Investigating the infection-rejection axis after lung transplantation

Long-term survival after LTx is limited, mainly attributed to the development of chronic lung allograft dysfunction (CLAD). In this doctoral thesis we investigated (i) CLAD, (ii) microbial invasion of the lung allograft as main risk factor for CLAD, and the interaction between both. We ultimately aimed for (iii) handling microbial invasion, preventing CLAD and improving long-term survival. In chapter 3A, the importance of an accurate diagnosis of the different obstructive and restrictive CLAD phenotypes has been highlighted. Identifying homogenous patient populations is of great importance for the set-up of clinical trials, to guide future therapeutic approaches and to inform patients about their prognosis. In addition, a chest CT at bronchiolitis obliterans syndrome (BOS) diagnosis, analysed via an adapted Brody score and subscores, provides extra prognostic information, as shown in chapter 3B. Moreover, in response to this study, it can be hypothesized that BOS is not a homogenous patient group, but includes at least 2 different endotypes with a distinct prognosis: one "wet" endotype and one "dry" endotype. Microbial invasion of the allograft with Pseudomonas aeruginosa (PA) is associated with worse CLAD-free and graft survival. These established findings were confirmed in our LTx population in chapter 4. Additionally, eradication treatment of PA after LTx was associated with improved CLAD-free and graft survival. Therefore, early detection and treatment of PA (and possibly other infections) might be an important therapeutic strategy in the future to prevent CLAD and improve graft survival. Finally, in Chapter 5, early treatment with azithromycin after LTx has been investigated. The primary endpoint, improving early pulmonary function after LTx, was not reached. However, the anti-inflammatory activity of azithromycin was confirmed. In addition, long-term azithromycin treatment has previously been shown to prevent CLAD and to improve pulmonary function in established CLAD. Therefore, azithromycin should still be considered an important (early) treatment option for (preventing) CLAD.status: publishe