New clinical diagnostic criteria for allergic bronchopulmonary aspergillosis/mycosis and its validation

Asano, Koichiro; Hebisawa, Akira; Ishiguro, Takashi; Takayanagi, Noboru; Nakamura, Yasuhiko; Suzuki, Junko; Okada, Naoki; Tanaka, Jun; Fukutomi, Yuma; Ueki, Shigeharu; Fukunaga, Koichi; Konno, Satoshi; Matsuse, Hiroto; Kamei, Katsuhiko; Taniguchi, Masami; Shimoda, Terufumi; Oguma, Tsuyoshi

doi:10.1016/j.jaci.2020.08.029

Cited by 129 publications

(131 citation statements)

References 21 publications

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“…This has resulted in tautology where subjects with ABPA/M are preselected using characteristics which are then incorporated into the diagnostic criteria. 13 , 14 There is general agreement that the condition which comes under various headings (ABPA/M, SAFS, AFAD, airway mycosis or fungal asthma) is due to an immunological response to lung-colonising, thermotolerant, filamentous fungi, marked by IgE sensitisation to genera such as Aspergillus and Penicillium , with mucus plugging likely to be an important factor in pathogenesis. 15 This process usually, though not invariably, occurs in the context of another airway disease, particularly asthma or cystic fibrosis, but also COPD and primary bronchiectasis.…”

Section: Semantics and Definitionsmentioning

confidence: 99%

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

Wardlaw¹,

Rick²,

Özyiğit³

et al. 2021

JAA

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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.

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Section: Semantics and Definitionsmentioning

confidence: 99%

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

Wardlaw¹,

Rick²,

Özyiğit³

et al. 2021

JAA

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“…However, overactivation of the tissue repair process causes tissue fibrosis (73). Various stimuli, including HDM and fungal infection, cause fibrosis in the lung (73)(74)(75). In fact, house dust mite (HDM)-induced allergic airway inflammation has been demonstrated to be dependent on HDM antigen-specific CD4 + T RM cells in the lungs in experimental mouse models (74,76).…”

Section: The Protective and Pathogenic Roles Of Cd4 + T Rm Cells At Local Inflammatory Sitesmentioning

confidence: 99%

“…These unique transcriptomic feature of Th2 T RM cells suggests the pathogenic role of Th2 T RM cells in the induction of fibrotic responses. Regarding fungal infection, patients with allergic bronchopulmonary aspergillosis/mycosis (ABPA/ABPM) have recurrent bronchial asthma attacks accompanied by bronchial dilatation and fibrotic changes in the lung (75). In the lungs of mice with repeated exposure to the Aspergillus fumigatus antigen, CD4 + T RM cells, which produce various type of inflammatory cytokines accompanied by the low expression of CD103 and the enhanced expression of fibrosisrelated genes, induce fibrotic responses (78).…”

Section: The Protective and Pathogenic Roles Of Cd4 + T Rm Cells At Local Inflammatory Sitesmentioning

confidence: 99%

The Role of CD4+ Resident Memory T Cells in Local Immunity in the Mucosal Tissue – Protection Versus Pathology –

et al. 2021

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Memory T cells are crucial for both local and systemic protection against pathogens over a long period of time. Three major subsets of memory T cells; effector memory T (TEM) cells, central memory T (TCM) cells, and tissue-resident memory T (TRM) cells have been identified. The most recently identified subset, TRM cells, is characterized by the expression of the C-type lectin CD69 and/or the integrin CD103. TRM cells persist locally at sites of mucosal tissue, such as the lung, where they provide frontline defense against various pathogens. Importantly, however, TRM cells are also involved in shaping the pathology of inflammatory diseases. A number of pioneering studies revealed important roles of CD8+ TRM cells, particularly those in the local control of viral infection. However, the protective function and pathogenic role of CD4+ TRM cells that reside within the mucosal tissue remain largely unknown. In this review, we discuss the ambivalent feature of CD4+ TRM cells in the protective and pathological immune responses. We also review the transcriptional and epigenetic characteristics of CD4+ TRM cells in the lung that have been elucidated by recent technical approaches. A better understanding of the function of CD4+ TRM cells is crucial for the development of both effective vaccination against pathogens and new therapeutic strategies for intractable inflammatory diseases, such as inflammatory bowel diseases and chronic allergic diseases.

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“…The optimal cut‐off value of A. fumigatus specific IgG measured by ImmunoCAP method has recently been proposed for the diagnosis of ABPA and is not required for SAFS [50 ]. A recently proposed revision of the criteria for the diagnosis of ABPA using a lower IgE of 417 IU/mL (as in the original definition) has been published with an overall excellent sensitivity of 96% [51 ]. A lateral flow assay for Aspergillus fumigatus IgG and IgM had a 92% sensitivity and 82–91% specificity [52, 53 ].…”

Section: Main Textmentioning

confidence: 99%

The role of antifungals in the management of patients with severe asthma

Rapeport

Ito

Denning

2020

Clin Transl Allergy

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In patients with asthma, the inhalation of elevated amounts of fungal spores and hyphae may precipitate the onset of asthma or worsen control to the extent of being life-threatening. Sensitisation to fungi, especially Aspergillus fumigatus, is found in 15% to 48% of asthmatics in secondary care and is linked to worse asthma control, hospitalisation, bronchiectasis and fixed airflow obstruction, irrespective of whether allergic bronchopulmonary aspergillosis (ABPA) is diagnosed. ABPA represents a florid response to the presence of Aspergillus spp. but up to 70% of patients with severe asthma exhibit sensitisation to different fungi without meeting the diagnostic criteria for ABPA. The presence of persistent endobronchial colonisation with fungi, especially A. fumigatus, is linked to significantly higher rates of radiological abnormalities, lower post-bronchodilator FEV1 and significantly less reversibility to short acting bronchodilators. The therapeutic benefit for antifungal intervention in severe asthma is based on the assumption that reductions in airway fungal burden may result in improvements in asthma control, lung function and symptoms (especially cough). This contention is supported by several prospective studies which demonstrate the effectiveness of antifungals for the treatment of ABPA. Significantly, these studies confirm lower toxicity of treatment with azoles versus high dose oral corticosteroid dosing regimens for ABPA. Here we review recent evidence for the role of fungi in the progression of severe asthma and provide recommendations for the use of antifungal agents in patients with severe asthma, airways fungal infection (mycosis) and fungal colonisation. Documenting fungal airways colonisation and sensitisation in those with severe asthma opens up alternative therapy options of antifungal therapy, which may be particularly valuable in low resource settings.

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New clinical diagnostic criteria for allergic bronchopulmonary aspergillosis/mycosis and its validation

Cited by 129 publications

References 21 publications

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

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

The Role of CD4+ Resident Memory T Cells in Local Immunity in the Mucosal Tissue – Protection Versus Pathology –

The role of antifungals in the management of patients with severe asthma

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