Thursday 14 march 2019
12:33 - 12:36h
Categories: Klinisch, Postersessie
Parallel session: Postersessies 4 - Clinical
A.E.S. de Zwart1, A. Riezebos-Brilman2, D. Jochmans3, H.A.M. Kerstjens1, J.W.C. Alffenaar4, J. Neyts3, E.A.M. Verschuuren1.
1Dept. of Pulmonary Diseases and Tuberculosis, University Medical Center Groningen, Groningen,The Netherlands. 2Dept. of Medical Microbiology and Virology, University Medical Center Utrecht, Utrecht,The Netherlands. 3Dept. of Microbiology and Immunology, University of Leuven, Rega Institute, Leuven,Belgium. 4Dept. of Clinical Pharmacy & Pharmacology, University Medical Center Groningen, Groningen,The Netherlands.
Background: Parainfluenza virus (PIV) infections have been recognized as a significant cause of morbidity in the form of Bronchiolitis Obliterans Syndrome (BOS) in lung transplant recipients (LTR).
Methods: We report a bedside to bench and back strategy by using an in vitro model of human airway epithelium cells of bronchial origin (HuAEC) in an air-liquid interface to study the efficacy of experimental PIV-3 inhibitors with subsequent retrospective assessment of the effectiveness of ribavirin treatment in these patients.
Results: 12 LTR were identified with a PIV infection and FEV1 decline of 8.3% (IQR 21%); 9 had BOS grade < 3 of whom 6 developed new or progressive BOS. We then studied the replication of PIV-3 on HuAEC and the antiviral effect of nucleoside analogues. Apical infection of these cultures with a clinical isolate of PIV-3 showed significant viral replication. To explore the effect of antiviral treatment cells were exposed, at the basal site, to nucleosides (100 µM Ribavirin or 100 µM of Favipiravir) from day -2 until day 4 post-infection A clear inhibition (>4 log PIV-RNA reduction) of PIV-3 replication in the presence of Ribavirin could be observed while there was no effect of Favipiravir. When Ribavirin treatment was stopped, PIV-3 replication increased in 48 h to the level of untreated cultures. We then compared outcomes of 21 ribavirin treated vs. the 12 untreated PIV infected LTRs. Overall incidence of new or progressive BOS at 6 mo. post infection was 10/28 (< BOS 3; 36%), with a median FEV1 decline of 4.9% compared to pre-infection (p<0.01). Hospitalization rate was 61% (median 5 d. range 2-49 d.); there were no deaths. At baseline no differences in BOS grade pre-infection, FEV1 decline at presentation, underlying disease, time since transplantation, coinfections, PIV subtype or total delay between the groups were seen. The ribavirin treated group had a significantly lower median FEV1 decline 6 mo. post-infection vs.pre-infection compared to ribavirin untreated LTR (2.9% [IQR 4.7%] vs.8.3% [IQR 21%] p=0.04). Incidence of new or progressive BOS was also significantly lower in the ribavirin group compared to ribavirin untreated (4/19 [21%] vs.6/9 [67%] p=0.04).
Conclusions: In conclusion, in vitroresults of ribavirin are confirmed by observational data of ribavirin on PIV infections in LTR. Preservation of long-term FEV1 in LTR seems a potential benefit of ribavirin but needs to be studied in a larger cohort.