支气管肺泡灌洗液半乳甘露聚糖检测对侵袭性肺曲霉病诊断价值的meta分析

摘要/Abstract

摘要：

目的通过系统评价分析支气管肺泡灌洗液（BALF）半乳甘露聚糖（GM）检测对侵袭性肺曲霉病（IPA）的诊断准确性并确定最佳诊断界值。方法检索Pubmed、EMBASE、OVID、Cochrane Library、中国知网（CNKI）、万方、中国生物医学（CBM）等数据库，自建库至2018年10月31日的相关数据，不限制语言，纳入符合标准的26个研究（71组数据），对其进行质量评价、异质性分析，然后分析计算每个诊断界值的合并指标，绘制受试者工作特征曲线，最终确定最佳诊断界值。结果 BALF-GM（诊断界值为0.5时）诊断IPA（确诊和临床诊断IPA）的合并灵敏度为0.87（95% CI 0.84~0.89），合并特异度为0.79（95% CI 0.77~0.81），合并阳性似然比为4.60（95% CI 3.49~6.05），合并阴性似然比为0.19（95% CI 0.14~0.25），合并诊断比值比为38.84（95% CI 22.99~52.81），集成受试者工作特征（SROC）曲线下面积（AUC）为0.92（95% CI 0.90~0.95）。在BALF-GM诊断界值为1.0时，受试者工作特征（ROC）曲线下面积（AUC）最大为0.94（95% CI 0.93~0.97）。结论 BALF-GM易于检测，对IPA的诊断准确性高，可以对IPA进行早期诊断，早期治疗，降低病死率，目前建议BALF-GM最佳诊断界值为1.0。

关键词: 支气管肺泡灌洗液, 半乳甘露聚糖, 侵袭性肺曲霉病, 界值

Abstract:

Objective To evaluate the diagnostic accuracy of bronchoalveolar lavage fluid (BALF) galactomannan (GM) for invasive pulmonary aspergillosis (IPA) and determine the optimal cut-off value by meta-analysis. Methods The Pubmed, EMBASE, OVID, Cochrane Library, CNKI(China National Knowledge Infrastructure),WANFANG,CBM(China Biology Medicine) databases were searched for relevant studies published in all languages up until October 31, 2018. Twenty-six studies (71 sets of data) meeting the criteria were included in this meta-analysis, conducted quality evaluation and heterogeneity analysis. Then, the pooled indicators of each diagnostic cut-off value, drew the receiver operating characteristic (ROC) curve were analyzed and calculated, and finally the optimal diagnostic cut-off was determined. Results The summary estimates of pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of the BALF-GM (cut-off value 0.5) for the diagnosis of IPA (proven and probable IPA) were 0.87 (95% CI 0.84-0.89), 0.79 (95% CI 0.77-0.81), 4.60 (95% CI 3.49-6.05), 0.19 (95% CI 0.14-0.25), 38.84 (95% CI 22.99-52.81).The area under the curve (AUC) of the summary receiver operating characteristics (SROC) was 0.92 (95% CI 0.90-0.95). When the BALF-GM diagnostic cutoff value in 1.0, the area under curve(AUC) of the summary receiver operating characteristic (SROC) was a maximum of 0.94 (95% CI 0.93-0.97). Conclusions BALF GM was easy to detect and had high diagnostic accuracy for IPA. It could be used for diagnosis of IPA early, so as to implement early treatment and reduce mortality. At present, the recommended diagnostic cut-off was 1.0.

Key words: bronchoalveolar lavage fluid, galactomannan, invasive pulmonary aspergillosis, cut-off value

中图分类号:

R379.6

蔡开霞, 周晶, 曹薇, 王胜昱. 支气管肺泡灌洗液半乳甘露聚糖检测对侵袭性肺曲霉病诊断价值的meta分析[J]. 中国真菌学杂志, 2019, 14(5): 284-291.

CAI Kai-xia, ZHOU Jing, CAO Wei, WANG Sheng-yu. Detecting galactomannan in bronchoalveolar lavage fluid for diagnosing invasive pulmonary aspergillosis: a meta-analysis[J]. Chinese Journal of Mycology, 2019, 14(5): 284-291.

参考文献

[1] 中华医学会呼吸病学分会感染学组.肺真菌病诊断和治疗专家共识[J].中华结核和呼吸杂志,2007,30(11):821-834.
[2] 何礼贤,邵长周.侵袭性肺曲霉病的分级诊断和治疗[J].中华结核和呼吸杂志,2006,29(5):297-298.
[3] 司淑一.侵袭性肺曲霉病诊断进展[J].中国临床医生杂志,2016,44(7):20-23.
[4] Pinel C, Fricker-Hidalgo H, Lebeau B, et al. Detection of circulating Aspergillus fumigatus galactomannan:value and limits of the Platelia test for diagnosing invasive aspergillosis[J]. J Clin Microbiol, 2003,41(5):2184-2186.
[5] Ascioglu S, Rex JH, de Pauw B, et al. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants:an international consensus[J]. Clin Infect Dis, 2002,34(1):7-14.
[6] DePauw B, Walsh TJ, Donnelly JP, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group[J]. Clin Infect Dis, 2008,46(12):1813-1821.
[7] Maertens JA, Klont R, Masson C, et al. Optimization of the cutoff value for the Aspergillus double-sandwich enzyme immunoassay[J]. Clin Infect Dis, 2007,44(10):1329-1336.
[8] Zou M, Tang L, Zhao S, et al. Systematic review and meta-analysis of detecting galactomannan inbronchoalveolar lavage fluid for diagnosing invasive aspergillosis[J]. PloS one,2012,7(8):e43347.
[9] 王俊玲,周正,马源慧,等.支气管肺泡灌洗液半乳甘露聚糖检测对侵袭性肺曲霉菌病感染诊断价值的meta分析[J].检验医学,2014,29(12):1248-1253.
[10] Whiting PF,Rutjes AW, Westwood ME, et al. QUADAS-2:a revised tool for the quality assessment of diagnostic accuracy studies[J]. Ann Intern Med,2011,155(8):529-536.
[11] 曲艳吉,杨智荣,孙凤等.偏倚风险评估系列:(六)诊断实验[J].中华流行病学杂志,2018,39(4):524-531.
[12] Deng J, Wu SY, Liu Y, et al. Galactomannan tests of bronchoalveolar lavage fluid for diagnosing invasive pulmonary aspergillosis[J]. Sichuan Da Xue Xue Bao Yi Xue Ban,2018,49(1):124-128.
[13] Zhou W, Li H, Zhang Y, et al. Diagnosticvalue of galactomannan antigen test in serum and bronchoalveolar lavage fluid samples from patients with nonneutropenic invasive pulmonary aspergillosis[J]. J Clin Microbiol,2017,55(7):2153-2161.
[14] Zhuang Q, Ma H, Zhang Y, et al. Galactomannan inbronchoalveolar lavage fluid for diagnosis of invasive pulmonary aspergillosis with nonneutropenic patients[J]. Can Respir J,2017,2017:3685261.
[15] Orasch T, Prattes J, Faserl K, et al. Bronchoalveolar lavage triacetylfusarinine C (TAFC) determination for diagnosis of invasive pulmonary aspergillosis in patients with hematological malignancies[J]. J Infect,2017,75(4):370-373.
[16] 郝晟瑜. 半乳甘露聚糖检测对非免疫功能受损患者侵袭性肺曲霉病的诊断价值[D].济南:山东大学,2017.
[17] Fortun J, Martin-Davila P, Gomez Garcia de la Pedrosa E, et al. Galactomannan in bronchoalveolar lavage fluid for diagnosis of invasive aspergillosis in non-hematological patients[J]. J Infect,2016,72(6):738-744.
[18] Lahmer T, Neuenhahn M, Held J, et al. Comparison of 1,3-beta-d-glucan with galactomannan in serum and bronchoalveolar fluid for the detection of Aspergillus species in immunosuppressed mechanical ventilated critically ill patients[J]. J Crit Care,2016,36:259-264.
[19] Lin PC, Lai QQ, Zhou Y, et al. The diagnostic performance of galactomannan detection for invasive pulmonary aspergillosis in non-neutropenic hosts[J]. Zhonghua Jie He He Hu Xi Za Zhi,2016,39(12):929-933.
[20] Zhang S, Wang S, Wan Z,et al. The diagnosis of invasive and noninvasive pulmonary aspergillosis by serum and bronchoalveolar lavage fluid galactomannan assay[J]. Biomed Res Int,2015,2015:943691.
[21] Mohammadi S, Khalilzadeh S, Goudarzipour K, et al. Bronchoalveolar galactomannan in invasive pulmonary aspergillosis:a prospective study in pediatric patients[J]. Med Mycol, 2015,53(7):709-716.
[22] Boch T, Buchheidt D, Spiess B, et al. Direct comparison of galactomannan performance in concurrent serum and bronchoalveolar lavage samples in immunocompromised patients at risk for invasive pulmonary aspergillosis[J]. Mycoses,2016,59(2):80-85.
[23] Heng SC, Chen SC, Morrissey CO, et al. Clinical utility of Aspergillus galactomannan and PCR in bronchoalveolar lavage fluid for the diagnosis of invasive pulmonary aspergillosis in patients with haematological malignancies[J]. Diagn Microbiol Infect Dis,2014,79(3):322-327.
[24] Hoenigl M, Prattes J, Spiess B, et al. Performance of galactomannan, beta-d-glucan, Aspergillus lateral-flow device, conventional culture, and PCR tests with bronchoalveolar lavage fluid for diagnosis of invasive pulmonary aspergillosis[J]. J Clin Microbiol, 2014,52(6):2039-2045.
[25] Kim SW, Rhee CK, Kang HS, et al. Diagnostic value of bronchoscopy in patients with hematologic malignancy and pulmonary infiltrates[J]. Ann Hematol, 2015,94(1):153-159.
[26] Prattes J, Flick H, Pruller F, et al. Novel tests for diagnosis of invasive aspergillosis in patients with underlying respiratory diseases[J]. Am J Respir Crit Care Med,2014,190(8):922-929.
[27] Zhang XB, Chen GP, Lin QC,et al. Bronchoalveolar lavage fluid galactomannan detection for diagnosis of invasive pulmonary aspergillosis in chronic obstructive pulmonary disease[J]. Med Mycol J,2013,51(7):688-695.
[28] D'Haese J, Theunissen K, Vermeulen E, et al. Detection of galactomannan in bronchoalveolar lavage fluid samples of patients at risk for invasive pulmonary aspergillosis:analytical and clinical validity[J]. J Clin Microbiol,2012,50(4):1258-1263.
[29] 张孝斌. 支气管肺泡灌洗液半乳甘露聚糖检测在肺部疾病合并侵袭性肺曲霉病诊断中的应用价值[D]. 福州:福建医科大学,2012.
[30] de Mol M, deJongste JC, van Westreenen M, et al. Diagnosis of invasive pulmonary aspergillosis in children with bronchoalveolar lavage galactomannan[J]. Pediatr Pulmonol,2013,48(8):789-796.
[31] He H, Ding L, Sun B,et al. Role of galactomannan determinations in bronchoalveolar lavage fluid samples from critically ill patients with chronic obstructive pulmonary disease for the diagnosis of invasive pulmonary aspergillosis:a prospective study[J]. Crit Care, 2012,16(4):R138.
[32] Nguyen MH, Leather H, Clancy CJ, et al. Galactomannan testing inbronchoalveolar lavage fluid facilitates the diagnosis of invasive pulmonary aspergillosis in patients with hematologic malignancies and stem cell transplant recipients[J]. Biol Blood Marrow Transplant,2011,17(7):1043-1050.
[33] 金欣,陈建魁,于农,等.支气管肺泡灌洗液中的GM检测对侵袭性肺曲霉病的诊断意义[J].中国卫生检验杂志,2010,20(11):2900-2902.
[34] Hsu LY, Ding Y,Phua J, et al. Galactomannan testing of bronchoalveolar lavage fluid is useful for diagnosis of invasive pulmonary aspergillosis in hematology patients[J]. BMC Infect Dis,2010,10:44.
[35] Maertens J, Maertens V, Theunissen K, et al. Bronchoalveolar lavage fluid galactomannan for the diagnosis of invasive pulmonary aspergillosis in patients with hematologic diseases[J]. Clin Infect Dis, 2009,49(11):1688-1693.
[36] Clancy CJ,Jaber RA, Leather HL, et al. Bronchoalveolar lavage galactomannan in diagnosis of invasive pulmonary aspergillosis among solid-organ transplant recipients[J]. J Clin Microbiol, 2007,45(6):1759-1765.
[37] Musher B,Fredricks D, Leisenring W,et al. Aspergillus galactomannan enzyme immunoassay and quantitative PCR for diagnosis of invasive aspergillosis with bronchoalveolar lavage fluid[J]. J Clin Microbiol, 2004,42(12):5517-5522.
[38] Patterson TF, Thompson GR 3rd, Denning DW, 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.
[39] Kanj A, Abdallah N, Soubani AO. The spectrum of pulmonary aspergillosis[J]. Respir Med,2018,141:121-131.
[40] Bao Z, Chen H, Zhou M, et al. Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease:a case report and review of the literature[J]. Oncotarget, 2017,8(23):38069-38074.
[41] Barberan J, Mensa J. Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease[J]. Rev Iberoam Micol,2014,31(4):237-241.
[42] Bulpa P, Bihin B, Dimopoulos G, et al. Which algorithm diagnoses invasive pulmonary aspergillosis best in ICU patients with COPD[J]? Eur Respir J,2017,50(3):1700532.
[43] Xu H, Li L, Huang WJ,et al. Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease:a case control study from China[J]. Clin Microbiol Infect,2012,18(4):403-408.
[44] Moreno-Gonzalez G,Ricart de Mesones A, Tazi-Mezalek R, et al. Invasive pulmonary aspergillosis with disseminated infection in immunocompetent patient[J]. Can Respir J, 2016,2016:7984032.
[45] Zhang RR, Wang SF, Lu HW,et al. Clinical in vestigation of misdiagnosis of invasive pulmonary aspergillosis in 26 immunocompetent patients[J]. Int J Clin Exp Med,2014,7(11):4139-4146.
[46] Shah MM, Hsiao EI, Kirsch CM,et al. Invasive pulmonary aspergillosis and influenza co-infection in immunocompetent hosts:case reports and review of the literature[J]. Diagn Microbiol Infect Dis, 2018,91(2):147-152.
[47] 周黎明. 内参标化的肺泡灌洗液半乳甘露聚糖试验在侵袭性肺曲霉病诊断中的价值研究[D].南昌:南昌大学,2018.