Evidence of endotypes in pediatric acute hypoxemic respiratory failure caused by sepsis

Nadir Yehya, Neal Thomas, Hector R. Wong

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)110-112
Number of pages3
JournalPediatric Critical Care Medicine
Volume20
Issue number2
DOIs
StatePublished - Feb 1 2019

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Respiratory Insufficiency
Sepsis
Pediatrics
Septic Shock
Odds Ratio
Messenger RNA
Mortality
Biomarkers

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Critical Care and Intensive Care Medicine

Cite this

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title = "Evidence of endotypes in pediatric acute hypoxemic respiratory failure caused by sepsis",
abstract = "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.",
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Evidence of endotypes in pediatric acute hypoxemic respiratory failure caused by sepsis. / Yehya, Nadir; Thomas, Neal; Wong, Hector R.

In: Pediatric Critical Care Medicine, Vol. 20, No. 2, 01.02.2019, p. 110-112.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Evidence of endotypes in pediatric acute hypoxemic respiratory failure caused by sepsis

AU - Yehya, Nadir

AU - Thomas, Neal

AU - Wong, Hector R.

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N2 - 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.

AB - 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.

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