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

Respir Res. 2021 May 13;22(1):149. doi: 10.1186/s12931-021-01740-w.


Background: To investigate whether the administration of hydrogen/oxygen mixture was superior to oxygen in improving symptoms in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).

Methods: This prospective, randomized, double-blind, controlled clinical trial in 10 centres enrolled patient with AECOPD and a Breathlessness, Cough, and Sputum Scale (BCSS) score of at least 6 points. Eligible patients were randomly assigned (in a 1:1 ratio) to receive either hydrogen/oxygen mixture or oxygen therapy. Primary endpoint was the change from baseline in BCSS score at day 7. Adverse events (AEs) were recorded to evaluate safety.

Results: Change of BCSS score in Hydrogen/oxygen group was larger than that in Oxygen group (- 5.3 vs. - 2.4 point; difference: - 2.75 [95% CI - 3.27 to - 2.22], meeting criteria for superiority). Similar results were observed in other time points from day 2 through day 6. There was a significant reduction of Cough Assessment Test score in Hydrogen/oxygen group compared to control (- 11.00 vs. - 6.00, p < 0.001). Changes in pulmonary function, arterial blood gas and noninvasive oxygen saturation did not differ significantly between groups as well as other endpoints. AEs were reported in 34 (63.0%) patients in Hydrogen/oxygen group and 42 (77.8%) in Oxygen group. No death and equipment defects were reported during study period.

Conclusions: The trial demonstrated that hydrogen/oxygen therapy is superior to oxygen therapy in patient with AECOPD with acceptable safety and tolerability profile.

Trial registration: Name of the registry: U.S National Library of Medicine Clinical Trials; Trial registration number: NCT04000451; Date of registration: June 27, 2019-Retrospectively registered; URL of trial registry record: https://www.clinicaltrials.gov/ct2/show/study/NCT04000451?term=04000451&draw=2&rank=1 .

Keywords: Acute exacerbation; Chronic obstructive pulmonary disease; Hydrogen; Outcome; Oxygen.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Inhalation
  • Aged
  • China
  • Disease Progression
  • Double-Blind Method
  • Female
  • Humans
  • Hydrogen / administration & dosage*
  • Hydrogen / adverse effects
  • Lung / physiopathology*
  • Male
  • Middle Aged
  • Oxygen Inhalation Therapy* / adverse effects
  • Prospective Studies
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Pulmonary Disease, Chronic Obstructive / therapy*
  • Time Factors
  • Treatment Outcome


  • Hydrogen

Associated data

  • ClinicalTrials.gov/NCT04000451