Detection of Pulmonary Tuberculosis Via Exhaled Volatile Organic Compounds by a Breath Test

Background: Diagnostics for tuberculosis are usually either inaccurate, too expensive or complicated in their use. The exhaled breath test, which detects volatile organic compounds (VOCs) by real-time high-pressure photon ionization time-of-flight mass spectrometry (HPPI-TOFMS), may be an attractive option for the diagnosis of tuberculosis, and we aimed to evaluate its performance in diagnosing pulmonary tuberculosis (PTB). Methods: In this cross-sectional study, confirmed PTB patients and healthy controls were prospectively and consecutively recruited in a tuberculosis hospital in Shenzhen city, China. Exhaled breath samples were collected and stored in customized bags and then tested by HPPI-TOFMS. The support vector machine (SVM) algorithm was employed for feature selection and model construction. Participants were randomly assigned in a 4:1 ratio for the training and external validation datasets. We calculated the sensitivity, specificity, accuracy and relative 95% confidence interval (CI) of the VOC model overall, and we stratified by the clinical characteristics. Age, sex and treatment had no significant impact on the diagnostic performance of the VOC detection model. Results: A total of 812 healthy controls and 522 PTB patients were included in the final analysis. The VOC model reached an accuracy of 95.6% (95% CI, 93.4–97.9), a sensitivity of 93.7% (95% CI 89.4–97.9), and a specificity of 96.9% (95% CI 94.5–99.3) in the training set (n=1064). In the external validation set (n=270), the VOC model had an accuracy of 97.4% (95% CI 95.5–99.3), a sensitivity of 95.2% (95% CI 91.2–99.3), and a specificity of 98.8% (95% CI 97.1–100.0). Age, sex and treatment had no significant impact on diagnostic performance of the VOCs detection model. Conclusions: The breath test via HPPI-TOFMS is simple, noninvasive, inexpensive, and fast for PTB diagnosis, with a high sensitivity and specificity. Its diagnostic performance, especially for PTB screening, should be further investigated. Funding: This work was supported by the National Key Research and Development Plan (No. 2020YFA0907200, 2019YFC0840602), the Guangdong Foundation for Basic and Applied Basic Research (No. 2019B1515120041), the Guangdong Science and Technology Plan (No. 2020B1111170014), the Shenzhen Scientific and Technological Foundation (No. KCXFZ202002011007083, JCYJ20180228162112889) and Summit Plan for Foshan High-level Hospital Construction (No. FSSYKF-2020001). Declaration of Interest: None to declare. Ethical Approval: The Ethical Committee of the Shenzhen Third People's Hospital approved this study.