Chronic obstructive pulmonary disease (COPD) is an inflammatory disease of the lungs which results in the narrowing of the airway, making breathing more difficult for sufferers. The primary cause of this condition is smoking, and it is the third largest cause of death in Ireland. COPD causes patients to become more susceptible to severe infections, which can be life threatening. One reason why these individuals may be more susceptible to infection is linked to excessive iron deposition inside their alveolar macrophages (AMs), immune cells that fight infection. Prof. Patrick Mitchell, supervisor of this project along with Dr Natalia Munoz-Wolf (HRB awardee) and Prof. Suzanne Cloonan have recently established the first ever human COPD research study at Tallaght University Hospital (Ethics Approval Number: 3620). They have preliminary data to show that lowering iron levels inside the AMs isolated by bronchoscopy from subjects enrolled in this lowers their susceptibility to infection with Streptococcus pneumoniae, a bacterium commonly associated with COPD disease flare-ups.
The aim of this research project is to build on these preliminary findings and utilise an iron chelator termed deferiprone, as a therapeutic intervention for AMs already infected with S. pneumoniae. This is based on the hypothesis that anaerobic bacteria such as S. pneumoniae utilize iron as a form of nutrition and such high levels of iron in the AMs of COPD subjects accelerates the growth of these bacteria inside AMs. Our secondary hypothesis is that administering the iron chelator deferiprone to infected macrophages will reduce bacterial burden and enhance host response to infection.