Lack of association between beta-herpesvirus infection and bronchiolitis obliterans syndrome in lung transplant recipients in the era of antiviral prophylaxis.
BACKGROUND
Cytomegalovirus (CMV), human herpesvirus-6 and -7 (HHV-6 and -7) are beta-herpesviruses that commonly reactivate and have been proposed to trigger acute rejection and chronic allograft injury. We assessed the contribution of these viruses in the development of bronchiolitis obliterans syndrome (BOS) after lung transplantation.


METHODS
Quantitative real-time polymerase chain reaction of bronchoalveolar lavage samples were performed for CMV, HHV-6 and -7 in a prospective cohort of lung transplant recipients. A time-dependent Cox regression analysis was used to correlate the risk of BOS and acute rejection in patients with and without beta-herpesviruses infection.


RESULTS
Ninety-three patients were included in the study over a period of 3 years. A total of 581 samples from bronchoalveolar lavage were obtained. Sixty-one patients (65.6%) had at least one positive result for one of the beta-herpesviruses: 48 patients (51.6%) for CMV and 19 patients (20.4%) for both HHV-6 and -7. Median peak viral load was 3419 copies/mL for CMV, 258 copies/mL for HHV-6, and 665 copies/mL for HHV-7. Acute rejection (>or=grade 2) occurred in 46.2% and BOS (>or=stage 1) in 19.4% of the patients. In the Cox regression model the relative risk of acute rejection or BOS was not increased in patients with any beta-herpesviruses reactivation. Acute rejection was the only independently associated risk factor for BOS.


CONCLUSIONS
In lung transplant recipients receiving prolonged antiviral prophylaxis, reactivation of beta-herpesviruses within the allograft was common. However, despite high viral loads in many patients, virus replication was not associated with the development of rejection or BOS.
Manuel
Oriol
O
Transplant Infectious Diseases, University of Alberta, Edmonton, AB, Canada.
Kumar
Deepali
D
Moussa
George
G
Chen
Maggie H
MH
Pilewski
Joseph
J
McCurry
Kenneth R
KR
Studer
Sean M
SM
Crespo
Maria
M
Husain
Shahid
S
Humar
Atul
A
D000328:Adult; D000935:Antifungal Agents / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use*; D001989:Bronchiolitis Obliterans / Q000150:complications / Q000453:epidemiology* / Q000601:surgery*; D003587:Cytomegalovirus / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000453:epidemiology / Q000517:prevention & control*; D004359:Drug Therapy, Combination; D005260:Female; D015774:Ganciclovir / Q000031:analogs & derivatives / Q000627:therapeutic use; D006084:Graft Rejection / Q000453:epidemiology; D015654:Herpesvirus 6, Human / Q000302:isolation & purification; D016199:Herpesvirus 7, Human / Q000302:isolation & purification; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016040:Lung Transplantation / Q000009:adverse effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011743:Pyrimidines / Q000627:therapeutic use; D013577:Syndrome; D014230:Triazoles / Q000627:therapeutic use; D000077562:Valganciclovir; D065819:Voriconazole
D000935:Antifungal Agents; D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D011743:Pyrimidines; D014230:Triazoles; D000077562:Valganciclovir; D065819:Voriconazole; D015774:Ganciclovir