Abstract
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.
Highlights
Fungal sensitisation, severe asthma and allergic bronchopulmonary aspergillosis (ABPA) Fungal sensitisation to thermotolerant species such as Aspergillus has been linked with uncontrolled asthma but the natural history in this population has not been documented in longitudinal studies [3, 5]
Whilst ABPA represents a florid response to the presence of Aspergillus spp., up to 70% of patients with severe asthma exhibit sensitisation to different fungi but do not meet the diagnostic criteria for ABPA [1, 3, 5]
Given the increasing consensus regarding the overlap of ABPA and severe asthma, fungal sensitisation and radiological features of lung damage, it seems likely that antifungal therapy would offer significant therapeutic benefit to the majority of patients who meet some of the criteria for ABPA irrespective of total IgE levels [4, 6, 39, 40]
Summary
Severe asthma is a complex heterogenous disease which has been described as “the requirement for high dose inhaled corticosteroids plus a second controller and/ or systemic corticosteroids to prevent it from becoming ‘‘uncontrolled’’ or which remains ‘‘uncontrolled’’ despite this therapy” [1]. Whilst ABPA represents a florid response to the presence of Aspergillus spp., up to 70% of patients with severe asthma exhibit sensitisation to different fungi but do not meet the diagnostic criteria for ABPA [1, 3, 5]. This heterogeneous population has been termed “severe asthma with fungal sensitisation” (SAFS) which is diagnosed with the use of skin prick tests (SPT) and fungal specific IgE responses (Table 1). The conventional diagnostic criteria for ABPA have been subject to revision as a growing recognition that there is broad overlap with a population with fungal sensitisation, airways obstruction and lung tissue damage [3, 4, 6]. Additional file 1: Table S1 shows some of the most important allergic fungi and the genera they belong to and the summary names we use in this paper (see Additional file 1: Table S1)
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