Respiratory viruses and chronic rejection in lung transplant recipients.
BACKGROUND; Chronic rejection manifested as obliterative bronchiolitis (OB) and bronchiolitis obliterans syndrome (BOS) continue to be major causes of morbidity and mortality after lung transplantation. Community respiratory virus (CRV) infection, including respiratory syncytial virus, parainfluenza virus, and influenza virus, can infect and also cause morbidity in lung transplant recipients. Because CRV and OB/BOS affect the small airways, we sought to determine whether CRV infections predisposed patients to OB/BOS.


METHODS
To determine whether CRV predisposed to OB/BOS, a proportional hazards regression analysis of time to OB/BOS was performed with CRV as a time-dependent covariate. To determine the influence of OB/BOS on the subsequent development of CRV infection, we reversed the outcome and time-dependent covariate. To illustrate the effect of CRV on OB/BOS and the effect of OB/BOS on CRV, landmark plots were generated at specific time points. Time to development of OB/BOS was then compared using the Kaplan-Meier method.


RESULTS
In our institution, we documented 40 infections caused by CRV in 33 lung transplant recipients during an 11-year period. Community respiratory virus infections occurred predominantly during seasonal community outbreaks, except for parainfluenza infections, which occurred throughout the year. The diagnosis of OB/BOS occurred throughout the year and was not associated with seasonal outbreaks of CRV. Community respiratory virus infection involving both upper and lower respiratory tracts did not predispose to OB or BOS (relative risk [RR], 1.1; 95% confidence interval [CI], 0.52-2.3; p = 0.81). However, patients with documented CRV infection of the lower respiratory tract were predisposed to high-grade BOS development (RR, 2.3; 95% CI, 1.1-4.9; p = 0.04). In addition, a patient with pre-existing OB or BOS was predisposed to developing both upper and lower respiratory tract infection with CRV (RR, 4.2; 95% CI, 1.9-9.4; p < 0.001).


CONCLUSIONS
Patients with CRV infection of the lower respiratory tract were predisposed to high-grade BOS development, and patients with OB and BOS were predisposed to CRV infections.
Billings
Joanne L
JL
Division of Pulmonary, Allergy and Critical Care, Department of Medicine, Minneapolis, Minnesota 55455, USA. billi001@tc.umn.edu
Hertz
Marshall I
MI
Savik
Kay
K
Wendt
Christine H
CH
D017714:Community-Acquired Infections / Q000821:virology; D006084:Graft Rejection / Q000473:pathology / Q000821:virology*; D006801:Humans; D016040:Lung Transplantation; D008875:Middle Aged; D009894:Opportunistic Infections / Q000821:virology*; D011183:Postoperative Complications; D015995:Prevalence; D016016:Proportional Hazards Models; D012141:Respiratory Tract Infections / Q000453:epidemiology / Q000821:virology*; D012189:Retrospective Studies; D012621:Seasons