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: fungi, Aspergillus, ABPA, SAFS, asthma, eosinophils

中文翻译：

---

过敏性真菌气道疾病诊断与治疗的新观点

摘要：对气道定殖，耐热，丝状真菌的过敏代表了通常为严重肺部疾病的独特嗜酸性内型。这种内型特别影响成年哮喘，但也使其他气道疾病复杂化，有时甚至从头发生，具有异质性表现，从严重的嗜酸性哮喘到大叶塌陷。它的标志是肺损伤，其特征是固定气流阻塞（FAO），支气管扩张和肺纤维化。它有很多名称，包括带有真菌致敏性的严重哮喘（SAFS）和过敏性支气管肺曲霉病/霉菌病（ABPA / M），但这些专有术语仅构成该病症的子集。为了全面了解该综合征，我们建议使用术语“过敏性真菌气道疾病”（AFAD），IgE对与气道疾病有关的真菌致敏的标准。涉及的主要真菌是烟曲霉（Aspergillus fumigatus），但也涉及来自多个属的许多其他耐热物种。统一的机制涉及在IgE致敏的情况下吸入的真菌孢子在肺中萌发，从而导致持续而剧烈的嗜酸性粒细胞炎症反应，并释放出真菌蛋白酶。大多数过敏性真菌，包括链格孢和克拉德孢菌，都不耐热，不能在呼吸道中发芽，因此只能作为气敏原，不会引起AFAD。对气道菌群的研究表明，烟曲霉它能使哮喘患者的气道正常地繁殖，这表明对IgE敏感的趋势是AFAD的关键触发因素，而不是其本身的克隆。治疗的目的是预防糖皮质激素的加重，并越来越多地通过使用抗T2生物疗法来治疗。抗真菌疗法在管理上的位置有限，但是对于真菌性支气管炎是一种有效的治疗方法，约10％的病例使AFAD复杂化。

关键词：真菌，曲霉菌，ABPA，SAFS，哮喘，嗜酸性粒细胞