Michael Ripple, MD, PhD (he/him/his)
Children's Egleston Hospital
Atlanta, Georgia
Disclosure information not submitted.
Milad Rad, MS
Graduate Student
Georgia Institute of Technology, United States
Disclosure information not submitted.
Susan Stephenson, PhD
Laboratory Manager
Emory University, United States
Disclosure information not submitted.
Ahmad Mohammad, BS
Laboratory Technician
Emory University, United States
Disclosure information not submitted.
Cydney Opolka, BS
Clinical Research Coordinator
Children's Healthcare of Atlanta, United States
Disclosure information not submitted.
Anne Fitzpatrick, PhD, CPNP
Professor
Emory University School of Medicine, United States
Disclosure information not submitted.
Rishikesan Kamaleswaran, PhD
Associate Professor
Emory University School of Medicine
Atlanta, Georgia
Disclosure information not submitted.
Jocelyn Grunwell, MD, PhD
Assistant Professor
Emory University/Children's Healthcare of Atlanta Egleston
Atlanta, Georgia, United States
Disclosure information not submitted.
Title: Cluster Analysis and Profiling of Airway Fluid Metabolites in Pediatric ARDS
INTRODUCTION: Pediatric ARDS (PARDS) is a heterogenous disease with no targeted therapy due to a poor understanding of the underlying immune response. Multiple studies in adults have utilized metabolomic methods to stratify ARDS subtypes with different mortality rates and to identify ARDS biomarkers. To date, there have been no investigations into the metabolomic profiles of pediatric patients with ARDS. The goal of this study was to identify differentially expressed amino acids and metabolic pathways from the tracheal aspirate airway fluid of children with and without PARDS.
Methods: We performed a prospective cohort study in a 36-bed pediatric intensive care unit of 74 immunocompetent children with acute hypoxemic respiratory failure who were between 2 days to 18 years of age. We obtained tracheal aspirate samples within 72 hours of intubation and stratified patients based on the development of PARDS (n=41, 55.4%) or no PARDS (n=33, 44.6%). We utilized a quantitative EZ-Faast amino acid analysis LC-MS/MS kit to profile the amino acid metabolite profile of each tracheal aspirate followed by analysis using hierarchal clustering and partial least squares-discriminant analysis to explore clusters of metabolites that correlated with PARDS severity and ventilator-free days.
Results: Three clusters were identified. Cluster 1 was predominated by children with moderate or severe PARDS (52%) compared with Cluster 2 (36%) or Cluster 3 (17%, p = 0.01). Children in Cluster 2 (23, IQR: 12 – 26) had higher median PRISM III scores compared to Cluster 1 (15, IQR: 9 – 16) and Cluster 3 (12.5, IQR: 8 – 18), p = 0.01). Children in Clusters 1 and 2 spent a median of 7 days on a ventilator compared with children in Cluster 3 (3.5 days, p = 0.002). Quantitative pathway enrichment analysis showed that cysteine and methionine metabolism, selenocompound metabolism, glycine, serine and threonine metabolism, arginine biosynthesis, and valine, leucine, and isoleucine biosynthesis were the top five enriched, impactful pathways.
Conclusions: We identified three clusters of amino acid metabolites found in the airway fluid of intubated children important to the PARDS severity that correlated with ventilator-free days < 21 days. Further studies are needed to validate our findings and to test our models.