A prospective investigation of interleukin-8 levels in pediatric acute respiratory failure and acute respiratory distress syndrome

Heidi Flori, Anil Sapru, Michael W. Quasney, Ginny Gildengorin, Martha A.Q. Curley, Michael A. Matthay, Mary K. Dahmer*, Scot T. Bateman, M. D. Berg, Santiago Borasino, G. Kris Bysani, Allison S. Cowl, Cindy Darnell Bowens, E. Vincent S. Faustino, Lori D. Fineman, A. J. Godshall, Ellie Hirshberg, Aileen L. Kirby, Gwenn E. McLaughlin, Shivanand Medar & 10 others Phineas P. Oren, James B. Schneider, Adam J. Schwarz, Thomas Patrick Shanley, Lauren R. Sorce, Edward J. Truemper, Michele A. Vander Heyden, Kim Wittmayer, Athena Zuppa, David Wypij

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: The association of plasma interleukin-8 (IL-8), or IL-8 genetic variants, with pediatric acute respiratory distress syndrome (PARDS) in children with acute respiratory failure at risk for PARDS has not been examined. The purpose of this study was to examine the association of early and sequential measurement of plasma IL-8 and/or its genetic variants with development of PARDS and other clinical outcomes in mechanically ventilated children with acute respiratory failure. Methods: This was a prospective cohort study of children 2 weeks to 17 years of age with acute airways and/or parenchymal lung disease done in 22 pediatric intensive care units participating in the multi-center clinical trial, Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE). Plasma IL-8 levels were measured within 24 h of consent and 24 and 48 h later. DNA was purified from whole blood, and IL-8 single nucleotide polymorphisms, rs4073, rs2227306, and rs2227307, were genotyped. Results: Five hundred forty-nine patients were enrolled; 480 had blood sampling. Plasma IL-8 levels ranged widely from 4 to 7373 pg/mL. Highest IL-8 levels were observed on the day of intubation with subsequent tapering. Levels of IL-8 varied significantly across primary diagnoses with the highest levels occurring in patients with sepsis and the lowest levels in those with asthma. Plasma IL-8 was strongly correlated with oxygenation defect and severity of illness. IL-8 was consistently higher in PARDS patients compared to those without PARDS; levels were 4-12 fold higher in non-survivors compared to survivors. On multivariable analysis, IL-8 was independently associated with death, duration of mechanical ventilation, and PICU length of stay on all days measured, but was not associated with PARDS development. There was no association between the IL-8 single nucleotide polymorphisms, rs4073, rs2227306, and rs2227307, and PARDS development or plasma IL-8 level. Conclusions: When measured sequentially, plasma IL-8 was robustly associated with multiple, relevant clinical outcomes including mortality, but was not associated with PARDS development. The wide range of plasma IL-8 levels exhibited in this cohort suggests that further study into the heterogeneity of this patient population and its impact on individual responses to PARDS treatment is warranted.

Original languageEnglish (US)
Article number128
JournalCritical Care
Volume23
Issue number1
DOIs
StatePublished - Apr 17 2019

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Adult Respiratory Distress Syndrome
Interleukin-8
Respiratory Insufficiency
Pediatrics
Single Nucleotide Polymorphism
Pediatric Intensive Care Units
Population Characteristics
Artificial Respiration
Intubation
Lung Diseases
Survivors
Length of Stay
Sepsis

Keywords

  • ARDS
  • Acute respiratory distress syndrome
  • Biomarkers
  • Critical illness
  • Genetic variants
  • PARDS
  • SNP

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Flori, H., Sapru, A., Quasney, M. W., Gildengorin, G., Curley, M. A. Q., Matthay, M. A., ... Wypij, D. (2019). A prospective investigation of interleukin-8 levels in pediatric acute respiratory failure and acute respiratory distress syndrome. Critical Care, 23(1), [128]. https://doi.org/10.1186/s13054-019-2342-8
Flori, Heidi ; Sapru, Anil ; Quasney, Michael W. ; Gildengorin, Ginny ; Curley, Martha A.Q. ; Matthay, Michael A. ; Dahmer, Mary K. ; Bateman, Scot T. ; Berg, M. D. ; Borasino, Santiago ; Bysani, G. Kris ; Cowl, Allison S. ; Bowens, Cindy Darnell ; Faustino, E. Vincent S. ; Fineman, Lori D. ; Godshall, A. J. ; Hirshberg, Ellie ; Kirby, Aileen L. ; McLaughlin, Gwenn E. ; Medar, Shivanand ; Oren, Phineas P. ; Schneider, James B. ; Schwarz, Adam J. ; Shanley, Thomas Patrick ; Sorce, Lauren R. ; Truemper, Edward J. ; Vander Heyden, Michele A. ; Wittmayer, Kim ; Zuppa, Athena ; Wypij, David. / A prospective investigation of interleukin-8 levels in pediatric acute respiratory failure and acute respiratory distress syndrome. In: Critical Care. 2019 ; Vol. 23, No. 1.
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title = "A prospective investigation of interleukin-8 levels in pediatric acute respiratory failure and acute respiratory distress syndrome",
abstract = "Background: The association of plasma interleukin-8 (IL-8), or IL-8 genetic variants, with pediatric acute respiratory distress syndrome (PARDS) in children with acute respiratory failure at risk for PARDS has not been examined. The purpose of this study was to examine the association of early and sequential measurement of plasma IL-8 and/or its genetic variants with development of PARDS and other clinical outcomes in mechanically ventilated children with acute respiratory failure. Methods: This was a prospective cohort study of children 2 weeks to 17 years of age with acute airways and/or parenchymal lung disease done in 22 pediatric intensive care units participating in the multi-center clinical trial, Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE). Plasma IL-8 levels were measured within 24 h of consent and 24 and 48 h later. DNA was purified from whole blood, and IL-8 single nucleotide polymorphisms, rs4073, rs2227306, and rs2227307, were genotyped. Results: Five hundred forty-nine patients were enrolled; 480 had blood sampling. Plasma IL-8 levels ranged widely from 4 to 7373 pg/mL. Highest IL-8 levels were observed on the day of intubation with subsequent tapering. Levels of IL-8 varied significantly across primary diagnoses with the highest levels occurring in patients with sepsis and the lowest levels in those with asthma. Plasma IL-8 was strongly correlated with oxygenation defect and severity of illness. IL-8 was consistently higher in PARDS patients compared to those without PARDS; levels were 4-12 fold higher in non-survivors compared to survivors. On multivariable analysis, IL-8 was independently associated with death, duration of mechanical ventilation, and PICU length of stay on all days measured, but was not associated with PARDS development. There was no association between the IL-8 single nucleotide polymorphisms, rs4073, rs2227306, and rs2227307, and PARDS development or plasma IL-8 level. Conclusions: When measured sequentially, plasma IL-8 was robustly associated with multiple, relevant clinical outcomes including mortality, but was not associated with PARDS development. The wide range of plasma IL-8 levels exhibited in this cohort suggests that further study into the heterogeneity of this patient population and its impact on individual responses to PARDS treatment is warranted.",
keywords = "ARDS, Acute respiratory distress syndrome, Biomarkers, Critical illness, Genetic variants, PARDS, SNP",
author = "Heidi Flori and Anil Sapru and Quasney, {Michael W.} and Ginny Gildengorin and Curley, {Martha A.Q.} and Matthay, {Michael A.} and Dahmer, {Mary K.} and Bateman, {Scot T.} and Berg, {M. D.} and Santiago Borasino and Bysani, {G. Kris} and Cowl, {Allison S.} and Bowens, {Cindy Darnell} and Faustino, {E. Vincent S.} and Fineman, {Lori D.} and Godshall, {A. J.} and Ellie Hirshberg and Kirby, {Aileen L.} and McLaughlin, {Gwenn E.} and Shivanand Medar and Oren, {Phineas P.} and Schneider, {James B.} and Schwarz, {Adam J.} and Shanley, {Thomas Patrick} and Sorce, {Lauren R.} and Truemper, {Edward J.} and {Vander Heyden}, {Michele A.} and Kim Wittmayer and Athena Zuppa and David Wypij",
year = "2019",
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doi = "10.1186/s13054-019-2342-8",
language = "English (US)",
volume = "23",
journal = "Critical Care",
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Flori, H, Sapru, A, Quasney, MW, Gildengorin, G, Curley, MAQ, Matthay, MA, Dahmer, MK, Bateman, ST, Berg, MD, Borasino, S, Bysani, GK, Cowl, AS, Bowens, CD, Faustino, EVS, Fineman, LD, Godshall, AJ, Hirshberg, E, Kirby, AL, McLaughlin, GE, Medar, S, Oren, PP, Schneider, JB, Schwarz, AJ, Shanley, TP, Sorce, LR, Truemper, EJ, Vander Heyden, MA, Wittmayer, K, Zuppa, A & Wypij, D 2019, 'A prospective investigation of interleukin-8 levels in pediatric acute respiratory failure and acute respiratory distress syndrome', Critical Care, vol. 23, no. 1, 128. https://doi.org/10.1186/s13054-019-2342-8

A prospective investigation of interleukin-8 levels in pediatric acute respiratory failure and acute respiratory distress syndrome. / Flori, Heidi; Sapru, Anil; Quasney, Michael W.; Gildengorin, Ginny; Curley, Martha A.Q.; Matthay, Michael A.; Dahmer, Mary K.; Bateman, Scot T.; Berg, M. D.; Borasino, Santiago; Bysani, G. Kris; Cowl, Allison S.; Bowens, Cindy Darnell; Faustino, E. Vincent S.; Fineman, Lori D.; Godshall, A. J.; Hirshberg, Ellie; Kirby, Aileen L.; McLaughlin, Gwenn E.; Medar, Shivanand; Oren, Phineas P.; Schneider, James B.; Schwarz, Adam J.; Shanley, Thomas Patrick; Sorce, Lauren R.; Truemper, Edward J.; Vander Heyden, Michele A.; Wittmayer, Kim; Zuppa, Athena; Wypij, David.

In: Critical Care, Vol. 23, No. 1, 128, 17.04.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A prospective investigation of interleukin-8 levels in pediatric acute respiratory failure and acute respiratory distress syndrome

AU - Flori, Heidi

AU - Sapru, Anil

AU - Quasney, Michael W.

AU - Gildengorin, Ginny

AU - Curley, Martha A.Q.

AU - Matthay, Michael A.

AU - Dahmer, Mary K.

AU - Bateman, Scot T.

AU - Berg, M. D.

AU - Borasino, Santiago

AU - Bysani, G. Kris

AU - Cowl, Allison S.

AU - Bowens, Cindy Darnell

AU - Faustino, E. Vincent S.

AU - Fineman, Lori D.

AU - Godshall, A. J.

AU - Hirshberg, Ellie

AU - Kirby, Aileen L.

AU - McLaughlin, Gwenn E.

AU - Medar, Shivanand

AU - Oren, Phineas P.

AU - Schneider, James B.

AU - Schwarz, Adam J.

AU - Shanley, Thomas Patrick

AU - Sorce, Lauren R.

AU - Truemper, Edward J.

AU - Vander Heyden, Michele A.

AU - Wittmayer, Kim

AU - Zuppa, Athena

AU - Wypij, David

PY - 2019/4/17

Y1 - 2019/4/17

N2 - Background: The association of plasma interleukin-8 (IL-8), or IL-8 genetic variants, with pediatric acute respiratory distress syndrome (PARDS) in children with acute respiratory failure at risk for PARDS has not been examined. The purpose of this study was to examine the association of early and sequential measurement of plasma IL-8 and/or its genetic variants with development of PARDS and other clinical outcomes in mechanically ventilated children with acute respiratory failure. Methods: This was a prospective cohort study of children 2 weeks to 17 years of age with acute airways and/or parenchymal lung disease done in 22 pediatric intensive care units participating in the multi-center clinical trial, Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE). Plasma IL-8 levels were measured within 24 h of consent and 24 and 48 h later. DNA was purified from whole blood, and IL-8 single nucleotide polymorphisms, rs4073, rs2227306, and rs2227307, were genotyped. Results: Five hundred forty-nine patients were enrolled; 480 had blood sampling. Plasma IL-8 levels ranged widely from 4 to 7373 pg/mL. Highest IL-8 levels were observed on the day of intubation with subsequent tapering. Levels of IL-8 varied significantly across primary diagnoses with the highest levels occurring in patients with sepsis and the lowest levels in those with asthma. Plasma IL-8 was strongly correlated with oxygenation defect and severity of illness. IL-8 was consistently higher in PARDS patients compared to those without PARDS; levels were 4-12 fold higher in non-survivors compared to survivors. On multivariable analysis, IL-8 was independently associated with death, duration of mechanical ventilation, and PICU length of stay on all days measured, but was not associated with PARDS development. There was no association between the IL-8 single nucleotide polymorphisms, rs4073, rs2227306, and rs2227307, and PARDS development or plasma IL-8 level. Conclusions: When measured sequentially, plasma IL-8 was robustly associated with multiple, relevant clinical outcomes including mortality, but was not associated with PARDS development. The wide range of plasma IL-8 levels exhibited in this cohort suggests that further study into the heterogeneity of this patient population and its impact on individual responses to PARDS treatment is warranted.

AB - Background: The association of plasma interleukin-8 (IL-8), or IL-8 genetic variants, with pediatric acute respiratory distress syndrome (PARDS) in children with acute respiratory failure at risk for PARDS has not been examined. The purpose of this study was to examine the association of early and sequential measurement of plasma IL-8 and/or its genetic variants with development of PARDS and other clinical outcomes in mechanically ventilated children with acute respiratory failure. Methods: This was a prospective cohort study of children 2 weeks to 17 years of age with acute airways and/or parenchymal lung disease done in 22 pediatric intensive care units participating in the multi-center clinical trial, Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE). Plasma IL-8 levels were measured within 24 h of consent and 24 and 48 h later. DNA was purified from whole blood, and IL-8 single nucleotide polymorphisms, rs4073, rs2227306, and rs2227307, were genotyped. Results: Five hundred forty-nine patients were enrolled; 480 had blood sampling. Plasma IL-8 levels ranged widely from 4 to 7373 pg/mL. Highest IL-8 levels were observed on the day of intubation with subsequent tapering. Levels of IL-8 varied significantly across primary diagnoses with the highest levels occurring in patients with sepsis and the lowest levels in those with asthma. Plasma IL-8 was strongly correlated with oxygenation defect and severity of illness. IL-8 was consistently higher in PARDS patients compared to those without PARDS; levels were 4-12 fold higher in non-survivors compared to survivors. On multivariable analysis, IL-8 was independently associated with death, duration of mechanical ventilation, and PICU length of stay on all days measured, but was not associated with PARDS development. There was no association between the IL-8 single nucleotide polymorphisms, rs4073, rs2227306, and rs2227307, and PARDS development or plasma IL-8 level. Conclusions: When measured sequentially, plasma IL-8 was robustly associated with multiple, relevant clinical outcomes including mortality, but was not associated with PARDS development. The wide range of plasma IL-8 levels exhibited in this cohort suggests that further study into the heterogeneity of this patient population and its impact on individual responses to PARDS treatment is warranted.

KW - ARDS

KW - Acute respiratory distress syndrome

KW - Biomarkers

KW - Critical illness

KW - Genetic variants

KW - PARDS

KW - SNP

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U2 - 10.1186/s13054-019-2342-8

DO - 10.1186/s13054-019-2342-8

M3 - Article

VL - 23

JO - Critical Care

JF - Critical Care

SN - 1466-609X

IS - 1

M1 - 128

ER -