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Title: Endogenous nitric oxide production in airways of patients with cystic fibrosis
Author: Ho, Ling-Pei
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1999
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Nitric oxide (NO) is a highly reactive molecule with physiological and pathological roles in the airways. This thesis first investigated the production of NO in the airways of cystic fibrosis patients compared to normal and asthmatic subjects after validating a method to measure this which excluded known confounding factors. The first finding was that exhaled NO, against expectation were not increased in cystic fibrosis patients, even during infective exacerbations. I hypothesised that this could be due to lack of detection of NO (secondary to removal of NO by reaction with other reactive molecules and/or impedance of diffusion of this gaseous molecule into the airway) or lack of production (secondary to decreased expression of nitric oxide synthase II (NOS II), the gene thought to be responsible for NO production within an inflammatory setting). The thesis thus explored these possibilities by investigating a) exhaled NO levels in patients with bronchiectasis, a group of patients with similar suppurative airway disease to cystic fibrosis b) breath condensate levels of hydrogen peroxide, another highly reactive volatile molecule in cystic fibrosis patients compared to normal subjects c) expression of NOS II in cystic fibrosis and nominal primary epithelial cells and epithelial cell lines at baseline and in response to pro inflammatory stimuli and d) nitrite levels in breath condensate of CF patients. In order to perform the above, methods for measuring hydrogen peroxide and nitrite in breath condensate were developed. The correlation between the levels of these molecules and lung function and circulating leucocytes were also determined. The thesis found that like exhaled gaseous NO, hydrogen peroxide levels were not elevated in exhaled air of patients with CF. However nitrite levels were increased and this correlated with the levels of circulating leucocytes. The expression of NOS II were normal in primary cystic fibrosis epithelial cells and epithelial cell lines in vitro. Therefore, it is concluded that exhaled NO is not helpful as a marker of airways inflammation in chronic suppurative airway diseases of cystic fibrosis and bronchiectasis. This is likely to be due to lack of detection rather than production of NO from the epithelium. Breath condensate nitrite levels may be a more useful tool for measuring airways inflammation in these conditions and further developments in this area are suggested.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral