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Title: Clinical consequences of Aspergillus colonisation & disease in cystic fibrosis & the role of environment in acquisition & infection
Author: Collier, Lisa
ISNI:       0000 0005 0290 2857
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2020
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Cystic fibrosis (CF) is the most common fatal genetic disease in the Caucasian population. It is a multisystem disease, however respiratory disease is almost universal and is characterised by colonisation of respiratory pathogens, repeated infection resulting in inflammation and structural change, with death occurring secondary to progressive respiratory failure. One such respiratory pathogen commonly found in CF patients is the fungus Aspergillus fumigatus, which is the most common disease causing fungus in CF. Aspergillus can cause a spectrum of disease, and novel immunological classification of Aspergillus disease phenotype was suggested by Baxter and colleagues (Baxter et al. 2013a) to comprise; Class 1, no disease; Class 2, allergic bronchopulmonary aspergillosis (ABPA); Class 3, Aspergillus sensitised; and Class 4, Aspergillus bronchitis. This thesis provides the first long-term follow-up of the original patient cohort to investigate what influence Aspergillus disease phenotype may have on the clinical outcomes of adult CF patients, revealing no difference in mortality, transplant rates, decline in forced expiratory volume in 1 second (FEV1), body mass index (BMI), or intravenous (IV) antibiotic therapy required over time when comparing Aspergillus Class 1-4. Indeed, baseline FEV1 remains the sole predictor of survival in this patient cohort. Further to this, this study re-classifies the same patient cohort 10 years after Baxter's original work to ascertain if patients change disease class over time. It appears that using the corrected diagnostic algorithm set forth by Baxter and colleagues reveals a large shift towards the Class 4 phenotype. It is unclear however, if this represents a true migration of disease, or is reflective of sputum galactomannan levels which were significantly raised in comparison to the previous study, and likely reflects an older population and more expansive lifetime exposure to Aspergillus. Given that Aspergillus fumigatus is a ubiquitous environmental fungus, work was also undertaken to investigate the environmental fungal burden within the Manchester Adult Cystic Fibrosis Centre, and in patient's homes, to determine if environmental Aspergillus could influence clinical disease. A seasonal rise in Aspergillus fumigatus was noted in the ward environment over the testing period, which also coincided with building works being undertaken, in-keeping with published literature. Examination of protective environmental factors in the form of ventilation systems and air filtration were therefore undertaken to elucidate if a minimum ventilation and filtration requirement could be suggested for a specialist CF centre, with >10 air changes per hour (ACH) appearing to be reliable in effectively reducing fungal burden, however high-efficiency particle air (HEPA) and Q40 filters did not appear to effectively reduce environmental fungal burden. Patient homes grew relatively low counts of Aspergillus and other fungi. There appears to be no relationship between Aspergillus levels, either in the CF centre or in patient homes, and Aspergillus disease phenotype.
Supervisor: Richardson, Malcolm Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: CF ; environmental fungi ; Aspergillus bronchitis ; Aspergillus ; cystic fibrosis