Single cell transcriptomics identifies distinct profiles in pediatric acute respiratory distress syndrome

Abstract

Acute respiratory distress syndrome (ARDS), termed pediatric ARDS (pARDS) in children, is a severe form of acute respiratory failure (ARF). Pathologic immune responses are implicated in pARDS pathogenesis. Here, we present a description of microbial sequencing and single cell gene expression in tracheal aspirates (TAs) obtained longitudinally from infants with ARF. We show reduced interferon stimulated gene (ISG) expression, altered mononuclear phagocyte (MNP) transcriptional programs, and progressive airway neutrophilia associated with unique transcriptional profiles in patients with moderate to severe pARDS compared to those with no or mild pARDS. We additionally show that an innate immune cell product, Folate Receptor 3 (FOLR3), is enriched in moderate or severe pARDS. Our findings demonstrate distinct inflammatory responses in pARDS that are dependent upon etiology and severity and specifically implicate reduced ISG expression, altered macrophage repair-associated transcriptional programs, and accumulation of aged neutrophils in the pathogenesis of moderate to severe pARDS caused by RSV.

Developing a mechanistic understanding of pediatric acute respiratory distress syndrome one cell at a time

“…10 These monocytes were more common in patients with a lower level of illness severity and were hypothesised to be critical for the clearance of pro-inflammatory cells thus paving the way for repair and regeneration. 10 Additionally, there is evidence that cross talk between multiple different reparative macrophage phenotypes may help promote repair and regeneration in pediatric patients with severe lung injury. 11 Taken together, these studies have begun to delve into the cell populations, pathways, and cell-cell crosstalk involved in repair and regeneration in pediatric patients recovering from PARDS.…”

“…9 Another analysed tracheal aspirates of intubated PARDS patients using single-cell RNAseq and found a subset of monocytes that expressed repair related transcripts. 10 These monocytes were more common in patients with a lower level of illness severity and were hypothesised to be critical for the clearance of pro-inflammatory cells thus paving the way for repair and regeneration. 10 Additionally, there is evidence that cross talk between multiple different reparative macrophage phenotypes may help promote repair and regeneration in pediatric patients with severe lung injury.…”

“…One recent study using bulk mRNAseq to evaluate the nasal epithelial transcriptome of PARDS patients found that one subgroup of patients had loss of epithelial stem cells genes and those patients had a longer course of PARDS 9 . Another analysed tracheal aspirates of intubated PARDS patients using single‐cell RNAseq and found a subset of monocytes that expressed repair related transcripts 10 . These monocytes were more common in patients with a lower level of illness severity and were hypothesised to be critical for the clearance of pro‐inflammatory cells thus paving the way for repair and regeneration 10 .…”