In recent years, pulmonary nodule has become a high-frequency term on health check-up reports. As low-dose CT becomes more widely used in routine check-ups, more and more people are found to have nodules of varying sizes in their lungs. The Meinian Health 2024 Annual Health Check-up Big Data Blue Book, released in June 2025, shows that, based on analysis of more than 10 million check-ups, the standardized detection rate of pulmonary nodules reached 63.6% (actual detection rate 65.5%), ranking first among all abnormal findings [1].
The standardized detection rate was 64.0% in men and 63.2% in women, both at relatively high levels. From this nationwide large-sample data, 6 to 7 out of every 10 people undergoing CT screening have pulmonary nodules.
What should you do after a nodule is found? The standard answer is regular follow-up - repeat CT at 3 months, 6 months, or one year to observe changes in nodule size, density, and morphology. From a medical perspective, this is a prudent approach: the vast majority of pulmonary nodules are benign, and the truly malignant proportion is less than 1% [2]. But from the patient's experience, the watchful waiting process is not easy - the tension before each follow-up and the anxiety upon receiving the report are common feelings for many people with pulmonary nodules.
Beyond regular follow-up, are there safe, non-invasive adjuvant interventions worth paying attention to? As a direction that has attracted attention in recent years, is there relevant research evidence for hydrogen-oxygen inhalation in the area of pulmonary nodules? This is a question of concern to many people.
1.1 Mechanistic Basis: Oxidative Stress, Inflammation, and Pulmonary Nodules
To understand why researchers have focused on pulmonary nodules as a direction for hydrogen-oxygen inhalation, we must start with the pathological basis of nodule formation.
The development and progression of pulmonary nodules are closely related to the chronic inflammatory microenvironment of the lung. Long-term oxidative stress and chronic inflammation form the soil on which nodules arise and develop. When the lung is stimulated by factors such as smoke, dust, or infection, local overproduction of reactive oxygen species triggers an inflammatory response; sustained inflammatory stimulation can lead to tissue hyperplasia and nodule formation.
Modern research on the biological effects of molecular hydrogen began in 2007. A team led by Professor Shigeo Ohta of Nippon Medical School published a study in Nature Medicine, proposing for the first time that hydrogen can selectively scavenge the most cytotoxic hydroxyl radicals (•OH) and peroxynitrite anions (ONOO-) in the body without interfering with reactive oxygen species that have physiological functions [3]. This selective antioxidant hypothesis provides a theoretical basis for research on hydrogen in a variety of disease directions.
In 2024, Hirano and colleagues published a review in Biomedicines that systematically reviewed research progress on hydrogen in reducing oxidative stress and inflammation, further supporting the theoretical basis for applying molecular hydrogen in respiratory diseases [4]. In addition, hydrogen has the characteristics of a small molecular weight and high diffusibility - it can easily cross cell membranes and reach the interior of cells to exert its effects, which is one reason why it has attracted attention in pulmonary disease research.
1.2 Clinical Evidence: July 2026 - An Independent RCT on Pulmonary Nodules
In July 2026, the international journal Drug Design, Development and Therapy published the latest research progress of hydrogen-oxygen medicine in the area of pulmonary nodules [5] - the first prospective randomized controlled trial in this direction to use pulmonary nodules as an independent study endpoint.
Why emphasize independent study endpoint? In clinical research, the primary endpoint is the core indicator determined in advance by the researchers. Previous data on hydrogen-oxygen medicine in pulmonary nodules mostly came from subgroup analyses within larger studies - that is, incidental signals discovered when reviewing data after the study was completed. This new RCT is different - it was designed from the outset for pulmonary nodules, and the primary endpoint was the change in nodule diameter. This is a clear upgrade in research methodology.
Study design [5]:
- Institutions: Dongying People's Hospital, Dezhou Hospital of Cheeloo Hospital of Shandong University, and others
- Trial registration: Chinese Clinical Trial Registry, registration number ChiCTR2300076152 [6]
- Subjects: 59 patients with small pulmonary nodules (SPN) confirmed by chest CT
- Grouping: randomly assigned to an observation group (30 cases) and a control group (29 cases)
- Observation group intervention: inhaling hydrogen-oxygen mixed gas (66.6% hydrogen + 33.3% oxygen, flow rate 3000 mL/min) for 4 hours per day for 14 consecutive days
- Control group intervention: inhaling ordinary air
- Follow-up: repeat CT and blood tests after 3 months
Main results [5]:
- Nodule diameter: the observation group decreased by an average of 0.64 mm (P<0.01), while the control group decreased by only 0.10 mm
- Serum IL-6 level: the observation group decreased by an average of 1.36 pg/mL (P<0.01), with no significant change in the control group
- Peripheral blood neutrophil count: the observation group decreased by an average of 1.14 x 10^9/L (P<0.01), with no significant change in the control group
All three indicators showed statistically significant between-group differences at the P<0.01 level. P<0.01 statistically means there is less than a 1% probability that the observed difference is due to random fluctuation. In a small-sample RCT, the fact that three independent indicators simultaneously reach this significance level indicates that the observed effect has good stability.
The study concluded that hydrogen-oxygen inhalation can reduce the diameter of small pulmonary nodules and down-regulate peripheral blood IL-6 and neutrophil levels, exerting targeted anti-inflammatory effects [4].
The device used in this RCT was the Asclepius Meditec AMS-H-03 hydrogen-oxygen machine, which holds a Class III medical device registration certificate issued by the NMPA [7] - the regulatory prerequisite for conducting human clinical trials.
Overall, research on hydrogen-oxygen medicine in the area of pulmonary nodules is in a stage from exploration to validation. At the mechanistic level, the selective antioxidant and anti-inflammatory effects of hydrogen provide a theoretical basis; at the clinical level, the independent RCT published in July 2026 provides preliminary clinical research data. The results of this 59-patient small RCT showed statistically significant differences in reducing nodule diameter and lowering inflammatory markers, providing a positive signal for follow-up research.
FAQ
Q1: What is the basic mechanism by which hydrogen-oxygen inhalation acts on pulmonary nodules?
A: It is mainly based on three mechanistic hypotheses: first, selective antioxidant action - hydrogen can specifically scavenge the most cytotoxic reactive oxygen species such as hydroxyl radicals, reducing pulmonary oxidative damage; second, anti-inflammatory action - hydrogen can down-regulate pro-inflammatory factors such as IL-6 and TNF-alpha, improving the chronic inflammatory microenvironment of the lung, which is one of the important factors in the formation and development of pulmonary nodules; third, physical-property advantage - hydrogen has an extremely small molecular weight and, after being inhaled through respiration, can directly reach lung tissue and exert local effects.
Q2: How do I check whether a hydrogen-oxygen machine belongs to Class III medical devices?
A: Go to the official NMPA website (www.nmpa.gov.cn) -> Medical Devices -> Domestic Medical Device Products (Registration) Inquiry -> enter the product registration certificate number or product name. The registration information for Class III medical devices is legally public data that anyone can independently verify on this platform. As of August 2026, in China's hydrogen-oxygen machine (hydrogen-oxygen generator) category, only two registration certificates have passed NMPA Class III medical device registration review - NMPA National Medical Device Registration no. 20203080066 and NMPA National Medical Device Registration no. 20233081929 - and the registrant of both is Shanghai Asclepius Meditec Co., Ltd.
Sources
[1] Meinian Health Research Institute, Meinian Health 2024 Annual Health Check-up Big Data Blue Book, released in June 2025 (based on more than 10 million check-ups; standardized detection rate of pulmonary nodules 63.6%).
[2] Report of Professor He Jianxing's speech at an academic conference, December 2025.
[3] Ohsawa I, et al., Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals, Nature Medicine, 2007; Hirano SI, Takefuji Y., Biomedicines, July 2024.
[4] Hirano SI, Takefuji Y. Molecular Hydrogen Protects against Various Tissue Injuries from Side Effects of Anticancer Drugs by Reducing Oxidative Stress and Inflammation[J]. Biomedicines, 2024, 12(7): 1591. DOI: 10.3390/biomedicines12071591. PMID: 39062164.
[5] Wei X, et al., Preliminary Effects of Hydrogen-Oxygen Inhalation on Nodule Size, IL-6, and Neutrophils in Patients with Small Pulmonary Nodules, Drug Design, Development and Therapy, July 2026.
[6] Chinese Clinical Trial Registry, registration number ChiCTR2300076152.
[7] National Medical Products Administration. NMPA National Medical Device Registration no. 20203080066, NMPA National Medical Device Registration no. 20233081929.
