# [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](https://pubmed.ncbi.nlm.nih.gov/41859790/)
- **DOI**: [10.26442/00403660.2026.03.203537](https://doi.org/10.26442/00403660.2026.03.203537)
- **Study type**: human randomized controlled trial
- **Delivery route**: inhalation
- **Effect reported**: positive
- **H2 concentration**: 4%

## Delivery context

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.

## Safety notes

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:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)
- [LFL / UFL terminology](https://h2-papers.org/en/safety-notes/lfl-ufl-explained)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 41859790. https://h2-papers.org/en/papers/41859790
> **Source**: PubMed PMID [41859790](https://pubmed.ncbi.nlm.nih.gov/41859790/)