Influence of azithromycin and allograft rejection on the post–lung transplant microbiota

Christopher D. Spence, Bart Vanaudenaerde, Gísli G. Einarsson, John Mcdonough, Andrew J. Lee, Elinor Johnston, Geert M. Verleden, J. Stuart Elborn, Lieven J. Dupont, Anke Van Herck, Deirdre F. Gilpin, Robin Vos, Michael M. Tunney, Stijn E. Verleden*

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

BACKGROUND: Alterations in the lung microbiota may drive disease development and progression in patients with chronic respiratory diseases. Following lung transplantation (LTx), azithromycin is used to both treat and prevent chronic lung allograft dysfunction (CLAD). The objective of this study was to determine the association between azithromycin use, CLAD, acute rejection, airway inflammation, and bacterial microbiota composition and structure after LTx. METHODS: Bronchoalveolar lavage samples (n = 219) from 69 LTx recipients (azithromycin, n = 32; placebo, n = 37) from a previously conducted randomized placebo-controlled trial with azithromycin were analyzed. Samples were collected at discharge, 1, and 2 years following randomization and at CLAD diagnosis. Bacterial microbial community composition and structure was determined using 16S ribosomal RNA gene sequencing and associated with clinically important variables. RESULTS: At discharge and following 1 and 2 years of azithromycin therapy, no clear differences in microbial community composition or overall diversity were observed. Moreover, no changes in microbiota composition were observed in CLAD phenotypes. However, acute rejection was associated with a reduction in community diversity (p = 0.0009). Significant correlations were observed between microbiota composition, overall diversity, and levels of inflammatory cytokines in bronchoalveolar lavage, particularly CXCL8. CONCLUSIONS: Chronic azithromycin usage did not disturb the bacterial microbiota. However, acute rejection episodes were associated with bacterial dysbiosis.

Original languageEnglish
JournalJournal of Heart and Lung Transplantation
Early online date21 Nov 2019
DOIs
Publication statusEarly online date - 21 Nov 2019

Keywords

  • azithromycin
  • chronic lung allograft dysfunction
  • lung transplantation
  • microbiome
  • Pseudomonas

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

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