The BACTERIA-INFLAMMATION-REJECTION AXIS IN CHRONIC LUNG ALLOGRAFT DYSFUNCTION

Chronic lung allograft dysfunction (CLAD) remains the major long term complication after lung transplantation with a 5- year incidence of 50%, leading to loss of quality of life and increased mortality. Although azithromycin, a neomacrolide antibiotic, increases CLAD-free survival, a large proportion of patients nevertheless develop CLAD (either bronchiolitis obliterans syndrome, BOS or restrictive allograft syndrome, RAS). Within this project, we will investigate, by next-generation sequencing tools, the association between the microbiome, inflammation and CLAD. Using already collected patients samples from our biobank, we will 1/ investigate the change in microbial content in the post-transplant follow-up (with special consideration for CLAD) and the effect of prophylactic azithromycin on the lung allograft microbiome and the association with inflammation. 2/ Assess the microbiome in explant CLAD specimens (either BOS or RAS) and compare this to unused donor lungs with specific attention to the regional variety within the lung. Using immunohistochemistry, we will relate the microbiome to the host response and determine if certain microbes trigger more pronounced or a specific type of immune response. This knowledge will be crucial to obtain novel insights into the pathophysiology of CLAD post lung transplantation.