Liquid-based Cytopathology Test In Bronchoalveolar Lavage Fluid For Diagnosis Of Invasive Pulmonary Fungal Disease With Nonneutropenic Patients

Objective:To evaluate and compare the value of liquid-based cytology test(LCT)of bronchoalveolar lavage fluid(BALF)following special staining with periodic acid-schiff staining(PAS)and Grocott’s methenamine silver(GMS)and BALF culture for the diagnosis of invasive pulmonary fungal disease(IPFD)in non-neutropenic patients.Materials and Methods:The study was conducted by reviewing the medical records of 62suspected IPFD patients with non-neutropenia in Department of Pulmonary and Critical Care Medicine at The Affiliated Hospital of Medical School of Ningbo University from January 2017 to January 2019.All the patients underwent bronchoscopy with BALF,of which 60 patients had one BALF specimen and 2 patients had two BALF specimens,so a total of 64 BALF specimens were included in the study.All the BALF specimens were processed LCT with special staining(PAS and GMS)and cultured,respectively.The 2008 EORTC/MSG guidelines and 2016 IDSA guidelines were used as the diagnostic criteria of IPFD in this study,the value of BALF LCT stained by PAS and GMS and BALF culture for the diagnosis of IPFD were calculated and compared,respectively.Statistical methods:SPSS 18.0 software was used for data analysis to calculate the sensitivity,specificity,false positive rate,false negative rate of BALF culture,BALF LCT stained by GMS and PAS.The enumeration data was expressed as a percentage,and P<0.05 was considered statistically significant by theX~2test.The sensitivity and specificity of BALF LCT stained by PAS and GMS in series or in parallel were calculated.Results:Total 36 patients were diagnosed as IPFD in the study,including 25 invasive pulmonary aspergillosis(IPA,21 probable/4 proven),8 pulmonary cryptococcosis(4 probable/4proven),1 probable pulmonary coccidioidomycosis,1 probable pulmonary talaromyces marneffei,1 proven schizophyllum commune-induced pulmonary mycosis.The positive rate of BALF LCT stained by GMS and PAS were 62.50%and 59.38%,respectively,which were significantly higher than that of BALF culture(35.94%),and the difference was statistically significant(P<0.05).The sensitivity,specificity,the false positive rate and the false negative rate of BALF LCT stained by GMS were 92.11%,80.78%,19.23%and 7.89%,respectively.The sensitivity,specificity,the false positive rate and the false negative rate of BALF LCT stained by PAS were 81.58%,73.08%,26.92%,18.42%,respectively.The sensitivity,specificity,the false positive rate and the false negative rate of BALF culture were 60.53%,100%,0,39.47%,respectively.Therefore,the sensitivity of BALF LCT stained by GMS and PAS were all higher than that of BALF culture(P<0.05).The sensitivity of BALF LCT stained by GMS was higher than that of BALF LCT stained by PAS,but the difference was not statistically significant(P>0.05).Although the specificity of BALF culture was higher than that of BALF LCT stained by PAS and GMS(P<0.05),the specificity of BALF LCT stained by PAS and GMS remained above 70%.The specificity of BALF LCT stained by GMS was higher than that of BALF LCT stained by PAS,but the difference was not statistically significant(P>0.05).The sensitivity and specificity of the series test of BALF LCT stained by PAS and GMS were 68.42%and 84.62%,respectively,and of the parallel test of BALF LCT stained by PAS and GMS were 97.37%and 69.23%,respectively.Conclusions:BALF LCT stained by GMS and PAS are a valuable adjunctive tool for the diagnosis of IPFD in non-neutropenic patients.Compared with BALF culture,both BALF LCT stained by GMS and PAS can improve the positive rate and sensitivity,and the specificity both can be maintained above 70%.Moreover,among the two special staining methods of BALF LCT,GMS may be superior to PAS for the diagnosis of IPFD.