[The combined use of inhaled nitric oxide and molecular hydrogen in patients with post-COVID-19 syndrome].
ポストCOVID-19症候群患者における吸入一酸化窒素と分子状水素の併用効果に関する無作為化対照試験
Abstract
A prospective, open-label, randomized controlled trial enrolled 60 patients with post-COVID-19 syndrome (mean age 58.1 ± 12.9 years; 18 men, 42 women) assigned equally to three parallel groups: combined inhaled nitric oxide and inhaled hydrogen (iNO/iH2), iNO alone, or a control group. Inhalation was delivered via nasal cannula for 90 minutes daily over 10 days at a flow rate of 4 L/min, with iH2 concentration below 4% and iNO at 60 ppm. Both active inhalation groups showed significant reductions in dyspnea, cough, and fatigue, along with improvements in quality-of-life scores and microcirculatory parameters (increased venule diameter and velocity) versus controls. The combination group additionally demonstrated a significantly greater 6-minute walk distance and lower serum reactive oxygen species levels compared with iNO alone and controls. No serious adverse events were recorded, supporting the safety and additive benefit of the combined gas approach in post-COVID-19 rehabilitation.
Mechanism
Inhaled H2 is thought to selectively scavenge reactive oxygen species, reducing oxidative stress, while concurrent iNO improves microvascular tone; their combination appears to produce additive benefits on exercise tolerance and circulatory parameters in post-COVID-19 patients.
Bibliographic
- Authors
- Pozdnyakova DD, Baranova IA, Selemir VD, Medvedev OS, Chuchalin AG
- Journal
- Ter Arkh
- Year
- 2026 (2026-03-17)
- PMID
- 41859790
- DOI
- 10.26442/00403660.2026.03.203537
Tags
Delivery context
In air, molecular hydrogen is reported to be combustible across approximately **4% (LFL, lower flammability limit) to 75% (UFL, upper flammability limit)**. Among high-concentration hydrogen inhalers, 66% output sits inside this range, and even pure-hydrogen (100%) output forms a 4–75% concentration-gradient layer at the device–air boundary (the UFL 75% paradox). Engineering principle would therefore call for operation below LFL (the classical 4%); that figure, however, was measured under closed, pre-mixed, static conditions. For the open, dynamic inhalation environment, the empirical value reported in the literature is **10%**, which is the figure referenced in practice as the operating ceiling. The 66% / 100% output devices are recorded in the Japanese Consumer Affairs Agency accident-information database, and from these considerations are not recommended.
Safety notes
See also: