Fungal Infections and ABPA

An increased fungal presence in the cystic fibrosis (CF) airway is associated with immune and clinical consequences including sensitisation to fungal allergens, reduced lung function and allergic bronchopulmonary aspergillosis (ABPA). Key drivers of fungal colonisation in CF remain unclear and are related to impaired mucociliary clearance, aberrant innate immunity and a skewed Th2 airway hyperresponsiveness. The commonest fungal pathogen, Aspergillus fumigatus, represents the predominant species that chronically colonises the CF lung, perpetuating a spectrum of varied disease states that each pose scientific, diagnostic and therapeutic challenges to CF scientists and clinicians. Recent progress in this field has explored the emergence of other fungal genera including Candida, Scedosporium, Exophiala, Rasamsonia and Malassezia, in the setting of CF, while culture-independent studies including next-generation sequencing provide a new perspective on the diversity, complexity and resistance profile of the CF mycobiome. System-based analyses of microbial-host interaction have further uncovered novel paradigms in CF pathogenesis including inter-kingdom signalling and the gut-lung axis, where fungi play an emerging and critical role. Current treatment modalities against CF-associated fungal pathogens aim at targeting host inflammation (with steroids) and fungal presence (with antifungals), and the approaches are accompanied by a weak evidence base coupled to a dearth of randomised controlled clinical trials proving efficacy. More specifically, emerging immunotherapeutic approaches targeting Th2-mediated hyperresponsiveness, multi-omics technologies and fungal sequencing platforms represent promising areas for future work that require strong and sustained investment to improve our understanding of the complex host-microbe-immunological interaction that underpins CF-associated fungal diseases.