Fungal-Associated Endotypes as a Treatable Trait in Bronchiectasis

Emerging evidence demonstrates the evolving role of fungi in the pathophysiology and disease progression observed in bronchiectasis. Fungal-associated traits are linked to disease severity, exacerbation frequency and airway inflammation. Structural abnormalities and impaired mucociliary clearance, characteristic of bronchiectasis, predispose to fungal colonisation, with subsequent immunopathogenic responses dependent on underlying host immunity. The diagnosis of fungal infection remains challenging in clinical settings, owing to the limitations of existing diagnostic modalities; however, the development of culture-independent molecular techniques shows promise. The use of next-generation sequencing has significantly advanced our understanding of the fungal microbiome in bronchiectasis, identifying fungi that are challenging to culture. Integrative microbiomics further elucidates the intricate and dynamic role of fungi in relation to other microbial kingdoms, and across distant organs such as the gut, revealing important relationships with bacterial pathogens including Pseudomonas aeruginosa. Airway inflammatory profiling has shown fungal-associated inflammatory endotypes which may serve as treatable traits. Environmental influences on fungi and bronchiectasis-exacerbated by air pollution and climate change-underscore the key role of the exposome in fungal-associated endotypes in bronchiectasis. This review outlines the clinical significance of fungi in bronchiectasis, the current diagnostic and treatment challenges, and emerging fungal-associated endotypes in the context of environmental influence on disease.