Immunological corollary of the pulmonary mycobiome in bronchiectasis: The Cameb study

Introduction: Understanding the composition and clinical importance of the fungal mycobiome was recently identified as a key topic in a "research priorities" consensus statement for bronchiectasis. Methods: Patients were recruited as part of the CAMEB study: an international multicentre cross-sectional Cohort of Asian and Matched European Bronchiectasis patients. The mycobiome was determined in 238 patients by targeted amplicon shotgun sequencing of the 18S-28S rRNA internally transcribed spacer regions ITS1 and ITS2. Specific qPCR for detection of and conidial quantification for a range of airway Aspergillus species was performed. Sputum galactomannan, Aspergillus-specific IgE, IgG and Thymus and Activation Regulated Chemokine levels were measured systemically and associated to clinical outcomes. Results: The bronchiectasis mycobiome is distinct, and characterised by specific fungal genera including Aspergillus, Cryptococcus, and ClavisporaA. fumigatus (in Singapore/Kuala Lumpur) and A. terreus (in Dundee) dominated profiles, the latter associating with exacerbations. High frequencies of Aspergillus-associated disease including sensitization and allergic bronchopulmonary aspergillosis were detected. Each revealed distinct mycobiome profiles and associated with more severe disease, poorer pulmonary function and increased exacerbations. Conclusion: The pulmonary mycobiome is of clinical relevance in bronchiectasis. Screening for Aspergillus-associated disease should be considered even in apparently stable patients.