An exploration of asthma phenotypes

In this thesis the long term stability of eosinophilic bronchitis has been investigated in a longitudinal study. Induced sputum has been used to investigate a possible difference in expression of IL-13 in asthma and eosinophilic bronchitis. Bronchoscopy has been used to compare the airway immunopathology of eosinophilic and non eosinophilic asthma and the long term stability and response to inhaled corticosteroids in non eosinophilic asthma was studied in a prospective randomised controlled trial. Alveolar nitric oxide concentration has been validated as a measure of distal lung inflammation. Finally the role of TNF-alpha and response to etanercept has been investigated in patients with refractory asthma. Evolution from eosinophilic bronchitis into asthma was rare, decline in lung function was not increased, although female gender, smoking and prolonged eosinophilic airway inflammation were independent risk factors for an accelerated decline. IL-13 concentrations were elevated in asthma compared to eosinophilic bronchitis, suggesting a role for this cytokine in the development of airway hyperresponsiveness. Non eosinophilic asthma remained stable over the period of investigation and was associated with reduced response to inhaled corticosteroids. Mast cells were present in airway smooth muscle in eosinophilic and non eosinophilic asthma but not normal controls. Subepithelial layer thickening was a feature of eosinophilic but not non eosinophilic asthma. Alveolar nitric oxide was increased in refractory asthma and reduced by oral but not inhaled corticosteroids.