宏基因组下一代测序在老年肺部感染中的应用与价值探讨 ^*

Evaluation of the detection efficacy of metagenomic next-generation sequencing for pulmonary infections in the elderly

摘要

目的 探讨宏基因组下一代测序 (mNGS) 技术对老年肺部感染的检测效果。 方法 选取 2021 年 7 月—2023 年 12 月新疆维吾尔自治区人民医院收治的 60 岁以上、 临床疑似肺部感染的 289 例老年患者作为研究对象, 所有患者完成支气管镜气管抽吸物的 mNGS 与常规微生物学检测, 以临床诊断结果为金标准, 比较 mNGS 和传统微生物学检测的诊断性能。 结果 老年肺部感染以多种微生物感染为主, 占比 40.5% (117/289)。mNGS 的诊断准确度和灵敏度分别为 78.5%和 89.2%, 优于传统微生物学检测 (诊断准确度为 37.4%, 灵敏度为 28.8%)。 对于大部分病原体, mNGS 的检出率高于传统微生物学检测。 免疫功能低下的患者多种微生物感染率为 73.1% (38/52)。 不同群体的病原体谱也不同。 阳性预测值取决于病原体类型以及患者的免疫状态。 结论 老年肺部感染以多种微生物感染最多见。mNGS 可以大大提高老年肺部感染患者病原体检测的准确度、 灵敏度和检出率。 此外, 在解释 mNGS 结果时, 应考虑病原体的合并症和类型。mNGS 在老年肺部感染患者的诊断中有较高的临床应用价值。

Abstract

Objective To explore the detection effect of metagenomic next-generation sequencing (mNGS) technology on elderly pulmonary infections. Methods A total of 289 elderly patients aged over 60 years with clinically suspected pulmonary infections admitted to the People's Hospital of Xinjiang Uygur Autonomous Region from July 2021 to December 2023 were selected as study subjects. All patients underwent mNGS of bronchoscopic tracheal aspirates and conventional microbiological tests. The diagnostic performance of mNGS and conventional microbiological tests was compared, using clinical diagnostic results as the gold standard. Results Elderly pulmonary infections were predominantly polymicrobial, accounting for 40.5% (117/289). The diagnostic accuracy and sensitivity of mNGS were 78.5% and 89.2% respectively, surpassing those of conventional microbiological test (37.4% diagnostic accuracy, 28.8% sensitivity). For the majority of pathogens, the detection rate of mNGS was higher than that of conventional microbiological test. The polymicrobial infection rate in immunocompromised patients was 73.1% (38/52). The pathogen spectrum was also observed to vary among different populations. The positive predictive value was found to depend on the type of pathogen and the patient's immune status. Conclusion In elderly patients with pulmonary infections, polymicrobial infections are the most common. mNGS can greatly improve the accuracy and detection rate of pathogens in elderly patients with pulmonary infections. In addition, when interpreting mNGS results, the comorbidities and types of pathogens should be considered. mNGS has a high clinical application value in the diagnosis of pulmonary infections in elderly patients.

关键词

宏基因组下一代测序 / 气管抽吸物 / 肺部感染 / 病原体检测 / 合并症

Key words

Metagenomic next-generation sequencing / Tracheal aspiration / Pulmonary infection / Pathogen detection / Comorbidity

参考文献

[1] Peng Q, Yang Q . Risk factors and management of pulmonary infection in elderly patients with heart failure: a retrospective analysis [J]. Medicine (Baltimore), 2021, 100(38): e27238.

[2] Wang C, Yan D, Huang J, et al. The clinical application of metagenomic next—generation sequencing in infectious diseases at a tertiary hospital in China[J]. Front Cell Infect Microbiol, 2022, 12: 957073.

[3] Liu Y, Zhu W, Jiao M, et al. Clinical application value of metagenomic next—generation sequencing in the diagnosis of central nervous system infections[J]. Front Bioeng Biotechnol, 2023, 11: 885877.

[4] Zhou X, Huang C, Zhang J . Pulmonary tropheryma whipplei infection diagnosed by metagenomic next—generation sequencing: a case report [J]. Arch Bronconeumol, 2024, 60(11): 729-730.

[5] Mansoor H, Hirani N, Chavan V, et al. Clinical utility of target—based next—generation sequencing for drug—resistant TB[J]. Int J Tuberc Lung Dis, 2023, 27(1): 41-48.

[6] McGrath B, Broadhurst M, Roman C . Infectious disease considerations in immunocompromised patients[J]. JAAPA, 2020, 33(9): 16-25.

[7] Peng J M, Du B, Qin H Y, et al. Metagenomic next—generation sequencing for the diagnosis of suspected pneumonia in immunocompromised patients[J]. J Infect, 2021, 82(4): 22-27.

[8] 中华医学会呼吸病学分会 . 中国成人社区获得性肺炎诊断和治疗指南(2016 年版) [J]. 中华结核和呼吸杂志, 2016, 39(4): 253-279.

[9] Chinese Thoracic Society , Chinese Medical Association . Guidelines for the diagnosis and treatment of community—acquired pneumonia in adults in China (2016 Edition) [J]. Chin J Tubere Respir Dis, 2016, 39(4): 253-279.

[10] Chen Y, Feng W, Ye K, et al. Application of metagenomic next—generation sequencing in the diagnosis of pulmonary infectious pathogens from bronchoalveolar lavage samples[J]. Front Cell Infect Microbiol, 2021, 11: 541092.

[11] Ramirez J A, Musher D M, Evans S E, et al. Treatment of community—acquired pneumonia in immunocompromised adults: a consensus statement regarding initial strategies[J]. Chest, 2020, 158(5): 1896-1911.

[12] Zhao N, Cao J, Xu J, et al. Targeting RNA with next—and third—generation sequencing improves pathogen identification in clinical samples [J]. Adv Sci (Weinh), 2021, 8(23): e2102593.

[13] Wu X, Li Y, Zhang M, et al. Etiology of severe community—acquired pneumonia in adults based on metagenomic next—generation sequencing: a prospective multicenter study[J]. Infect Dis Ther, 2020, 9(4): 1003-1015.

[14] Long Y, Xia X, Feng H, et al. Improving pulmonary infection diagnosis with metagenomic next—generation sequencing of bronchoalveolar lavage fluid[J]. J Med Microbiol, 2024, 73(2). doi: 10.1099/jmm.0.001808.

[15] Wei P, Wu L, Li Y, et al. Metagenomic next—generation sequencing for the detection of pathogenic microorganisms in patients with pulmonary infection [J]. Am J Transl Res, 2022, 14(9): 6382-6388.

[16] Fang X, Mei Q, Fan X, et al. Diagnostic value of metagenomic next—generation sequencing for the detection of pathogens in bronchoalveolar lavage fluid in ventilator—associated pneumonia patients[J]. Front Microbiol, 2020, 11: 599756.

[17] Russo A, Bruni A, Gulli S, et al. Efficacy of cefiderocol—vs colistin—containing regimen for treatment of bacteraemic ventilator—associated pneumonia caused by carbapenem—resistant Acinetobacter baumannii in patients with COVID—19 [J]. Int J Antimicrob Agents, 2023, 62(1): 106825.

[18] Howard L M, Edwards K M, Zhu Y, et al. Parainfluenza virus types 1—3 infections among children and adults hospitalized with community—acquired pneumonia [J]. Clin Infect Dis, 2021, 73(11): e4433-e4443.

[19] Liu H, Zhang Y, Yang J, et al. Application of mNGS in the etiological analysis of lower respiratory tract infections and the prediction of drug resistance[J]. Microbiol Spectr, 2022, 10(1): e250221.

[20] Bhowmik D, Zhu F . Evasion of intracellular DNA sensing by human herpesviruses[J]. Front Cell Infect Microbiol, 2021, 11: 647992.

[21] Lane J R, Tata M, Yasmin R, et al. PspA—mediated aggregation protects Streptococcus pneumoniae against desiccation on fomites[J]. mBio, 2023, 14(6): e0263423.

[22] Dickson R P, Erb—Downward J R, Freeman C M, et al. Bacterial topography of the healthy human lower respiratory tract[J]. mBio, 2017, 8(1): e02287—16.

[23] Wu D, Wang W, Xun Q, et al. Metagenomic next—generation sequencing indicates more precise pathogens in patients with pulmonary infection: a retrospective study [J]. Front Cell Infect Microbiol, 2022, 12: 977591.

基金资助

^*新疆维吾尔自治区区域协同创新专项-科技援疆计划项目(2022E02045)