Galactomannan Testing To Diagnose Of Invasive Pulmonary Aspergillosis:Bronchoalveolar Lavage Fluid Performs Better Than Serum In Non-immunocompromised Patients

Background:Invasive pulmonary aspergillosis(IPA)is an aggressive disease,caused by Aspergillus species,and invades the bronchial wall and the accompanying arterioles by the hyohae.It is also a common type of invasive fungai infection(IFI).Recently the morbidity of IFI has increased,because of antibiotic abuse,transplantation of hemopoietic stem cell and organs,the increase of immunodeficiency patents and so on.According to the EORTC/MSG 2008 criteria,the diagnosis basis involves high risk factors,clinical evidences,microbiotic evidence and histopatological examination.It is supposed that IPA mainly infects the patients with high risk factors defined in the EORTC/MSG 2008 criteria.However,more and more reports and clinical practices show that IPA also occurs in some patients with underlying disease including cancer,diabetes,connective tissue diseases,tuberculosis,chronic obstruction pulmonary disease.It also occurs in health people under special conditions,such as near-drowning,postinfectious condition and inhaling large amount of spore.In immunocompetent patients,the diagnosis of IPA is difficult in differentiating among pneumonia,tuberculosis,lung cancer and other pulmonary lesions in early stage.Furthermore,the clinical and radiographic manifestations are various.These result in misdiagnosis,mistherapy,delaying treatment,increasing the economic burden patients and disease to deteriorate.GM is a component of the fungal cell wall.According to Practice Guidelines for the Diagnosis and Management ofAspergillosis:2016 Update by the Infectious DiseasesSociety of America,the level of GM in serum is important microbial marker in diagnosis of IPA,which has been widely discussed in patients with high risks.Most studies confirm that the sensitivity of BAL GM is higher than that of serum GM.However,it is difficult to know the performance of GM in immunocompetent patients,because of the differences in immune status and the prevalence of IPA between patients with normal immunity and high risks,as well as the few studies in this population.The aim of the present study was to analyze the diagnostic performance of BAL GM and serum GM for the diagnosis of IPA in immumocompetent patients.Methods:A retrospective case-control study in patients,who had no high risk factors defined in EORTC/MSG and were clinically suspected to have lower pulmonary tract infection and underwent diagnostic bronchoscopy,was performed in the Respiratory Department of Shandong Provincial Hospital from October 2010 to June 2016.The OD values of GM in serum and BALF,clinical characteristic including gender,age,underlying diseases were collected.The sensitivity,specificity,negative predictive value(NPV),and positive predictive value(PPV)between the assays calculated using SPSS 23 software(Chicago,WA,USA).All estimations were reported with 95%confidence intervals(CI).A P value of<0.05 was considered significant.Optimal OD value was selected by ROC curve analysis.Then the diagnosis value was evaluated by comparing GM test results in serum and BALF.Results:1.In total,22 cases and 31 controlswere evaluated.52 were male and 30 were female.Among the IPA patients,the median age is 62years old(range,26?82y);12 patients had chronic underlying pulmonary diseases involving COPD(27.3%;6/22),lung cancer(9.1%;2/22),TB(4.5%;1/22),and bronchiectasis(13.6%;3/22);9 patients had chronic underlying diseases,such as diabetes(31.8%;7/22),CAD(22.7%;5/22),hypertension(27.3%;6/22),and ANCA(9.1%;2/22);3 patients had some specific conditions such as post-infectious condition(1)and near-drowning (1).Among controls,the median age is 51 years old(range,16-77 y).2.According tothe receiver operating characteristic(ROC)analysis,the area under ROC curve was 0.765 for the BAL GM antigen detection test,and 0.499 for the serum GM antigen detection test;the optimal value of BALF GM is 0.773ug/L.The sensitivity,specificity,positive,negative predictive values and diagnostic odds ration of BALFGM using an OD index of ?0.8ugLwere77.3%?71%?65.4%and 81.5%respectively,which was adapted to clinical diagnosis.3.The cases had higher BAL GM OD indices(median 5.00ug/L,range 0.18-23.9ug/L)compared with serum GM(median 0.39ug/L,range 0.03-3.1ug/L),control BAL GM(median 0.38ug/L,range 0.00-13.32ug/L)and control serum GM(median 0.47ug/L,range 0.01-1.14ug/L).Conclusions:1.IPA can attack non-immunocompromised patients,and the probable risk factors involving pulmonary and/or whole-body underlying diseases,as well as exposure to some specific condition.2.BAL GM test has higher OD indicescompared with serum GM,control BAL GM and control serum GM.Furthermore,the area under ROC curve was higher than serum GM test,which suggest that BAL GM test is significantly superior to serum GM test.