Explore the Application Value of Metagenomic Next-Generation Sequencing of Bronchoalveolar Lavage Fluid in the Early Diagnosis of Pulmonary Tuberculosis

Yangni Lu,1,&ast; Chunlan Zhang,1,&ast; Jianlin Wu,1 Xianli Xu,1 Ailian Lu,1 Huiya Huang,2 Maowei Chen1 1Department of Infectious Diseases, Wuming Hospital Affiliated to Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Department of General Medicine, Wuming Hospital Affiliated to Guangxi Medical University, Nanning, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Maowei Chen, Email [email protected] Jianlin Wu, Email [email protected]: Compare the diagnostic efficacy of bronchoalveolar lavage fluid (BALF) metagenomic next-generation sequencing (mNGS) with that of four traditional methods in the diagnosis of pulmonary tuberculosis (PTB), and explore the application value of BALF mNGS in the early diagnosis of PTB.Methods: A retrospective analysis was performed on 102 patients with suspected PTB in Wuming Hospital Affiliated with Guangxi Medical University from January 2021 to August 2024, among which 61 cases were PTB and 41 cases were non - PTB. Diagnostic performance metrics (sensitivity, specificity, positive/negative predictive value [PPV/NPV], accuracy) were calculated for BALF mNGS, sputum TB-DNA, sputum acid-fast bacilli (AFB) smear, BALF AFB smear, and BALF TB-DNA, using clinical diagnosis as the reference standard.Results: BALF mNGS demonstrated a sensitivity of 75.41% (46/61), specificity of 87.80% (36/41), PPV of 90.20% (46/51), NPV of 70.59% (36/51), and accuracy of 80.39% (82/102). Its accuracy was significantly higher than sputum-based methods (53.03– 58.82%, P < 0.0125) and second only to BALF TB-DNA (84.13%, P > 0.0125). BALF mNGS exhibited superior sensitivity compared to sputum TB-DNA (38.00%), sputum AFB smear (41.67%), and BALF AFB smear (41.50%) (P < 0.0125). While specificity and PPV showed no significant differences among methods, BALF mNGS had a higher NPV than sputum-based assays (53.03– 54.17%) but lower than BALF TB-DNA (82.53%, P < 0.0125). Both BALF mNGS (Kappa = 0.608, P < 0.001) and BALF TB-DNA (Kappa = 0.670, P < 0.001) showed strong concordance with clinical diagnosis.Conclusion: BALF mNGS demonstrates high sensitivity and accuracy for PTB diagnosis, outperforming conventional sputum-based methods. Although BALF TB-DNA achieved the highest specificity and NPV, BALF mNGS serves as a robust supplementary tool, particularly for early-stage or paucibacillary PTB. Integration of these molecular techniques may optimize diagnostic workflows in high-TB-burden settings.Keywords: pulmonary tuberculosis, metagenomics next-generation sequencing, bronchoalveolar lavage fluid, diagnostic efficiency