宏基因组二代测序技术在慢性肺曲霉病诊断中的价值

目的：评估宏基因组二代测序技术在慢性肺曲霉病诊断中的价值。方法：回顾性收集2017年9月至2019年9月在复旦大学附属中山医院感染病科住院的疑似慢性肺曲霉病患者，并同步采集标本进行传统培养、血清烟曲霉特异性抗体IgG检测及mNGS检测，分析mNGS在慢性肺曲霉病诊断中的价值。 结果：共有78例疑似慢性肺曲霉病的患者纳入分析，根据诊断标准，最终诊断CPA 35例，non-CPA 43例。送检的的78例样本中，痰标本55例、支气管肺泡灌洗液(bronchoalveolar lavage fluid, BALF)标本17例、肺组织标本6例。与最终诊断相比，mNGS诊断CPA的敏感度和特异度分别为65.7%和86.0%，烟曲霉特异性抗体IgG的敏感度和特异度分别为48.6%和90.7%，传统培养的敏感度和特异度分别为28.6%和93.0%，其中mNGS的敏感度显著高于传统培养方法(P=0.001)。对于临床诊断的CPA患者，mNGS检测的阳性率为50.0%。mNGS、烟曲霉特异性抗体IgG和传统培养方法的ROC曲线下面积(Area Under Curve, AUC)分别为0.759、0.696和0.608。在所有最终诊断为CPA的35例患者的样本中，痰标本、BALF标本和肺组织标本的mNGS阳性率分别为56.5%(13/23)、77.8%(7/9)和100%(3/3)，但三组之间的差异无统计学意义。结论：在CPA的诊断中，mNGS的敏感度显著高于传统培养方法，在传统诊断方法无法确诊的患者中，mNGS仍有较高的阳性率，同时在检测时间上具有明显优势。

The application of metagenomic next-generation sequencing(mNGS) in chronic pulmonary aspergillosis

Objective: To evaluate the diagnosis performance of mNGS in chronic pulmonary aspergillosis. Methods: We retrospectively reviewed the suspected CPA patients between September 2017 and September 2019, and the diagnostic performance of mNGS for detection of fungi was compared with conventional culture and Aspergillus fumigatus-specific antibody IgG. Results: A total of 78 patients with suspected CPA were included in analysis and 35 patients were finally diagnosed with CPA. Among the 78 samples submitted for mNGS test, 55 were sputum specimens, 17 were bronchoalveolar lavage fluid (BALF) specimens, and 6 were lung tissue specimens. Compared with the final diagnosis, the sensitivity of mNGS, A. fumigatus-specific antibody IgG and traditional culture in the diagnosis of CPA were 65.7%, 48.6% and 28.6%, respectively; the specificity of mNGS, A. fumigatus-specific antibody IgG and traditional culture in the diagnosis of CPA were 86.0%, 90.7% and 93.0% respectively. The sensitivity of mNGS was significantly higher than that of traditional culture (P=0.001).For clinically diagnosed CPA patients, the positivity of mNGS detection is 50.0%. The Area Under Curve (AUC) of mNGS, A. fumigatus-specific antibody IgG and traditional culture were 0.759, 0.696 and 0.608, respectively. Among all the 35 CPA patient, the mNGS positive rates of sputum, BALF and lung tissue samples were 56.5%(13/23), 77.8%(7/9) and 100%(3/3), but the differences among the three groups were not statistically significant. Conclusions: In the diagnosis of CPA, the sensitivity of mNGS is significantly higher than that of traditional culture methods. In patients who cannot be diagnosed by traditional diagnostic methods, mNGS still has a higher positive rate. At the same time, it has obvious advantages in detection time.