Acute lung injury: an integrated view of molecular drivers, immune dysregulation, and emerging therapeutic strategies

Acute lung injury (ALI, a term widely used in preclinical animal studies, while the clinical definition of ALI was eliminated in the Berlin criteria) and its severe human clinical counterpart, acute respiratory distress syndrome (ARDS), constitute life-threatening clinical syndromes characterized by diffuse alveolar damage, pulmonary edema, and severe hypoxemia. These conditions are associated with dismal mortality rates and significantly impair patient survival and recovery. Over the past decades, advancements in critical care medicine and molecular biology have deepened our understanding of the pathological mechanisms underlying ALI and ARDS. Aberrantly activated signaling pathways and molecular and cellular events have emerged as key elements to decipher core pathogenic processes, identify early biomarkers, and develop novel therapeutic strategies. This review aims to provide a comprehensive overview of ALI and ARDS, encompassing their definition, historical context, epidemiology, and common etiological factors, with a focus on recent advances in pathological mechanisms, signaling pathways, epigenetic regulation, and therapeutic interventions. Treatment approaches include lung-protective ventilation, fluid management, targeted pharmacotherapy, mesenchymal stromal cell therapy, and nanomaterial-based delivery systems. These developments offer valuable insights into the complex mechanisms of preclinical ALI and human ARDS and contribute to the advancement of clinical diagnosis and treatment.