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Title: Assessing treatment strategies to disrupt the vicious cycle of infection and inflammation in bronchiectasis
Author: Smith, Maeve Patricia
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2012
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Background: Non-cystic fibrosis bronchiectasis is a chronic debilitating disease. A perpetual cycle of excessive neutrophilic inflammation and chronic bacterial infection is thought to occur within the permanently damaged and dilated airways. Aim: The aims of this thesis were to explore whether the vicious cycle of infection and inflammation in bronchiectasis can be disrupted, improving the clinical features of the disease and to identify potentially useful clinical markers for monitoring treatment response. Methods: Patients with a radiological diagnosis of bronchiectasis and a clinical history of a daily productive cough, recurrent infective exacerbations and evidence of chronically infected sputum were recruited. The first study was a randomised crossover trial of regular chest physiotherapy in 20 patients assessing whether augmentation of the impaired mucociliary system can improve health related quality of life (HRQL) and the clinical features of bronchiectasis. The second study was a prospective cohort study of 32 infective exacerbations of bronchiectasis managed with two weeks' intravenous antibiotic therapy and assessed the impact of reducing bacterial infection in the airways during acute exacerbations on HRQL, sputum bacteriology, purulence and volume as well as lung function and systemic markers of inflammation. The third study was a randomised crossover trial of regular, long term nebulised gentamicin over 12 months in 57 patients exploring the impact on airways infection and inflammation, lung function, exercise capacity, HRQL and exacerbation frequency. The fourth study sought to identify potentially useful markers of response to chronic treatment strategies for stable disease by analysing markers common to the preceding two interventional studies to assess their robustness and relevance, including sputum bacteriology and purulence, lung function, exercise capacity, systemic inflammatory markers and exacerbation frequency. Results: Augmenting the impaired mucociliary system with regular chest physiotherapy improved HRQL and exercise capacity as well as increasing 24 hour sputum volume. Treatment of acute infective exacerbations improved patients' HRQL and exercise capacity as well as reducing 24 hour sputum volume, improving sputum purulence and decreasing systemic inflammation. Long term regular nebulised gentamicin significantly reduced sputum bacterial density and airways inflammation. Exercise capacity and HRQL improved with treatment and patients suffered fewer exacerbations. Parameters that may be useful in predicting a successful response to long term treatment strategies for clinically stable disease include an improvement of ≥ 50m in the incremental shuttle walk test and eradication of pathogens from the sputum. Conclusion: Augmentation of the impaired mucociliary system, effective treatment of acute infective insults and reducing chronic bacterial infection improves the clinical features of bronchiectasis and suppresses the vicious cycle of infection and inflammation. Potentially useful markers of a successful treatment response in the management of stable disease are exercise capacity and sputum bacterial clearance.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available