Department of Pathology, Beijing Key Laboratory for Drug Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, 101149, China.
Senior Department of Tuberculosis, the Eighth Medical Center of Chinese PLA General Hospital, Beijing, 100091, China.
Mil Med Res. 2024 Aug 22;11(1):60. doi: 10.1186/s40779-024-00567-y.
The diagnosis of tuberculous pleurisy (TP) presents a significant challenge due to the low bacterial load in pleural effusion (PE) samples. Cell-free Mycobacterium tuberculosis DNA (cf-TB) in PE samples is considered an optimal biomarker for diagnosing TP. This study aimed to evaluate the applicability of cf-TB testing across diverse research sites with a relatively large sample size.
Patients suspected of TP and presenting with clinical symptoms and radiological evidence of PE were consecutively enrolled by treating physicians from 11 research sites across 6 provinces in China between April 2020 and August 2022. Following centrifugation, sediments obtained from PE were used for Xpert MTB/RIF (Xpert) and mycobacterial culture, while the supernatants were subjected to cf-TB testing. This study employed a composite reference standard to definite TP, which was characterized by any positive result for Mycobacterium tuberculosis (MTB) through either PE culture, PE Xpert, or pleural biopsy.
A total of 1412 participants underwent screening, and 1344 (95.2%) were subsequently enrolled in this study. Data from 1241 (92.3%) participants were included, comprising 284 with definite TP, 677 with clinically diagnosed TP, and 280 without TP. The sensitivity of cf-TB testing in definite TP was 73.6% (95% CI 68.2-78.4), significantly higher than both Xpert (40.8%, 95% CI 35.3-46.7, P < 0.001) and mycobacterial culture (54.2%, 95% CI 48.4-59.9, P < 0.001). When clinically diagnosed TP was incorporated into the composite reference standard for sensitivity analysis, cf-TB testing showed a sensitivity of 46.8% (450/961, 95% CI 43.7-50.0), significantly higher than both Xpert (116/961, 12.1%, 95% CI 10.2-14.3, P < 0.001) and mycobacterial culture (154/961, 16.0%, 95% CI 13.8-18.5, P < 0.001). The specificities of cf-TB testing, Xpert, and mycobacterial culture were all 100.0%.
The performance of cf-TB testing is significantly superior to that of Xpert and mycobacterial culture methods, indicating that it can be considered as the primary diagnostic approach for improving TP detection. Trial registration The trial was registered on Chictr.org.cn (ChiCTR2000031680, https://www.chictr.org.cn/showproj.html?proj=49316 ).
由于胸腔积液（PE）样本中的细菌负荷较低，结核性胸膜炎（TP）的诊断极具挑战性。PE 样本中的无细胞结核分枝杆菌 DNA（cf-TB）被认为是诊断 TP 的最佳生物标志物。本研究旨在评估 cf-TB 检测在具有较大样本量的多个研究地点的适用性。
2020 年 4 月至 2022 年 8 月，11 个研究地点的治疗医生连续招募疑似 TP 且具有临床症状和 PE 影像学证据的患者。离心后，从 PE 沉淀物中提取 Xpert MTB/RIF（Xpert）和分枝杆菌培养物，上清液用于 cf-TB 检测。本研究采用复合参考标准来确定 TP，其特征是通过 PE 培养、PE Xpert 或胸膜活检任何 MTB 结果阳性。
共有 1412 名参与者接受了筛查，其中 1344 名（95.2%）随后被纳入本研究。共有 1241 名参与者（92.3%）的数据被纳入，其中 284 名患有明确的 TP，677 名患有临床诊断的 TP，280 名没有 TP。cf-TB 检测在明确 TP 中的敏感性为 73.6%（95%CI 68.2-78.4），明显高于 Xpert（40.8%，95%CI 35.3-46.7，P<0.001）和分枝杆菌培养（54.2%，95%CI 48.4-59.9，P<0.001）。当将临床诊断的 TP 纳入复合参考标准进行敏感性分析时，cf-TB 检测的敏感性为 46.8%（450/961，95%CI 43.7-50.0），明显高于 Xpert（116/961，12.1%，95%CI 10.2-14.3，P<0.001）和分枝杆菌培养（154/961，16.0%，95%CI 13.8-18.5，P<0.001）。cf-TB 检测、Xpert 和分枝杆菌培养的特异性均为 100.0%。
cf-TB 检测的性能明显优于 Xpert 和分枝杆菌培养方法，表明它可以作为提高 TP 检测的主要诊断方法。
该试验在中国临床试验注册中心注册（ChiCTR2000031680，https://www.chictr.org.cn/showproj.html?proj=49316）。
