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Transient Populations of the Human Pulmonary Virome Are Not Associated with Acute Rejection After Lung Transplantation

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A7371 - Transient Populations of the Human Pulmonary Virome Are Not Associated with Acute Rejection After Lung Transplantation
Author Block: A. Mitchell1, B. Mourad2, L. Morgan3, B. Oliver2, A. R. Glanville4; 1Lung Transplant Unit, St.Vincent's Hospital, Sydney, Australia, 2Woolcock Institute, Sydney, Australia, 3Concord Hospital, Sydney, Australia, 4Lung Transplant Unit, St.Vincents Hospital, Sydney, Australia.
Introduction/Aim: Lung transplantation (LTX) provides a unique opportunity to investigate the dynamics of the human pulmonary virome which is transplanted within the donor lungs. The pulmonary virome comprises both resident and transient viruses. Our aim was to analyse the relationship between transient members of the pulmonary virome, predominantly community acquired respiratory viruses (CARV), and outcomes after LTX. Methods: Single center ongoing prospective longitudinal study of pre-LTX nasopharyngeal swabs (NPS), swabs of explanted lung proximal and distal airways, swabs of donor proximal airways and bronchoalveolar lavage (BAL) on post-operative (POD) days 1, 7, 21, 42, 63, 84. Uniplex PCRs were performed for CARV: human rhinovirus (HRV), respiratory syncytial virus (RSV), influenza A, B, (Flu A, B), parainfluenza (PIV) 1, 2, 3 and human metapneumovirus. Results: 70 consecutive LTX were recruited. Outcomes were analysed on the first 52: (bilateral: heart lung: bilateral lung-liver = 48:2:2) (age 48 ± 15 years, mean ±SD) (range 20-63) (M=27). Indications: emphysema (n=20), cystic fibrosis (n=11), chronic lung allograft dysfunction (CLAD) (n=7), pulmonary fibrosis (n=9) and other (n=5). Follow up: 276±125 days, range 37-474. 17/45 explanted lungs examined were positive for Flu (A=14, B=2, A+B=1) despite recipient vaccination and negative NPS while 4 had HRV and 2 PIV. Donor swabs showed Flu (A=1, B=1), and HRV (n=3). Day 1 BAL showed Flu A (n=28), HRV (n=9) and PIV (n=1), 16 of which (Flu A 12, HRV 4) were not detected in the donor or explant. 47/52 recipients had virus positive BAL (38/47 on multiple BAL). 27/52 had Flu persistent for 59 ± 38 days (range 4-147), 14 had a single isolate. 13/52 had HRV persistent for 95 ± 84 days (range 22-174), 13 had a single isolate. 114 paired transbronchial biopsies and BAL were performed. 21/114 had acute cellular rejection (ACR) (Grade A2B0=3, Grade A1B1=6, Grade A1B0=12), 11 of which were virus positive. 93 were negative for ACR (Grade A0B0), 51/93 were virus positive. There was no significant association between concurrent CARV and ACR (Fisher’s exact test, 2 tailed, p=1.00). Conclusion: CARV detection rate was higher than expected and CARV were often persistent. In this prospective, longitudinal study of the role of transient members of the pulmonary virome after LTX, CARV were not associated with concurrent ACR which contrasts with some previous studies. Furthermore it supports an alternative pathogenesis of chronic lung allograft dysfunction (CLAD) after CARV.
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