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[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

human randomized controlled trial inhalation positive 4%

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
DOI
10.26442/00403660.2024.03.202639

Tags

Disease:COVID-19 (25) Delivery:inhalation delivery (196) Mechanism:antioxidant enzymes (423) endothelial function (35) anti-inflammatory (743) oxidative stress (899) reactive oxygen species (774)

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.

→ Evidence by delivery route

Safety notes

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.

See also:

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