支气管肺泡灌洗液宏基因组二代测序在诊断PD-1抑制剂相关性肺炎中的价值

The Research of Metagenomics Next-Generation Sequencing in Bronchoalveolar Lavage Fluid on the Clinical Application of Immune Checkpoint Inhibitor

目的探讨支气管肺泡灌洗液(BALF)宏基因组二代测序(mNGS)在程序性细胞死亡蛋白(PD-1)抑制剂相关免疫性肺炎(CIP)的临床应用价值。方法收集使用PD-1抑制剂联合化疗后出现CIP的晚期非小细胞肺癌(NSCLC)患者30例,行BALF mNGS检测、BALF/痰培养和抗酸染色涂片,并于气管镜检查当天行白细胞计数、超敏-C反应蛋白(Hs-CRP)、降钙素原(PCT)、血清1,3-β-D-葡聚糖含量测定(G试验)、半乳甘露聚糖(GM)实验。mNGS阴性患者拟诊"CIP"并予规范激素抗炎治疗;mNGS阳性患者拟诊"CIP合并肺部感染"并予规范激素联合抗感染治疗。结果两组患者治疗后病情均改善,mNGS阴性可基本排除肺部感染,对于合并肺部感染的CIP患者,mNGS检出率高于传统病原微生物检测方法,对于检出孢子菌、曲霉菌、结核杆菌等机会性感染的优势明显。结论 BALF mNGS检测协助确诊CIP有一定临床价值;在CIP合并肺部机会性感染或混合感染的检出率及准确性均高于传统病原微生物检测方法,尤其对合并真菌感染的检测,能早期进行真菌分型和载量分析。

Objective To investigate the clinical application of bronchoalveolar lavage fluid(BALF) metagenomics next-generation sequencing(mNGS) in programmed cell death protein 1(PD-1) immune checkpoint inhibitor. Methods Retrospectively analyzed 30 cases with advanced non-small cell lung cancer(non-small cell lung cancer, NSCLC) who had CIP due to the combination of PD-1 inhibitors and chemotherapy. BALF mNGS, BALF/sputum culture and acid-fast staining smears were tested, and white blood cell count, high-sensitivity C-reactive protein(Hs-CRP), procalcitonin(PCT), 1,3-β-D-glucan(G test), Galactomannan(GM) in the serum were examined on the same day of tracheoscopy. The mNGS-negative group was pre-diagnosed as "CIP" and treated with standard glucocorticosteroid anti-inflammatory treatment, while the mNGS-positive group was pre-diagnosed as "CIP combined with pulmonary infection" and treated with the combination of standard glucocorticosteroid and anti-infection treatment. Results Both groups of patients improved after treatment and pulmonary infection can be completely excluded in mNGS-negative cases. For CIP patients combined with pulmonary infection, detection rate by mNGS was higher than by traditional pathogenic microbiological detection methods, especially in mixed infection and opportunistic infection. Conclusions BALF mNGS detection performs better in the diagnosis of CIP. Compared with traditional pathogenic microbial detection methods, BALF mNGS provides higher detection rate and accuracy for CIP combined with pulmonary opportunistic and mixed infection, especially for fungal infection, which provides an early detection for fungal type and load analysis method.