Advances in research on hyperoxia-induced acute lung injury: from pathogenesis to therapy

Hyperoxia-induced acute lung injury (HALI) is a serious complication of excessive oxygen exposure, yet its pathogenesis and treatment remain incompletely understood. A growing body of evidence suggests that HALI results from the interplay of oxidative stress, inflammation, immune dysregulation, organelle dysfunction, alveolar barrier disruption, and regulated cell death. In this review, we summarize recent advances in our understanding of these processes and discuss therapeutic strategies that have been investigated in experimental models. These approaches include antioxidant and anti-inflammatory agents, metabolic and mitochondrial modulators, interventions targeting iron metabolism and ferroptosis, barrier-protective therapies, and cell- or extracellular vesicle-based treatments. We also consider the limitations of the current evidence, particularly the differences between experimental models and clinical settings and the safety, delivery, and reproducibility challenges associated with emerging therapies. Further studies are needed to define the key regulatory mechanisms and temporal features of HALI, establish clinically relevant experimental models, and generate stronger clinical evidence to determine whether promising experimental interventions can be translated into effective therapies.