Bile Acids as a host trigger of Chronic infecting Pathogens in Respiratory Disease

This study will investigate the unexplained link between bile aspiration and the chronic infection/inflammation characteristic of severe respiratory disease in patients. Despite advances in the clinical management of respiratory disease, patients continue to develop lung damage even from an early age. We know that harmful bacteria contribute to the onset of lung damage, but we are less clear on what causes these harmful bacteria to persist in the lungs of patients with respiratory disorders such as CF and COPD. If we could identify the cause(s) of pathogen persistence, we could identify patients at risk and potentially instigate corrective therapies to counter the development of chronic untreatable infections. This would have a major impact on the quality of life and general health of these patients, and would be predicted to markedly improve their lung function.

Recent research in our ccllaborating centres has demonstrated strong evidence that the aspiration of bile into the respiratory tract may trigger chronic infection/inflammation.

To address this innovative and translational hypothesis, we will use state of the art technologies,clinical trial material and an animal model system to establish the causal link between bile aspiration, chronic infection, and chronic inflammation.This will include a longitudinal study of a large cohort of pediatric CF patients. A new antiinfective therapeutict that we have developed will also be tested in a mouse respiratory disease model for controlling the emergence of difficult to treat Fungal pathogens such as Aspergillus. The direct short term impact of these measures on patient health will be changes in clinical management towards prevention of bile aspiration to avert the onset of chronic infections/inflammation. Longer term impacts will lead to the progression of new intervention targets (molecular or metabolic) to break the link between bile aspiration and lung function decline in respiratory disease.

Award Date

27 June 2019

Award Value

€367,992.30

Principal Investigator

Professor Fergal O'Gara

Host Institution

University College Cork

Scheme

Investigator Led Projects