The role of Aspergillus fumigatus and other thermotolerant moulds in asthma
thesisposted on 2017-09-04, 11:46 authored by Joshua Ekundayo Agbetile
The fungal kingdom contains well over a million species, of which about 80,000 have been named and approximately 600 species cause some form of human disease. Fungal spores are ubiquitous in the airborne environment and inhaled daily often in large numbers though seldom lead to disease. Atopy is a common clinical feature of asthma highlighting the genetic and environment interactions that give rise to clinical phenotypes. Allergy towards fungi is recognised to play an important role in asthma and fungal sensitisation in asthma is associated with an increased risk of multiple hospital and ITU admissions. It is thought that fungal allergy arises from a disproportionate Th2 response to fungal allergens present in spores and hyphae. The risk of IgE sensitisation to fungi may be increased by the capacity of some thermotolerant fungi (typified by Aspergillus fumigatus), to colonise the airways, with an extreme though unusual form exemplified by the condition allergic bronchopulmonary aspergillosis (ABPA). This relationship however is imperfectly understood and lesser displays of fungal allergy in severe asthma are increasingly recognised. The aim was to characterise the relationship between fungal colonisation as defined by a positive sputum culture, fungal sensitisation and the clinical features of mainly moderate-severe asthma. Secondly, this information would guide a placebo controlled trial targeting airway colonisation with Voriconazole. Over 25 species of filamentous fungi were cultured from asthmatics sputum with the flora dominated by Aspergillus fumigatus. There was a correlation between IgE sensitisation to A. fumigatus and evidence of lung damage defined by fixed airflow obstruction and bronchiectasis. There was a demonstrable association between lung damage and fungal colonisation. A three-month randomised trial of oral Voriconazole in patients with asthma and Aspergillus sensitisation failed to improve asthma control or reduce exacerbations. The place of Voriconazole in patients with fungal associated asthma remains to be established.
Date of award2017-09-15
Author affiliationDepartment of Infection, Immunity and Inflammation
Awarding institutionUniversity of Leicester