Azithromycin, Oesophageal Function, and Cough in Chronic Respiratory Disease

Chronic cough is a disabling feature of many chronic respiratory diseases and is now recognised as a distinct disease. Despite being amongst the commonest causes for healthcare contact, there are no licenced treatments for chronic cough in the UK. The role of the gut-lung axis in respiratory disease is increasingly recognised. However, much of the current research has been centred around gastro-oesophageal reflux disease, with little research on the potential co-existence of oesophageal dysfunction in chronic respiratory conditions. The macrolide antibiotic azithromycin is used to prevent exacerbations in various respiratory diseases; however, its mechanism of action remains unclear. It is known that azithromycin improves gastrointestinal motility through agonism of motilin receptors. We hypothesise that this mechanism may contribute to the beneficial effects of azithromycin.
In this thesis we aimed to explore different elements of this hypothesis through multiple methodologies. First, we establish the prevalence of oesophageal dysmotility in respiratory disease through a retrospective analysis of high-resolution oesophageal manometry (HROM) studies in patients with persistent respiratory symptoms. We then perform a systematic review and meta-analysis to examine the effect of azithromycin on objective and subjective measures of cough in patients with chronic respiratory disease. Using the established methodology of a feasibility study, we evaluate the practicability of performing repeated HROM measures and continuous cough monitoring in patients with chronic respiratory disease. Finally, we perform an exploratory analysis of the effect of azithromycin on continuously recorded objective cough frequency using both traditional and novel methods of cough analysis.
We have addressed multiple aspects of our hypothesis with the studies conducted in this thesis. We have highlighted the high prevalence of oesophageal dysmotility in those with chronic cough and shown that azithromycin has shown early promise as a potential antitussive agent. Moreover, we demonstrate that using both HROM and continuous cough monitoring is feasible and acceptable to patients. This study provides rationale for a large-scale, randomised controlled trial using mixed methodologies to investigate azithromycin's potential as a treatment for chronic cough.