Abstract
BackgroundFungal sensitization is common in severe asthma, but the clinical relevance of this and the relationship with airway colonization by fungi remain unclear. The range of fungi that may colonize the airways in asthma is unknown.ObjectiveTo provide a comprehensive analysis on the range of filamentous fungi isolated in sputum from people with asthma and report the relationship with their clinico-immunological features of their disease.MethodsWe recruited 126 subjects with a diagnosis of asthma, 94% with moderate-severe disease, and 18 healthy volunteers. At a single stable visit, subjects underwent spirometry; sputum fungal culture and a sputum cell differential count; skin prick testing to both common aeroallergens and an extended fungal panel; specific IgE to Aspergillus fumigatus. Fungi were identified by morphology and species identity was confirmed by sequencing. Four patients had allergic bronchopulmonary aspergillosis.ResultsForty-eight percent of asthma subjects were IgE-sensitized to one fungal allergen and 22% to ≥ 2. Twenty-seven different taxa of filamentous fungi were isolated from 54% of their sputa, more than one species being detected in 17%. This compared with 3 (17%) healthy controls culturing any fungus (P < 0.01). Aspergillus species were most frequently cultured in isolation followed by Penicillium species. Post-bronchodilator FEV1 (% predicted) in the subjects with asthma was 71(± 25) in those with a positive fungal culture vs. 83 (± 25) in those culture-negative, (P < 0.01).Conclusion and Clinical RelevanceNumerous thermotolerant fungi other than A. fumigatus can be cultured from sputum of people with moderate-to-severe asthma; a positive culture is associated with an impaired post-bronchodilator FEV1, which might be partly responsible for the development of fixed airflow obstruction in asthma. Sensitization to these fungi is also common.
Highlights
Asthma is a condition characterized by variable airflow obstruction, airway hyperresponsiveness (AHR) and airway inflammation that is usually eosinophilic [1]
allergic bronchopulmonary aspergillosis (ABPA) is regarded as being unusual; IgE sensitization to one or more fungal allergens is relatively common in severe asthma with up to 66% of people with severe asthma sensitized in a panel of six fungal allergens in one study [13]
Patients sensitized to A. fumigatus had lower postbronchodilator FEV1 than the non-sensitized group, suggesting that fungal colonization could contribute to the development of fixed airflow obstruction in asthma [15]
Summary
Asthma is a condition characterized by variable airflow obstruction, airway hyperresponsiveness (AHR) and airway inflammation that is usually eosinophilic [1]. The term severe asthma with fungal sensitization (SAFS) [4] has been coined to describe this phenotype, and the possibility that colonization with fungi might be pathogenic was suggested by the beneficial effect of a course of itraconazole [14] In support of this concept, using a dedicated approach towards filamentous fungal detection, we were able to culture A. fumigatus from the sputum of 63% of asthmatics who were IgE-sensitized to the fungus on a single stable visit, in contrast to 31% of non-sensitized asthmatics and < 8% of healthy subjects. Patients sensitized to A. fumigatus had lower postbronchodilator FEV1 than the non-sensitized group, suggesting that fungal colonization could contribute to the development of fixed airflow obstruction in asthma [15] This idea is supported independently [16] and by data from people with cystic fibrosis (CF), suggesting a pathogenic role for A. fumigatus in the absence of a complete set of criteria to diagnose ABPA [17]
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