Tu180 - Whole Blood Transcriptome Profiles Predict Worse Clinical Outcomes in Children Developing Acute Respiratory Distress Syndrome from Influenza Infection

Abstract Text:

Background: Influenza virus is a frequent cause of acute lower respiratory tract infection in children sometimes leading to life-threatening hypoxic respiratory failure called pediatric acute respiratory distress syndrome (PARDS). In children with PARDS, some will recover within weeks whereas others will have a prolonged clinical course that can lead to death. Immunologic predictors of more rapid recovery may lead insight into potential therapies.

Methods: Children admitted to US pediatric intensive care units requiring invasive mechanical ventilation for influenza virus infection who met criteria for pediatric ARDS (n=69) were enrolled with parental consent. We compared bulk RNA-sequencing data from whole blood obtained from 39 (56.5%) pediatric patients who were liberated from invasive mechanical ventilator support within 14 days compared to 30 (43.5%) patients with more prolonged PARDS including 4 deaths. Differential gene expression analysis (fold change of at least 1.5 and FDR < 0.25) was performed using Partek Flow software.

Results: Patients with prolonged recovery or death from influenza-related PARDS had significant enrichment of differentially expressed genes in pathways associated with neutrophil degranulation (corrected p< 0.01) including BPI, LCN2, MMP8, OLFM4, RETN, SERPINB10, TCN1, VAT1.

Conclusions: These findings support the need for further investigation of the role of neutrophils and neutrophil extracellular traps in pediatric influenza-associated PARDS and death.