靶向高通量测序技术在老年呼吸道感染性疾病诊疗中的应用

Application of targeted next-generation sequencing in the diagnosis and treatment of respiratory infections in the elderly

摘要

目的 通过对呼吸道多种病原体的靶向高通量测序(tNGS)技术检测结果分析,为老年呼吸道感染性疾病的预防及诊疗提供数据支持。方法 选取吉林省一汽总医院2023年11月—2024年11月收治的580例呼吸道感染的老年住院患者的临床资料,依据呼吸道病原体tNGS检测数据,比较不同性别、不同年龄组、不同标本类型、不同季节以及单一感染与多重感染病原体检出率差异与分布关系。结果 580份标本经tNGS检测分析,其中具有诊断意义的病原体检出例数为551例(95.0%)。共检测出病原微生物40种,其中包括5种常见病原体,4种罕见病原体。男、女总检出率差异无统计学意义(P＞0.05),其中人类疱疹病毒和结核分枝杆菌复合群的男性感染检出率均高于女性(P＜0.05)。不同年龄组病原体检出率:60～70岁组为95.3%(142/149),71～80岁组为94.5%(224/237),≥81岁组为95.4%(185/194),差异均无统计学意义(P＞0.05)。下呼吸道来源的标本检出率[96.4%(502/521)]高于非下呼吸道来源的标本[83.1%(49/59)],差异有统计学意义(P＜0.05)。咽拭子、肺泡灌洗液、痰液以及胸腹水四种类型标本的阳性检出率比较,差异有统计学意义(P＜0.05),其中灌洗液和痰液中病原体的检出率最高。四个季节的总病原体检出率比较,差异无统计学意义(P＞0.05),但是人呼吸道合胞病毒A型& B型、甲型流感病毒、新型冠状病毒、鼻病毒A型& C型、克柔念珠菌、流感嗜血杆菌、鲍曼不动杆菌、金黄色葡萄球菌、铜绿假单胞菌和具核梭杆菌季节检出率比较,差异均有统计学意义(P＜0.05);其余致病菌季节检出率比较,差异无统计学意义(P＞0.05)。单一感染检出率(5.2%)低于混合感染检出率(89.8%)。结论 老年呼吸道感染性疾病病原体较为复杂,tNGS检测方法可帮助临床快速检出罕见、少见病原体和多重性感染,为老年患者在呼吸道感染性病原体的检测方面提供了较高应用价值。

Abstract

Objective To provide data support for the prevention and treatment of respiratory infections in the elderly by analyzing the results of targeted next～generation sequencing (tNGS) for multiple respiratory pathogens. Methods A retrospective review was conducted using the clinical data of 580 elderly inpatients suspected with respiratory infections from November 2023 to November 2024 at FAW General Hospital of Jilin Province. We compared the detection rates and distribution of respiratory pathogens based on tNGS data, examining variations by gender, age group, specimen type, season, and between single and multiple infections. Results Out of 580 specimens analyzed by tNGS, 551 cases (95%) had pathogenic organisms of diagnostic significance. A total of 40 types of pathogenic microorganisms were detected, including 5 common and 4 rare pathogens. The overall detection rates between males and females showed no significant statistical difference(P＞0.05), although the detection rates for Human herpes virus and Mycobacterium tuberculosis complex were higher in males (P＜0.05).Pathogen detection rates across different age groups were as follows: 95.3% (142/149) for the 60～70 age group, 94.5% (224/237) for the 71～80 age group, and 95.4% (185/194) for those 81 years and older, with no statistically significant differences (P＞0.05).Samples derived from the lower respiratory tract exhibited a significantly higher detection rate of 96.4% (502/521) compared to those from non-lower respiratory tract sources of 83.1% (49/59), with a statistically significant difference (P＜0.05). There was a statistically significant difference in the positivity rates among the four types of specimens: throat swabs, bronchoalveolar lavage fluid, sputum, and pleuropulmonary effusions (P＜0.05). Notably, the highest detection rates were found in the bronchoalveolar lavage fluid and sputum.The overall detection rates of pathogens across four seasons showed no significant statistical differences (P＞0.05), particularly for Human Respiratory Syncytial Virus A & B, Influenza A, SARS-CoV-2, Rhinovirus A & C, Candida parapsilosis, Haemophilus influenzae, Acinetobacter baumannii, Staphylococcus aureus, Pseudomonas aeruginosa, and Clostridium perfringens, which showed significant seasonal differences in detection rates (P＜0.05). Comparison of seasonal detection rates of other pathogens showed no statistically significant differences (P＞ 0.05). The detection rate of single infections(5.2%) was significantly lower than that of mixed infections(89.8%). Conclusion The elderly respiratory tract infections are relatively complex. The tNGS detection method aids in the rapid identification of rare and uncommon pathogensa as well as multiple infections, offering high clinical application value in the detection of respiratory pathogens among the elderly.

关键词

呼吸道病原体 / 感染性疾病 / 靶向高通量测序 / 感染分布

Key words

Respiratory pathogens / Infectious diseases / Targeted next-generation sequencing / Distribution of infections