TY - JOUR
T1 - Biological subphenotypes of acute respiratory distress syndrome show prognostic enrichment in mechanically ventilated patients without acute respiratory distress syndrome
AU - Heijnen, Nanon F. L.
AU - Hagens, Laura A.
AU - Smit, Marry R.
AU - Cremer, Olaf L.
AU - Ong, David S. Y.
AU - der Poll, Tom Van
AU - van Vught, Lonneke A.
AU - Scicluna, Brendon P.
AU - Schnabel, Ronny M.
AU - van der Horst, Iwan C. C.
AU - Schultz, Marcus J.
AU - Bergmans, Dennis C. J. J.
AU - Bos, Lieuwe D. J.
AU - de Beer, Friso M.
AU - Bos, Lieuwe D.
AU - Glas, Gerie J.
AU - Horn, Janneke
AU - Hoogendijk, Arie J.
AU - van Hooijdonk, Roosmarijn T.
AU - Huson, Mischa A.
AU - van der Poll, Tom
AU - Scicluna, Brendon
AU - Schouten, Laura R.
AU - Schultz, Marcus J.
AU - Straat, Marleen
AU - van Vught, Lonneke A.
AU - Wieske, Luuk
AU - Wievel, Maryse A.
AU - Witteveen, Esther
AU - MARS consortium
AU - Bonten, Marc J.
AU - Cremer, Olaf L.
AU - Frencken, Jos F.
AU - van de Groep, Kirsten
AU - Klein Klouwenberg, Peter M.
AU - Koster-Brouwer, Maria E.
AU - Ong, David S.
AU - Varkila, Meri R.
AU - Verboom, Diana M.
N1 - Funding Information:
Supported by the Center for Translational Molecular Medicine (main applicant: T.v.d.P.) with additional support from the Longfonds (Dutch Lung Foundation) private-partnership program.
Publisher Copyright:
Copyright © 2021 by the American Thoracic Society.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/6/15
Y1 - 2021/6/15
N2 - Rationale: Recent studies showed that biological subphenotypes in acute respiratory distress syndrome (ARDS) provide prognostic enrichment and show potential for predictive enrichment. Objectives: To determine whether these subphenotypes and their prognostic and potential for predictive enrichment could be extended to other patients in the ICU, irrespective of fulfilling the definition of ARDS. Methods: This is a secondary analysis of a prospective observational study of adult patients admitted to the ICU. We tested the prognostic enrichment of both cluster-derived and latentclass analysis (LCA)-derived biological ARDS subphenotypes by evaluating the association with clinical outcome (ICU-day, 30-day mortality, and ventilator-free days) using logistic regression and Cox regression analysis. We performed a principal component analysis to compare blood leukocyte gene expression profiles between subphenotypes and the presence of ARDS. Measurements and Main Results: We included 2,499 mechanically ventilated patients (674 with and 1,825 without ARDS). The cluster-derived "reactive"subphenotype was, independently of ARDS, significantly associated with a higher probability of ICU mortality, higher 30-day mortality, and a lower probability of successful extubation while alive compared with the "uninflamed"subphenotype. The blood leukocyte gene expression profiles of individual subphenotypes were similar for patients with and without ARDS. LCA-derived subphenotypes also showed similar profiles. Conclusions: The prognostic and potential for predictive enrichment of biological ARDS subphenotypes may be extended to mechanically ventilated critically ill patients without ARDS. Using the concept of biological subphenotypes for splitting cohorts of critically ill patients could add to improving future precision-based trial strategies and lead to identifying treatable traits for all critically ill patients.
AB - Rationale: Recent studies showed that biological subphenotypes in acute respiratory distress syndrome (ARDS) provide prognostic enrichment and show potential for predictive enrichment. Objectives: To determine whether these subphenotypes and their prognostic and potential for predictive enrichment could be extended to other patients in the ICU, irrespective of fulfilling the definition of ARDS. Methods: This is a secondary analysis of a prospective observational study of adult patients admitted to the ICU. We tested the prognostic enrichment of both cluster-derived and latentclass analysis (LCA)-derived biological ARDS subphenotypes by evaluating the association with clinical outcome (ICU-day, 30-day mortality, and ventilator-free days) using logistic regression and Cox regression analysis. We performed a principal component analysis to compare blood leukocyte gene expression profiles between subphenotypes and the presence of ARDS. Measurements and Main Results: We included 2,499 mechanically ventilated patients (674 with and 1,825 without ARDS). The cluster-derived "reactive"subphenotype was, independently of ARDS, significantly associated with a higher probability of ICU mortality, higher 30-day mortality, and a lower probability of successful extubation while alive compared with the "uninflamed"subphenotype. The blood leukocyte gene expression profiles of individual subphenotypes were similar for patients with and without ARDS. LCA-derived subphenotypes also showed similar profiles. Conclusions: The prognostic and potential for predictive enrichment of biological ARDS subphenotypes may be extended to mechanically ventilated critically ill patients without ARDS. Using the concept of biological subphenotypes for splitting cohorts of critically ill patients could add to improving future precision-based trial strategies and lead to identifying treatable traits for all critically ill patients.
KW - Acute respiratory distress syndrome
KW - Critically ill
KW - Personalized medicine
KW - Phenotypes
UR - http://www.scopus.com/inward/record.url?scp=85107042993&partnerID=8YFLogxK
U2 - 10.1164/rccm.202006-2522OC
DO - 10.1164/rccm.202006-2522OC
M3 - Article
C2 - 33465019
SN - 1073-449X
VL - 203
SP - 1503
EP - 1511
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
IS - 12
ER -