| Summary: | Background Airways diseases are increasingly recognised to be poorly defined phenomena with overlapping pathophysiology and symptoms. They are a significant and growing cause of morbidity, with increasing numbers of people affected globally and no improvement in key outcomes in the UK for the last decade despite ever increasing expenditure. The classification of airway diseases has changed little in the last 50 years, and may no longer be fit for purpose due to the growing appreciation of the complexity and heterogeneity of airways disease and the advent of molecular-based diagnostic techniques to target specific treatment. Aim To investigate whether strategies based on the measurement of selected phenotypic and biological characteristics of airways disease can help to improve the understanding of their pathogenesis and targeting of treatment. Methods Three characteristics of airways disease, namely (1) exhaled nitric oxide, (2) chronic productive cough of unknown cause and (3) the airway microbiota were described/measured in selected cohorts of patients in three clinical studies. Measurement of each of these characteristics was used to answer focused clinical questions regarding the pathogenesis and treatment of aspects of airways disease. Results (1) The baseline measurement of FENO in steroid naïve subjects with symptoms suggestive of asthma had a low diagnostic value for asthma but was an excellent predictor of inhaled steroid treatment response. (2) A cohort of subjects with chronic productive cough of unknown cause was described. These subjects tended to have radiological evidence of airway dilatation and chronic inflammatory changes but not significant bronchiectasis. Their cough responded well to treatment with azithromycin, with ongoing neutrophilic airway inflammation a particularly strong predictor of treatment response. (3) There were no significant differences in the abundance or community structure of the bacterial communities in the airways between subjects with mild (BTS 2) or severe (BTS 4) asthma or between severe (BTS 4) asthma patients taking inhaled fluticasone or budesonide. However a number of differences in relative abundance of certain species (including enrichment of Haemophilus parainfluenzae in the fluticasone group) were noted on comparison of the groups. Conclusions This thesis provides support for a new approach to the classification and treatment of airways disease. The recognition of pathologically important processes (treatable traits) which can be used to predict response to targeted treatment has the potential to revolutionise the management of airways disease and result in improved patient outcomes.
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