495 - Systemic Corticosteroids and Acute Bronchiolitis: An Analysis of Serial Plasma and Endotracheal Aspirate Inflammatory Proteomic Markers

Publication Number: 495.6747

Alexa R. Roberts, Johns Hopkins All Children’s Hospital, Seminole, FL, United States; Steven Bruzek, Johns Hopkins All Children's Hospital, Saint Petersburg, FL, United States; Kayla Delaney, Johns Hopkins All Children's Hospital, St. Petersburg, FL, United States; Jennifer Leiding, Johns Hopkins University, St. Petersburg, FL, United States; Neil Goldenberg, Johns Hopkins University School of Medicine, St. Petersburg, FL, United States; Vera Ignjatovic, Johns Hopkins All Children's Hospital Institute for Clinical and Translational Research, St. Petersburg, FL, United States; Anthony A. Sochet, Johns Hopkins All Children's Hospital, St. Petersburg, FL, United States

Background: Critically ill children undergoing invasive mechanical ventilation (IMV) for acute viral bronchiolitis are frequently prescribed systemic corticosteroids as immunomodulation, despite the American Academy of Pediatrics recommendations against routine prescription thereof. It is thought that systemic corticosteroids mitigate life-threatening, inflammatory-mediated acute sequelae and chronic pathologic pulmonary remodeling resulting from severe viral infection. Yet, the mechanism(s) of action are not fully delineated.

Objective: Using targeted proteomics, we sought to characterize the levels of inflammatory cytokines in serial plasma and endotracheal aspirate samples obtained from critically ill children undergoing IMV for acute bronchiolitis.

Design/Methods: In a single-center prospective cohort study of children < 3 years of age undergoing IMV for acute viral bronchiolitis from 2018-2020, blood (processed to platelet-poor plasma) and endotracheal aspirate were serially collected at < 24 and 48-72 hours after endotracheal intubation. Samples were analyzed using the Olink Target 48 Cytokine multiplex protein affinity assay yielding relative protein abundance. Using the Mass Dynamics data platform, proteins of interest (POIs) were identified and Reactome Analyses performed based on sub-cohorts defined by the prescription of systemic corticosteroids within 24 hours of hospitalization.

Results: Samples from 17 children were studied, of which 7 received systemic corticosteroids. No differences in demographics, comorbidities, mortality, or duration of IMV were detected between study sub-groups. In paired analysis between < 24 and 48-72 hours samples, CCL13, CSF2, LTA, and FLT3L were increased at 48-hours in the no corticosteroid group, and for endotracheal aspirate IL7 and TNFSF12 were increased, while IL10, TNF, and IL17A were decreased in the no corticosteroid group. At 48–72-hours, 12 plasma cytokines (CCL2, CCL3, CCL13, CCL19, FLT3LG, IL6, IL17a, IL17c, IL17f, LTA, MMP12, and TNF, Figure 1) and 1 endotracheal aspirate cytokine (MMP12, Figure 2) were significantly lower in abundance for children who received corticosteroids compared to those who did not. Reactome Analyses revealed downregulation of POIs clustered under IL-4, IL-10 and IL-13 signaling pathways.

Conclusion(s): Using targeted proteomics, we identified several POI and related cellular signaling pathways that were downregulated among children undergoing IMV for acute bronchiolitis who were prescribed systemic corticosteroid as compared to those who were not, revealing potential targets for future immunomodulation.

Figure 1: Composite violin plot comparing plasma chemokines concentrations at 48h in the non-steroid exposed cohort and steroid exposed cohort of infants requiring IMV
ABC2_Figure1 (1).pdfComposite violin plot comparing plasma chemokines concentrations at 48h in the non-steroid exposed cohort and steroid exposed cohort of infants requiring IMV

Figure 2: Violin plot comparing relative abundance of tracheal matrix metalloproteinase –12 at 48h in non-steroid exposed cohort and steroid exposed cohort among critically ill children invasively ventilated for acute viral bronchiolitis.
ABC2_Figure2 (1).pdfViolin plot comparing relative abundance of tracheal matrix metalloproteinase –12 at 48h in non-steroid exposed cohort and steroid exposed cohort among critically ill children invasively ventilated for acute viral bronchiolitis.