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The Utility of Galactomannan and Polymerase Chain Reaction Assays in Bronchoalveolar Lavage for Diagnosis of Chronic Pulmonary Aspergillosis

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Abstract

The diagnosis of chronic pulmonary aspergillosis (CPA) is established by combined clinic-radio-microbiological criteria. Out of the different microbiological criteria, a positive serology for Aspergillus-specific IgG levels is the cornerstone of diagnosis. Alternatively, other microbiological evidence are sometimes sought viz., positive Aspergillus antigen (broncho-alveolar lavage fluid, i.e., BALF galactomannan ≥ 1.0), histopathological demonstration of the fungi following lung biopsy or resection, demonstration of hyaline septate hyphae in direct microscopy resembling Aspergillus spp. or its growth on a respiratory specimen. However, the exact roles of BALF- GM and the newer BALF-PCR have not been confirmed by studies till date. This study enrolled 210 patients with suspected CPA. Of the participants, 88 patients met the criteria for CPA, whereas 122 patients had an alternative diagnosis. The sensitivity—specificity of AsperGenius® PCR and "in-house” PCR were 52.27(36.69–67.54) %—33.78 (23.19–45.72) % and 36.36 (22.41–52.23) %—39.19 (28.04–51.23) % respectively. The sensitivity/specificity of BALF (> 1.0) and serum galactomannan (> 1.0) were 46.55% (33.34–60.13)/64.08% (54.03–73.3) and 29.82% (22.05–37.6)/86.84% (81.1–92.59) respectively. The optimal cut-off values for BALF-Galactomannan and serum galactomannan in diagnosing CPA were found to be 0.69 (sensitivity: 64%; specificity: 53%) and 0.458 (sensitivity: 67%; specificity: 64%) respectively. This results of this study suggests that Aspergillus PCR from BAL may not be a good “rule-in” test for diagnosing CPA. While the performances of GM in BAL and serum may be better than PCR, it should be best used in conjunction with other clinical, radiological, and other microbiological characteristics.

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References

  1. Urabe N, Sakamoto S, Sano G, et al. Usefulness of two aspergillus PCR assays and aspergillus galactomannan and β-d-glucan testing of bronchoalveolar lavage fluid for diagnosis of chronic pulmonary aspergillosis. J Clin Microbiol. 2017;55(6):1738–46. https://doi.org/10.1128/JCM.02497-16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Swain S, Sharma K, Ray A, et al. Post-COVID-19-invasive pulmonary mycosis. Libyan Int Med Univ J. 2022;7(01):007–11.

    Article  Google Scholar 

  3. Swain S, Ray A, Sarda R, et al. COVID-19-associated subacute invasive pulmonary aspergillosis. Mycoses. 2022;65(1):57–64.

    Article  CAS  PubMed  Google Scholar 

  4. Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management—PubMed. Accessed March 1, 2023. https://pubmed.ncbi.nlm.nih.gov/26699723/.

  5. Ray A, Chowdhury M, Sachdev J, et al. Efficacy of LD bio aspergillus ICT lateral flow assay for serodiagnosis of chronic pulmonary aspergillosis. J Fungi Basel Switz. 2022;8(4):400. https://doi.org/10.3390/jof8040400.

    Article  CAS  Google Scholar 

  6. Ray A, Manikanta J, Singh K, et al. An open-label non-inferiority randomised control trial comparing nebulised amphotericin B with oral itraconazole in patients with pulmonary aspergilloma. Mycoses. 2021;64(9):1038–44.

    Article  CAS  PubMed  Google Scholar 

  7. Aggarwal N, Ghosh T, Bhan M, et al. Post-tuberculosis sequelae and their correlation with quality of life: An observational study at a tertiary care center of north India. mexiv. Published online 2021;2021–10.

  8. Ray A, Aayilliath K A, Banerjee S, Chakrabarti A, Denning DW. Burden of Serious Fungal Infections in India. Open Forum Infect Dis. 2022;9(12):ofac603. https://doi.org/10.1093/ofid/ofac603

  9. Denning DW, Cole DC, Ray A. New estimation of the prevalence of chronic pulmonary aspergillosis (CPA) related to pulmonary TB - a revised burden for India. IJID Reg. 2023;6:7–14. https://doi.org/10.1016/j.ijregi.2022.11.005.

    Article  PubMed  Google Scholar 

  10. Baluku JB, Nuwagira E, Bongomin F, Denning DW. Pulmonary TB and chronic pulmonary aspergillosis: clinical differences and similarities. Int J Tuberc Lung Dis Off J Int Union Tuberc Lung Dis. 2021;25(7):537–46. https://doi.org/10.5588/ijtld.21.0034.

    Article  CAS  Google Scholar 

  11. Sarda R, Ray A. Pulmonary TB and chronic pulmonary aspergillosis. Int J Tuberc Lung Dis. 2021;25(12):1042–3.

    Article  CAS  PubMed  Google Scholar 

  12. Denning DW, Caanel J, Beigelman-Aubry C, et al. Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management. Eur Respir J. 2016;47(1):45–68. https://doi.org/10.1183/13993003.00583-2015.

    Article  CAS  PubMed  Google Scholar 

  13. Bharath BG, Ray A, Jorwal P, et al. Diagnostic utility of chest computerized tomography in the diagnosis of recurrence among sputum scarce and sputum negative previously treated pulmonary tuberculosis suspects. Lung India Off Organ Indian Chest Soc. 2022;39(2):145.

    Article  CAS  Google Scholar 

  14. Ullmann AJ, Aguado JM, Arikan-Akdagli S, et al. Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin Microbiol Infect. 2018;24:e1–38. https://doi.org/10.1016/j.cmi.2018.01.002.

    Article  PubMed  Google Scholar 

  15. Sehgal IS, Dhooria S, Choudhary H, et al. Utility of serum and bronchoalveolar lavage fluid galactomannan in diagnosis of chronic pulmonary aspergillosis. J Clin Microbiol. 2019;57(3):e01821-e1918. https://doi.org/10.1128/JCM.01821-18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Shin B, Koh WJ, Jeong BH, et al. Serum galactomannan antigen test for the diagnosis of chronic pulmonary aspergillosis. J Infect. 2014;68(5):494–9. https://doi.org/10.1016/j.jinf.2014.01.005.

    Article  PubMed  Google Scholar 

  17. Izumikawa K, Yamamoto Y, Mihara T, et al. Bronchoalveolar lavage galactomannan for the diagnosis of chronic pulmonary aspergillosis. Med Mycol. 2012;50(8):811–7. https://doi.org/10.3109/13693786.2012.682228.

    Article  CAS  PubMed  Google Scholar 

  18. Salzer HJF, Prattes J, Flick H, et al. Evaluation of galactomannan testing, the aspergillus-specific lateral-flow device test and levels of cytokines in bronchoalveolar lavage fluid for diagnosis of chronic pulmonary aspergillosis. Front Microbiol. 2018;9. Accessed October 10, 2022. https://www.frontiersin.org/articles/https://doi.org/10.3389/fmicb.2018.02223.

  19. Imbert S, Meyer I, Palous M, et al. Aspergillus PCR in bronchoalveolar lavage fluid for the diagnosis and prognosis of aspergillosis in patients with hematological and non-hematological conditions. Front Microbiol. 2018;9:1877. https://doi.org/10.3389/fmicb.2018.01877.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Denning DW, Page ID, Chakaya J et al. Case definition of chronic pulmonary aspergillosis in resource-constrained settings. Emerg Infect Dis. 2018;24(8):e171312. https://doi.org/10.3201/eid2408.171312.

  21. Stucky Hunter E, Richardson MD, Denning DW. Evaluation of LDBio aspergillus ICT lateral flow assay for igg and igm antibody detection in chronic pulmonary aspergillosis. J Clin Microbiol. 2019;57(9):e00538-e619. https://doi.org/10.1128/JCM.00538-19.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Bialek R, Konrad F, Kern J, et al. PCR based identification and discrimination of agents of mucormycosis and aspergillosis in paraffin wax embedded tissue. J Clin Pathol. 2005;58(11):1180–4. https://doi.org/10.1136/jcp.2004.024703.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Pandey M, Xess I, Sachdev J et al. Development of a sensitive and specific novel qpcr assay for simultaneous detection and differentiation of mucormycosis and aspergillosis by melting curve analysis. Front Fungal Biol. 2022;2. Accessed April 6, 2023. https://www.frontiersin.org/articles/https://doi.org/10.3389/ffunb.2021.800898.

  24. Bretagne S, Costa JM, Marmorat-Khuong A, et al. Detection of aspergillus species DNA in bronchoalveolar lavage samples by competitive PCR. J Clin Microbiol. 1995;33(5):1164–8. https://doi.org/10.1128/jcm.33.5.1164-1168.1995.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Verweij PE, Latgé JP, Rijs AJ, et al. Comparison of antigen detection and PCR assay using bronchoalveolar lavage fluid for diagnosing invasive pulmonary aspergillosis in patients receiving treatment for hematological malignancies. J Clin Microbiol. 1995;33(12):3150–3. https://doi.org/10.1128/jcm.33.12.3150-3153.1995.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Bassetti M, Azoulay E, Kullberg BJ, et al. EORTC/MSGERC definitions of invasive fungal diseases: summary of activities of the intensive care unit working group. Clin Infect Dis Off Publ Infect Dis Soc Am. 2021;72(Suppl 2):S121–7. https://doi.org/10.1093/cid/ciaa1751.

    Article  Google Scholar 

  27. White PL, Posso RB, Barnes RA. Analytical and clinical evaluation of the pathonostics aspergenius assay for detection of invasive aspergillosis and resistance to azole antifungal ugs during testing of serum samples. J Clin Microbiol. 2015;53(7):2115–21. https://doi.org/10.1128/JCM.00667-15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Chong GLM, van de Sande WWJ, Dingemans GJH, et al. Validation of a new aspergillus real-time PCR assay for direct detection of aspergillus and azole resistance of aspergillus fumigatus on bronchoalveolar lavage fluid. J Clin Microbiol. 2015;53(3):868–74. https://doi.org/10.1128/JCM.03216-14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Hung YH, Lai HH, Lin HC, Sun KS, Chen CY. Investigating factors of false-positive results of aspergillus galactomannan assay: a case-control study in intensive care units. Front Pharmacol. 2021;12:747280. doi:https://doi.org/10.3389/fphar.2021.747280.

  30. Kitasato Y, Tao Y, Hoshino T, et al. Comparison of Aspergillus galactomannan antigen testing with a new cut-off index and Aspergillus precipitating antibody testing for the diagnosis of chronic pulmonary aspergillosis. Respirol Carlton Vic. 2009;14(5):701–8. https://doi.org/10.1111/j.1440-1843.2009.01548.x.

    Article  Google Scholar 

  31. Sehgal IS, Dhooria S, Choudhary H, et al. Efficiency of A fumigatus-specific IgG and galactomannan testing in the diagnosis of simple aspergilloma. Mycoses. 2019;62(12):1108–15. https://doi.org/10.1111/myc.12987.

    Article  CAS  PubMed  Google Scholar 

  32. Takazono T, Ito Y, Tashiro M, et al. Evaluation of aspergillus-specific lateral-flow device test using serum and bronchoalveolar lavage fluid for diagnosis of chronic pulmonary aspergillosis. J Clin Microbiol. 2019;57(5):e00095-e119. https://doi.org/10.1128/JCM.00095-19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Kono Y, Tsushima K, Yamaguchi K, et al. The utility of galactomannan antigen in the bronchial washing and serum for diagnosing pulmonary aspergillosis. Respir Med. 2013;107(7):1094–100. https://doi.org/10.1016/j.rmed.2013.04.007.

    Article  PubMed  Google Scholar 

  34. Fujiuchi S, Yamamoto Y, Takeda A, et al. Evaluation of galactomannan antigen and beta-D-glucan value for diagnosis of chronic necrotizing pulmomary aspergillosis. Nihon Kokyuki Gakkai Zasshi. 2009;47(1):7–11.

    PubMed  Google Scholar 

  35. Denning DW, Park S, Lass-Florl C, et al. High-frequency triazole resistance found in nonculturable aspergillus fumigatus from lungs of patients with chronic fungal disease. Clin Infect Dis Off Publ Infect Dis Soc Am. 2011;52(9):1123–9. https://doi.org/10.1093/cid/cir179.

    Article  CAS  Google Scholar 

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Funding

This study investigator-initiated and did not receive any funding.

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  1. Mohit Chowdhury and Gagandeep Singh are both first authors.

Authors and Affiliations

  1. Department of Medicine, AIIMS, New Delhi, 110029, India

    Mohit Chowdhury, Ved Prakash Meena, Prayas Sethi, Amandeep Singh, Bindu Prakash, Sanjeev Sinha, Naveet Wig & Animesh Ray

  2. Department of Microbiology, AIIMS, New Delhi, 110029, India

    Gagandeep Singh, Mragnayani Pandey, Himanshu Mishra & Immaculata Xess

  3. Department of Biostatistics (Clinical Research Unit), AIIMS, New Delhi, 110029, India

    Ashish Datt Upadhyay

  4. Department of Pulmonary, Critical Care and Sleep Medicine, AIIMS, New Delhi, 110029, India

    Anant Mohan

  5. Department of Paediatrics, AIIMS, New Delhi, 110029, India

    Sushil Kumar Kabra

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All authors contributed to the study conception and design. All authors have commented on previous versions of the manuscript, and have read and approved the final manuscript.

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Chowdhury, M., Singh, G., Pandey, M. et al. The Utility of Galactomannan and Polymerase Chain Reaction Assays in Bronchoalveolar Lavage for Diagnosis of Chronic Pulmonary Aspergillosis. Mycopathologia 188, 1041–1053 (2023). https://doi.org/10.1007/s11046-023-00797-z

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