(1214) Metabolomic Analysis of the Lower Respiratory Tract in Intubated Infants With Severe Bronchiolitis

Introduction: Limited studies in respiratory metabolomics in infants with severe bronchiolitis exist and molecular analysis could yield biomarkers for targeted testing, characterization, or treatment. We aim to determine whether lung metabolomes of intubated infants differ between respiratory syncytial virus (RSV) and rhinovirus/enterovirus (REV) infected patients and whether they change over the course of illness. This study also establishes the feasibility of lower respiratory tract metabolite research in a pediatric intensive care unit (PICU).

Methods: Intubated infants with RSV or REV infection were recruited over four years at Helen DeVos Children’s Hospital PICU. Endotracheal aspirates were obtained during routine suctioning. Liquid chromatography-mass spectrometry was performed to identify each metabolite. Clinical data from the electronic medical record included antibiotic exposure, age, sex, and length of stay. T-test and partial least-squares discriminant analysis (PLS-DA) were used to analyze metabolite diversity.

Results: From 25 recruited patients (RSV=18; REV=6, Control=1), seventy-nine individual, non-drug metabolites were identified; 27 were significant based on the T-test and PLS-DA (variable importance of projection [VIP] > 1.5). The data depicts differences in inflammatory metabolites, such as phosphocholines (PCs) and lyso-phosphocholines (LPCs), over the course of illness and between the two study groups. There was a higher abundance of physiologic surfactant components in RSV patients later in their illness course. Sphingomyelin and propionylcarnitine were also abundant in RSV patients, with a high abundance of LPC acyl chains.

Conclusions: Findings suggest inflammation from cellular breakdown late in the disease course of RSV compared to REV. Changes in surfactant components suggest early surfactant dysfunction followed by recovery. These components may play a role in disruption of viral binding to host cell membranes, which could instead indicate an immune response. The data also suggests lung injury due to hydrolysis of PCs, dysregulated metabolic pathways of sphingolipids and phospholipids, as well as potential for future pulmonary reactivity. A targeted study could clarify the significance of these metabolites and identify targets for directed therapies or prognostic indicators.