Introduction and Objectives Chronic Lung Allograft Dysfunction (CLAD) is a major limiting factor to survival post-lung transplant (LTx), restricting 5 year survival to approximately 55%. The mechanism by which CLAD and its sub-types occur are not fully understood and changes in the microbiota may play a role in the development of this condition. Moreover, azithromycin prolongs CLAD-free post-transplantation. This study aims to determine the effect of azithromycin over time on the airway microbiota post-LTx and how the microbiota changes with the development of CLAD.

Methods As part of a double-blind RCT in UZ Gasthuisberg, Leuven, Belgium,¹patients undergoing LTx were previously randomised to receive either azithromycin (n=43; 250 mg three times per week) or placebo (n=40) treatment following discharge post-transplant. Regular routine bronchoscopy was carried out on all patients and bronchoalveolar lavage (BAL) samples from discharge, 12, 24 months and at diagnosis of suspected rejection were processed for microbiota analysis using 16S Illumina sequencing and 16S quantitative PCR.

Results To date, 42 azithromycin treated (n=17 patients) and 52 (n=22 patients) placebo samples have been analysed. Microbiota diversity was significantly higher (p=0.0467) in the azithromycin group compared to placebo. Furthermore, a trend for reduced dominance by Pseudomonas, with re-emergence of taxa considered to constitute a ‘healthy’ microbiota (e.g., Prevotella, Veillonella, Streptococcus) was observed. There were no significant differences in 16S copies per mL BAL between the two groups. Eight samples (n=5 azithromyin, n=3 placebo) at suspected rejection have also been analysed. The azithromycin group exhibited low relative abundances of Pseudomonas (mean 7.7%), while the placebo group showed dominance by this taxa (mean 84.87%).

Conclusions Restoration of a diverse microbiota, while preventing dominance by Pseudomonas, may be a factor contributing towards the prophylactic effects of azithromycin observed in LTx patients¹. Further analysis of microbiota data alongside clinical data e.g., development of CLAD, CLAD-free survival time, etc. is ongoing.

Reference

1. Vos R, Vanaudenaerde BM, Verleden SE, et al. A randomised controlled trial of azithromycin to prevent chronic rejection after lung transplantation. European Respiratory Journal 2011;37:164–172.