Association between Cytomegalovirus (CMV) and Chronic Lung Allograft Dysfunction (CLAD) in Lung Transplant Recipients

Purpose Bronchiolitis obliterans syndrome (BOS), restrictive allograft syndrome (RAS), and mixed are major phenotypes of CLAD. In previous, older studies, CMV viremia has been associated with reduced survival. We hypothesized that, in a more modern era of CMV prophylaxis, CMV viremia would remain associated with death, but also represent a risk factor for CLAD and specifically RAS/mixed phenotype. Methods This is a retrospective cohort study of all consecutive adult, first, bilateral-/single-lung transplants performed 2010-2016 who had ≥4 pulmonary function tests and ≥1 CMV-PCR measurement. CMV-PCR levels were divided into 3 categories: undetectable, Results Of 645 patients, 257 developed CLAD (143 BOS, 44 RAS/mixed, 66 undefined/unclassified) and 388 were CLAD-free at last follow-up. In univariate analysis, CMV-PCR≥1000 IU/mL was a significant risk factor for CLAD (HR 1.33, p=0.05). In multivariate analysis, CMV-PCR was not a significant risk factor for CLAD, whereas CMV serostatus mismatch was (Table). CMV-PCR was not a significant risk factor for RAS/mixed (CMV-PCR Conclusion CMV viremia was significantly associated with death/re-transplantation. Conversely, CMV viremia was not strongly associated with CLAD or RAS/mixed, while CMV serostatus mismatch was. CMV serostatus mismatch may have an impact on CLAD through mechanisms independent of viremia. In light of these paradoxical results, we are further assessing the relationship between immunosuppression, immune function, and CMV.