Birgitta Versluijs

162 Predictors for allo-LS With regard to the role of GVHD in Allo-LS, our results are in strong contrast with the other publications. We found that treatment of aGVHD (II-IV) was protective for Allo-LS (OR 0.1, 95%CI 0.02-0.47, p=0.004). In our cohort of patients, with a high prevalence of RV and a high incidence of Allo-LS related to RV, prior aGVHD requiring systemic steroid therapy prevented the development of Allo-LS. This could be explained as fol- lows. Tissue damage by RV makes the lung a target for allo-immunity. However in case of prior GVHD in another organ, as gut and skin seem to be preferential target organs for GVHD, increased immunosuppression will have a preventive effect, hampering the immune damage in the lung. Why study respiratory viruses after lung transplantation and HCT? We started studying the role of RV in immune mediated lung disease after HCT, inspired by publications on RV after lung transplantation. There is an obvious analogy between immune mediated lung problems after HCT (graft versus host) and graft rejection after lung transplantation (host versus graft). HLA dis- parity between donor and recipient, with the lung as the target organ for inflammation, is comparable to a certain extent. However in lung transplant immune tolerance will not occur, because the recipients’ immune system does not have mechanisms to induce immunity for the allograft. So, in contrast with HCT, prolonged immunosuppression is always needed, and graft survival is relatively short with allo-immunity and graft rejec- tion occurring very often. 22,23 Despite this difference, much can be learnt from pathophy- siology and treatment of acute and chronic rejection in lung transplantation. Kumar et al. showed that community acquired RV infection in the first 100 days after lung transplantation predisposed for immune mediated graft rejection(24). As described in Chapter 3 and Chapter 7 we found that the presence of a respiratory virus (RV) prior to HCT is an important risk factor for developing Allo-LS. And when we analyzed the data from paired NPA and Broncho Alveolar Lavage (BAL) samples, this association seemed particularly true for RV from pre-HCT BAL. Our hypothesis is that RV gives epithelial da- mage and triggers the allogeneic immune response leading to severe lung disease. In our opinion lung disease does not occur primarily from progressive viral infection during the period of low immunity, but from allo-immune mediated damage weeks after HCT. This hypothesis should largely influence the therapeutic decision of delaying transplant, treating RV and most important increasing or decreasing immune suppression after transplant. Respiratory viruses and progressive infection There are many reports on RV prior to, or early after, HCT. Most studies discuss the risk of progressive pneumonia, for various types of RV. Only few groups looked at long term outcome. Results are conflicting, reported risk of progression is 5-75%. 25-27 In general 9