Investigate the impact of bile aspiration on chronic respiratory infection - bile paradigm

This study proposes to investigate the unexplained link between gastro-oesophageal reflux (GOR) and severe respiratory disease. During GOR, bile, normally found in the duodenum and stomach, is refluxed to the throat and subsequently aspirated into the airways and lungs of patients. A high prevalence of this phenomenon is seen in patients with respiratory disease, with the highest incidence observed in cystic fibrosis (CF), a life threatening disease, characterised by persistent lung infections that are practically impossible to eradicate. Recent research in the BIOMERIT Research Centre (BRC) demonstrated that bile can influence the virulence behaviour of bacteria responsible for these persistent lung infections. While to date, bile aspiration has been linked with reduced lung function, inflammation, and other complications in patients with respiratory disease, its impact on the microbiology of the lung has not been investigated.
Therefore, we propose to compare the bacteria present in lung fluids of CF patients with, and without, bile aspiration. Diagnostic technologies have been developed in the BRC that allow early and rapid detection of aspirated bile in biological samples, including sputum. These technologies are particularly important given the high incidence of symptomless 'silent aspiration' in CF patients, a leading cause of reflux misdiagnosis.
State-of-the-art DNA sequencing technologies that can detect and identify bacteria that can and cannot be grown using conventional methods, will be employed to discover the different types of bacteria that exist in these samples. In tandem, the activity of virulence genes associated with persistent infection will be measured. This will provide insight as to how microbes respond to bile in the respiratory tract. All results will be correlated with the clinical status and disease severity of patients. This work will support the development of innovative strategies to manage and combat respiratory infections, particularly in vulnerable populations such as those with CF.

Award Date: 19 June 2014
Award Value: €108,226
Principal Investigator: Miss Suzanne McCormack
Host Institution: Irish Thoracic Society
Scheme: MRCG-HRB Joint Funding Scheme