Abstract Background Chronic Obstructive Pulmonary Disease (COPD) ranks as the third leading cause of death globally and imposes a major health burden. Acute exacerbations (AECOPD) are the principal cause of COPD-related mortality. Early identification of patients at high risk for exacerbations is critical to improving outcomes. The latest GOLD guidelines introduced the A/B/E classification, highlighting the importance of targeted management for Group E patients, who have a high exacerbation risk. However, current classification relies mainly on subjective clinical assessments. Exhaled volatile organic compounds (VOCs), a novel noninvasive biomarker technology, can reflect local airway inflammation and metabolic disturbances. Our study aims to explore exhaled VOC biomarkers in COPD Group E patients, potentially contributing to more objective patient classification and individualized disease management. Methods Patients with clinically diagnosed COPD were enrolled between May 2024 and September 2025. Individuals with comorbidities that could affect exhaled gas composition were excluded. Demographic and clinical data were recorded. According to the GOLD(Global Initiative for Chronic Obstructive Lung Disease) guidelines, patients were categorized into Groups A, B, and E. Exhaled breath samples were analyzed using Thermal Desorption Comprehensive Two-Dimensional Gas Chromatography-Time-of-Flight Mass Spectrometry (TD-GCxGC-TOF/MS). VOC profiles were compared among Groups A/B, and E, as well as between patients in acute exacerbation and stable phases. Statistical analyses were performed using the Mann-Whitney U test to identify characteristic differential biomarkers. Results A total of 261 COPD patients were included: Group A (n = 87), Group B (n = 87), and Group E (n = 74). Among them, 115 were in acute exacerbation and 136 were in a stable phase. Compared with Groups A and B, Group E patients exhibited reduced levels of tetrahydrofuran, ethyl acetate, and 1,2-dichloroethane, while benzonitrile concentrations were significantly elevated. In comparisons between disease phases, patients in the acute exacerbation phase showed increased levels of benzonitrile, acetophenone, and limonene relative to those in the stable phase. In patients experiencing acute exacerbations, the concentrations of 1,3-pentadiene, cyclohexane, dimethyl carbonate, 3-methylthiophene, chlorobenzene, allene, p-isopropyltoluene, decane, methyl butyrate, isobutyric acid methyl ester, and 1-methoxycyclohexene were found to be significantly reduced compared with those in the stable phase. Conclusion Exhaled VOCs show potential as objective molecular biomarkers for accurate classification of COPD patients. Elevated benzonitrile may serve as a promising indicator of high exacerbation risk, providing new insights for early intervention and individualized COPD management. This abstract is funded by: National Science and Technology Innovation 2030 Major Project for Prevention and Treatment of Cancer, Cardiovascular, Respiratory and Metabolic Diseases (2023ZD0506106, 2023ZD0506100)
Chen et al. (Fri,) studied this question.