Scripties UMCG - Rijksuniversiteit Groningen
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Ribavirin for paramyxovirus infections in lung transplantation : Efficacy in preventing chronic lung allograft dysfunction in upper- and lower respiratory tract infections

(2017) Zwart, E.A.S. de (Auke)

Lung transplant recipients (LTR) are predisposed to respiratory viral infections due their
immunosuppressive therapy and altered physiology of the transplanted lung.
Paramyxoviruses (PMV) are a family of respiratory viruses and can cause serious morbidity
and mortality in LTR. PMV are increasingly associated with subsequent graft dysfunction and
the development of Bronchiolitis Obliterans Syndrome (BOS). It is unclear however if this
association applies to both upper respiratory tract infections (URTI) and lower tract infections
(LRTI). Ribavirin may help to prevent the development of graft dysfunction, though there is
no consensus over the effectiveness. We analyzed the impact of PMV infections on the graft
function and the effect of ribavirin in both LRTI and URTI. Additionally we studied the
ribavirin treatment regimens used in the UMCG for side effects and efficacy.
We retrospectively studied all PMV infections in LTR in the UMCG from 2008-2016. Graft
function (FEV1) was evaluated at four time-points: pre-infection, at infection, three months
and six months post-infection. Primary endpoint was the FEV1 at six months post-infection,
as percentage of pre-infection FEV1. First the total patient cohort was analysed using a
multivariate model to identify independent factors determining graft function at six months
post infection. Next, patients were divided into patients with an URTI (FEV1 decline <10% at
infection) and patients with a LRTI (FEV1 decline >10% at infection) and subsequently
divided into subgroups depending on whether they received ribavirin in any form or not.
Lastly all patients that had received ribavirin were divided into three groups, depending on the
ribavirin treatment regimen: aerosolized or systemically (high-dose or low dose)
In total 98 PMV cases were included in the study. LRTI was present in 63 cases (64%), of
which 38 received ribavirin and URTI was present in 35 cases (36%), 10 of which received
ribavirin. Lung function decline at presentation and ribavirin use proved to be significant
independent factors predicting post infection FEV1 in the multivariate regression (p<0,01 for
In patients with LRTI, median FEV1 at six months post-infection was significantly
higher in the ribavirin group compared to the non-ribavirin group (98.2% (IQR 8,8) vs. 90.5%
(IQR 15,3) p<0,01). In patients with URTI, FEV1 recovered fully at three months and
sustained at six months after infection, irrespectively of ribavirin treatment (p=0.15). No
significant differences in post-infection FEV1 were found between the different treatment
regimens (p=0,30). High-dose ribavirin seemed to induce a larger drop in haemoglobin
compared to the other regimens.
Ribavirin seemed to have a positive effect on long-term recovery of FEV1 after LRTI with
PMV. Yet, LTR with a PMV causing an URTI, recovered at six months regardless of
ribavirin treatment. Ribavirin was well tolerated, but induced a significant drop in
haemoglobin, with a trend towards a larger drop when high-dose systemic ribavirin was used.
These results support the indication for ribavirin treatment of PMVI in LTR with LRTI,
however a large randomized controlled trial is needed to evaluate the true effectiveness of
ribavirin for PMV infections in LTR.

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