Bridging iron and lung injury: the emerging role of ferroptosis in ARDS.

Acute respiratory distress syndrome (ARDS) is a severe and diffuse inflammatory lung injury induced by various pulmonary or systemic insults. Its characteristics include disruption of the alveolar-capillary barrier, protein-rich exudates, and refractory hypoxemia. It has a high clinical mortality rate and lacks specific therapies targeting the core mechanisms. Ferroptosis is a regulated, non-apoptotic form of cell death that depends on iron ions and lipid peroxidation. Since its discovery, it has been shown to play a significant role in the pathogenesis of various diseases. Recent studies have demonstrated that ferroptosis plays a critical role in acute lung injury/ARDS. Moreover, it exhibits both commonalities and differences across ARDS of various etiologies. This review systematically summarizes the definition and key mechanisms of ferroptosis, as well as its functional characteristics in different types of ARDS. It also discusses the interaction mechanisms between ferroptosis and ARDS, ferroptosis-targeted interventions, and relevant clinical studies. In addition, it analyzes existing controversies in this field. It also presents prospects for potential breakthroughs in ferroptosis research related to ARDS. The aim is to provide a reference for the study of ARDS pathogenesis and the development of diagnostic and therapeutic strategies based on ferroptosis.