敗血症関連ARDSにおける早期生物学的・力学的プロファイリング (EARLY-SARDS)

Sepsis or Septic shock requiring mechanical ventilation

Adult ICU patients with sepsis or septic shock requiring invasive mechanical ventilation within 72 hours from sepsis diagnosis will be consecutively enrolled and followed for 96 hours after sepsis diagnosis.

診断テスト：Serial bronchoalveolar lavage and biological-physiological assessment

At baseline (T0), blood samples and standardized respiratory physiological measurements, including gas exchange and ventilatory mechanics, will be obtained from all participants.

Bronchoalveolar lavage (BAL) will be performed only in invasively mechanically ventilated patients meeting predefined safety criteria.

T1 will occur 24 hours after T0 in patients already intubated or at the time of endotracheal intubation if this occurs within 72 hours of sepsis diagnosis.

T2 will be performed 96 hours after sepsis diagnosis and at least 24 hours after the previous assessment.

At each study point plasma sampling and physiological measurements will be repeated, while BAL will be repeated only when predefined safety criteria are fulfilled. All clinical management will remain at the discretion of the treating ICU team.

Early lung injury trajectory within 96 hours of sepsis onset

Early lung injury trajectory, assessed as an ordinal composite endpoint integrating:

1. occurrence of ARDS according to the Berlin Definition,
2. time from sepsis diagnosis to ARDS onset,
3. the highest Berlin ARDS severity stage (mild, moderate, or severe) reached during the 96-hour observation period.

This endpoint will serve as the outcome for development and internal validation of an integrated biological-physiological prediction model combining alveolar and systemic biomarkers with respiratory physiological variables.

Alveolar-systemic biological compartmentalization

Alveolar-to-plasma biomarker gradients, concordance between paired bronchoalveolar lavage (BAL) and plasma biomarkers, and identification of compartmentalized biological profiles associated with early lung injury.

Incremental predictive performance of integrated biological-physiological models

Improvement in model discrimination, calibration, reclassification, and clinical utility after incorporation of alveolar biomarkers and respiratory physiological variables into conventional clinical and plasma-based prediction models.

Reproducibility and external validation of biological-physiological models

Assessment of biomarker distributions, alveolar-systemic gradients, biological-physiological subphenotype assignment, and prediction model performance across the prospective multicentre derivation cohort, including Vall d'Hebron and Uppsala University, with external validation in an independent retrospective Amsterdam UMC cohort.