Chronic lung disease is a very common cause of morbidity and mortality across Europe. For example, chronic obstructive pulmonary disease (COPD) causes over 30,000 deaths/year in the UK with a rising incidence and it is estimated that by 2020 COPD will become the third leading cause of death and the fifth leading cause of chronic disability worldwide. In the EU approximately 41,300 lost work days per 100’000 population are due to COPD while productivity losses amount to €28.5 billion annually and patient care totals €10.3 billion annually. To date, therapies to limit/reverse fibrosis in the lung have failed to provide long-term beneficial effects and new therapeutic targets are desperately needed. The work proposed in this application will allow me to investigate the role of the immune system in general, and more specifically the macrophage, in fibrosis and identify new therapeutic targets. The themes highlighted in this proposal complement priority areas identified within the FP7: Health program including Innovative therapeutic approaches and intervention and Translational research in major diseases. In this fellowship I will investigate the role of cellular immunity and in particular the macrophage in orchestrating the environment in the lung that determines the fibrotic response to injury. I will investigate whether specific macrophage phenotypes contribute to loss of function by driving aberrant epithelial repair and fibrotic remodeling in the lung. I hypothesis that manipulation of lung macrophage phenotype by treatment with azithromycin may limit fibrosis in the lung.
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