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早期囊性纤维化肺病患者的下呼吸道微生物组:一项纵向分析。

The lower airway microbiota in early cystic fibrosis lung disease: a longitudinal analysis.

机构信息

Department of Respiratory and Sleep Medicine, Royal Children's Hospital, Parkville, Victoria, Australia.

Respiratory Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia.

出版信息

Thorax. 2017 Dec;72(12):1104-1112. doi: 10.1136/thoraxjnl-2016-209279. Epub 2017 Mar 9.

DOI:10.1136/thoraxjnl-2016-209279
PMID:28280235
Abstract

RATIONALE

In infants and young children with cystic fibrosis, lower airway infection and inflammation are associated with adverse respiratory outcomes. However, the role of lower airway microbiota in the pathogenesis of early cystic fibrosis lung disease remains uncertain.

OBJECTIVES

To assess the development of the lower airway microbiota over time in infants and young children with cystic fibrosis, and to explore its association with airway inflammation and pulmonary function at age 6 years.

METHODS

Serial, semi-annual bronchoscopies and bronchoalveolar lavage (BAL) procedures were performed in infants newly diagnosed with cystic fibrosis following newborn screening. Quantitative microbiological cultures and inflammatory marker (interleukin 8 and neutrophil elastase) measurements were undertaken contemporaneously. 16S ribosomal RNA gene sequencing was conducted on stored BAL samples. Spirometry results recorded at 6 years of age were extracted from medical records.

MEASUREMENTS AND MAIN RESULTS

Ninety-five BAL samples provided 16S ribosomal RNA gene data. These were collected from 48 subjects aged 1.2-78.3 months, including longitudinal samples from 27 subjects and 13 before age 6 months. The lower airway microbiota varied, but diversity decreased with advancing age. Detection of recognised cystic fibrosis bacterial pathogens was associated with reduced microbial diversity and greater lower airway inflammation. There was no association between the lower airway microbiota and pulmonary function at age 6 years.

CONCLUSIONS

In infants with cystic fibrosis, the lower airway microbiota is dynamic. Dominance of the microbiota by recognised cystic fibrosis bacterial pathogens is associated with increased lower airway inflammation, however early microbial diversity is not associated with pulmonary function at 6 years of age.

摘要

背景

在患有囊性纤维化的婴儿和幼儿中,下呼吸道感染和炎症与不良的呼吸结局相关。然而,下呼吸道微生物群在早期囊性纤维化肺病发病机制中的作用仍不确定。

目的

评估患有囊性纤维化的婴儿和幼儿的下呼吸道微生物群随时间的发展,并探索其与 6 岁时气道炎症和肺功能的关系。

方法

对通过新生儿筛查确诊为囊性纤维化的婴儿进行定期、半年度支气管镜检查和支气管肺泡灌洗(BAL)。同时进行定量微生物培养和炎症标志物(白细胞介素 8 和中性粒细胞弹性蛋白酶)测量。对储存的 BAL 样本进行 16S 核糖体 RNA 基因测序。从病历中提取 6 岁时记录的肺活量测定结果。

测量和主要结果

95 个 BAL 样本提供了 16S 核糖体 RNA 基因数据。这些样本来自 48 名年龄在 1.2-78.3 个月的受试者,其中包括 27 名受试者的纵向样本和 13 名 6 岁以下的样本。下呼吸道微生物群存在差异,但随着年龄的增长多样性降低。识别出的囊性纤维化细菌病原体的检测与微生物多样性降低和下呼吸道炎症增加相关。下呼吸道微生物群与 6 岁时的肺功能之间没有关联。

结论

在患有囊性纤维化的婴儿中,下呼吸道微生物群是动态的。被公认的囊性纤维化细菌病原体主导的微生物群与下呼吸道炎症增加相关,但早期微生物多样性与 6 岁时的肺功能无关。

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