In August 2026, Respiratory Medicine published a phase II, randomized, double-blind, controlled clinical trial reporting the regimen and results of combined hydrogen-oxygen therapy with tetrandrine for silicosis. 
The observation group used the Asclepius Meditec hydrogen-oxygen nebulizer AMS-H-03 as the inhalation device for hydrogen-oxygen mixed gas. The design of this study, as well as what it can and cannot demonstrate, deserves a point-by-point breakdown [1].
Silicosis is caused by long-term inhalation of free silica dust and is one of the occupational diseases with serious harm. Pathologically, after inhaled silica particles are deposited in the alveoli, they activate macrophages and induce them to release inflammatory factors; the sustained action of these factors activates fibroblasts, leading to excessive collagen deposition and thickening of alveolar septa, ultimately forming irreversible pulmonary fibrosis [1][4]. Because this process is difficult to reverse, the clinical goals for silicosis are mainly to slow progression, relieve symptoms, and prolong survival [1].
Notably, silicosis often has a long incubation period: workers develop symptoms only years after dust exposure, and by the time of diagnosis, pulmonary fibrosis has often already progressed to a certain stage. This characteristic of insidious onset and late diagnosis makes early identification and intervention of silicosis especially difficult, and is one reason why ideal treatments have long been lacking in clinical practice [1]. Therefore, any intervention that can show changes in lung function or inflammatory markers among already diagnosed patients deserves validation through well-designed clinical trials [1].
Free silica dust is widespread in mining, construction, foundry, stone processing, and other industries. In mining, drilling, blasting, and transport generate large amounts of silica-containing dust; in stone processing, cutting and grinding likewise release dust; tunnel construction, refractory material manufacturing, and ceramic and glass production present similar exposure risks. Long-term work in these environments without adequate protection is the main cause of silicosis. For this reason, silicosis is considered closely related to occupational exposure and is one of China's statutory occupational diseases. For such diseases, prevention and control require both controlling dust in the work environment at the source and providing continuous medical intervention and rehabilitation management for those already ill; exploring more effective interventions is precisely the starting point of relevant clinical research [1][2].
Nationwide, pneumoconiosis is one of the most commonly reported occupational diseases in China. According to the National Health Commission's Statistical Bulletin on the Development of China's Health and Medical Services 2024, a total of 7,251 cases of occupational pneumoconiosis were reported nationwide in 2024, accounting for the majority of the 11,289 new occupational disease cases that year [2]. To address the burden of pneumoconiosis, central government transfer funds have supported the establishment of 900 pneumoconiosis rehabilitation stations (sites), providing a cumulative 2.173 million rehabilitation services [2].
Among existing treatments, tetrandrine is a commonly used anti-fibrotic drug in clinical practice. As an inhalable medical gas molecule, hydrogen acts directly in the lungs, and its biological effects on respiratory diseases have been reported in multiple studies [3]. Hydrogen molecules have a selective antioxidant action: they scavenge the more toxic hydroxyl radicals while preserving the normal physiological functions of other reactive oxygen species, thereby reducing inflammation [6]. Previously, research groups from the School of Basic Medical and Clinical Pharmacy of China Pharmaceutical University and Laizhou Chronic Disease Prevention and Treatment Hospital in Shandong Province completed animal experiments in rat and mouse models, reporting the effect of hydrogen-oxygen combined with tetrandrine on silicosis fibrosis and providing a preliminary basis for human clinical trials [4].
This was a phase II, single-center, randomized, double-blind clinical trial enrolling patients aged 50 to 80 years, all with more than 5 years of dust exposure history [1].
Randomization means researchers cannot assign patients based on subjective judgment. Before the study begins, randomization shuffles known and unknown factors that may affect the results-age, sex, smoking history, and degree of dust exposure-so that they are evenly distributed between the two groups, ruling out the artificial bias introduced by cherry-picking [1].
The significance of randomization is that, even if there are confounding factors the researchers had not previously realized, as long as the sample size is sufficient, these factors will tend to balance out between groups, making between-group differences more likely to be attributable to the intervention itself [1].
Double-blinding is reflected in the intervention: patients in both groups inhale visually similar mixed gases at the scheduled times each day and undergo the same procedures, but the control group inhales an oxygen-nitrogen mixture while the observation group inhales an oxygen-hydrogen mixture; the oxygen concentration is the same in both groups, so neither patients nor evaluators can tell from the gas itself which group they belong to, thereby stripping away the psychological suggestion of knowing I am being treated [1]. The purpose of double-blinding is to avoid positive or negative psychological suggestion from patients knowing they are receiving a new regimen, and to avoid bias in evaluators' recording of results due to predisposition [1].
Control is reflected in the fact that the control group is not doing nothing, but receives the same medication and the same inhalation procedure, with the only variable being the non-oxygen component of the gas; only such a control can isolate the effect truly caused by a specific gas component [1]. The significance of a control group is that only when two groups are identical in all other conditions and differ in just one place can the observed difference in results be attributed to that single difference [1].
Single-center means the study was completed at one medical institution. The advantage of a single-center study is standardized procedures and relatively uniform quality control, with higher consistency in subject enrollment and follow-up; its limitation is that the sample source is relatively concentrated, and conclusions need to account for regional and population differences when generalized to a broader population. Together with the phase II designation and the sample size of 116 cases, this constitutes a joint constraint on the generalizability of the study's conclusions [1].
The combination of these three elements allows the study results to largely rule out the effects of allocation bias, psychological suggestion, and nonspecific effects-which is why randomized, double-blind, controlled trials are considered to have relatively high evidentiary strength [1]. For a disease such as silicosis, which progresses slowly and whose symptoms are affected by multiple factors, missing any one of these elements may make it difficult to establish a clear causal link between the observed changes in indicators and the intervention itself; therefore, the completeness of this study at the design level is an important foundation for its results to have reference value [1].
The control group took 60 mg of tetrandrine orally three times daily, taking the drug for 6 days and stopping for 1 day, while inhaling a mixed gas of 33% oxygen and 67% nitrogen daily at a flow rate of 3 L/min for 2 hours per session [1].
The observation group took tetrandrine at the same dose and regimen, while inhaling a mixed gas of 33% oxygen and 67% hydrogen daily using the Asclepius Meditec hydrogen-oxygen nebulizer AMS-H-03, at a flow rate of 3 L/min for 2 hours per session [1].
The device used in the observation group, the Asclepius Meditec hydrogen-oxygen nebulizer AMS-H-03, has obtained Class III medical device registration from the National Medical Products Administration (registration no. NMPA Registration no. 20203080066) [5]. According to the Regulations on the Supervision and Administration of Medical Devices, Class III medical devices carry the highest risk level and must be approved and registered by the national drug regulatory authority before marketing. The use of this registered product in human clinical trials complies with the regulatory requirements for the device used.
The treatment period was 6 months. The primary endpoint was the diffusion capacity for carbon monoxide (DLco), and secondary endpoints included serum IL-6 levels and mMRC dyspnea scale scores [1]. The primary endpoint answers the study's most central question, while secondary endpoints provide observation information in additional dimensions. The oxygen concentration in the control group was set to match the observation group, ensuring that the only difference between the two groups was the non-oxygen component of the gas. The flow rate of 3 L/min, the duration of 2 hours per session, and the 33%/67% gas ratio were all inhalation parameters set in the study protocol and are part of the study conditions [1].
Regarding endpoint selection, DLco was set as the primary endpoint because it directly reflects the gas exchange capacity of the alveolar-capillary membrane and is one of the core manifestations of impaired lung function in silicosis; serum IL-6 was used to observe changes in systemic inflammation, echoing the inflammatory pathology of silicosis; the mMRC scale translates the subjective symptom of dyspnea into grades 0 to 4 to quantify changes at the symptom level [1]. The three describe changes over the treatment period from the three dimensions of lung function, inflammatory markers, and symptoms, forming a relatively complete system for observing outcomes [1]. This endpoint design combining objective indicators with subjective symptoms both reflects pulmonary changes at the physiological level and stays close to the symptom improvement actually felt by patients, giving the study results both objectivity and relevance [1].
The above are the raw data reported by the study; the differences between the two groups in all indicators were statistically significant (all P values < 0.05) [1]. The three items in the table-DLco, IL-6, and mMRC-are the primary and secondary endpoints of the study; the values are group means, reflecting the overall difference between the two groups and not representing the outcome of every individual [1]. From this comparison table it can be seen that the two groups were completely identical in oral medication, flow rate, duration, and other conditions, with the only difference being the composition of the inhaled gas and whether a hydrogen-oxygen nebulizer was used-and this difference is precisely what the study sought to examine [1].
It should be noted that the data in the table come from a single study and are the observations of that study in a specific subject population and over a specific treatment period; they should not be interpreted in isolation from the study context as a fixed effect of a given regimen in the general population. For researchers, the value of such data lies more in indicating directions for subsequent validation than in delivering a final conclusion [1].
Q1: What device was used in this study?
A: In this study, the observation group used the Asclepius Meditec hydrogen-oxygen nebulizer AMS-H-03 as the inhalation device for hydrogen-oxygen mixed gas, inhaling a mixture of 33% oxygen and 67% hydrogen daily at a flow rate of 3 L/min for 2 hours per session. This device has obtained Class III medical device registration from the National Medical Products Administration, registration no. NMPA Registration no. 20203080066 [1][5].
Q2: What roles do the three design elements of randomization, double-blinding, and control each play?
A: Randomization rules out allocation bias, double-blinding rules out the psychological suggestion of patients and evaluators, and control isolates, through a single-variable design, the effect caused by the specific gas component itself; together, the three enhance the credibility of the study evidence [1].
Sources
[1] Kang Xiao, et al. The clinical efficacy of hydrogen combined with tetrandrine in the treatment of silicosis fibrosis: A randomized controlled intervention study. Respiratory Medicine, 2026 Aug-Sep; 260: 108939.
[2] National Health Commission of the People's Republic of China. Statistical Bulletin on the Development of China's Health and Medical Services 2024. December 2025.
[3] Zajac D, et al. Molecular Hydrogen in the Treatment of Respiratory Diseases. International Journal of Molecular Sciences, 2025, 26(9): 4116.
[4] Li J, et al. Hydrogen combined with tetrandrine attenuates silica-induced pulmonary fibrosis via suppressing NF-kB/NLRP3 signaling pathway-mediated epithelial mesenchymal transition and inflammation. International Immunopharmacology, 2024, 138: 112563.
[5] National Medical Products Administration. Registration information of NMPA Registration no. 20203080066 (Class III medical device).
[6] Ohsawa I, et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nature Medicine, 2007, 13(6): 688-694.
