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

Ze-Guang Zheng, Wu-Zhuang Sun, Jie-Ying Hu, Zhi-Jun Jie, Jin-Fu Xu, Jie Cao, Yuan-Lin Song, Chang-Hui Wang, Jing Wang, Hui Zhao, Zhong-Liang Guo, Nan-Shan Zhong, Ze-Guang Zheng, Wu-Zhuang Sun, Jie-Ying Hu, Zhi-Jun Jie, Jin-Fu Xu, Jie Cao, Yuan-Lin Song, Chang-Hui Wang, Jing Wang, Hui Zhao, Zhong-Liang Guo, Nan-Shan Zhong

Abstract

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.

Conflict of interest statement

Jin-Fu Xu is an Associate Editor of Respirology Research. All other authors (Ze-Guang Zheng, Wu-Zhuang Sun, Jie-Ying Hu, Zhi-Jun Jie, Jie Cao, Yuan-Lin Song, Chang-Hui Wang, Jing Wang, Hui Zhao, Zhong-Liang Guo, Nan-Shan Zhong) declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Study schema. Blue spots: follow-up time point; Red asterisk: Primary efficacy time point
Fig. 2
Fig. 2
Patient flow diagram
Fig. 3
Fig. 3
Seven-days changes from baseline in BCSS score in FAS (a) and PPS (b) population. BCSS breathlessness, Cough and Sputum Scale, FAS full analysis set, PPS per-protocol set. *p < 0.05. Red asterisk represent that the BCSS score change from baseline at day 7 is the primary efficacy endpoint
Fig. 4
Fig. 4
Changes from baseline in CAT score in in FAS (a) and PPS (b) population. CAT Cough Assessment Test, FAS full analysis set, PPS per-protocol set. ***p < 0.001
Fig. 5
Fig. 5
Seven-days changes from baseline in SpO2 in FAS (a) and PPS (b) population. SpO2, noninvasive oxygen saturation; FAS full analysis set, PPS per-protocol set. *p < 0.05

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