Diagnosis of Chronic Pulmonary Aspergillosis: Challenges and Limitations Response to “Diagnosis of Chronic Pulmonary Aspergillosis: Which Is the Best Investigation?” and “Diagnosis of Chronic Pulmonary Aspergillosis”

Vítor Falcão De Oliveira Department of Infectious and Parasitic Diseases Hospital das Clínicas University of São Paulo São Paulo, Brazil E-mail: vitorfalcaodeoliveira@gmail.com

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Marcello Mihailenko Chaves Magri Department of Infectious and Parasitic Diseases Hospital das Clínicas University of São Paulo São Paulo, Brazil E-mail: marcello.magri@hc.fm.usp.br

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Dear Editor,

We are grateful for the interest in our recently published article on the diagnosis of chronic pulmonary aspergillosis (CPA).1 We feel that it is important to discuss the challenges and limitations of diagnosis, mainly in low- and middle-income countries.2 This is especially important because diagnostic assays are not available in limited resource countries, and there is a gap in knowledge on diagnostic aspects, such as the cutoff for galactomannan (GM).

Serology by immunoprecipitation methods (immunodiffusion or counterimmunoelectrophoresis) may be considered inferior to serum Aspergillus fumigatus-specific IgG for CPA, but immunoprecipitation tests are still the main available tests in many countries, including Brazil.3 The current use of precipitation tests can be explained by the low cost of this technique and its greater availability.3 Serology is the best non-invasive assay for diagnosis,4,5 even if performed by immunoprecipitation, with a positivity rate of 81%, and it was the best assay for diagnosis in our study.1

The updated European Society for Clinical Microbiology and Infectious Diseases and European Respiratory Society guidelines for the diagnosis of CPA are recommended, with modifications in resource-constrained settings.6,7 We disagree that histology is the gold standard for diagnosing CPA, as it may not be positive in all cases, especially for specimens that are collected blindly and may not be obtained from the preferred site.8 Our positivity rate of histology was 78%, reinforcing the limited sensitivity of this assay for diagnosing CPA.

Several studies that have evaluated GM cutoffs, with variable results, and variable sensitivity and specificity.915 Thus, a clear cutoff value has not been established for CPA.11 In addition, the measurement of GM in bronchoalveolar lavage fluid is challenging in resource-limited settings given that bronchoscopy is not routinely performed.16

We agree with the limitations highlighted by Bongomin and colleagues. Despite the limitations, our results can inspire other studies. Diagnosing CPA in low- and middle-income countries is challenging, justifying studies that may identify simpler alternatives to invasive and/or expensive tests.

REFERENCES

  • 1.

    de Oliveira VF , Viana JA , Sawamura MVY , Magri ASGK , Nathan Costa A , Abdala E , Mariani AW , Benard G , Chaves Magri MM , 2023. Sensitivity of antigen, serology, and microbiology assays for diagnosis of the subtypes of chronic pulmonary aspergillosis at a teaching hospital in São Paulo, Brazil. Am J Trop Med Hyg 108: 2226.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    de Oliveira VF , Viana JA , Sawamura MVY , Magri ASGK , Benard G , Costa AN , Abdala E , Mariani AW , Magri MMC , 2022. Challenges, characteristics, and outcomes of chronic pulmonary aspergillosis: a 11-year experience in a middle-income country. Mycopathologia (In press). doi:10.1007/s11046-022-00676-z.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Volpe Chaves CE , do Valle Leone de Oliveira SM , Venturini J , Grande AJ , Sylvestre TF , Poncio Mendes R , Mello Miranda Paniago A , 2020. Accuracy of serological tests for diagnosis of chronic pulmonary aspergillosis: a systematic review and meta-analysis. PLoS One 15: e0222738.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Kitasato Y et al., 2009 .Comparison of Aspergillus galactomannan antigen testing with a new cut-off index and Aspergillus precipitating antibody testing for the diagnosis of chronic pulmonary aspergillosis. Respirology 14: 701708.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    van Toorenenbergen AW , 2012. Between-laboratory quality control of automated analysis of IgG antibodies against Aspergillus fumigatus. Diagn Microbiol Infect Dis 74: 278281.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Denning DW , Cadranel J , Beigelman-Aubry C , Ader F , Chakrabarti A , Blot S , Ullmann AJ , Dimopoulos G , Lange C ; European Society for Clinical Microbiology and Infectious Diseases and European Respiratory Society , 2016. Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management. Eur Respir J 47: 4568.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Denning D W et al., 2018. Case definition of chronic pulmonary Aspergillosis in resource-constrained settings. Emerg Infect Dis 24: e171312.

  • 8.

    Takazono T , Izumikawa K , 2018. Recent advances in diagnosing chronic pulmonary aspergillosis. Front Microbiol 9: 1810.

  • 9.

    Sehgal IS , Dhooria S , Choudhary H , Aggarwal AN , Garg M , Chakrabarti A , Agarwal R , 2019. Utility of serum and bronchoalveolar lavage fluid galactomannan in diagnosis of chronic pulmonary aspergillosis. J Clin Microbiol 57: e01821-18.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Izumikawa K et al., 2012. Bronchoalveolar lavage galactomannan for the diagnosis of chronic pulmonary aspergillosis. Med Mycol 50: 811817.

  • 11.

    Urabe N , Sakamoto S , Sano G , Suzuki J , Hebisawa A , Nakamura Y , Koyama K , Ishii Y , Tateda K , Homma S , 2017. 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 55: 17381746.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Shin B , Koh WJ , Jeong BH , Yoo H , Park HY , Suh GY , Kwon OJ , Jeon K , 2014. Serum galactomannan antigen test for the diagnosis of chronic pulmonary aspergillosis. J Infect 68: 494499.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Salzer H J F et al., 2018. Evaluation of galactomannan testing, the specific lateral-flow device test and levels of cytokines in bronchoalveolar lavage fluid for diagnosis of chronic pulmonary aspergillosis. Front Microbiol 9: 2223.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Ye F , Zeng P , Li Z , Tang C , Liu W , Su D , Zhan Y , Li S , 2021. Detection of Aspergillus DNA in BALF by real-time PCR and galactomannan antigen for the early diagnosis of chronic pulmonary aspergillosis. Ann Clin Lab Sci 51: 698704.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Takazono T. et al., 2019. Evaluation of Aspergillus-specific lateral-flow device test using serum and bronchoalveolar lavage fluid for diagnosis of chronic pulmonary aspergillosis. J Clin Microbiol 57: e00095-19.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Bongomin F , Asio LG , Baluku JB , Kwizera R , Denning DW , 2020. Chronic pulmonary aspergillosis: notes for a clinician in a resource-limited setting where there is no mycologist. J Fungi (Basel) 6: 75.

    • PubMed
    • Search Google Scholar
    • Export Citation

Author Notes

  • 1.

    de Oliveira VF , Viana JA , Sawamura MVY , Magri ASGK , Nathan Costa A , Abdala E , Mariani AW , Benard G , Chaves Magri MM , 2023. Sensitivity of antigen, serology, and microbiology assays for diagnosis of the subtypes of chronic pulmonary aspergillosis at a teaching hospital in São Paulo, Brazil. Am J Trop Med Hyg 108: 2226.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    de Oliveira VF , Viana JA , Sawamura MVY , Magri ASGK , Benard G , Costa AN , Abdala E , Mariani AW , Magri MMC , 2022. Challenges, characteristics, and outcomes of chronic pulmonary aspergillosis: a 11-year experience in a middle-income country. Mycopathologia (In press). doi:10.1007/s11046-022-00676-z.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Volpe Chaves CE , do Valle Leone de Oliveira SM , Venturini J , Grande AJ , Sylvestre TF , Poncio Mendes R , Mello Miranda Paniago A , 2020. Accuracy of serological tests for diagnosis of chronic pulmonary aspergillosis: a systematic review and meta-analysis. PLoS One 15: e0222738.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Kitasato Y et al., 2009 .Comparison of Aspergillus galactomannan antigen testing with a new cut-off index and Aspergillus precipitating antibody testing for the diagnosis of chronic pulmonary aspergillosis. Respirology 14: 701708.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    van Toorenenbergen AW , 2012. Between-laboratory quality control of automated analysis of IgG antibodies against Aspergillus fumigatus. Diagn Microbiol Infect Dis 74: 278281.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Denning DW , Cadranel J , Beigelman-Aubry C , Ader F , Chakrabarti A , Blot S , Ullmann AJ , Dimopoulos G , Lange C ; European Society for Clinical Microbiology and Infectious Diseases and European Respiratory Society , 2016. Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management. Eur Respir J 47: 4568.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Denning D W et al., 2018. Case definition of chronic pulmonary Aspergillosis in resource-constrained settings. Emerg Infect Dis 24: e171312.

  • 8.

    Takazono T , Izumikawa K , 2018. Recent advances in diagnosing chronic pulmonary aspergillosis. Front Microbiol 9: 1810.

  • 9.

    Sehgal IS , Dhooria S , Choudhary H , Aggarwal AN , Garg M , Chakrabarti A , Agarwal R , 2019. Utility of serum and bronchoalveolar lavage fluid galactomannan in diagnosis of chronic pulmonary aspergillosis. J Clin Microbiol 57: e01821-18.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Izumikawa K et al., 2012. Bronchoalveolar lavage galactomannan for the diagnosis of chronic pulmonary aspergillosis. Med Mycol 50: 811817.

  • 11.

    Urabe N , Sakamoto S , Sano G , Suzuki J , Hebisawa A , Nakamura Y , Koyama K , Ishii Y , Tateda K , Homma S , 2017. 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 55: 17381746.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Shin B , Koh WJ , Jeong BH , Yoo H , Park HY , Suh GY , Kwon OJ , Jeon K , 2014. Serum galactomannan antigen test for the diagnosis of chronic pulmonary aspergillosis. J Infect 68: 494499.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Salzer H J F et al., 2018. Evaluation of galactomannan testing, the specific lateral-flow device test and levels of cytokines in bronchoalveolar lavage fluid for diagnosis of chronic pulmonary aspergillosis. Front Microbiol 9: 2223.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Ye F , Zeng P , Li Z , Tang C , Liu W , Su D , Zhan Y , Li S , 2021. Detection of Aspergillus DNA in BALF by real-time PCR and galactomannan antigen for the early diagnosis of chronic pulmonary aspergillosis. Ann Clin Lab Sci 51: 698704.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Takazono T. et al., 2019. Evaluation of Aspergillus-specific lateral-flow device test using serum and bronchoalveolar lavage fluid for diagnosis of chronic pulmonary aspergillosis. J Clin Microbiol 57: e00095-19.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Bongomin F , Asio LG , Baluku JB , Kwizera R , Denning DW , 2020. Chronic pulmonary aspergillosis: notes for a clinician in a resource-limited setting where there is no mycologist. J Fungi (Basel) 6: 75.

    • PubMed
    • Search Google Scholar
    • Export Citation
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