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Review
. 2021 May 25:14:557-573.
doi: 10.2147/JAA.S251709. eCollection 2021.

New Perspectives in the Diagnosis and Management of Allergic Fungal Airway Disease

Andrew J Wardlaw  1 , Eva-Maria Rick  1 , Leyla Pur Ozyigit  2 , Alys Scadding  2 , Erol A Gaillard  3 , Catherine H Pashley  1
Affiliations
Review

New Perspectives in the Diagnosis and Management of Allergic Fungal Airway Disease

Andrew J Wardlaw et al. J Asthma Allergy. .

Abstract

Allergy to airway-colonising, thermotolerant, filamentous fungi represents a distinct eosinophilic endotype of often severe lung disease. This endotype, which particularly affects adult asthma, but also complicates other airway diseases and sometimes occurs de novo, has a heterogeneous presentation ranging from severe eosinophilic asthma to lobar collapse. Its hallmark is lung damage, characterised by fixed airflow obstruction (FAO), bronchiectasis and lung fibrosis. It has a number of monikers including severe asthma with fungal sensitisation (SAFS) and allergic bronchopulmonary aspergillosis/mycosis (ABPA/M), but these exclusive terms constitute only sub-sets of the condition. In order to capture the full extent of the syndrome we prefer the inclusive term allergic fungal airway disease (AFAD), the criteria for which are IgE sensitisation to relevant fungi in association with airway disease. The primary fungus involved is Aspergillus fumigatus, but a number of other thermotolerant species from several genera have been implicated. The unifying mechanism involves germination of inhaled fungal spores in the lung in the context of IgE sensitisation, leading to a persistent and vigorous eosinophilic inflammatory response in association with release of fungal proteases. Most allergenic fungi, including Alternaria and Cladosporium species, are not thermotolerant and cannot germinate in the airways so only act as aeroallergens and do not cause AFAD. Studies of the airway mycobiome have shown that A. fumigatus colonises the normal as much as the asthmatic airway, suggesting it is the tendency to become IgE-sensitised that is the critical triggering factor for AFAD rather than colonisation per se. Treatment is aimed at preventing exacerbations with glucocorticoids and increasingly by the use of anti-T2 biological therapies. Anti-fungal therapy has a limited place in management, but is an effective treatment for fungal bronchitis which complicates AFAD in about 10% of cases.

Keywords: ABPA; Aspergillus; SAFS; asthma; eosinophils; fungi.

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Conflict of interest statement

AJW has received funding for advisory work from GSK and Pulmocide and grants for research from GSK, AstraZeneca and Pulmocide. He holds £1000 in GSK shares. EAG reports personal fees from Boehringer Ingelheim, grants from Circassia, non-financial support from Medimmune, outside the submitted work. CHP has received funding for her research from Pulmocide. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Various presentations of fungal involvement in lung disease.
Figure 2
Figure 2
A Venn diagram showing the relationship between the various terms used to describe AFAD.
Figure 3
Figure 3
Schematic diagram outlining the pathways involved in the pathogenesis of AFAD.
None
See this image and copyright information in PMC

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References

    1. Denning DW, O’Driscoll BR, Hogaboam CM, Bowyer P, Niven RM. The link between fungi and severe asthma: a summary of the evidence. Eur Respir J. 2006;27(3):615–626. doi:10.1183/09031936.06.00074705 - DOI - PubMed
    1. Denning DW, Pashley C, Hartl D, et al. Fungal allergy in asthma-state of the art and research needs. Clin Transl Allerg. 2014;4:14. doi:10.1186/2045-7022-4-14 - DOI - PMC - PubMed
    1. Knutsen AP, Bush RK, Demain JG, et al. Fungi and allergic lower respiratory tract diseases. J Allergy Clin Immunol. 2012;129(2):280–283. doi:10.1016/j.jaci.2011.12.970 - DOI - PubMed
    1. Wardlaw AJ, Woolnough K, Pashley CH. Lassoing a chimera: the semantics of allergic fungal airway disease. Clin Exp Allergy. 2015;45(12):1746–1749. doi:10.1111/cea.12659 - DOI - PubMed
    1. Ozyigit LP, Monteiro W, Rick EM, Satchwell J, Pashley CH, Wardlaw AJ. Fungal bronchitis is a distinct clinical entity which is responsive to antifungal therapy. Chronic Respir Dis. 2021;18:1479973120964448. doi:10.1177/1479973120964448 - DOI - PMC - PubMed

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