Abstract

Introduction: Pediatric acute respiratory distress syndrome (PARDS) is a heterogeneous illness affecting 6% of mechanically ventilated children and with an overall mortality of 17%. Studies in PARDS have mainly focused on plasma biomarkers which may not reflect airway biomarkers. We lack adequate understanding of the inflammatory mediators and underlying immune responses in the airways of PARDS patients. Our objective was to compare the levels of cytokines in the airway fluid of intubated children with severe versus non-severe PARDS. Methods: We performed a prospective observational cohort study in a single 36-bed quaternary care academic safety-net hospital pediatric ICU. We enrolled children aged 14 days - 17 years intubated for acute respiratory failure between January 2018 and November 2021 that met PALICC-1 criteria for PARDS. We measured levels of 23 cytokines, chemokines, and protein biomarkers in the tracheal aspirate from 49 intubated children with PARDS and stratified patients as severe PARDS (OI>16 or OSI>12.3) or non-severe (OI 4 to 16 or OSI 5 to 12.3). Results: Cytokine levels were normalized to total protein and compared between patients with severe and non-severe PARDS. Levels of interleukin (IL) -4, -5, -6, -7, -8, -12(p-70), -17a, -21, fractalkine, IFN-γ, macrophage inflammatory protein-1a (MIP-1a), and MIP-1b were higher in patients with severe versus non-severe PARDS. Conclusions: This is the first large study to measure levels of multiple cytokines in the airway fluid of patients with PARDS, demonstrating numerous cytokines that are elevated in patients with severe PARDS compared to non-severe disease. Whether clusters of children with a hyperinflammatory vs. hypoinflammatory cytokine profile exist requires a larger sample size and external cohort for discovery and validation.

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