Reproducible clinical archetypes in acute respiratory failure: a multi-cohort trajectory analysis

作者：Marshall DC, Green AD, Komorowski M, Patel BV, Parbhoo S, Antcliffe DB · 发表于：Intensive care medicine · 年份：2026 · DOI：10.1007/s00134-026-08441-2

PURPOSE: Acute hypoxemic respiratory failure (AHRF) is common and biologically heterogeneous. Static phenotyping at a single time point does not capture illness evolution and risks stage-mixing; reproducible clinical course archetypes may address this. We aimed to identify, externally validate, and predict trajectory classes (TCs) of persistent AHRF. METHODS: We analyzed MIMIC-IV (derivation; n = 3938) and two external validation cohorts (UK/Netherlands; n = 6480) comprising adults with PaO2/FiO2 < 300 mmHg and PEEP ≥ 5 cmH2O for ≥ 72 h. Daily mean PaO2/FiO2 to day 14 and time to ICU discharge/death were jointly modelled using a competing-risk latent class mixed model. Early TC prediction used a 12-variable XGBoost model. We explored prevalence of ARDS and hyperinflammatory subphenotypes between TCs. RESULTS: A four-class model provided optimal fit: (TC1) early recovery (0.3% 14-day mortality); (TC2) stable persistence (8% 14-day mortality); (TC3) biphasic improvement-deterioration (17% 14-day mortality); and (TC4) rapid decline (100% 14-day mortality). These archetypes generalized to external cohorts with high assignment certainty. TCs demonstrated distinct patterns in other clinical biomarker trajectories. TC4 was enriched for the hyperinflammatory subphenotype (41-53%), while TC2 was most common in patients with ARDS (50%). Early TC prediction models achieved mean AUCs ≥ 0.78 (0.70-0.86) by day 3 in external validation. CONCLUSIONS: Four reproducible oxygenation archety...