Incidence, Risk Factors and Outcomes of Delayed-onset Cytomegalovirus Disease in a Large Retrospective Cohort of Lung Transplant Recipients

Abstract

Background: Cytomegalovirus (CMV) replication and disease commonly occur in lung transplant recipients after stopping anti-CMV prophylaxis. The epidemiology of CMV disease is not well studied, given the difficulties in assembling representative study populations with prolonged follow-up. We hypothesized that delayed-onset CMV disease (>100 days after transplantation) occurs more commonly than early-onset CMV disease in lung transplant recipients, and is associated with an increased risk of death.

Methods: We assembled a large cohort of lung transplant recipients using 2004 to 2010 International Classification of Diseases, Ninth Revision, Clinical Modification billing data from 3 Agency for Healthcare Research and Quality State Inpatient Databases, and identified demographics, comorbidities, CMV disease coded during hospital readmission and inpatient death. We used Cox proportional hazard multivariate analyses to assess for an independent association between delayed-onset CMV disease and death.

Results: In the cohort of 1528 lung transplant recipients from 12 transplant centers, delayed-onset CMV disease occurred in 13.7% (n = 210) and early-onset CMV disease occurred in 3.3% (n = 51). Delayed-onset CMV pneumonitis was associated with inpatient death longer than 100 days after transplantation (adjusted hazard ratio, 1.6; 95% confidence interval [95% CI], 1.1-2.5), after adjusting for transplant failure/rejection (aHR, 2.5; 95% CI, 1.5-4.1), bacterial pneumonia (aHR, 2.8; 95% CI, 2.0-3.9), viral pneumonia (aHR, 1.5; 95% CI, 1.1-2.1), fungal pneumonia (aHR, 1.8; 95% CI, 1.3-2.3), single lung transplant (aHR, 1.3; 95% CI, 1.0-1.7), and idiopathic pulmonary fibrosis (aHR, 1.4; 95% CI, 1.0-1.8).

Conclusions: Delayed-onset CMV disease occurred more commonly than early-onset CMV disease among lung transplant recipients. These results suggest that delayed-onset CMV pneumonitis was independently associated with an increased risk of death.

Figure 1

Time (days) to inpatient death > 100 days post-transplant in a cohort of adult lung transplant recipients, stratified according to presence or absence of delayed-onset CMV disease (A), bacterial pneumonia (B), viral pneumonia (C) and fungal pneumonia (D).