Hydrogen/oxygen therapy for the treatment of an acute exacerbation of chronic obstructive pulmonary disease: results of a multicenter, randomized, double-blind, parallel-group controlled trial
Zheng ZG, Sun WZ, Hu JY, Jie ZJ, Xu JF, Cao J, Song YL, Wang CH, Wang J, Zhao H, Guo ZL, Zhong NS. · Respiratory Research. 2021;22:149.
Study at a glance
Human
Adults aged at least 40 years hospitalized with acute exacerbation of COPD, obstructive spirometry and baseline Breathlessness, Cough and Sputum Scale score of at least 6.
Nasal-mask inhalation for six to eight hours daily on seven consecutive days, alongside usual treatment. · Total mixture flow was 3.0 L/min. The article explicitly reports H₂ flow 2.0 L/min and O₂ flow 1.0 L/min.
Six to eight hours daily for up to seven days; mean device exposure was 6.4 days and roughly 365–379 minutes/day.
BCSS and cough scores improved more with H₂/O₂ than with the active oxygen comparator. Changes in FVC, FEV₁, FEV₁/FVC, pH, PaO₂, PaCO₂ and bicarbonate did not differ significantly. Adverse-event frequency and severity did not differ significantly; no deaths or device defects were reported.
Relatively small short trial, retrospectively registered, subjective symptom primary endpoint, 14 randomized participants absent from the per-protocol set, no heliox comparator and no long-term outcomes. The device was identified by manufacturer/model, although the study reported no specific funding; one author was a journal associate editor and the others declared no competing interests.
What kind of evidence is this?
Human
Ten-centre randomized double-blind active-controlled superiority trial
Respiratory health
Inhaled H₂
Information not yet classified
Some editorial classification fields are still pending. The source-reported outcomes and result are shown below; Hydrogenology does not infer a positive or negative signal from prose automatically.
Methods
Adults aged at least 40 years hospitalized with acute exacerbation of COPD, obstructive spirometry and baseline Breathlessness, Cough and Sputum Scale score of at least 6.
108 randomized, 54 per group; 107 in the full-analysis set and 93 in the per-protocol analysis.
Six to eight hours daily for up to seven days; mean device exposure was 6.4 days and roughly 365–379 minutes/day.
Nasal-mask inhalation for six to eight hours daily on seven consecutive days, alongside usual treatment.
Brown's gas / oxyhydrogen generated at an H₂:O₂ volume ratio of 2:1.
Total mixture flow was 3.0 L/min. The article explicitly reports H₂ flow 2.0 L/min and O₂ flow 1.0 L/min.
2,000 mL/min.
1,000 mL/min; additional oxygen was permitted if SpO₂ fell below 88%.
A visually matched oxygen concentrator delivering 2 L/min air plus 1 L/min O₂; both groups received standard care.
Outcomes and reported result
Day-7 BCSS symptom score, daily BCSS, cough assessment, spirometry, arterial blood gas, oxygen saturation, additional respiratory support, adverse events and device performance.
BCSS and cough scores improved more with H₂/O₂ than with the active oxygen comparator. Changes in FVC, FEV₁, FEV₁/FVC, pH, PaO₂, PaCO₂ and bicarbonate did not differ significantly. Adverse-event frequency and severity did not differ significantly; no deaths or device defects were reported.
The complete free PMC article and tables were checked for randomization, masking, participant flow, exact component flows, treatment exposure, primary and null respiratory outcomes, adverse events, funding and conflicts.
A reported association, difference or mechanism is not automatically a clinical benefit.
Limitations and applicability
Relatively small short trial, retrospectively registered, subjective symptom primary endpoint, 14 randomized participants absent from the per-protocol set, no heliox comparator and no long-term outcomes. The device was identified by manufacturer/model, although the study reported no specific funding; one author was a journal associate editor and the others declared no competing interests.
Hospitalized acute COPD exacerbations receiving concurrent standard care; it does not establish long-term home treatment or replacement of indicated oxygen/ventilatory support.
No single-study GRADE certainty rating is assigned. Read how records and evidence assessments are prepared.
Sources and record status
PMID: 33985501 · DOI: 10.1186/s12931-021-01740-w
Free full article in PubMed Central.
Complete PMC article, supplementary participant-flow information and PubMed metadata; full-text extraction checked 9 August 2026.
10 August 2026
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