Metagenomic Next-Generation Sequencing for Pulmonary Tuberculosis Diagnosis and Infection Risk Factor Analysis in...

Background: Pulmonary tuberculosis (TB) is a significant trigger of acute exacerbations of chronic obstructive pulmonary disease (AECOPD), so its timely and accurate diagnosis is essential. Also, the risk factors for TB occurrence in this population remain unclear. This study aimed to evaluate the performance of metagenomic next-generation sequencing (mNGS) for TB diagnosis in AECOPD patients, as well as to identify the associated risk factors. Methods: A retrospective observational cohort of 659 AECOPD patients with suspected pulmonary infection was enrolled. The microbial cell-free nucleic acids in bronchoalveolar lavage fluid samples were extracted and subjected to mNGS detection. The clinical data for each patient were collected from the hospital information system. The statistical analyses were performed with SPSS version 25.0. Results: A total of 170 cases, included for final analyses, were categorized into TB (n = 41), bacterial infection (n = 73), and non-infective control (n = 56) groups. Among these groups, the TB group had the highest intensive care unit (ICU) admission rate (46.34%) and longest median hospital stay (19.50 days) (p < 0.01). For TB diagnosis, mNGS demonstrated a greater sensitivity (86.00%), a lower specificity (93.30%), and a higher area under the curve (AUC, 0.877) than TB-DNA detection (70.21%, 100%, 0.848, respectively) and Xpert Mycobacterium tuberculosis/rifampicin (MTB/RIF) assay (63.83%, 100.00%, 0.870, respectively). Notably, mNGS identified the bacterial or viral co-infections in 18.00% of TB cases. Furthermore, the stringently mapped read number determined by mNGS showed a positive correlation with ICU admission rate (r = 0.76) and in-hospital mortality (r = 0.77). The lower body mass index (BMI) and reduced natural killer (NK) cell count were identified as the independent risk factors in the TB group (both p < 0.05). Conclusions: For the diagnosis of pulmonary TB in AECOPD patients, mNGS demonstrated comparable performance to TB-DNA detection and Xpert MTB/RIF assay, and also mNGS identified co-infections. In addition, a lower BMI and reduced NK cell count were identified as the independent risk factors for TB occurrence in this cohort.