Manuel Gonzalez-Plascencia, Margarita L. Martinez-Fierro, Alfredo Salazar de Santiago, Ana G. Castañeda-Miranda, Jose Isaias Badillo-Almaraz, Idalia Garza-Veloz
Acute respiratory distress syndrome (ARDS) remains a leading cause of morbidity and mortality in critically ill patients despite advances in supportive care and lung-protective ventilation. The syndrome is characterized by biological heterogeneity involving epithelial and endothelial injury, dysregulated inflammation, surfactant dysfunction, and impaired alveolar-capillary barrier integrity. This review integrates experimental, translational, and clinical evidence to examine the biological and molecular basis underlying ARDS, with particular emphasis on alveolar-capillary architecture, immune dysregulation, pulmonary mechanics, and the temporal evolution of diffuse alveolar damage. We further discuss emerging concepts in ARDS phenotyping and biomarker-based stratification as tools to address therapeutic heterogeneity and improve prognostic precision. Collectively, the evidence supports a shift from syndromic management toward biologically informed, precision-based approaches that may enable targeted interventions and improved clinical outcomes in ARDS.