Sepsis-induced ALI/ARDS beyond supportive care: molecular mechanisms and cutting-edge therapies

Sepsis-induced ALI/ARDS are severe conditions driven by complex molecular and cellular mechanisms, including endothelial dysfunction, immunological dysregulation, epigenetic changes, and oxidative stress. These factors disrupt endothelial integrity and promote cell death, worsening lung injury and respiratory failure. COVID-19-related ARDS, similar to sepsis-induced ALI, is more severe, involving immune dysregulation, cytokine storms, and microthrombi. Despite extensive research, sepsis-induced ALI/ARDS has gained the status of the Bermuda Triangle, as no effective pharmacological treatments are currently available, and supportive therapies remain the mainstay of treatment. Consequently, a critical need exists to explore innovative treatment options. This review highlights the molecular and cellular mechanisms of sepsis-induced ALI/ARDS, key cellular signaling pathways in sepsis-induced ALI/ARDS, clinical insights into COVID-19-related ALI/ARDS, existing and emerging treatments, and the limitations of current therapies. It emphasizes the need for innovative approaches to improve patient outcomes and underscores the importance of advancing research to enhance understanding and treatment development.