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Title: Phenotyping bronchiectasis based on aetiology, exacerbation characteristics and response to erythromycin
Author: Scadding, Alys Jane
ISNI:       0000 0004 7231 8034
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2018
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Background: Recurrent infections and daily symptoms are the main features of non-cystic fibrosis bronchiectasis. The beneficial effect of low-dose macrolides in these patients had been noted but at the time of initiation of this study no clinical trials had been undertaken. The aims were to assess the response to the drug and to determine how best to monitor the response. Informal clinic data had suggested a large improvement in the FEV1 would be seen particularly in those with small airway disease, evident in the lung clearance index and the CT scoring data, and neutrophilic disease would have the best response to erythromycin. Methods: Forty participants with CT proven non-cystic fibrosis bronchiectasis were recruited onto a single centre, open label, non-randomised clinical trial involving 7 visits at 12 week intervals. The first year (visits 1-5) were observational and provided the control data for the intervention of 250mg daily erythromycin which was taken for 12 weeks between visits 5 and 6. The remaining 12 weeks were used to monitor whether the response was maintained. A further 28 participants were recruited to provide further baseline data. Data was collected to assess quality of life, lung function, airway inflammation and airway micro- and mycobiology. Results: The population predominantly had post-infectious and idiopathic bronchiectasis with normal spirometry but an abnormal lung clearance index. Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae were the most commonly cultured bacteria and Aspergillus fumigatus the most commonly identified filamentous fungus. The primary end-point of a 200ml improvement in FEV1 was not found however a response to erythromycin was seen in terms of a reduction in sputum production, improved lung clearance index and transient bacterial clearance. The lung clearance index demonstrated a significantly negative correlation with FEV1 and a significantly positive correlation with the visual analogue scale scores but not the St George’s Respiratory Questionnaire or Leicester Cough Questionnaire. Conclusions: Erythromycin therapy was well-tolerated and had a beneficial effect on the daily symptoms of some participants so would be a useful therapy to trial in non-cystic fibrosis bronchiectasis.
Supervisor: Wardlaw, Andrew ; Pavord, Ian Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available