Improved diagnosis of tuberculous pleural effusion by combining medical thoracoscopy with Interferon-Gamma Release Assay and adenosine deaminase activity

Abstract Rapid, accurate, affordable, point-of-care tuberculosis (TB) diagnostic tests are essential for controlling TB. We aimed evaluate the diagnostic performance of tuberculous pleural effusion by combining medical thoracoscopy with blood interferon-gamma release assay (IGRA) and pleural fluid adenosine deaminase (ADA). Patients with undiagnosed pleural effusion measured by chest X-ray or ultrasound were prospectively enrolled in this study. Medical thoracoscopy, blood IGRA and pleural fluid ADA were conducted.A total of 154 patients with undiagnosed pleural effusion were enrolled. Among them, 98 patients (63.6%) were diagnosed as TPE. Patients in TPE+ groups were significantly younger. The diagnostic thresholds obtained via receiver operating characteristic curve analysis were: ADA 23.4 U/L with AUC 0.91 (95% CI: 0.85-0.97, Figure 2) and IFN-γ 6.9 pg/mL with AUC 0.87 (95% CI: 0.82-0.93). By combining all three test together, we achieved sensitivity of 0.92, perfect specificity and NLR of 0.082. The AUC of the combination test was 0.96 (0.93-0.99), which was significant higher than any individual test (p < 0.001). The combination of medical thoracoscopy with Interferon-Gamma release assay and adenosine deaminase performs better than individual test in diagnosis TPE. The combination diagnosis has very high diagnostic rate, can be easily and safely carried out.

摘要 快速、准确、经济且适用于床旁的结核（Tuberculosis, TB）诊断检测，对于结核病防控至关重要。本研究旨在探讨联合内科胸腔镜、血液γ干扰素释放试验（Interferon-Gamma Release Assay, IGRA）以及胸腔积液腺苷脱氨酶（Adenosine Deaminase, ADA）对结核性胸腔积液的诊断效能。本研究前瞻性纳入经胸部X线或超声检查发现的不明原因胸腔积液患者，对所有入组对象均实施内科胸腔镜检查、血液IGRA及胸腔积液ADA检测。本研究共纳入154例不明原因胸腔积液患者，其中98例（63.6%）最终确诊为结核性胸腔积液（Tuberculous Pleural Effusion, TPE）。结核性胸腔积液阳性组患者的年龄显著更轻。经受试者工作特征（Receiver Operating Characteristic, ROC）曲线分析得到的诊断阈值为：ADA 23.4 U/L，曲线下面积（Area Under Curve, AUC）为0.91（95%置信区间：0.85~0.97，图2）；IFN-γ 6.9 pg/mL，AUC为0.87（95%置信区间：0.82~0.93）。联合三项检测后，本研究获得的灵敏度为0.92，特异度为1.0（完美特异度），阴性似然比（Negative Likelihood Ratio, NLR）为0.082。联合检测的AUC为0.96（95% CI：0.93~0.99），显著高于任一单项检测（p<0.001）。联合内科胸腔镜、γ干扰素释放试验与腺苷脱氨酶的诊断方案，在结核性胸腔积液诊断中的效能优于任一单项检测。该联合诊断方案诊断效能优异，且操作简便、安全性良好。