Skip to main content
SpringerLink
Log in

Allergic Bronchopulmonary Aspergillosis: Pathogenesis, Diagnosis, and Management

  • REVIEW
  • Published:
Current Pulmonology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

This review highlights the role of eosinophilic mucus plugs in the bronchi and IgE immune responses in the pathogenesis, diagnosis, and management of allergic bronchopulmonary aspergillosis (ABPA).

Recent Findings

In addition to type I hypersensitivity to fungi, extracellular trap cell death of eosinophils is closely associated with disease mechanisms. In addition, biologics targeting either the IgE- or eosinophil-mediated pathways may be effective in the treatment of ABPA. Therefore, new diagnostic criteria focusing on both pathways have been validated as being more useful than the existing criteria.

Summary

Eosinophilic mucus plug formation in the bronchi due to the IL-5/IL-5 receptor/eosinophil pathway and type I hypersensitivity to fungi due to allergic or IgE-mediated pathway are important for disease pathogenesis, diagnosis, and management.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: •  Of importance •• Of major importance

  1. Hinson KF, Moon AJ, Plummer NS. Broncho-pulmonary aspergillosis; a review and a report of eight new cases. Thorax. 1952;7(4):317–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Ishizaka K, Ishizaka T, Hornbrook MM. Physicochemical properties of reaginic antibody. V. Correlation of reaginic activity wth gamma-E-globulin antibody. J Immunol. 1966;97(6):840–53.

    Article  CAS  PubMed  Google Scholar 

  3. Katzenstein AL, Liebow AA, Friedman PJ. Bronchocentric granulomatosis, mucoid impaction, and hypersensitivity reactions to fungi. Am Rev Respir Dis. 1975;111(4):497–537. https://doi.org/10.1164/arrd.1975.111.4.497.

    Article  CAS  PubMed  Google Scholar 

  4. Bosken CH, Myers JL, Greenberger PA, Katzenstein AL. Pathologic features of allergic bronchopulmonary aspergillosis. Am J Surg Pathol. 1988;12(3):216–22.

    Article  CAS  PubMed  Google Scholar 

  5. Hebisawa A, Tamura A, Kurashima A, Oobayashi C, Kawamata M, Maeda M, et al. Pathologic reconsideration on allergic bronchopulmonary aspergillosis and mycosis. Nihon Kokyuki Gakkai Zasshi. 1998;36(4):330–7. (in Japanese).

    CAS  PubMed  Google Scholar 

  6. Rosenberg M, Patterson R, Mintzer R, Cooper BJ, Roberts M, Harris KE. Clinical and immunologic criteria for the diagnosis of allergic bronchopulmonary aspergillosis. Ann Intern Med. 1977;86(4):405–14.

    Article  CAS  PubMed  Google Scholar 

  7. Greenberger PA, Patterson R. Allergic bronchopulmonary aspergillosis and the evaluation of the patient with asthma. J Allergy Clin Immunol. 1988;81(4):646–50.

    Article  CAS  PubMed  Google Scholar 

  8. Agarwal R, Chakrabarti A, Shah A, Gupta D, Meis JF, Guleria R, et al. Allergic bronchopulmonary aspergillosis: review of literature and proposal of new diagnostic and classification criteria. Clin Exp Allergy. 2013;43(8):850–73. https://doi.org/10.1111/cea.12141.

    Article  CAS  PubMed  Google Scholar 

  9. Asano K, Kamei K, Hebisawa A. Allergic bronchopulmonary mycosis - pathophysiology, histology, diagnosis, and treatment. Asia Pac Allergy. 2018;8(3):e24. https://doi.org/10.5415/apallergy.2018.8.e24.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Araujo R, Rodrigues AG. Variability of germinative potential among pathogenic species of Aspergillus. J Clin Microbiol. 2004;42(9):4335–7. https://doi.org/10.1128/JCM.42.9.4335-4337.2004.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Oguma T, Asano K, Tomomatsu K, Kodama M, Fukunaga K, Shiomi T, et al. Induction of mucin and MUC5AC expression by the protease activity of Aspergillus fumigatus in airway epithelial cells. J Immunol. 2011;187(2):999–1005. https://doi.org/10.4049/jimmunol.1002257.

    Article  CAS  PubMed  Google Scholar 

  12. • Muniz VS, Silva JC, Braga YAV, Melo RCN, Ueki S, Takeda M, et al. Eosinophils release extracellular DNA traps in response to Aspergillus fumigatus. J Allergy Clin Immunol. 2018;141(2):571–585 e577. https://doi.org/10.1016/j.jaci.2017.07.048. This study demonstrates the release of extracellular traps from eosinophils in contact with A. fumigatus and in the mucus plugs of patients with ABPA.

  13. Dunican EM, Elicker BM, Gierada DS, Nagle SK, Schiebler ML, Newell JD, et al. Mucus plugs in patients with asthma linked to eosinophilia and airflow obstruction. J Clin Invest. 2018;128(3):997–1009. https://doi.org/10.1172/JCI95693.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Silva JDC, Thompson-Souza GA, Barroso MV, Neves JS, Figueiredo RT. Neutrophil and eosinophil DNA extracellular trap formation: Lessons from pathogenic fungi. Front Microbiol. 2021;12:634043. https://doi.org/10.3389/fmicb.2021.634043.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Ueki S, Tokunaga T, Melo RCN, Saito H, Honda K, Fukuchi M, et al. Charcot-Leyden crystal formation is closely associated with eosinophil extracellular trap cell death. Blood. 2018;132(20):2183–7. https://doi.org/10.1182/blood-2018-04-842260.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Bent JP 3rd, Kuhn FA. Diagnosis of allergic fungal sinusitis. Otolaryngol Head Neck Surg. 1994;111(5):580–8. https://doi.org/10.1177/019459989411100508.

    Article  PubMed  Google Scholar 

  17. deShazo RD, Swain RE. Diagnostic criteria for allergic fungal sinusitis. J Allergy Clin Immunol. 1995;96(1):24–35.

    Article  CAS  PubMed  Google Scholar 

  18. Fokkens WJ, Lund VJ, Hopkins C, Hellings PW, Kern R, Reitsma S, et al. Executive summary of EPOS 2020 including integrated care pathways. Rhinology. 2020;58(2):82–111. https://doi.org/10.4193/Rhin20.601.

    Article  CAS  PubMed  Google Scholar 

  19. Wardlaw AJ, Rick EM, Pur Ozyigit L, Scadding A, Gaillard EA, Pashley CH. New perspectives in the diagnosis and management of allergic fungal airway disease. J Asthma Allergy. 2021;14:557–73. https://doi.org/10.2147/JAA.S251709.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. •• Saxena P, Choudhary H, Muthu V, Sehgal IS, Dhooria S, Prasad KT, et al. Which are the optimal criteria for the diagnosis of allergic bronchopulmonary aspergillosis? A latent class analysis. J Allergy Clin Immunol Pract. 2021;9(1):328–335 e321. https://doi.org/10.1016/j.jaip.2020.08.043. This study has validated the sensitivity and specificity of the existing diagnostic criteria and proposed a modification of ISHAM criteria.

  21. •• Asano K, Hebisawa A, Ishiguro T, Takayanagi N, Nakamura Y, Suzuki J, et al. New clinical diagnostic criteria for allergic bronchopulmonary aspergillosis/mycosis and its validation. J Allergy Clin Immunol. 2021;147(4):1261–1268 e1265. https://doi.org/10.1016/j.jaci.2020.08.029. This study has also validated the sensitivity and specificity of the existing diagnostic criteria and proposed new 10-component criteria applicable not only for ABPA but also for ABPM.

  22. Sehgal IS, Dhooria S, Muthu V, Rudramurthy SM, Prasad KT, Chakrabarti A, et al. Identification of distinct immunophenotypes in chronic pulmonary aspergillosis using cluster analysis. Mycoses. 2023;66(4):299–303. https://doi.org/10.1111/myc.13553.

    Article  CAS  PubMed  Google Scholar 

  23. Asano K, Suzuki Y, Tanaka J, Kobayashi K, Kamide Y. Treatments of refractory eosinophilic lung diseases with biologics. Allergol Int. 2023;72(1):31–40. https://doi.org/10.1016/j.alit.2022.10.004.

    Article  CAS  PubMed  Google Scholar 

  24. Agarwal R, Aggarwal AN, Dhooria S, Singh Sehgal I, Garg M, Saikia B, et al. A randomised trial of glucocorticoids in acute-stage allergic bronchopulmonary aspergillosis complicating asthma. Eur Respir J. 2016;47(2):490–8. https://doi.org/10.1183/13993003.01475-2015.

    Article  CAS  PubMed  Google Scholar 

  25. Ishiguro T, Takayanagi N, Baba Y, Takaku Y, Kagiyama N, Sugita Y. Pulmonary nontuberculous mycobacteriosis and chronic lower respiratory tract infections in patients with allergic bronchopulmonary mycosis without cystic fibrosis. Intern Med. 2016;55(9):1067–70. https://doi.org/10.2169/internalmedicine.55.5561.

    Article  PubMed  Google Scholar 

  26. Liu VX, Winthrop KL, Lu Y, Sharifi H, Nasiri HU, Ruoss SJ. Association between inhaled corticosteroid use and pulmonary nontuberculous mycobacterial infection. Ann Am Thorac Soc. 2018. https://doi.org/10.1513/AnnalsATS.201804-245OC.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Suzuki S, Asakura T, Namkoong H, Okamori S, Yagi K, Kamata H, et al. Aspergillus precipitating antibody in patients with Mycobacterium avium complex lung disease: a cross-sectional study. Respir Med. 2018;138:1–6. https://doi.org/10.1016/j.rmed.2018.03.013.

    Article  PubMed  Google Scholar 

  28. Agarwal R, Dhooria S, Sehgal IS, Aggarwal AN, Garg M, Saikia B, et al. A randomised trial of voriconazole and prednisolone monotherapy in acute-stage allergic bronchopulmonary aspergillosis complicating asthma. Eur Respir J. 2018;52(3). https://doi.org/10.1183/13993003.01159-2018.

  29. Agarwal R, Dhooria S, Singh Sehgal I, Aggarwal AN, Garg M, Saikia B, et al. A randomized trial of itraconazole vs prednisolone in acute-stage allergic bronchopulmonary aspergillosis complicating asthma. Chest. 2018;153(3):656–64. https://doi.org/10.1016/j.chest.2018.01.005.

    Article  PubMed  Google Scholar 

  30. Agarwal R, Muthu V, Sehgal IS, Dhooria S, Prasad KT, Garg M, et al. A randomised trial of prednisolone versus prednisolone and itraconazole in acute-stage allergic bronchopulmonary aspergillosis complicating asthma. Eur Respir J. 2022;59(4). https://doi.org/10.1183/13993003.01787-2021.

  31. Tillie-Leblond I, Germaud P, Leroyer C, Tetu L, Girard F, Devouassoux G, et al. Allergic bronchopulmonary aspergillosis and omalizumab. Allergy. 2011;66(9):1254–6. https://doi.org/10.1111/j.1398-9995.2011.02599.x.

    Article  CAS  PubMed  Google Scholar 

  32. Aydin O, Sozener ZC, Soyyigit S, Kendirlinan R, Gencturk Z, Misirligil Z, et al. Omalizumab in the treatment of allergic bronchopulmonary aspergillosis: one center’s experience with 14 cases. Allergy Asthma Proc. 2015;36(6):493–500. https://doi.org/10.2500/aap.2015.36.3909.

    Article  PubMed  Google Scholar 

  33. Voskamp AL, Gillman A, Symons K, Sandrini A, Rolland JM, O’Hehir RE, et al. Clinical efficacy and immunologic effects of omalizumab in allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol Pract. 2015;3(2):192–9. https://doi.org/10.1016/j.jaip.2014.12.008.

    Article  PubMed  Google Scholar 

  34. Tomomatsu K, Oguma T, Baba T, Toyoshima M, Komase Y, Taniguchi M, et al. Effectiveness and safety of omalizumab in patients with allergic bronchopulmonary aspergillosis complicated by chronic bacterial infection in the airways. Int Arch Allergy Immunol. 2020;181(7):499–506. https://doi.org/10.1159/000507216.

    Article  CAS  PubMed  Google Scholar 

  35. • Jin M, Douglass JA, Elborn JS, Agarwal R, Calhoun WJ, Lazarewicz S, et al. Omalizumab in allergic bronchopulmonary aspergillosis: a systematic review and meta-analysis. J Allergy Clin Immunol Pract. 2023;11(3):896–905. https://doi.org/10.1016/j.jaip.2022.12.012. This study demonstrates a meta-analysis of 186 cases of ABPA with asthma or cystic fibrosis treated with omalizumab.

    Article  CAS  PubMed  Google Scholar 

  36. Schleich F, Vaia ES, Pilette C, Vandenplas O, Halloy JL, Michils A, et al. Mepolizumab for allergic bronchopulmonary aspergillosis: report of 20 cases from the Belgian Severe Asthma Registry and review of the literature. J Allergy Clin Immunol Pract. 2020. https://doi.org/10.1016/j.jaip.2020.03.023.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Dhariwal J, Hearn AP, Kavanagh JE, d’Ancona G, Green L, Fernandes M, et al. Real-world effectiveness of anti-IL-5/5R therapy in severe atopic eosinophilic asthma with fungal sensitization. J Allergy Clin Immunol Pract. 2021;9(6):2315–2320 e2311. https://doi.org/10.1016/j.jaip.2021.02.048.

    Article  CAS  PubMed  Google Scholar 

  38. Caminati M, Batani V, Guidolin L, Festi G, Senna G. One-year mepolizumab for allergic bronchopulmonary aspergillosis: focus on steroid sparing effect and markers of response. Eur J Intern Med. 2022;99:112–5. https://doi.org/10.1016/j.ejim.2021.12.026.

    Article  PubMed  Google Scholar 

  39. • Tomomatsu K, Yasuba H, Ishiguro T, Imokawa S, Hara J, Soeda S, et al. Real-world efficacy of anti-IL-5 treatment in patients with allergic bronchopulmonary aspergillosis. Sci Rep. 2023;13(1):5468. https://doi.org/10.1038/s41598-023-32246-8. This is a case series study of 29 ABPA cases treated with mepolizumab/benralizumab, which was effective without changing serum IgE levels.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Ramonell RP, Lee FE, Swenson C, Kuruvilla M. Dupilumab treatment for allergic bronchopulmonary aspergillosis: a case series. J Allergy Clin Immunol Pract. 2020;8(2):742–3. https://doi.org/10.1016/j.jaip.2019.11.031.

    Article  PubMed  Google Scholar 

  41. van der Veer T, Dallinga MA, van der Valk JPM, Kappen JH, van der Eerden MM, et al. Reduced exacerbation frequency and prednisone dose in patients with ABPA and asthma treated with dupilumab. Clin Transl Allergy. 2021;11(10):e12081. https://doi.org/10.1002/clt2.12081.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was partially supported by a research grant on allergic diseases and immunology from the Japan Agency for Medical Research and Development (Grant Number JP22ek0410098).

Author information

Authors and Affiliations

  1. Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 2591193, Japan

    Koichiro Asano

Authors
  1. Koichiro Asano
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Koichiro Asano.

Ethics declarations

Conflict of Interest

KA has received speaker honorarium from AstraZeneca K.K., GlaxoSmithKline plc., Novartis Pharma K.K., and Sanofi K.K.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by the author.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Asano, K. Allergic Bronchopulmonary Aspergillosis: Pathogenesis, Diagnosis, and Management. Curr Pulmonol Rep 12, 91–96 (2023). https://doi.org/10.1007/s13665-023-00316-x

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13665-023-00316-x

Keywords

Search

Navigation