# Hinhalation therapy in patients with moderate COVID-19 (HCOVID): a prospective ascending-dose phase I clinical trial.
> 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）


## Abstract

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).

### Mechanism

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.

## Bibliographic

- **Authors**: Salomez-Ihl C, Giai J, Barbado M, Paris A, Touati S, Alcaraz JP, et al.
- **Journal**: Antimicrob Agents Chemother
- **Year**: 2024 (2024-08-07)
- **PMID**: [39016593](https://pubmed.ncbi.nlm.nih.gov/39016593/)
- **DOI**: [10.1128/aac.00573-24](https://doi.org/10.1128/aac.00573-24)
- **PMC**: [PMC11304737](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11304737/)
- **Study type**: human case report
- **Delivery route**: inhalation
- **Effect reported**: positive
- **H2 concentration**: 3.6%

## 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 39016593. https://h2-papers.org/en/papers/39016593
> **Source**: PubMed PMID [39016593](https://pubmed.ncbi.nlm.nih.gov/39016593/)