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Acute respiratory distress syndrome (ARDS) is heterogeneous in etiology, which may affect outcomes. Stratification into biologically-defined subtypes may reduce heterogeneity. However, it is unknown whether pediatric ARDS has clinically relevant subtypes. We aimed to determine whether clinical characteristics and predictors of mortality differed between direct and indirect ARDS, and separately between infectious and non-infectious ARDS. This was a single center, prospective cohort study of 544 children with ARDS (Berlin) between July 2011 and June 2017, stratified into direct versus indirect ARDS, and separately into infectious versus non-infectious ARDS. Multiple logistic regression was used to test for predictors of mortality in the entire cohort, and separately within subtypes. Effect modification by subtype was assessed using interaction tests. Direct ARDS had lower severity of illness (p

PURPOSE: Acute respiratory distress syndrome (ARDS) is heterogeneous in etiology, which may affect outcomes. Stratification into biologically-defined subtypes may reduce heterogeneity. However, it is unknown whether pediatric ARDS has clinically relevant subtypes. We aimed to determine whether clinical characteristics and predictors of mortality differed between direct and indirect ARDS, and separately between infectious and non-infectious ARDS. METHODS: Single center, prospective cohort study of 544 children with ARDS (Berlin) between July 2011 and June 2017, stratified into direct versus indirect ARDS, and separately into infectious versus non-infectious ARDS. Multiple logistic regression was used to test for predictors of mortality in the entire cohort, and separately within subtypes. Effect modification by subtype was assessed using interaction tests. RESULTS: Direct ARDS had lower severity of illness (p < 0.001) but worse oxygenation (p < 0.001), relative to indirect. Predictors of mortality were similar for direct and indirect ARDS. When comparing infectious and non-infectious ARDS, infectious ARDS had lower severity of illness (p < 0.001), worse oxygenation (p = 0.014), and lower mortality (p = 0.013). In multivariable analysis, immunocompromised status demonstrated effect modification between infectious and non-infectious ARDS (p = 0.005 for interaction), with no association with mortality in non-infectious ARDS. CONCLUSIONS: In children, direct and indirect ARDS have distinct clinical characteristics, but similar outcomes and similar predictors of mortality. In contrast, infectious and non-infectious ARDS demonstrate heterogeneity of clinical characteristics, mortality, and predictors of mortality, with traditional predictors of ARDS mortality only applicable to infectious ARDS.

Use of systemic corticosteroids in acute respiratory distress syndrome (ARDS) remains controversial, and studies in children are lacking. We performed an observational, single-center study in a prospectively enrolled cohort of children meeting criteria for ARDS (both Berlin 2012 and AECC 1994 acute lung injury) and pediatric ARDS (PARDS, as defined by PALICC 2015). Comprehensive analysis of corticosteroid utilization was planned, and detailed information collected on corticosteroid use, timing, treatment duration, and cumulative dose while mechanically ventilated. We assessed the association between corticosteroid exposure >24 h and outcomes. Of the 283 children with PARDS (37 deaths, 13 %), 169 (60 %) received corticosteroids for >24 h while ventilated: 51 % hydrocortisone, 41 % methylprednisolone, 5 % dexamethasone, 3 % combination of corticosteroids. Corticosteroid exposure >24 h was associated with increased mortality, fewer ventilator-free days at 28 days (VFD), and longer duration of ventilation in survivors in unadjusted analyses (all p 24 h in patients with ≥3 organ failures and immunocompromised patients. Corticosteroid exposure >24 h was independently associated with fewer VFD and longer duration of ventilation in survivors, even after adjustment for key potential confounders, including severity of illness, oxygenation index, immunocompromised status, and number of organ failures.

Angiopoietin 2 (Ang2) and soluble receptor for advanced glycation end products (sRAGE) are markers of endothelial and pulmonary epithelial damage with prognostic implications in adult acute respiratory distress syndrome (ARDS), but unclear significance in pediatric ARDS (PARDS). This was a prospective, observational study in children with PARDS (2012 Berlin and 2015 PALICC definitions) at the Children’s Hospital of Philadelphia. Plasma was collected within 48 h of PARDS onset and biomarkers quantified by enzyme-linked immunosorbent assay. In 82 children with PARDS (12 deaths, 15 %), Ang2 and sRAGE were higher in non-survivors than survivors (p