Background::Although existing mycological tests (bronchoalveolar lavage [BAL] galactomannan [GM], serum GM, serum (1,3)-β-D-glucan [BDG], and fungal culture) are widely used for diagnosing invasive pulmonary aspergillosis (IPA) in non-hematological patients with respiratory diseases, their clinical utility in this large population is actually unclear. We aimed to resolve this clinical uncertainty by evaluating the diagnostic accuracy and utility of existing tests and explore the efficacy of novel sputum-based Aspergillus assays. Methods::Existing tests were assessed in a prospective and consecutive cohort of patients with respiratory diseases in West China Hospital between 2016 and 2019 while novel sputum assays (especially sputum GM and Aspergillus-specific lateral-flow device [LFD]) in a case-controlled subcohort. IPA was defined according to the modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. Sensitivity and specificity were computed for each test and receiver operating characteristic (ROC) curve analysis was performed. Results::The entire cohort included 3530 admissions (proven/probable IPA = 66, no IPA = 3464) and the subcohort included 127 admissions (proven/probable IPA = 38, no IPA = 89). Sensitivity of BAL GM (≥1.0 optical density index [ODI]: 86% [24/28]) was substantially higher than that of serum GM (≥0.5 ODI: 38% [39/102]) ( χ2 = 19.83, P < 0.001), serum BDG (≥70 pg/mL: 33% [31/95]) ( χ2 = 24.65, P < 0.001), and fungal culture (33% [84/253]) ( χ2 = 29.38, P < 0.001). Specificity varied between BAL GM (≥1.0 ODI: 94% [377/402]), serum GM (≥0.5 ODI: 95% [2130/2248]), BDG (89% [1878/2106]), and culture (98% [4936/5055]). Sputum GM (≥2.0 ODI) had similar sensitivity (84% [32/38]) (Fisher’s exact P = 1.000) to and slightly lower specificity (87% [77/89]) ( χ2 = 5.52, P = 0.019) than BAL GM (≥1.0 ODI). Area under the ROC curve values were comparable between sputum GM (0.883 [0.812-0.953]) and BAL GM (0.901 [0.824-0.977]) ( P = 0.734). Sputum LFD had similar specificity (91% [81/89]) ( χ2 = 0.89, P = 0.345) to and lower sensitivity (63% [24/38]) ( χ2 = 4.14, P = 0.042) than BAL GM (≥1.0 ODI), but significantly higher sensitivity than serum GM (≥0.5 ODI) ( χ2 = 6.95, P = 0.008), BDG ( χ2 = 10.43, P = 0.001), and fungal culture ( χ2 = 12.70, P < 0.001). Conclusions::Serum GM, serum BDG, and fungal culture lack sufficient sensitivity for diagnosing IPA in respiratory patients. Sputum GM and LFD assays hold promise as rapid, sensitive, and non-invasive alternatives to the BAL GM test.

Invasive pulmonary aspergillosis;Sputum;Bronchoalveolar lavage;Galactomannan;Lateral-flow device

Xiao Wei;Du Longyi;Cai Linli;Miao Tiwei;Mao Bing;Wen Fuqiang;Gibson Peter Gerard;Gong Deying;Zeng Yan;Kang Mei;Du Xinmiao;Qu Junyan;Wang Yan;Liu Xuemei;Feng Ruizhi;Fu Juanjuan

Respiratory Group, Department of Integrated Traditional Chinese and Western Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China;Divison of Pulmonary Diseases, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan 610093, China;West China School of Medicine, Sichuan University, Chengdu, Sichuan 610041, China;Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China;Priority Research Centre for Healthy Lungs, The University of Newcastle, Newcastle, NSW 2305, Australia;Priority Research Centre for Asthma and Respiratory Diseases, Hunter Medical Research Institute, Newcastle, NSW 2305, Australia;Department of Respiratory and Sleep Medicine, John Hunter Hospital, Newcastle, NSW 2305, Australia;Laboratory of Anesthesia and Critical Care Medicine, Translational Neuroscience Center, West China Hospital of Sichuan University, Chengdu, Sichuan 610093, China;Department of Pneumology, Pidu District of Traditional Chinese Medicine, The Third Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611730, China;Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China;Center of Infectious Disease, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China;Research Core Facility, West China Hospital of Sichuan University, Chengdu, Sichuan 610093, China

中华医学杂志（英文版）

[1]Xiao Wei;Du Longyi;Cai Linli;Miao Tiwei;Mao Bing;Wen Fuqiang;Gibson Peter Gerard;Gong Deying;Zeng Yan;Kang Mei;Du Xinmiao;Qu Junyan;Wang Yan;Liu Xuemei;Feng Ruizhi;Fu Juanjuan-.Existing tests vs. novel non-invasive assays for detection of invasive aspergillosis in patients with respiratory diseases )[J].中华医学杂志（英文版）,2022(13):1545-1554

diseases ,mycological,based ,subcohort,Mycoses,Sputum,Galactomannan

Existing,tests,novel,invasive,assays,detection,aspergillosis,patients,respiratory,Background,Although,existing,bronchoalveolar,lavage,BAL,galactomannan,GM,serum,glucan,BDG,fungal,culture,are,widely,used,diagnosing,pulmonary,IPA,hematological,their,clinical,utility,this,large,population,actually,unclear,aimed,resolve,uncertainty,by,evaluating,diagnostic,accuracy,explore,efficacy,sputum,Aspergillus,Methods,were,assessed,prospective,consecutive,West,China,Hospital,between,while,especially,lateral,flow,device,LFD,case,controlled,was,defined,according,modified,European,Organization,Research,Treatment,Cancer,Study,Group,criteria,Sensitivity,specificity,computed,each,receiver,operating,characteristic,curve,analysis,performed,Results,entire,included,admissions,proven,probable,optical,density,ODI,substantially,higher,than,that,pg,Specificity,varied,had,similar,sensitivity,Fisher,exact,slightly,lower,Area,under,values,comparable,but,significantly,Conclusions,Serum,lack,sufficient,hold,promise,rapid,sensitive,alternatives,Invasive,Bronchoalveolar,Lateral

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