Molecular hydrogen therapy in respiratory diseases: mechanisms, evidence, and technical considerations hydrogen therapy in respiratory diseases

Molecular hydrogen (H₂) has emerged as a promising therapeutic gas in respiratory medicine due to its antioxidative, anti-inflammatory, anti-apoptotic, and immunomodulatory effects. With the rising prevalence of acute and chronic respiratory diseases, H₂ offers potential as a novel adjunctive therapy. This review integrates mechanistic insights, preclinical findings, clinical data, and technical considerations. Mechanistically, H₂ selectively scavenges hydroxyl radicals and peroxynitrite, protects mitochondrial function, activates Nrf2-mediated antioxidant responses, inhibits inflammasome and NF-κB signaling, and modulates immune cell polarization and apoptosis pathways. Following Ferrari’s narrative review framework, literature searches were performed across MEDLINE, EMBASE, and Google Scholar through June 2025, supplemented by grey literature. Preclinical studies consistently demonstrate protective effects in models of COPD, asthma, pulmonary fibrosis, pulmonary hypertension, acute lung injury, lung cancer, and COVID-19. Early clinical trials and case reports support improvements in oxygenation, exercise tolerance, and inflammatory markers, alongside a strong safety profile. Recent engineering advances enable safe delivery of high-concentration hydrogen, though challenges remain in standardizing dosing and ensuring ventilator compatibility. Overall, molecular hydrogen shows substantial translational potential as a safe and versatile therapeutic gas. Future research must focus on multicenter randomized trials, dose–response studies, and device integration to establish its role in evidence-based respiratory care.