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. 2019 Apr 17;23(1):128.
doi: 10.1186/s13054-019-2342-8.

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

Heidi Flori  1 , Anil Sapru  2 , Michael W Quasney  1 , Ginny Gildengorin  3 , Martha A Q Curley  4   5 , Michael A Matthay  6 , Mary K Dahmer  7 ; BALI and RESTORE Study Investigators, Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network
Collaborators, Affiliations

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

Heidi Flori et al. Crit Care. .

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.

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Conflict of interest statement

Ethics approval and consent to participate

The study was approved by the Institutional Review Boards at all participating sites as described under Materials and Methods.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Plasma interleukin-8 is higher in children with pediatric acute respiratory distress syndrome and in non-survivors. a Comparison of plasma IL-8 in children with or without PARDS. The group with PARDS included children meeting the criteria for PARDS on the indicated day or any previous day. Plasma IL-8 was significantly higher in patients with PARDS across all days (p < 0.0001 using GEE methods as described in the “Methods” section), but when examining each day only achieved significance on day 2 (p = 0.02). b Comparison of plasma IL-8 in children who died or survived. IL-8 is significantly higher in non-survivors on each day (p < 0.05). Day 0 is the day of intubation. The number inside each bar indicates the number of plasma samples analyzed from the indicated days. IL-8 interleukin-8, PARDS pediatric acute respiratory distress syndrome
Fig. 2
Fig. 2
Comparison of plasma interleukin-8 levels in survivors and non-survivors with or without pediatric acute respiratory distress syndrome. a Comparison of plasma IL-8 in survivors with acute respiratory failure with or without PARDS. IL-8 is significantly higher in survivors with PARDS on each day (p < 0.05). b Comparison of plasma IL-8 in non-survivors with acute respiratory failure with or without PARDS. In non-survivors, IL-8 levels are not significantly different in children with or without PARDS. Day 0 is the day of intubation. The number inside each bar indicates the number of plasma samples analyzed from the indicated days. IL-8 interleukin-8, PARDS pediatric acute respiratory distress syndrome
Fig. 3
Fig. 3
Plasma interleukin-8 is higher in children with a longer duration of mechanical ventilation or length of stay. a Comparison of plasma IL-8 in children with acute respiratory failure who were mechanically ventilated for ≤ 7 days to those mechanically ventilated for > 7 days; p < 0.01 on each day. b Comparison of plasma IL-8 in children with acute respiratory failure who were in the PICU for ≤ 14 days to those in the PICU for > 14 days; p < 0.01 on each day. Day 0 is the day of intubation. The number inside each bar indicates the number of plasma samples analyzed from the indicated days. IL-8 interleukin-8, LOS length of stay in the PICU, MV mechanical ventilation, PICU pediatric intensive care unit
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