Pulmonology · Medical Literature
Preliminary Effects of Hydrogen-Oxygen Inhalation on Nodule Size, IL-6, and Neutrophils in Patients with Small Pulmonary Nodules.
Abstract
To evaluate the effects of hydrogen-oxygen inhalation on nodule diameter and peripheral blood inflammatory factors in patients with small pulmonary nodules (SPNs), and to further analyze its efficacy in the smoking subgroup. The primary endpoint was the change in pulmonary nodule diameter before and after intervention; secondary endpoints included alterations in serum IL-6, CRP, peripheral blood neutrophil count, and Mayo malignant transformation risk score. A total of 59 patients with SPNs confirmed by chest CT were enrolled and randomly divided into the observation group (hydrogen-oxygen inhalation, n=30) and control group (air inhalation, n=29). The intervention lasted 14 consecutive days, and all indicators were re-examined at 3-month follow-up. This study was registered in the Chinese Clinical Trial Registry (ChiCTR) with the registration number ChiCTR2300076152 (registration date: September 26, 2023). Baseline demographic and clinical characteristics were well balanced between the two groups (all P>0.05). After intervention, the observation group had a significant reduction in nodule diameter by 0.64 mm (95% CI: 0.20-1.08, P 0.05). In the smoking subgroup, IL-6 level and neutrophil count also decreased significantly after hydrogen-oxygen inhalation (both P<0.01), while CRP remained relatively stable. Within the limitations of this single-center, small-sample study with a 3-month follow-up, hydrogen-oxygen inhalation can reduce SPN diameter and downregulate peripheral blood IL-6 and neutrophil levels, exerting a targeted anti-inflammatory effect especially in smoking patients. It may serve as a safe non-invasive adjuvant intervention for SPNs, while further multicenter large-sample studies are needed to validate its general applicability.
Clinical relevance
In patients with small pulmonary nodules (SPNs) confirmed by chest CT, does 14-day hydrogen-oxygen inhalation reduce nodule diameter and modulate peripheral blood inflammatory markers (IL-6, CRP, neutrophil count) compared with air inhalation, and are effects amplified in smokers? __SNAPSHOT__ {"studyDesign":"Randomized controlled trial (single-center, open-label; blinding status not reported in available abstract or full-text excerpts)","setting":"Single-center; Department of Respiratory and Critical Care Medicine, China (institution name not reported); enrollment February 2024 – February 2025","sampleSize":"n=59 (observation/hydrogen-oxygen group: n=30; control/air inhalation group: n=29)","population":"Adults aged 60–75 years (mean 64.77 ± 3.12 years; 36 male, 23 female) with small pulmonary nodules confirmed by chest CT; baseline demographic and clinical characteristics were well balanced between groups (all P>0.05). Patients with varying smoking histories (current, former, never smokers) were included.","intervention":"Hydrogen-oxygen inhalation for 14 consecutive days","comparator":"Air inhalation for 14 consecutive days","primaryOutcome":"Change in pulmonary nodule diameter (mm) on chest CT before and after intervention","followUp":"3 months (all indicators re-examined at 3-month follow-up)","fundingSource":"Not reported"}
Key findings
PRIMARY OUTCOME: The observation group demonstrated a statistically significant reduction in nodule diameter of 0.64 mm (95% CI: 0.20–1.08; P 0.05). Mayo malignant transformation risk score did not change significantly in either group (all P>0.05); notably, Mayo score data were highly skewed, expressed as median (IQR), and analyzed with Wilcoxon signed-rank test, with no statistically significant intra-group or inter-group differences. SMOKING SUBGROUP (pre-specified exploratory): In smoking patients of the observation group, both IL-6 and neutrophil count decreased significantly after hydrogen-oxygen inhalation (both P 0.05). ADVERSE EVENTS: Systematic adverse event safety documentation was explicitly acknowledged as lacking; the study cannot definitively establish safety on the basis of these data.
Practice implications
This small, single-center, short-duration RCT found a statistically significant but numerically modest reduction in SPN diameter (0.64 mm) and decreases in IL-6 and peripheral blood neutrophil counts following 14 days of hydrogen-oxygen inhalation. Several important limitations circumscribe interpretation. First, the clinical importance of a 0.64 mm nodule diameter reduction is uncertain: it falls within the range of measurement variability for CT-assessed nodule size, and no threshold for clinical meaningfulness was pre-specified. Second, the Mayo malignant transformation risk score—a clinically meaningful surrogate for cancer risk—did not change in either group, providing no evidence that the intervention affects malignant transformation risk. Third, CRP, another objective inflammatory marker, was unchanged, raising questions about the specificity and robustness of the IL-6 and neutrophil signals. Fourth, blinding status is not reported, introducing potential performance and detection bias; the control arm inhaled air rather than a sham gas with equivalent sensory properties, making patient-level blinding unlikely. Fifth, the study population is narrowly defined (Chinese adults aged 60–75 years with SPNs in a single center), limiting generalizability to other populations, nodule types, and clinical settings. Sixth, lack of systematic adverse event documentation precludes safety conclusions. The smoking subgroup findings are exploratory and must not be interpreted as confirmatory; formal interaction testing was not performed, and the subgroup sample size is not reported. The authors themselves appropriately characterize findings as hypothesis-generating only. This study does not provide a basis for changing clinical practice in SPN management. NOTE: Only the published full-text web excerpts and the truncated abstract were available for this summary; certain specific numerical values (e.g., complete IL-6 CI, neutrophil count change magnitude, between-group comparison statistics) could not be fully retrieved and are noted as not reported. __LIMITATIONS__ Very small sample size (n=59 total), substantially underpowered for definitive efficacy or safety conclusions.,Single-center design in one Chinese institution; limited generalizability to other populations, ethnicities, healthcare systems, and nodule phenotypes.,Short follow-up (3 months); unable to assess durability of nodule response, effect on malignant transformation, or long-term safety.,Blinding status not explicitly reported; air (vs. hydrogen-oxygen) comparator likely does not achieve patient-level blinding, introducing performance and detection bias.,Primary endpoint (nodule diameter change of 0.64 mm) may fall within CT measurement variability and lacks a pre-specified minimum clinically important difference.,Mayo malignant transformation risk score—the most clinically relevant surrogate outcome—did not change significantly in either group, undermining claims of clinical impact.,CRP did not change, limiting confidence in the anti-inflammatory signal inferred from IL-6 and neutrophil data alone.,Systematic adverse event documentation was absent; safety cannot be established.,Smoking subgroup analysis was exploratory; no formal interaction testing was performed; subgroup sample sizes not reported.,Funding source not reported, precluding assessment of potential conflicts of interest.,Control was air inhalation rather than an indistinguishable sham, increasing risk of placebo effect and expectation bias.,Nodule etiology (benign vs. indeterminate vs. pre-malignant) and morphological subtype not clearly stratified; heterogeneous nodule population could mask or amplify effects. __BOTTOM_LINE_CATEGORY__ promising_but_preliminary __BOTTOM_LINE__ This preliminary single-center RCT (n=59) found that 14-day hydrogen-oxygen inhalation was associated with a 0.64 mm reduction in SPN diameter and decreases in IL-6 and neutrophil counts, but no change in CRP or Mayo malignant transformation risk score—the latter being the most clinically relevant surrogate endpoint. Given the very small sample, absent blinding, lack of systematic safety data, uncertain clinical significance of the diameter change, and absence of effect on malignant transformation risk, these findings are hypothesis-generating only and should not alter current clinical management of small pulmonary nodules. Adequately powered, multicenter, double-blind RCTs with pre-specified clinically meaningful endpoints and longer follow-up are required before any clinical application can be considered.