid associated features were found at the intersection of these approaches. Cluster analysis developed 6 clusters positively or negatively associated with aspiration. Clusters were evaluated against biomarkers CXCL9, CXCL10, MCP1, FoxP3 and GranzymeB. <h3>Results</h3> Bile acid aspiration was associated with a distinct metabolomic profile resolved using 3 bioinformatics approaches with a bias of increased small species in the bile positive samples, suggesting an increase in pulmonary permeability with aspiration. Presence of bile only weakly correlated with the other omic markers of injury (r .17-.26, p .09-.2). Individual bile acid associated clusters showed significant positive and negative correlation with known other markers of injury. [figure 1] <h3>Conclusions</h3> In this discovery phase study there is a strong association between metabolomic features of bile acid aspiration and known biomarkers of injury from other omic platforms. This strengthens the claim that aspiration of gastric contents is dangerous and also provides an avenue for risk stratification in a prospective cohort of patients.