Th173 - Systemic Cytokine Profiling of Pediatric Pulmonary and Extrapulmonary ARDS Reveals IL4 as a Common Putative Marker of Disease Severity

Abstract Text:

Introduction: Pediatric acute respiratory distress syndrome (PARDS) arises from direct insult to the lung parenchyma disrupting the alveolar epithelium [pulmonary PARDS (PARDSp)], or a systemic insult causing vascular endothelial damage [extrapulmonary PARDS (PARDSexp)]. This study profiles the circulating cytokines in PARDS to elucidate the underlying immunopathogenic differences between PARDSp and PARDSexp.

Methods: Plasma from 24 patients (sepsis/PARDSexp, n=8 and pneumonia/PARDSp, n=16) and 8 controls (post elective cardiopulmonary bypass) were studied. The Olink® target 48 cytokine panel (Olink Proteomics) was used to quantify protein levels and reported as normalized protein expression. Principal component analysis (PCA) was used to visualise differences between groups. Multivariable linear regression was used to determine the association between PARDS severity and cytokine levels, adjusting for age and presence of sepsis. Correlation between cytokine levels and oxygenation index was performed using Pearson’s correlation.

Results: The mean (standard deviation) age of the cohort was 5.1(5.4) years. PCA plot readily distinguishes severe and non-severe PARDSp, PARDSexp and control. PARDSexp was associated with changes in 36/48(75.0%) systemic cytokines, whereas PARDSp was associated with only 22/48(45.8%). In the multivariable model, greater PARDS severity was associated with increased CCL8, CXCL9, IL4, IL18, CXCL10, IFNɣ, IL10, CCL19 and TNFα levels. Only IL4, IL18, CXCL10 and IFNɣ showed a progressive increase across the mild, moderate and severe PARDS where CCL8(r=0.35,p=0.047), IL4(0.82,p < 0.001) and CXCL10(r=0.42,p=0.016 had a positive correlation with oxygenation index.

Conclusion: IL4, a cytokine reported to have anti-inflammatory effects and an inducer of trained immunity, was associated with PARDS severity in both PARDSp and PARDSexp.