Bronchiolitis obliterans syndrome and early human cytomegalovirus DNAaemia dynamics after lung transplantation.
BACKGROUND
Bronchiolitis obliterans syndrome (BOS) remains a major cause of morbidity and mortality after lung transplantation. The major identified risk factors for BOS are acute rejection and human cytomegalovirus (HCMV) infection, the latter despite the use of relatively insensitive and nonspecific measures such as HCMV pneumonitis and HCMV serostatus, respectively. We hypothesized that a more accurate prospective analysis of HCMV reactivation in lung transplant recipients (LTRs) would improve our understanding of the association between HCMV and BOS development.


METHODS
In 26 LTRs, HCMV DNAaemia was measured using quantitative polymerase chain reaction at monthly intervals during the initial 6 months posttransplantation. BOS was defined as a sustained irreversible 20% decrease in FEV1 compared with the best baseline FEV1 posttransplantation in the absence of any other cause.


RESULTS
Of the 26 LTRs, 23 were assessable with regard to the BOS outcome variable. At a median follow-up of 37 months, 10 patients had developed BOS. During the first 6-month monitoring period, HCMV DNAaemia was detected in 15 of the 23 patients on at least one occasion, and there were 12 episodes of HCMV pneumonitis in eight patients. Episodes of grade A3 or greater acute rejection occurred in eight LTRs, six of whom had been HCMV DNAaemia positive at least once and four of whom also demonstrated HCMV pneumonitis. Our results revealed a strong association between BOS and early HCMV DNAaemia detection (univariate analysis [P=0.002] and freedom from BOS analysis [P=0.006]).


CONCLUSIONS
Early HCMV DNAaemia in LTRs is associated with the development of BOS despite routine ganciclovir prophylaxis.
Westall
Glen P
GP
Department of Respiratory Medicine, Alfred Hospital, Prahan, Melbourne, Australia.
Michaelides
Alexandra
A
Williams
Trevor J
TJ
Snell
Greg I
GI
Kotsimbos
Thomas C
TC
D000328:Adult; D000704:Analysis of Variance; D000998:Antiviral Agents / Q000627:therapeutic use; D001989:Bronchiolitis Obliterans / Q000453:epidemiology* / Q000401:mortality; D015331:Cohort Studies; D003587:Cytomegalovirus / Q000235:genetics / Q000302:isolation & purification*; D003586:Cytomegalovirus Infections / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology; D004279:DNA, Viral / Q000097:blood*; D018572:Disease-Free Survival; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use; D006801:Humans; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011183:Postoperative Complications / Q000453:epidemiology*; D012189:Retrospective Studies; D013997:Time Factors
D000998:Antiviral Agents; D004279:DNA, Viral; D015774:Ganciclovir