(1200) Plasma Proteomic Markers of Respiratory Failure Severity of Illness Among Critically Ill Children

Introduction: Using discovery proteomics, we sought to characterize the plasma proteome to identify prognostic markers for extended invasive mechanical ventilation (IMV) duration and elevated oxygenation index (OI) for critically ill children.

Methods: In a single-center cohort study of children < 18 years of age undergoing IMV for acute respiratory failure from 2018-2020, blood was collected < 24- & 48-72 hours after endotracheal intubation and processed to platelet-poor plasma. Tandem Mass Tag (TMT)-labeled liquid chromatography mass spectrometry (LC-MS) performed. Protein abundance analyses were normalization, log2-transformation, missing data removal (>30%), z-scoring, imputation, and batch effects normalization. To identify proteins of interest (POIs), the Mass Dynamics platform was used to assess cohorts defined by upper (>16 days) and lower ( < 4 days) quartiles of IMV duration and those with a < 24-hour OI >16 as compared to OI < 8.

Results: 81 samples from 48 children were analyzed, with 759 proteins identified. Compared to those with shot IMV duration, those with long IMV duration had the following POIs noted < 24-hours of IMV: YWHAZ, TKT, ALDOA, SERPINB1, TALDO1, and RNPEP with higher abundance and CDH13, ACAN, MMRN2, ICAM2, CTSA, IGLV1-47, and IGHV3-43 with lower abundance. Of those, SERPINB1, TALDO1, and ICAM2 were differentially abundant at both < 24- and 48-72 hours of IMV. Compared to those with OI < 8, those with OI>16 had the following POIs noted < 24 hours of IMV: TKT, LTA4H, ICAM1, PIGR, RNH1, INHBE, HSPA5, CD163 with higher abundance and KIT, TFRC, KRT77, SELENOP, APOM, and TTR with lower abundance. Of those, LTA4H, ICAM1, PIGR, and KIT were differentially abundant at both < 24- and 48-72 hours of IMV. Univariate logistic models (yielding odds ratios with 95% confidence intervals for OI>16 and long IMV duration, respectively) identified SERPINB1 (5.6[1.1-29.9]; 7[1.3-38.3]), TALDO1 (2.7[1-7.2]; 3.5[1.2-10.2]), TKT (3.6[1.4-9.5]; 3[1.2-7.4]), RNH1 (7[1.5-32.1]; 4(1.1-14.5]), and HSPA5 (9.5[1.4-62.8]; 11.4[1.6-81.7]) (all p< 0.05) as POIs with differential abundance at 24-hours.

Conclusions: With a TMT-LC-MS approach, we identified 5 POIs that, after further validation, may represent putative prognostic indicators of respiratory failure severity.