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Influence of azithromycin and allograft rejection on the post-lung transplant microbiota.
The Journal of Heart and Lung Transplantation ( IF 8.9 ) Pub Date : 2019-11-21 , DOI: 10.1016/j.healun.2019.11.007
Christopher D Spence 1 , Bart Vanaudenaerde 2 , Gísli G Einarsson 3 , John Mcdonough 2 , Andrew J Lee 1 , Elinor Johnston 1 , Geert M Verleden 2 , J Stuart Elborn 3 , Lieven J Dupont 2 , Anke Van Herck 2 , Deirdre F Gilpin 1 , Robin Vos 2 , Michael M Tunney 1 , Stijn E Verleden 2
Affiliation  

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.

中文翻译:

阿奇霉素和同种异体移植排斥对肺移植后微生物群的影响。

背景技术肺微生物群的改变可以驱动患有慢性呼吸系统疾病的患者的疾病发展和进展。肺移植(LTx)后,阿奇霉素可用于治疗和预防慢性同种异体移植功能障碍(CLAD)。这项研究的目的是确定阿奇霉素的使用,CLAD,急性排斥反应,气道炎症与LTx后细菌菌群组成和结构之间的关系。方法分析了来自先前进行的阿奇霉素随机安慰剂对照试验的69名LTx接受者(阿奇霉素,n = 32;安慰剂,n = 37)的支气管肺泡灌洗样本(n = 219)。在出院时,随机分组后1年和2年以及CLAD诊断时收集样本。使用16S核糖体RNA基因测序确定细菌微生物群落的组成和结构,并与临床上重要的变量相关联。结果在出院后以及阿奇霉素治疗1年和2年后,未观察到微生物群落组成或总体多样性的明显差异。而且,在CLAD表型中未观察到微生物群组成的变化。但是,急性排斥反应与社区多样性的减少有关(p = 0.0009)。在支气管肺泡灌洗液,特别是CXCL8中,微生物群组成,总体多样性和炎性细胞因子水平之间存在显着相关性。结论长期使用阿奇霉素不会干扰细菌菌群。但是,急性排斥反应与细菌性营养不良有关。
更新日期:2019-11-21
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