Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.606574
Title: Clinical factors contributing to morbidity and mortality in cystic fibrosis
Author: Barr, Helen Louise
Awarding Body: University of Nottingham
Current Institution: University of Nottingham
Date of Award: 2013
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Abstract:
Cystic fibrosis (CF) is the commonest autosomal recessively inherited condition leading to reduced survival in the Caucasian population. It is caused by defective chloride regulation, resulting in premature death, predominantly from respiratory failure secondary to chronic infection and inflammation. Over the past 70 years, there have been vast improvements in survival in CF due to advances in early diagnosis, antibiotics, airway clearance, nutritional support and infection control. Accordingly, researchers and clinicians have endeavoured to identify prognostic indicators and outcome measures that can accurately assess response to treatment. Over 20 years ago, females and individuals of lower socioeconomic status were found to have a poorer prognosis than males or those of higher socioeconomic status. The first part of this thesis describes an epidemiological study that showed that these socioeconomic and gender disparities are still present today. The natural history of CF is a slow decline in lung function punctuated by episodes of increased respiratory symptoms, termed pulmonary exacerbations. These exacerbations are associated with reduced lung function, lower quality of life and increased mortality. The second part of this thesis describes the investigation of clinical and sputum factors that may influence the time between pulmonary exacerbations. The study showed that female gender, increased bacterial load in a patient's sputum and shorter duration of infection with the bacterium Pseudomonas aeruginosa are independent predictors for a shorter time to next the exacerbation. The third part of this thesis focuses on respiratory infection with P. aeruginosa, a key pathogen in CF. These bacteria thrive in the warm, moist environment of the CF airways where they form antibiotic resistant biofilms. As a community, the bacteria co-operative with each other to sense and respond to changes in environmental stimuli using a cell-to-cell communication system, known as quorum sensing (QS). QS 'signal' molecules have been detected in the sputum and plasma of patients with CF but little is understood about their clinical significance in the human host. This thesis describes a prospective observational clinical study showing that: (1) QS signal 2 molecules can be detected in the sputum, plasma and urine of patients with CF; (2) QS signal concentrations in the sputum, plasma and urine are correlated with quantitative measures of P. aeruginosa in the lung and (3) QS signal molecules have significant potential as biological markers for lung infection with P. aeruginosa. Overall, this thesis highlights several clinical factors associated with increased morbidity and mortality in CF patients and the potential use of biological markers of infection to measure and improve respiratory outcomes in future. It concludes by reflecting on the clinical significance of these observations and considering future areas of research that may increase our understanding of the biological processes involved. 3
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.606574  DOI: Not available
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