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Author Notes:

Jocelyn R. Grunwell, Email: jgrunwe@emory.edu

J.G., A.F., and R.K. conceived and developed the study, and supervised the acquisition of the biological data and the analysis and interpreted the data. K.C. and M.G.R. analyzed the data. K.C. and M.J.R. drafted and edited the manuscript. R.K. and A.F. assisted with drafting and editing the manuscript. M.G.R. helped with data analysis and edited the manuscript. M.T. helped with patient screening, obtaining informed consent and assent, and with patient sample acquisition. S.S. and A.M. helped with sample processing, performed experiments, and editing the manuscript. All authors edited and approved the final version of this manuscript.

This study was supported in part by the Emory Integrated Genomics Core (EIGC), which is subsidized by the Emory University School of Medicine and is one of the Emory Integrated Core Facilities. Additional support was provided by the Georgia Clinical and Translational Science Alliance of the National Institutes of Health under Award Number UL1TR002378. The content is solely the responsibility of the authors and does not necessarily reflect the official views of the National Institutes of Health. We thank Ms. Cydney Opolka who assisted in identifying, consenting, acquiring patient samples, and collecting clinical information about the participants.

The authors declare no competing interests.

Subject:

Research Funding:

Funding was provided by NIH grant T32 HL116271 to KC.

Funding was provided by NIH grants K23 HL151897 to JG.

Funding was provided by the NIH grant K24 NR018866 and R01 NR018666 to AF.

Funding was provided by the NIH grant numbers R01 GM139967 and UL1 TR002378 to RK.

Keywords:

  • Humans
  • Child
  • Cytokines
  • Cluster Analysis
  • Asthma
  • Inflammation
  • Intensive Care Units, Pediatric

Cluster analysis of plasma cytokines identifies two unique endotypes of children with asthma in the pediatric intensive care unit

Tools:

Journal Title:

Scientific Reports

Volume:

Volume 13, Number 1

Publisher:

, Pages 3521-3521

Type of Work:

Article | Final Publisher PDF

Abstract:

Children with life-threatening asthma exacerbations who are admitted to a pediatric intensive care unit (PICU) are a heterogeneous group with poorly studied inflammatory features. We hypothesized that distinct clusters of children with asthma in a PICU would be identified based on differences in plasma cytokine levels and that these clusters would have differing underlying inflammation and asthma outcomes within 1 year. Plasma cytokines and differential gene expression were measured in neutrophils isolated from children admitted to a PICU for asthma. Participants were clustered by differential plasma cytokine abundance. Gene expression differences were compared by cluster and pathway over-representation analysis was performed. We identified two clusters in 69 children with no clinical differences. Cluster 1 (n = 41) had higher cytokines compared to Cluster 2 (n = 28). Cluster 2 had a hazard ratio of 2.71 (95% CI 1.11–6.64) compared to Cluster 1 for time to subsequent exacerbation. Gene expression pathways that differed by cluster included interleukin-10 signaling; nucleotide-binding domain, leucine rich repeat containing receptor (NLR signaling); and toll-like receptor (TLR) signaling. These observations suggest that a subset of children may have a unique pattern of inflammation during PICU hospitalization that might require alternative treatment approaches.

Copyright information:

© The Author(s) 2023

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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