Cytomegalovirus Pneumonitis Is a Risk for Bronchiolitis Obliterans Syndrome in Lung Transplantation

Abstract

Rationale: Cytomegalovirus pneumonitis is one of the most prevalent opportunistic infections after lung transplantation. Early studies reported that cytomegalovirus pneumonitis was a risk factor for chronic allograft dysfunction. More recently, in the era of routine prophylaxis and ganciclovir treatment, the adverse impact of treated cytomegalovirus pneumonitis on bronchiolitis obliterans syndrome has been challenged. Objectives: We hypothesized that cytomegalovirus pneumonitis contributes to adverse outcomes in the current antiviral era. We sought to define the impact of treated cytomegalovirus pneumonitis on bronchiolitis obliterans syndrome and survival in a large singlecenter cohort (n 5 231) of consecutive patients undergoing lung transplantation from 2000 to 2004, all receiving short-course ganciclovir prophylaxis. Methods: Transbronchial biopsies were performed at defined intervals with prospective cytomegalovirus immunostaining on every biopsy (n 5 1,887). Cox proportional hazards models were used to assess the relationship between treated cytomegalovirus pneumonitis and clinical outcomes. Measurements and Main Results: Forty-nine (21%) recipients developed cytomegalovirus pneumonitis a median of 106 days after transplantation. Treated cytomegalovirus pneumonitis within the first 6 months after transplantation significantly increased the risk for bronchiolitis obliterans syndrome (P 5 0.001; hazard ratio, 2.19; 95% confidence interval, 1.36-3.51) and post-transplantation death (P 5 0.02; hazard ratio, 1.89; 95% confidence interval, 1.11-3.23). This risk persisted when cytomegalovirus pneumonitis was considered as a time-dependent predictor as well as in multivariable models controlling for other risk factors. Conclusions: Cytomegalovirus pneumonitis affects more than 20% of lung transplant recipients. Despite treatment, it increases the risk for bronchiolitis obliterans syndrome and death. More effective preventive strategies for cytomegalovirus pneumonitis are needed to improve long-term outcomes after lung transplantation.

Small airways diseases, excluding asthma and COPD: an overview

“…Development of class I or class II donor-specific anti-human leukocyte antigen (HLA) antibodies is also associated with an increased risk of BOS [99]. Cytomegalovirus (CMV) pneumonia and CMV mismatch between CMV-positive donor and CMV-negative receivers have been associated with BOS in some [100], but not all, studies [101]. Community-acquired respiratory virus infections have also been associated with BOS [102], although a recent meta-analysis did not confirm this association [103], probably due to the heterogeneity of published studies.…”

Overview of Clinical Lung Transplantation

“…Primary graft dysfunction, viral and bacterial infections of the graft, and gastroesophageal reflux and aspiration have been shown to predispose a graft toward CLAD Botha et al 2008;Snyder et al 2010). It is thought that these processes, in addition to damaging the graft directly, activate innate immune processes, which then propagate the injury via the adaptive immune system .…”

Polyfunctional T-Cell Signatures to Predict Protection from Cytomegalovirus after Lung Transplantation

“…Lung transplantation recipients are at the highest risk for CMV, with a significant number of at-risk patients developing infection or disease, particularly after prophylaxis ends. In a lung transplantation recipient, a single episode of CMV infection, even with current treatments, significantly increases the risk for chronic allograft dysfunction and death (3)(4)(5).…”