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严重阻塞性睡眠呼吸暂停与鼻腔微生物组改变和炎症增加有关。

Severe Obstructive Sleep Apnea Is Associated with Alterations in the Nasal Microbiome and an Increase in Inflammation.

机构信息

1 Division of Pulmonary, Critical Care, and Sleep Medicine, New York University School of Medicine, New York, New York.

2 Beijing Division of Pulmonary and Critical Care Medicine, Beijing Chaoyang Hospital, The Capital University of Medicine, Beijing, China.

出版信息

Am J Respir Crit Care Med. 2019 Jan 1;199(1):99-109. doi: 10.1164/rccm.201801-0119OC.

Abstract

RATIONALE

Obstructive sleep apnea (OSA) is associated with recurrent obstruction, subepithelial edema, and airway inflammation. The resultant inflammation may influence or be influenced by the nasal microbiome.

OBJECTIVES

To evaluate whether the composition of the nasal microbiota is associated with obstructive sleep apnea and inflammatory biomarkers.

METHODS

Two large cohorts were used: 1) a discovery cohort of 472 subjects from the WTCSNORE (Seated, Supine and Post-Decongestion Nasal Resistance in World Trade Center Rescue and Recovery Workers) cohort, and 2) a validation cohort of 93 subjects rom the Zaragoza Sleep cohort. Sleep apnea was diagnosed using home sleep tests. Nasal lavages were obtained from cohort subjects to measure: 1) microbiome composition (based on 16S rRNA gene sequencing), and 2) biomarkers for inflammation (inflammatory cells, IL-8, and IL-6). Longitudinal 3-month samples were obtained in the validation cohort, including after continuous positive airway pressure treatment when indicated.

MEASUREMENTS AND MAIN RESULTS

In both cohorts, we identified that: 1) severity of OSA correlated with differences in microbiome diversity and composition; 2) the nasal microbiome of subjects with severe OSA were enriched with Streptococcus, Prevotella, and Veillonella; and 3) the nasal microbiome differences were associated with inflammatory biomarkers. Network analysis identified clusters of cooccurring microbes that defined communities. Several common oral commensals (e.g., Streptococcus, Rothia, Veillonella, and Fusobacterium) correlated with apnea-hypopnea index. Three months of treatment with continuous positive airway pressure did not change the composition of the nasal microbiota.

CONCLUSIONS

We demonstrate that the presence of an altered microbiome in severe OSA is associated with inflammatory markers. Further experimental approaches to explore causal links are needed.

摘要

背景

阻塞性睡眠呼吸暂停(OSA)与反复阻塞、黏膜下水肿和气道炎症有关。由此产生的炎症可能会影响或受鼻腔微生物组的影响。

目的

评估鼻腔微生物组的组成是否与阻塞性睡眠呼吸暂停和炎症生物标志物有关。

方法

使用了两个大的队列:1)来自 WTCSNORE(世界贸易中心救援和恢复工作人员的坐姿、仰卧位和后充血鼻腔阻力)队列的 472 名受试者的发现队列,和 2)来自萨拉戈萨睡眠队列的 93 名受试者的验证队列。通过家庭睡眠测试诊断睡眠呼吸暂停。从队列受试者中获得鼻灌洗液以测量:1)微生物组组成(基于 16S rRNA 基因测序),和 2)炎症生物标志物(炎症细胞、IL-8 和 IL-6)。在验证队列中获得了纵向 3 个月的样本,包括在需要时进行持续气道正压通气治疗后。

测量和主要结果

在两个队列中,我们发现:1)OSA 的严重程度与微生物组多样性和组成的差异相关;2)严重 OSA 受试者的鼻腔微生物组富含链球菌、普雷沃菌和韦荣球菌;3)鼻腔微生物组的差异与炎症生物标志物相关。网络分析确定了定义群落的共同发生微生物簇。一些常见的口腔共生菌(例如链球菌、罗氏菌、韦荣球菌和梭杆菌)与呼吸暂停低通气指数相关。连续气道正压通气治疗 3 个月不会改变鼻腔微生物组的组成。

结论

我们证明了严重 OSA 中存在改变的微生物组与炎症标志物相关。需要进一步的实验方法来探索因果关系。

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