5种实验室检测方法对肺曲霉病的诊断效能对比分析

doi:10.19871/j.cnki.xfcrbzz.2026.04.004

摘要/Abstract

摘要： 目的评估并比较基于支气管肺泡灌洗液（bronchoalveolar lavage fluid,BALF）的真菌聚合酶链反应（polymerase chain reaction,PCR）法、曲霉半乳甘露聚糖抗原试验（galactomannan antigen test,GM试验）、真菌培养法（简称培养法）,以及基于血清的GM试验和（1,3）-β-D-葡聚糖检测[(1,3)-β-D-glucan test,G试验]5种实验室方法对肺曲霉病（pulmonary aspergillosis, PA）的临床诊断价值,为临床筛选高效的肺曲霉病诊断方案提供参考依据。方法采用回顾性分析方法,纳入2024年12月至2025年4月西安市胸科医院收治的841例疑似社区获得性肺炎的住院患者,所有患者均完成上述5项检测。以临床诊断为“金标准”,分别计算5种方法的敏感度、特异度、阳性预测值、阴性预测值、诊断符合率及Kappa值,绘制受试者工作特征（receiver operating characteristic,ROC）曲线并计算曲线下面积（area under curve,AUC）,综合对比各方法的诊断效能。结果单一检测中,PCR法和BALF-GM试验敏感度分别为0.519、0.577,显著高于血清GM试验（0.096）、G试验（0.077）和培养法（0.077）。培养法、PCR法阳性预测值分别为1.000、0.750,显著高于BALF-GM试验（0.484）、血清GM试验（0.156）、G试验（0.333）。ROC曲线显示,PCR法（0.754）与BALF-GM试验（0.768）的AUC值均显著高于血清GM试验（0.531）、G试验（0.533）、培养法（0.567）。联合检测中,以PCR法为基础,依次联合BALF-GM试验、血清GM试验后,诊断敏感度分别提升至0.673和0.712;继续G试验或培养法后,诊断敏感度无进一步提升（均为0.712）。结论 PCR法诊断PA的综合效能优异,临床应用价值较高。相较于单一检测,PCR法、BALF-GM试验及血清GM试验三者联合检测能够有效提升PA的诊断敏感度。

关键词: 肺曲霉病, 支气管肺泡灌洗液, 聚合酶链反应, 半乳甘露聚糖试验, (1,3)-β-D-葡聚糖试验, 诊断效能, 联合检测

Abstract: Objective To evaluate and compare the clinical diagnostic value of five laboratory methods for pulmonary aspergillosis (PA): fungal polymerase chain reaction (PCR) using bronchoalveolar lavage fluid (BALF), BALF galactomannan test (GM test), fungal culture (culture method), serum GM test, and serum (1,3)-β-D-glucan test (G test), and to provide evidence for selecting an efficient diagnostic strategy for PA in clinical practice. Method A retrospective analysis was conducted on 841 hospitalized patients with suspected community-acquired pneumonia admitted to Xi’an Chest Hospital from December 2024 to April 2025. All patients underwent the above five tests. Using clinical diagnosis as the gold standard, the sensitivity, specificity, positive predictive value, negative predictive value, diagnostic accuracy, and Kappa value were calculated for each method. Receiver operating characteristic (ROC) curves were plotted and the area under the curve (AUC) was computed to compare the diagnostic performance comprehensively. Result In single-test analysis, the sensitivities of PCR and BALF-GM were 0.519 and 0.577, respectively, significantly higher than those of serum GM (0.096), G test (0.077), and culture method (0.077). The positive predictive values of culture method (1.000) and PCR (0.750) were significantly higher than those of BALF-GM (0.484), serum GM (0.156), and G test (0.333). ROC curve analysis showed that the AUCs of PCR (0.754) and BALF-GM (0.768) were both significantly greater than those of serum GM (0.531), G test (0.533), and culture method (0.567). In combined testing, when PCR was used as the base test and sequentially combined with BALF-GM and serum GM, the diagnostic sensitivity increased to 0.673 and 0.712, respectively; further addition of G test or culture method did not improve the sensitivity further (both remained 0.712). Conclusion PCR alone demonstrates excellent overall diagnostic performance for PA and has high clinical application value. Compared with single tests, the combination of PCR, BALF-GM, and serum GM effectively improves the diagnostic sensitivity for PA.

Key words: Pulmonary aspergillosis, Bronchoalveolar lavage fluid, Polymerase chain reaction, Galactomannan test, (1,3)-β-D-glucan test, Diagnostic performance, Combined detection

中图分类号:

R446

武航, 李建英, 杨翰, 李爱芳, 杨静芬, 郑会强, 张欣, 马进宝, 李冬民. 5种实验室检测方法对肺曲霉病的诊断效能对比分析[J]. 新发传染病电子杂志, 2026, 11(4): 24-29.

Wu Hang, Li Jianying, Yang Han, Li Aifang, Yang Jingfen, Zheng Huiqiang, Zhang Xin, Ma Jinbao, Li Dongmin. Comparative analysis of diagnostic efficacy of five laboratory assays for pulmonary aspergillosis[J]. Electronic Journal of Emerging Infectious Diseases, 2026, 11(4): 24-29.

参考文献

[1] Castro-Fuentes C A, Duarte-Escalante E, Frías-De-León M G, et al. HTS and PCR Methods Are the Most Used in the Diagnosis of Aspergillosis: Advantages over Other Molecular Methods[J]. J Fungi (Basel), 2025,11(10):720.
[2] Lamoth F, Calandra T.Pulmonary aspergillosis: diagnosis and treatment[J]. Eur Respir Rev, 2022, 31(166): 220114.
[3] 蔡雨辰, 钟今今, 苏欣. 曲霉免疫相关基因单核苷酸多态性与曲霉易感性研究进展[J]. 中国呼吸与危重监护杂志, 2025,24(3):205-211.
[4] Sengupta A, Ray A, Upadhyay A D, et al.Mortality in chronic pulmonary aspergillosis: a systematic review and individual patient data meta-analysis[J]. Lancet Infect Dis, 2025,25(3):312-324.
[5] Abe Y, Narita K, Kobayashi H, et al.Higher frequency of false-positive serum galactomannan tests among older subjects and the association with elevated serum immunoglobulin G levels[J]. Mycoses, 2019,62(9):773-779.
[6] 甄拴平, 王华, 雷利强, 等. 658例血清半乳甘露聚糖试验检测结果分析[J]. 中国卫生检验杂志, 2016,26(16): 2336-2337.
[7] 张蕾, 赵钊, 沈彦, 等. 半乳甘露聚糖化学发光法与酶联免疫法检测对侵袭性肺曲霉病诊断价值的比较[J]. 中国真菌学杂志, 2024,19(3):268-272.
[8] 牛雨溪, 杨苏乔, 杨媛华. 半乳甘露聚糖试验诊断侵袭性曲霉病假阳性原因研究进展[J]. 中华结核和呼吸杂志, 2020,43(10):875-879.
[9] Xu C, Zhang L, Liu T, et al.Performance of Galactomannan, Aspergillus-PCR, and Metagenomic sequencing for the diagnosis of invasive pulmonary aspergillosis in hematological patients[J]. J Microbiol Immunol Infect, 2025,58(1): 123-131.
[10] 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(2024年版)[J]. 中华结核和呼吸杂志, 2024,47(1): 1-12.
[11] Patterson T F, Thompson G R R, Denning D W, et al. Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America[J]. Clin Infect Dis, 2016,63(4):e1-e60.
[12] 高晓慧, 葛艳芹, 刘斌. 荧光定量PCR联合GM试验检测肺泡灌洗液对侵袭性肺曲霉病的早期诊断价值[J]. 系统医学, 2025,10(7):27-30.
[13] 吕承秀, 王君君, 张凯, 等. 支气管肺泡灌洗液曲霉特异性荧光PCR联合GM试验在非粒细胞减少IPA中的诊断价值[J]. 中国热带医学, 2024,24(6):721-726.
[14] 张霄, 王成坦, 任犁. 支气管肺泡灌洗液多指标联合诊断在侵袭性肺部真菌感染中的应用价值[J]. 临床医学研究与实践, 2024,9(25): 114-117.
[15] Jaggi T K, Agarwal R, Tiew P Y, et al.Fungal lung disease[J]. Eur Respir J. 2024,64(5):2400803.
[16] Ao Z, Xu H, Li M, et al.Clinical characteristics, diagnosis, outcomes and lung microbiome analysis of invasive pulmonary aspergillosis in the community-acquired pneumonia patients[J]. BMJ Open Respir Res, 2023, 10(1): e001468.
[17] Tong X, Liu T, Jiang K, et al.Clinical Characteristics and Prognostic Risk Factors of Patients With Proven Invasive Pulmonary Aspergillosis: A Single-Institution Retrospective Study[J]. Front Med (Lausanne), 2021,8: 756237.
[18] 曾坚, 王瑾, 方木通,等. 结核后慢性肺曲霉病患者的临床特征及影响因素分析[J/CD]. 新发传染病电子杂志, 2024,9(5):25-30.
[19] Tashiro M, Takazono T, Izumikawa K.Chronic pulmonary aspergillosis: comprehensive insights into epidemiology, treatment, and unresolved challenges[J]. Ther Adv Infect Dis, 2024,11: 20499361241234867.
[20] Sedik S, Wolfgruber S, Hoenigl M, et al.Diagnosing fungal infections in clinical practice: a narrative review[J]. Expert Rev Anti Infect Ther. 2024,22(11):935-949.
[21] Jenks J D, White P L, Kidd S E, et al.An update on current and novel molecular diagnostics for the diagnosis of invasive fungal infections[J]. Expert Rev Mol Diagn. 2023,23(12):1135-1152.
[22] Zhang S X, Babady N E, Hanson K E, et al.Recognition of Diagnostic Gaps for Laboratory Diagnosis of Fungal Diseases: Expert Opinion from the Fungal Diagnostics Laboratories Consortium (FDLC)[J]. J Clin Microbiol. 2021,59(7):e0178420.
[23] Garg P, Suyal S, Deepak D, et al.Evaluating the causes associated with false positive Galactomannan assay in suspected cases of respiratory fungal infections[J]. J Family Med Prim Care, 2025, 14(2): 736-742.
[24] 刘利华, 李建美, 董海新, 等. 支气管肺泡灌洗液GM试验联合血清GM试验对侵袭性肺曲霉病的诊断价值[J]. 中华危重病急救医学, 2019, 31(3): 331-335.
[25] 程海燕, 陈先国, 徐元宏. 血清G试验、GM试验对非粒细胞缺乏侵袭性肺曲霉病的诊断价值[J]. 检验医学与临床, 2021, 18(12): 1695-1697.