目的:结核性胸膜炎是最常见的肺外结核之一,但是常规分枝杆菌培养(培养)或XpertMTB/RIF测定(Xpert)的敏感性并不令人满意。这项多中心队列研究评估了一种新的无细胞DNA液滴数字PCR检测(cf-ddPCR)诊断结核性胸膜炎的准确性。
方法:在2020年9月至2022年5月期间,从中国6个省的9个研究中心连续招募疑似肺结核(≥5岁)合并胸腔积液的患者。文化,Xpert,XpertMTB/RIFUltra测定(Ultra),对所有标本同时进行实时PCR和cf-ddPCR。
结果:共招募了321名参与者,281名(87.5%)参与者的数据可用,包括105个明确的结核性胸膜炎,根据复合参考标准,有113种可能的结核性胸膜炎和63种非结核性胸膜炎。在确定的结核性胸膜炎组中,cf-ddPCR的敏感性为90.5%(95/105,95%CI=82.8%至95.1%)。显著高于文化(57.1%,60/105,95%CI=47.1%至66.6%,P<0.001),Xpert(46.7%,49/105,95%CI=37.0%至56.6%,P<0.001),Ultra(69.5%,73/105,95%CI=59.7%至77.9%,P<0.001)和实时PCR(75.2%,79/105,95%CI:65.7%至82.9%,P<0.001)。可能是结核性胸膜炎,文化和Xpert的结果都是阴性的,cf-ddPCR的灵敏度为61.1%(69/113,95%CI=51.4%~70.0%),仍显著高于Ultra(27.4%,31/113,95%CI=19.7%至36.8%,P<0.001)和实时PCR(38.9%,44/113,95%CI:30.0%至48.6%,P<0.001)。
结论:cf-ddPCR的性能优于培养,Xpert,超和实时PCR,这表明通过引入这种新的检测方法可以预期诊断准确性的提高。
OBJECTIVE: Tuberculous pleurisy is one of the most common types of extra-pulmonary tuberculosis, but the sensitivity of conventional mycobacterial culture (Culture) or Xpert MTB/RIF assay (Xpert) is not satisfying. This multicentre cohort study evaluated the accuracy of a new cell-free DNA droplet digital PCR assay (cf-ddPCR) for diagnosing tuberculous pleurisy.
METHODS: Patients with suspected tuberculosis (≥5 years of age) with pleural effusion were consecutively recruited from nine research sites across six provinces in China between September 2020 to May 2022. Culture, Xpert, Xpert MTB/RIF Ultra assay (Ultra), real-time PCR, and cf-ddPCR were performed simultaneously for all specimens.
RESULTS: A total of 321 participants were enrolled, and data from 281 (87.5%) participants were available, including 105 definite tuberculous pleurisy, 113 possible tuberculous pleurisy and 63 non-tuberculous pleurisy according to the composite reference standard. The sensitivity of cf-ddPCR was 90.5% (95/105, 95% CI, 82.8-95.1%) in the definite tuberculous pleurisy group, which was significantly higher than those of Culture (57.1%, 60/105, 95% CI, 47.1-66.6%, p < 0.001), Xpert (46.7%, 49/105, 95% CI, 37.0-56.6%, p < 0.001), Ultra (69.5%, 73/105, 95% CI, 59.7-77.9%, p < 0.001) and real-time PCR (75.2%, 79/105, 95% CI, 65.7-82.9%, p < 0.001). In possible tuberculous pleurisy, whose results of Culture and Xpert were both negative, the sensitivity of cf-ddPCR was 61.1% (69/113, 95% CI, 51.4-70.0%), which was still significantly higher than that of Ultra (27.4%, 31/113, 95% CI, 19.7-36.8%, p < 0.001) and real-time PCR (38.9%, 44/113, 95% CI, 30.0-48.6%, p < 0.001).
CONCLUSIONS: The performance of cf-ddPCR is superior to Culture, Xpert, Ultra, and real-time PCR, indicating that improved diagnostic accuracy can be anticipated by incorporating this new assay.