Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2018 Mar;46(3):e242-e249.
doi: 10.1097/CCM.0000000000002932.

Endotype Transitions During the Acute Phase of Pediatric Septic Shock Reflect Changing Risk and Treatment Response

Hector R Wong  1   2 , Natalie Z Cvijanovich  3 , Nick Anas  4 , Geoffrey L Allen  5 , Neal J Thomas  6 , Michael T Bigham  7 , Scott L Weiss  8 , Julie C Fitzgerald  8 , Paul A Checchia  9 , Keith Meyer  10 , Michael Quasney  11 , Mark Hall  12 , Rainer Gedeit  13 , Robert J Freishtat  14 , Jeffrey Nowak  15 , Riad Lutfi  16 , Shira Gertz  17 , Jocelyn R Grunwell  18 , Christopher J Lindsell  19
Affiliations
Observational Study

Endotype Transitions During the Acute Phase of Pediatric Septic Shock Reflect Changing Risk and Treatment Response

Hector R Wong et al. Crit Care Med. 2018 Mar.

Abstract

Objective: We previously identified septic shock endotypes A and B based on 100 genes reflecting adaptive immunity and glucocorticoid receptor signaling. The endotypes differ with respect to outcome and corticosteroid responsiveness. We determined whether endotypes change during the initial 3 days of illness, and whether changes are associated with outcomes.

Design: Observational cohort study including existing and newly enrolled participants.

Setting: Multiple PICUs.

Patients: Children with septic shock.

Interventions: None.

Measurements and main results: We measured the 100 endotyping genes at day 1 and day 3 of illness in 375 patients. We determined if endotype assignment changes over time, and whether changing endotype is associated with corticosteroid response and outcomes. We used multivariable logistic regression to adjust for illness severity, age, and comorbidity burden. Among the 132 subjects assigned to endotype A on day 1, 56 (42%) transitioned to endotype B by day 3. Among 243 subjects assigned to endotype B on day 1, 77 (32%) transitioned to endotype A by day 3. Assignment to endotype A on day 1 was associated with increased odds of mortality. This risk was modified by the subsequent day 3 endotype assignment. Corticosteroids were associated with increased risk of mortality among subjects who persisted as endotype A.

Conclusions: A substantial proportion of children with septic shock transition endotypes during the acute phase of illness. The risk of poor outcome and the response to corticosteroids change with changes in endotype assignment. Patients persisting as endotype A are at highest risk of poor outcomes.

PubMed Disclaimer

Conflict of interest statement

COMPETING INTERESTS

The Cincinnati Children’s Hospital Research Foundation has submitted a provisional patent application for the temporal endotyping strategy reported in this manuscript. Drs. Wong and Lindsell are named as co-inventors on the patent application.

Figures

Figure 1
Figure 1. Graphical representations of the association between the sum of the raw day 1 and 3 GES values and poor outcome
(A), Mortality rates according to quartiles of the sum of the day 1 and day 3 GES values. P = 0.001, Chi-square, 3 degrees of freedom. (B), complicated course rates according to quartiles of the sum of the day 1 and day 3 GES values. P = 0.015, Chi-square, 3 degrees of freedom. The bars are colored to show the distribution of temporal endotypes within the four quartiles.
See this image and copyright information in PMC

References

    1. Cohen J, Vincent JL, Adhikari NK, et al. Sepsis: a roadmap for future research. Lancet Infect Dis. 2015;15(5):581–614. - PubMed
    1. Prescott HC, Calfee CS, Thompson BT, et al. Toward Smarter Lumping and Smarter Splitting: Rethinking Strategies for Sepsis and Acute Respiratory Distress Syndrome Clinical Trial Design. Am J Respir Crit Care Med. 2016;194(2):147–155. - PMC - PubMed
    1. Calfee CS, Delucchi K, Parsons PE, et al. Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials. Lancet Respir Med. 2014;2(8):611–620. - PMC - PubMed
    1. Davenport EE, Burnham KL, Radhakrishnan J, et al. Genomic landscape of the individual host response and outcomes in sepsis: a prospective cohort study. Lancet Respir Med. 2016;4(4):259–271. - PMC - PubMed
    1. Burnham KL, Davenport EE, Radhakrishnan J, et al. Shared and Distinct Aspects of the Sepsis Transcriptomic Response to Fecal Peritonitis and Pneumonia. Am J Respir Crit Care Med. 2016;196(3):328–339. - PMC - PubMed

Publication types

Substances