Recent advances in pharmacological and non-pharmacological strategies of pneumoprotection: a narrative review

Acute lung injury (ALI), acute respiratory distress syndrome (ARDS), ventilator-induced lung injury (VILI), pulmonary ischemia-reperfusion (I/R) injury, and inflammatory lung diseases remain major causes of morbidity and mortality in critically ill patients worldwide. Despite significant advances in respiratory support, lung injury continues to represent a major therapeutic challenge due to the complex interaction between inflammatory, oxidative, mechanical, and cellular pathways. The concept of pneumoprotection encompasses endogenous and exogenous mechanisms capable of attenuating pulmonary damage and preserving alveolar-capillary integrity. These protective responses may be stimulated by pharmacological interventions, including antioxidants, nitric oxide modulators, corticosteroids, mesenchymal stem cell-derived therapies, and mitochondrial-targeted agents, as well as non-pharmacological approaches such as lung-protective ventilation, prone positioning, ischemic conditioning, and physical rehabilitation strategies. Recent advances in molecular biology have revealed critical signaling pathways involved in pneumoprotection, including PI3K/Akt, Nrf2/HO-1, NF-κB, HIF-1α, mitochondrial permeability transition pore regulation, and inflammatory cytokine modulation. This narrative review summarizes current evidence regarding pharmacological and non-pharmacological strategies for pneumoprotection and discusses future perspectives for translational and clinical research.