Viral Respiratory Tract Infection During the First Postoperative Year Is a Risk Factor for Chronic Rejection After Lung Transplantation

Magnusson, Jesper; Westin, Johan; Andersson, Lars-Magnus; Lindh, Magnus; Brittain-Long, Robin; Nordén, Rickard; Riise, Gerdt C.

Background. Chronic lung allograft dysfunction (CLAD) is the major limiting factor for long-term survival in lung transplant recipients. Viral respiratory tract infection (VRTI) has been previously associated with CLAD development. The main purpose of this study was to evaluate the long-term effects of VRTI during the first year after lung transplantation in relation to CLAD development. Method. Ninety-eight patients undergoing lung transplantation were prospectively enrolled between 2009 and 2012. They were monitored for infections with predefined intervals and on extra visits during the first year, the total follow-up period ranged between 5 and 8 years. Nasopharyngeal swab and bronchoalveolar lavage samples were analyzed using a multiplex polymerase chain reaction panel for respiratory pathogens. Data regarding clinical characteristics and infectious events were recorded. Results. Viral respiratory tract infection during the first year was identified as a risk factor for long-term CLAD development (P = 0.041, hazard ratio 1.94 [1.03-3.66]) in a time-dependent multivariate Cox regression analysis. We also found that coronavirus in particular was associated with increased risk for CLAD development. Other identified risk factors were acute rejection and cyclosporine treatment. Conclusions. This study suggests that VRTI during the first year after lung transplantation is associated with longterm CLAD development and that coronavirus infections in particular might be a risk factor. L ung transplantation (LTx) is the only available therapeutic option for end-stage, nonmalignant lung disease. The yearly number of procedures has increased, but long-term survival has not improved markedly over the years. 1 The main limiting factor for long-term survival is chronic lung allograft dysfunction (CLAD), commonly in the form of bronchiolitis obliterans syndrome (BOS). 1 In recent years, restrictive allograft syndrome has also gained recognition. 2 The underlying pathophysiology of CLAD development is multifactorial and infections are a major risk factor. 3 Other risk factors include acute rejection (AR), antibody-mediated rejection, gastroesophageal reflux, and air pollution exposure. 4 The importance of viral respiratory tract infections (VRTI) for CLAD development and graft loss has been highlighted. [5] [6] [7] [8] However, a meta-analysis of 34 articles was unable to establish an association between VRTI and CLAD or graft loss, 9 possibly due to differences in diagnostic methods between the included studies. More recently, the development of multiplex real-time polymerase chain reaction (PCR) methods has promoted a more sensitive and a standardized detection of respiratory viral agents. 10 We previously showed an association between detection of viral pathogens in bronchoalveolar lavage (BAL) samples taken during the first year after LTx and the development of BOS. 11 Others have recently reported an increased risk of CLAD after VRTI, 12, 13 but the long-term effects of early VRTI as well as the importance of VRTI compared with other risk factors remain unclear.