中等症COVID-19患者における水素吸入の安全性・忍容性を評価するフェーズI用量漸増臨床試験（HCOVID）
This phase I open-label, prospective, monocentric, single ascending-dose trial investigated the safety and tolerability of inhaling a mixture of H2 (3.6%) and N2 (96.4%) in hospitalized patients with confirmed SARS-CoV-2 infection. Using a 3+3 design, three exposure durations were evaluated: 1 day, 3 days, and 6 days. All 12 enrolled patients demonstrated clinical improvement and excellent tolerability. The maximum tolerated duration was determined to be at least 3 days. The device used was specifically designed to eliminate explosion risk. H2 inhalation was explored as an adjunctive approach alongside nasal oxygen delivery, with interest in its potential to modulate inflammation-related intracellular signaling. The authors report this as the first clinical trial to establish the safety profile of this H2/N2 mixture in COVID-19 patients, and suggest that the findings support progression to larger controlled trials. The study is registered at ClinicalTrials.gov (NCT04633980).
H2 inhalation is proposed to suppress intracellular signaling pathways associated with inflammatory responses, potentially reducing COVID-19-related inflammation when administered early alongside oxygen supplementation.
For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information database and are not recommended.
See also:
https://h2-papers.org/en/papers/39016593