Temporal Transitions of the Hyperinflammatory and Hypoinflammatory Phenotypes in Critical Illness.

Autor:	van Amstel RBE; Amsterdam UMC Locatie AMC, Intensive Care Medicine, Amsterdam, Netherlands; r.b.vanamstel@amsterdamumc.nl., Bartek B; Washington University in St Louis, St Louis, Missouri, United States., Vlaar APJ; Amsterdam UMC, location AMC, Department of Intensive Care, Amsterdam, Netherlands., Gay E; Washington University School of Medicine in Saint Louis, St Louis, Missouri, United States., van Vught LA; Amsterdam UMC, Center for Experimental and Molecular Medicine, Amsterdam, Netherlands., Cremer OL; University Medical CenterUtrecht, Utrecht, Netherlands., Van der Poll T; Amsterdam UMC -AMC Campus, Center for Experimental Molecular Medicine, Amsterdam, Noord-Holland, Netherlands.; Amsterdam UMC -AMC Campus, Department of Medicine, Division of Infectious Diseases, Amsterdam, Noord-Holland, Netherlands., Shapiro NI; Beth Israel Deaconess Medical Center, Emergency Medicine, Boston, Massachusetts, United States., Matthay MA; Cardiovascular Research Institute (CVRI), University of San Francisco, Medicine and Anesthesia, San Francisco, California, United States., Calfee CS; UCSF, Medicine, San Francisco, California, United States., Sinha P; Washington University in St Louis, Department of Anesthesia, Division of Clinical and Translational Research, St Louis, Missouri, United States., Bos LDJ; Amsterdam UMC Locatie AMC, Intensive Care, Amsterdam, Netherlands.
Jazyk:	angličtina
Zdroj:	American journal of respiratory and critical care medicine [Am J Respir Crit Care Med] 2024 Dec 06. Date of Electronic Publication: 2024 Dec 06.
DOI:	10.1164/rccm.202406-1241OC
Abstrakt:	Rationale: Systemic molecular phenotypes of critical illness are prognostically informative, yet their temporal kinetics and implications of changing phenotypes remain incompletely understood. Objectives: To determine the temporal nature of the Hyperinflammatory and Hypoinflammatory phenotypes and assess the impact of transition between the phenotypes on mortality. Methods: We used data from one prospective observational cohort (MARS) and two randomized controlled trials in ARDS (ALVEOLI) and sepsis (CLOVERS). Critically ill patients having biomarkers available at multiple timepoints (Day 0-4) were included. We employed a validated classifier model incorporating plasma interleukin-8, protein C and serum bicarbonate to assign phenotypes on each day. We determined the association of longitudinal phenotype transition and 90-day all-cause mortality. Measurements and Main Results: Data from 2407, 527 and 868 patients were included in MARS, ALVEOLI and CLOVERS, respectively. In MARS, 36.0% were classified by the parsimonious model as Hyperinflammatory at day 0, decreasing to 15.6% by day 2 and 6.3% by day 4. In ALVEOLI and CLOVERS, 26.4% and 24.8% of patients were Hyperinflammatory at day 0, decreasing to 13.4% and 5.7% at day 3, respectively. In all three cohorts, switching classification from Hyperinflammatory (Day 0) to Hypoinflammatory over time was associated with significantly improved mortality compared to persistently Hyperinflammatory patients. Mediation analysis indicated that only a minor proportion of this improvement could be attributed to ameliorating organ failure. Conclusion: The prevalence of the Hyperinflammatory phenotype, as assigned by a parsimonious biomarker classifier model, decreases over the first several days of critical illness, irrespective of ARDS diagnosis. The transition from Hyperinflammatory to Hypoinflammatory mediates a trajectory towards recovery beyond the resolution of organ failure.
Databáze:	MEDLINE
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