Abstract

Introduction: Children with immunocompromising conditions (ICC) have a higher risk of pediatric acute respiratory distress syndrome (PARDS) and worse outcomes as compared to children without ICC. The degree to which ICC impacts PARDS presentation and prognosis has not been quantified. We hypothesize that this unique phenotype, IPARDS, warrants its own classification. Methods: This is a secondary analysis of the PARDIE study. PARDIE occurred in 145 PICUs in 27 countries during 10 weeks from 5/2016 to 6/2017. ICC was defined in a yes/no format. Wilcoxon rank sum test, logistic and linear regression, and mixed effects longitudinal analysis were used to compare groups. Results: Of 708 subjects in the cohort, 105 had an ICC. Prior to PARDS diagnosis they were more often hospitalized (70% vs 35%, p< 0.001), more likely to meet at-risk for PARDS criteria (p=0.046), and spent more hours at-risk for PARDS (20 (IQR:8-46) vs 11 (IQR:4-34), (p=0.002)). Initial IPARDS severity was bimodal with more noninvasive (38% vs 20%) and more severe PARDS (32% vs 23%) than those without ICC p< 0.001. Additionally, oxygenation indices were higher at diagnosis and had less improvement over the 1st 3 days of PARDS (p< 0.001). They had higher PELOD2 over the first 3 days of PARDS (all p< 0.05) and more markers of nonpulmonary organ dysfunction including use of blood products, dialysis, diuretics, vasoactives, parental nutrition and insulin (all p< 0.05). Adjusting for initial oxygenation index and PRISM IV, IPARDS had a higher PICU mortality (44% vs 12% OR:4.7 (95% CI:2.4, 8.9) p< 0.001), fewer median ventilator free days at 28 days (0 vs 21, β-5.3 (95%CI: -7.9,-2.8) p< 0.001), and were more likely to die with multiorgan failure (OR: 7.9 (95%CI: 3.7, 16.7) p< 0.001) and refractory shock (OR: 5.7 (95% 1.9, 17.3) p=0.002). Conclusions: This study characterizes IPARDS, a novel phenotype which includes: hospitalization prior to PARDS diagnosis, longer time spent at-risk for PARDS, worse oxygenation, more non-pulmonary organ dysfunction, increased mortality across all severity groups, and more death from refractory shock and multiorgan dysfunction. Future investigations should work to confirm these characteristics of IPARDS, determine mechanisms underlying the increased severity, and develop targeted therapies to improve overall outcomes.

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