The Fungal Airway Microbiome in Cystic Fibrosis and Bronchiectasis

Abstract

Background: The prevalence of fungal disease in cystic fibrosis (CF) and non-CF bronchiectasis is increasing and the clinical spectrum is widening. Poor sensitivity and a lack of standard diagnostic criteria renders interpretation of culture results challenging. In order to develop effective management strategies, a more accurate and comprehensive understanding of the airways fungal microbiome is required. The study aimed to use DNA sequences from sputum to assess the load and diversity of fungi in adults with CF and bronchiectasis. Methods: Next generation sequencing of the ITS2 region was used to examine fungal community composition (n = 176) by disease and underlying clinical subgroups including allergic bronchopulmonary aspergillosis, chronic necrotizing pulmonary aspergillosis, non-tuberculous mycobacteria, and fungal bronchitis. Patients with no known active fungal disease were included as disease controls. Findings: ITS2 sequencing greatly increased the detection of fungi from sputum. In patients with CF fungal diversity was lower, while burden was higher than those with bronchiectasis. The most common operational taxonomic unit (OTU) in patients with CF was Candida parapsilosis (20·4%), whereas in bronchiectasis sputum Candida albicans (21·8%) was most common. CF patients with overt fungal bronchitis were dominated by Aspergillus spp., Exophiala spp., Candida parapsilosis or Scedosporium spp. This study provides a framework to more accurately characterize the extended spectrum of fungal airways diseases in adult suppurative lung diseases. Funding Statement: The project was supported by the Asmarley Trust, the Wellcome Trust and the NIHR Respiratory Disease Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust, Imperial College London. IF was supported by an NIHR PhD studentship. Declaration of Interests: The authors have no conflicts of interests to disclose. Ethics Approval Statement: The study was approved by the Royal Brompton and Harefield Hospital Biomedical Research Unit Ethics Committee (Advanced Lung Disease Biobank Study Number: 10/H0504/9).