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.

We found no association between lower VRTI and CLAD in contrast to previous findings. However, the survey bronchoscopies that detected lower VRTI with a simultaneous finding of the same virus in upper airways were performed on asymptomatic patients in 70% of the cases. It is likely that some of the patients with asymptomatic upper VRTI, detected at surveillance sampling without bronchoscopy, also had a lower VRTI thus the true impact of lower VRTI may have been underestimated. A hypothetic mechanism for the graft damage is a disturbed repair mechanism due to decreased regulatory T (Treg) cell activity caused by the immunosuppressive treatment. A function of Treg cells is to suppress proliferation of fibroblasts triggered by cytotoxic T cells (CD8+ T cells) attacking infected respiratory epithelial cells. An absence of Treg cells in immunosuppressed patients might lead to poor control of inflammatory responses and dysregulated epithelial repair mechanisms. 28 Thus, immune response induced by VRTI early after lung transplant might not stop with clearance of the virus and cause epithelial injury and fibroproliferation leading to reduced lung function and CLAD. 29 This study has several limitations. First, the study was designed before the release of the standardization of definitions of infections in cardiothoracic transplant recipients, released by International Society for Heart and Lung Transplantation in 2011, 30 which would have been preferable for future reference. Only episodes that resulted in contact with a physician were recorded in the case report form, and no systematically recorded clinical data, except spirometry data, were available from these visits. The study did not evaluate other known risk factors, such as gastroesophageal reflux or environmental pollution exposure after LTx. Furthermore, with respect to the high number of asymptomatic VRTIs, it would have been preferable to keep sampling intervals constant, as increased time between sampling at end of the first year might introduce a bias toward the effect of early infections. More frequent surveillance bronchoscopies to analyze the frequency of asymptomatic lower VRTI after LTx would also have been preferable. No viral sequencing was performed which makes it difficult to be certain whether the 19 patients with the same virus in sequential samples suffered from persistent infections or experienced multiple reinfections with different subtypes of virus.