# [Rehabilitation program of post-COVID-19 syndrome with the use of nitric oxide and molecular hydrogen].
> ポストCOVID-19症候群に対する一酸化窒素と水素ガス吸入併用の安全性・有効性評価


## Abstract

A prospective open-label controlled trial enrolled 34 patients with post-COVID-19 syndrome (PS) averaging 60.0±11.7 years, approximately 641 days after confirmed COVID-19 infection. The intervention group (n=17) received combined inhalation of nitric oxide (60 ppm) and molecular hydrogen (<4% in gas mixture) for 90 minutes daily over 10 days, while the control group (n=17) received no inhalation. Compared with controls, the intervention group showed significant reductions in dyspnea, cough, fatigue, and palpitation severity (p<0.005), improved SF-36 quality-of-life scores (p=0.006), decreased fatigue assessment scale (FAS) scores (p=0.001), and lower anxiety subscores on HADS (p=0.02). Six-minute walk distance and SpO2 values also improved significantly. Additionally, venular blood flow velocity increased, serum oxidative damage markers decreased (p<0.001), and antioxidant activity improved (p=0.03), suggesting favorable effects on microcirculation and redox balance.

### Mechanism

Inhaled molecular hydrogen and nitric oxide are proposed to reduce oxidative stress markers in serum and enhance venular blood flow velocity in bulbar conjunctival microcirculation, thereby modulating pathophysiological mechanisms underlying post-COVID-19 respiratory manifestations.

## Bibliographic

- **Authors**: Pozdnyakova DD, Bakhareva T&#x410;, Baranova IA, Selemir VD, Chuchalin AG
- **Journal**: Ter Arkh
- **Year**: 2024 (2024-04-16)
- **PMID**: [38713041](https://pubmed.ncbi.nlm.nih.gov/38713041/)
- **DOI**: [10.26442/00403660.2024.03.202639](https://doi.org/10.26442/00403660.2024.03.202639)
- **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 38713041. https://h2-papers.org/en/papers/38713041
> **Source**: PubMed PMID [38713041](https://pubmed.ncbi.nlm.nih.gov/38713041/)