Tidal Breathing Exhaled Nitric Oxide Measurement Using A Novel Chemiluminescence Analyzer: Clinical Potential in Lung...

In 2024, Chinese first domestically developed chemiluminescence-based exhaled nitric oxide (eNO) analyzer, eNOglow, entered the market. This innovative device utilizes a novel methodology, termed the tidal breathing eNO method (TBNO), which enables rapid eNO measurement during natural tidal breathing without requiring patient cooperation for forced exhalation. This approach facilitates the diagnosis of airway inflammation, early detection, and precise treatment, particularly for patients unable to perform traditional fractional exhaled nitric oxide (FeNO₅₀, a constant flow rate of 50 mL/s sustained for 10 seconds) testing, such as children, the elderly, and severely ill patients. However, unlike FeNO₅₀, TBNO lacks established reference values for adult asthma patients globally.

This prospective validation study enrolled adult asthma patients and healthy volunteers from two tertiary hospitals in China. Participants were categorized into two subgroups: healthy volunteers and asthmatics. All the eNOglow (chemiluminescence-based) analyzer and conventional electrochemical-based analyzers (ECH) were utilized to measure eNO levels in all subjects at the pulmonary function clinic. Each participant underwent three FeNO₅₀ tests using both analyzers and three TBNO tests using the eNOglow device. The clinical performance and stability of eNOglow were evaluated in both healthy volunteers and asthmatic patients, comparing its results with conventional FeNO₅₀ parameters obtained from widely used clinical eNO analyzers. Additionally, a reference value range for TBNO was established based on the collected data. The receiver-operating characteristic (ROC) curve was applied, and the best cut-off value was selected based on the maximum Youden's index.

The study included 189 participants (131 asthma patients and 58 healthy volunteers), with a total of 1,701 tests performed. Both devices demonstrated reproducible FeNO₅₀ values across all subjects. The coefficient of variation (CV) for eNOglow was significantly lower than that of ECH, with overall CVs of 2.82% (1.81, 4.96) for eNOglow and 11.81% (6.31, 19.95) for ECH (P < 0.0001). FeNO₅₀ values showed a strong correlation between the two analyzers (r = 0.9093, P < 0.0001). ROC curve analysis revealed that eNOglow had slightly higher sensitivity and specificity than ECH. The optimal FeNO₅₀ cut-off value for eNOglow was 24.49 ppb, consistent with clinical guidelines and slightly higher than the 20.83 ppb cut-off for ECH. For TBNO values, the best cut-off values for predicting asthma were 7.67 ppb (corresponding to FeNO₅₀ = 25 ppb) and 12.5 ppb (corresponding to FeNO₅₀ = 50 ppb), based on the maximum Youden's index.

The eNOglow analyzer demonstrates reliable performance in asthmatic patients across varying degrees of airway inflammation, making it suitable for primary healthcare, large-scale clinical trials, and research applications. TBNO measurements offer clinical value, particularly for patients unable to perform FeNO₅₀ testing. These findings validate the reliability of eNOglow and support its applicability in clinical practice and research settings, while establishing the first global reference values for TBNO in adult asthma patients.