Temporal stability of phenotypes of acute respiratory distress syndrome: clinical implications for early corticosteroid therapy and mortality

Joris Pensier^{1

2}, Maxime Fosset^{2

3}, Béla-Simon Paschold², Dario von Wedel^{2

4}, Simone Redaelli², Ben L P Braeuer², Victor Novack⁵, Felix Balzer⁴, Boris Jung^{2

3

6}, Marcelo B P Amato⁷, Samir Jaber¹, Daniel Talmor², Elias Baedorf-Kassis^{2

6}, Maximilian S Schaefer^{8

9}

Affiliations

¹ Anesthesiology and Intensive Care, Anesthesia and Critical Care Department B, Saint Eloi Teaching Hospital, PhyMedExp, University of Montpellier, INSERM U1046, Montpellier, France.
² Department of Anesthesia, Critical Care and Pain Medicine, Center for Anesthesia Research Excellence Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA.
³ Medical Intensive Care Unit, Premedical Inria-Inserm Team Idesp, Montpellier University and Montpellier University Health Care Center, Montpellier, France.
⁴ Institute of Medical Informatics, Charité-Universitätsmedizin Berlin, Berlin, Germany.
⁵ Clinical Research Center, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beersheba, Israel.
⁶ Department of Pulmonary, Critical Care and Sleep Medicine, Beth Israel Deaconess Medical Center, Boston, USA.
⁷ Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Laboratório de Pneumologia LIM-09, Disciplina de Pneumologia, Heart Institute (Incor), São Paulo, Brazil.
⁸ Department of Anesthesia, Critical Care and Pain Medicine, Center for Anesthesia Research Excellence Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA. msschaef@bidmc.harvard.edu.
⁹ Department of Anesthesiology, Duesseldorf University Hospital, Duesseldorf, Germany. msschaef@bidmc.harvard.edu.

PMID: 40839098
DOI: 10.1007/s00134-025-08089-4

Multicenter Study

Temporal stability of phenotypes of acute respiratory distress syndrome: clinical implications for early corticosteroid therapy and mortality

Joris Pensier et al. Intensive Care Med. 2025 Oct.

. 2025 Oct;51(10):1784-1796.

doi: 10.1007/s00134-025-08089-4. Epub 2025 Aug 21.

Authors

Affiliations

¹ Anesthesiology and Intensive Care, Anesthesia and Critical Care Department B, Saint Eloi Teaching Hospital, PhyMedExp, University of Montpellier, INSERM U1046, Montpellier, France.
² Department of Anesthesia, Critical Care and Pain Medicine, Center for Anesthesia Research Excellence Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA.
³ Medical Intensive Care Unit, Premedical Inria-Inserm Team Idesp, Montpellier University and Montpellier University Health Care Center, Montpellier, France.
⁴ Institute of Medical Informatics, Charité-Universitätsmedizin Berlin, Berlin, Germany.
⁵ Clinical Research Center, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beersheba, Israel.
⁶ Department of Pulmonary, Critical Care and Sleep Medicine, Beth Israel Deaconess Medical Center, Boston, USA.
⁷ Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Laboratório de Pneumologia LIM-09, Disciplina de Pneumologia, Heart Institute (Incor), São Paulo, Brazil.
⁸ Department of Anesthesia, Critical Care and Pain Medicine, Center for Anesthesia Research Excellence Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA. msschaef@bidmc.harvard.edu.
⁹ Department of Anesthesiology, Duesseldorf University Hospital, Duesseldorf, Germany. msschaef@bidmc.harvard.edu.

PMID: 40839098
DOI: 10.1007/s00134-025-08089-4

Abstract

Purpose: Inflammatory phenotypes of acute respiratory distress syndrome (ARDS) can predict patient outcomes and potentially response to treatment. The aim was to assess whether inflammatory phenotypes can be characterized over time using clinical surrogate data and used to guide therapy with corticosteroids.

Methods: Individual patient data and biomarkers from six multicenter randomized controlled trials (development, n = 1207; validation, n = 2751) were analyzed to establish an open-source AI Clinical Classifier ( https://bostonmontpelliercare.shinyapps.io/AIClarity ) for inflammatory phenotypes of ARDS using routine clinical data. Then, patients from a retrospective cohort (investigation, n = 5578) underwent classification from baseline to day 30. A discrete-time Bayesian Markov model assessed temporal stability at 3-day intervals. A target trial emulation and longitudinal logistic regression assessed corticosteroid effect on 30-day mortality depending on phenotype.

Results: The AI Clinical Classifier identified 2169 (39%) hyperinflammatory and 3409 (61%) hypoinflammatory patients. 1053 (49%) and 826 (24%) patients died within 30 days, respectively (p < 0.001). Over 30 days, 49%(1072/2169) of hyperinflammatory patients at baseline transitioned to hypoinflammatory, and 7%(229/3409) of hypoinflammatory patients at baseline transitioned to hyperinflammatory (p < 0.001). Phenotypes predicted response to corticosteroids, with lower mortality in hyperinflammatory patients (IPW-weighted hazard ratio [HR]: 0.81 [0.67-0.98], p = 0.033), and higher mortality in hypoinflammatory patients (IPW-weighted HR: 1.26 [1.06-1.50], p = 0.009). At day 3, a positive response to corticosteroids only persisted among patients who remained hyperinflammatory (adjusted odds ratio = 0.51, 95% CI 0.32-0.80, p = 0.004).

Conclusion: Characterization of inflammatory ARDS phenotypes using clinical surrogate data allows physicians to monitor patients throughout the course of the disease and guide clinical treatment. Corticosteroids may be beneficial in hyperinflammatory ARDS and harmful in hypoinflammatory ARDS.

Keywords: Acute respiratory distress syndrome; Corticosteroids; Inflammation; Mechanical ventilation; Phenotyping.

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Conflict of interest statement

Declarations. Conflicts of interest: JP received funding from the Société Française d’Anesthésie-Réanimation, the Philippe Foundation, the Beth Israel Deaconess Medical Center (Boston, MA), and the University Hospital of Montpellier. MF received funding from the Société de Réanimation de Langue Française and a Fulbright scholarship. SJ received consulting fees from Drager, Medtronic, Mindray, Fresenius, Baxter, and Fisher & Paykel. EBK has received lecturing fees from Hamilton Medical Inc. outside the submitted work and has received a KL2 award from Harvard Catalyst, The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health award No. KL2 TR002542). MSS received funding for investigator-initiated studies from Merck & Co., which do not pertain to this manuscript. He is an associate editor for BMC Anesthesiology. He received honoraria for lectures from Fisher & Paykel Healthcare and Mindray Medical International Limited. He received an unrestricted philanthropic grant from Jeffrey and Judith Buzen. The other authors declare no competing interest. SJ is the Editor in Chief of Intensive Care Medicine. He has not taken part in the review or selection process of this article. Ethics approval: This study was approved by the institutional review board at Beth Israel Deaconess Medical Center, Boston, MA (protocol number: 2023D000928), and the requirement for informed consent was waived.

References

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Temporal stability of phenotypes of acute respiratory distress syndrome: clinical implications for early corticosteroid therapy and mortality

Affiliations

Temporal stability of phenotypes of acute respiratory distress syndrome: clinical implications for early corticosteroid therapy and mortality

Authors

Affiliations

Abstract

Conflict of interest statement

References

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LinkOut - more resources

Full Text Sources

Medical