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Corticosteroids are associated with repression of adaptive immunity gene programs in pediatric septic shock.

ABSTRACT: Corticosteroids are prescribed commonly for patients with septic shock, but their use remains controversial and concerns remain regarding side effects.To determine the effect of adjunctive corticosteroids on the genomic response of pediatric septic shock.We retrospectively analyzed an existing transcriptomic database of pediatric septic shock. Subjects receiving any formulation of systemic corticosteroids at the time of blood draw for microarray analysis were classified in the septic shock corticosteroid group. We compared normal control subjects (n = 52), a septic shock no corticosteroid group (n = 110), and a septic shock corticosteroid group (n = 70) using analysis of variance. Genes differentially regulated between the no corticosteroid group and the corticosteroid group were analyzed using Ingenuity Pathway Analysis.The two study groups did not differ with respect to illness severity, organ failure burden, mortality, or mortality risk. There were 319 gene probes differentially regulated between the no corticosteroid group and the corticosteroid group. These genes corresponded predominately to adaptive immunity-related signaling pathways, and were down-regulated relative to control subjects. Notably, the degree of down-regulation was significantly greater in the corticosteroid group, compared with the no corticosteroid group. A similar pattern was observed for genes corresponding to the glucocorticoid receptor signaling pathway.Administration of corticosteroids in pediatric septic shock is associated with additional repression of genes corresponding to adaptive immunity. These data should be taken into account when considering the benefit to risk ratio of adjunctive corticosteroids for septic shock.

SUBMITTER: Wong HR

PROVIDER: S-EPMC4098101 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Corticosteroids are associated with repression of adaptive immunity gene programs in pediatric septic shock.

Wong Hector R HR Cvijanovich Natalie Z NZ Allen Geoffrey L GL Thomas Neal J NJ Freishtat Robert J RJ Anas Nick N Meyer Keith K Checchia Paul A PA Weiss Scott L SL Shanley Thomas P TP Bigham Michael T MT Banschbach Sharon S Beckman Eileen E Harmon Kelli K Zimmerman Jerry J JJ

American journal of respiratory and critical care medicine 20140401 8

<h4>Rationale</h4>Corticosteroids are prescribed commonly for patients with septic shock, but their use remains controversial and concerns remain regarding side effects.<h4>Objectives</h4>To determine the effect of adjunctive corticosteroids on the genomic response of pediatric septic shock.<h4>Methods</h4>We retrospectively analyzed an existing transcriptomic database of pediatric septic shock. Subjects receiving any formulation of systemic corticosteroids at the time of blood draw for microarr ...[more]

PMID: 24650276

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Project description:ObjectivesCirculatory dysfunction has been associated with mortality in children with septic shock. However, the mortality risk attributable to myocardial dysfunction per se has not been established, and the association between myocardial dysfunction and mortality is confounded by illness severity. The objective was to determine if sepsis-associated myocardial dysfunction defined by low left ventricular ejection fraction or global longitudinal strain is associated with mortality in pediatric septic shock after adjusting for baseline mortality probability.DesignRetrospective, observational study.SettingSingle-center, quaternary-care PICU.PatientsChildren less than 18 years old admitted to the PICU from 2003 to 2018 who had an echocardiogram performed within 48 hours of septic shock identification and Pediatric Sepsis Biomarker Risk Model II data available.InterventionsNone.Measurements and main resultsAll echocardiograms were reread by a cardiologist blinded to patient data for left ventricular ejection fraction and global longitudinal strain. Low left ventricular ejection fraction was defined as less than 45%, and low global longitudinal strain was defined as greater than z score of -2 for body surface area. Multivariable logistic regression separately analyzed the associations of low left ventricular ejection fraction and low global longitudinal strain with mortality, adjusting for Pediatric Sepsis Biomarker Risk Model II mortality risk. A post hoc logistic regression analyzed the association of left ventricular ejection fraction as a continuous variable with mortality, where linearity was maintained for left ventricular ejection fraction less than 65%. Eighteen percent of 181 children had low left ventricular ejection fraction. After adjusting for baseline mortality risk, low left ventricular ejection fraction remained independently associated with mortality (odds ratio, 4.4 [1.0-19.8]; p = 0.0497). Likewise, left ventricular ejection fraction was associated with mortality (odds ratio, 0.96 [0.93-0.99]; p = 0.037) on multivariable analysis for left ventricular ejection fraction less than 65%. Thirty-six percent of 169 children had low global longitudinal strain, and low global longitudinal strain was also independently associated with mortality (odds ratio, 4.6 [1.2-18.0]; p = 0.027).ConclusionsSepsis-associated myocardial dysfunction, whether defined by low left ventricular ejection fraction or low global longitudinal strain, is an independent risk factor for mortality in pediatric septic shock after accounting for the confounding effects of septic shock severity.

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Corticosteroids are associated with repression of adaptive immunity gene programs in pediatric septic shock.

Publications

Corticosteroids are associated with repression of adaptive immunity gene programs in pediatric septic shock.

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