Discrimination of adult asthma severity via exhaled volatile organic compounds using high-pressure photoionization time-of-flight mass spectrometry: a pilot study.

Asthma is a heterogeneous airway disease that necessitates the identification of objective biomarkers to characterize inflammatory and metabolic phenotypes for precision medicine. In this study, exhaled breath from 40 adults, including 10 with moderate-persistent asthma (Mop-AS), 10 with mild-persistent asthma (Mip-AS), and 20 healthy controls (CTL), was analyzed using high-pressure photoionization time-of-flight mass spectrometry (HPPI-TOFMS) with an analysis time of 2 min. Twenty potential differential volatile organic compounds (VOCs) were identified at higher levels in the Mop-AS group than in the CTL group. A model constructed using acetone and dimethylamine classified Mop-AS from CTL with an area under the receiver operating characteristic (ROC) curve (AUC) value of 0.98 (95% CI: 0.936-1), 100% sensitivity, and 90% specificity. Ten differential metabolites were identified to differentiate Mip-AS from CTL, and a model based on acetaldehyde and niacin was constructed with an AUC of 0.94 (95% CI: 0.858-1), 85% sensitivity, and 90% specificity. Six differential metabolites were identified for the classification of patients with Mop-AS and Mip-AS. A predictive model was built using dimethylamine and methanol with an AUC of 0.95 (95% CI: 0.848-1), 100% sensitivity, and 90% specificity, which was superior to fractional exhaled nitric oxide (FeNO), blood eosinophils, and serum immunoglobulin E (IgE). Characteristic exhaled VOC profiles enable accurate discrimination between the asthma and CTL groups, as well as between clinically relevant asthma severity phenotypes. Thus, breathomics based on HPPI-TOFMS provides a rapid and noninvasive approach for accurate metabolic phenotyping and severity discrimination in asthma, with a performance that exceeds that of conventional inflammatory biomarkers.