Alghamdi, Nada Saeed A ORCID: https://orcid.org/0000-0002-0391-1235
(2021)
Fungi in the Lungs of People with Cystic Fibrosis: Immune Response and The Airway Mycobiome.
PhD thesis, University of Leeds.
Abstract
Cystic fibrosis (CF) is a genetic disease affecting multiple body organs; however, pulmonary complications remain the most common cause of morbidity and mortality. An increasing body of evidence has linked fungi to worsening CF disease, but their role has not been fully explored, partly due to challenges associated with diagnosis. The aim of this thesis was to better understand the role of immune response in the diagnosis of Aspergillus related diseases and to gain a full picture of fungi found in CF airways - the mycobiome, and how it relates to clinical conditions and treatments. Three studies were performed. First, serum samples were analysed from CF patients with Allergic Bronchopulmonary Aspergillosis (ABPA), Aspergillus sensitisation, and Aspergillus bronchitis for their IgE and IgG response to Aspergillus recombinant antigens. Second, 126 CF patients were recruited, and their sputum samples were analysed by conventional culture methods and next generation sequencing comparing two internal transcribed sequence ribosomal DNA regions to assess the mycobiome. In a subset of patients, lung mycobiome was investigated in relation to lung disease severity as well as CFTR modulator therapy. Third, the impact of antifungals on the lung mycobiome was investigated in a longitudinal study where sputum samples from before and during/post treatment were analysed. Asp f1 and f2 antigens were associated with Aspergillus bronchitis, with Asp f1 in particular was significantly linked to culture positivity. Patients with ABPA showed a more heterogeneous response ranging from allergy to infection like presentation. The mycobiome analysis revealed more fungi than conventional methods. Amplification of ITS2 rDNA provided better detection of Aspergillus and Exophiala species. However, fungal burden seems to decline in patients with severe lung disease and in those on CFTR modulators. In patients receiving antifungal therapy, the lung mycobiome remains largely stable.
Metadata
Supervisors: | Peckham, Daniel and Barton, Richard and Mitra, Suparna and Wilcox, Mark |
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Awarding institution: | University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) |
Academic unit: | Leeds Institute of Biomedical & Clinical Sciences (LIBACS) |
Depositing User: | Dr Nada Alghamdi |
Date Deposited: | 27 Jun 2022 07:33 |
Last Modified: | 01 Jul 2025 00:05 |
Open Archives Initiative ID (OAI ID): | oai:etheses.whiterose.ac.uk:30866 |
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