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Evidence of Endotypes in Pediatric Acute Hypoxemic Respiratory Failure Caused by Sepsis*

Yehya, Nadir, MD1; Thomas, Neal J., MD, MSc2; Wong, Hector R., MD3,4

Pediatric Critical Care Medicine: February 2019 - Volume 20 - Issue 2 - p 110–112
doi: 10.1097/PCC.0000000000001808
Late Breaker Articles

Objectives: Subclassification based on clinical or biologic commonalities (endotypes) is one approach to reduce heterogeneity in acute hypoxemic respiratory failure. In adults, biomarker-defined endotypes of respiratory failure have been described, with differential outcome profiles and response to therapy. To date, no studies have tested whether endotypes exist in pediatric acute hypoxemic respiratory failure, although messenger RNA expression-based endotypes have been described in pediatric sepsis. The aim of the present study was to test whether endotypes identified in pediatric sepsis are applicable to pediatric acute hypoxemic respiratory failure.

Design: Secondary analysis of a previously reported microarray-based study of pediatric sepsis.

Setting: Multiple PICUs in the United States.

Patients: Sixty-seven children with acute hypoxemic respiratory failure caused by sepsis.

Interventions: None.

Measurements and Main Results: Of the larger septic shock cohort, 67 met eligibility for acute hypoxemic respiratory failure. Twenty-three subjects were assigned to endotype A, and 44 to endotype B. Subjects assigned to endotype A had over four-fold greater unadjusted 28-day mortality, and nearly three-fold greater rates of complicated course. The association with mortality (odds ratio, 8.0; 95% CI, 1.6–41.0) and complicated course (odds ratio, 4.2; 95% CI, 1.2–14.9) persisted after adjustment for age, severity of illness, and PaO2/FIO2.

Conclusions: Applying a previously reported endotyping strategy in children with septic shock identified endotypes of pediatric acute hypoxemic respiratory failure secondary to sepsis, with differential risk for poor outcomes. To our knowledge, this is the first demonstration of endotypes in pediatric respiratory failure. Our results support an investigation into using transcriptomics to identify messenger RNA-based endotypes in a dedicated, well-defined acute hypoxemic respiratory failure cohort.

1Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA.

2Division of Pediatric Critical Care Medicine, Department of Pediatrics and Public Health Science, Penn State Hershey Children’s Hospital, Hershey, PA.

3Division of Critical Care Medicine, Cincinnati Children’s Hospital Medical Center and Cincinnati Children’s Research Foundation, Cincinnati, OH.

4Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH.

*See also p. 187.

Supported, in part, by grants from the National Institutes of Health K23-136688 (to Dr. Yehya); R35 GM-126943 (to Dr. Wong); RO1 GM-108025 (to Dr. Wong)

Drs. Yehya’s and Wong’s institution received funding from the National Institutes of Health (NIH), and they received support for article research from the NIH. Dr. Thomas’ institution received funding from the NIH and Gene Fluidics, and he received funding from Therabron and CareFusion.

This work was performed at the Cincinnati Children’s Hospital Medical Center and Children’s Hospital of Philadelphia.

Address requests for reprints to: Nadir Yehya, MD, CHOP Department of Anesthesiology and Critical Care Medicine, Wood Building 6040A, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104. E-mail:

©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies