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 single-center cohort (n = 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 = 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 = 0.001; hazard ratio, 2.19; 95% confidence interval, 1.36-3.51) and post-transplantation death (P = 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.

Figure 1.

Cytomegalovirus pneumonitis (CMV-P) within 6 months of transplantation increases the risk for bronchiolitis obliterans syndrome (BOS) (P = 0.0009; unadjusted hazard ratio, 2.19; 95% confidence interval, 1.36–3.51). Numbers under the graph indicate the recipients at risk for BOS and those who had developed BOS (failed) at each time point for CMV-P.

Figure 2.

Cytomegalovirus pneumonitis (CMV-P) within 6 months of transplantation increases the risk for death (P = 0.018; unadjusted hazard ratio, 1.89; 95% confidence interval, 1.11–3.23). Numbers under the graph indicate the recipients at risk for death and those who had died (failed) at each time point for CMV-P.