Acute lung injury induced by traumatic hemorrhagic shock: pathogenesis, biomarkers and therapeutic perspectives

<b>BACKGROUND:</b> Patients suffering from hemorrhagic shock (HS) complicated by severe trauma are at high risk of developing acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). The underlying pathophysiology is complex, and the lack of targeted therapeutic strategies remains a major clinical challenge. <b>METHODS:</b> In this narrative review, a literature search was conducted in the PubMed to identify articles published from 2006 to August 2025 concerning trauma, HS, traumatic HS (THS), biomarkers related to ALI, ARDS and HS, as well as their treatment. Through its multifactorial pathogenesis, we discuss the diagnostic and prognostic values of biomarkers, their potential role in treatment, and therapeutic advancements and perspectives. <b>RESULTS:</b> ALI and ARDS are serious complications in severe trauma patients with HS. Hypoperfusion, hypoxia, endothelial cell activation, inflammation, ischemia/reperfusion injury and the intestinal response, as well as chest trauma and transfusion-related events are potential causes of lung injury. The pulmonary epithelial biomarkers soluble receptor for advanced glycation end products (sRAGE) and surfactant protein-D provide indicators for evaluating the severity of lung contusion and injury, whereas Clara cell protein 16 may have clinical value for trauma patients with ALI complicated by pneumonia. Elevated endothelial biomarkers angiopoietin-2 and syndecan-1 are correlated with injury severity, transfusion, coagulopathy, the onset of ARDS, and patient outcomes. The role of biomarkers in therapeutic benefit is reviewed. <b>CONCLUSIONS:</b> Preventive and therapeutic strategies for THS-induced ALI/ARDS rely on the implementation of multi-target, multi-mechanism interventions that address the complex pathophysiology. Targeted phenotypic therapy guided by biomarkers would be of interest for future research aimed at improving clinical outcomes.