EARLY-SARDS: Early AlveolaR Lung biologY Underling Sepsis-Associated ARDS

Acute respiratory distress syndrome (ARDS) secondary to sepsis is a biologically heterogeneous syndrome that reflects multiple interacting mechanisms of lung injury rather than a single pathological process. Current clinical definitions rely on physiological manifestations of established lung injury and therefore provide limited insight into the underlying biological processes responsible for disease initiation and progression.

Experimental and translational studies indicate that the earliest phase of sepsis-associated lung injury is characterized by dynamic interactions between inflammatory activation, epithelial injury, endothelial dysfunction, disruption of the alveolar-capillary barrier, and alterations in pulmonary permeability. These processes evolve rapidly during the first days after sepsis onset and may precede the clinical diagnosis of ARDS by several hours or days. Longitudinal characterization is therefore essential to understand the temporal evolution of lung injury.

Because the primary site of injury is the alveolar compartment, circulating biomarkers incompletely reflect the biological events occurring within the lung. Inflammatory mediators, epithelial injury markers, and endothelial activation frequently demonstrate compartmentalization between bronchoalveolar lavage (BAL) fluid and plasma, suggesting that simultaneous assessment of both compartments may provide a more comprehensive characterization of early lung injury than either compartment alone.

Respiratory physiology represents a complementary dimension of ARDS pathophysiology. Parameters including respiratory system compliance, driving pressure, plateau pressure, ventilatory ratio, and gas exchange describe the functional consequences of biological injury and the mechanical environment to which the lung is exposed during invasive mechanical ventilation. Mechanical stress and biological injury are closely interconnected and likely contribute jointly to disease progression.

By combining repeated assessment of alveolar biology, systemic host response, and respiratory physiology during the earliest phase of sepsis-associated respiratory failure, this study is designed to characterize the temporal evolution of lung injury and provide an integrated description of the biological and physiological mechanisms underlying progression to ARDS.

Inclusion criteria

• Age ≥18 years.
• Sepsis or septic shock according to Sepsis-3 criteria.
• Requirement for invasive mechanical ventilation within 72 hours of sepsis diagnosis.
• Written informed consent provided by the participant or a legally authorized representative.

Exclusion criteria

• Pregnancy.
• Previous lung transplantation.
• Contraindication to bronchoscopy or bronchoalveolar lavage (BAL).Inability to complete at least two BAL procedures during the 96-hour study period.
• Expected death within 24 hours or limitation of life-sustaining treatment at enrollment.
• Written informed consent not obtained.