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慢性阻塞性肺疾病患者临床特征对鼻腔微生物组和真菌组的影响

Differences of the Nasal Microbiome and Mycobiome by Clinical Characteristics of COPD Patients.

作者信息

Alvarez Baumgartner Maura, Li Chengchen, Kuntz Thomas M, Nurhussien Lina, Synn Andrew J, Sun Wendy Y, Kang Jennifer E, Lai Peggy S, Wilkinson Jeremy E, Rice Mary B

机构信息

Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States.

Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States.

出版信息

Chronic Obstr Pulm Dis. 2022 Jul 29;9(3):309-324. doi: 10.15326/jcopdf.2021.0267.

Abstract

RATIONALE

While studies suggest that the lung microbiome may influence risk of chronic obstructive pulmonary disease (COPD) exacerbations, little is known about the relationship between the nasal biome and clinical characteristics of COPD patients.

METHODS

We sampled the nasal lining fluid by nasosorption of both nares of 20 people with moderate-to-severe COPD. All 40 samples, plus 4 negative controls, underwent DNA extraction, and 16SV4 ribosomal RNA (rRNA) (bacterial) and ribosomal internal transcribed spacer 2 (ITS2) (fungal) sequencing. We measured the proportion of variance (R) in beta diversity explained by clinical factors, including age, sex, body mass index (BMI), COPD treatment, disease severity (forced expiratory volume in 1 second [FEV], symptom/exacerbation frequency), peripheral eosinophil level (≥150 versus <150 cells/µL) and season of sampling, with the PERMANOVA test on the Bray-Curtis dissimilarities, accounting for within-person correlation of samples. We assessed the relative abundance of microbial features in the nasal community and their associations with clinical characteristics using the Microbiome Multivariable Association with Linear Models (MaAsLin2) package.

RESULTS

The most abundant nasal fluid bacterial taxa were , , , , and , and fungal taxa were , , , and . Bacterial microbiome composition was associated with short-acting muscarinic antagonist use (R 11.8%, =0.002), sex (R 8.3%, =0.044), nasal steroid use (R 7.7%, =0.064), and higher eosinophil level (R 7.6%, =0.084). Mycobiome composition was associated with higher eosinophil level (R 14.4%, =0.004) and low FEV (R 7.5%, =0.071). No specific bacterium or fungus differed significantly in relative abundance by clinical characteristics in the multivariate per-feature analysis.

CONCLUSION

The taxonomical composition of the nasal biome is heterogeneous in COPD patients and may be explained in part by clinical characteristics.

摘要

理论依据

虽然研究表明肺部微生物群可能影响慢性阻塞性肺疾病(COPD)急性加重的风险,但关于鼻腔微生物群与COPD患者临床特征之间的关系却知之甚少。

方法

我们通过对20名中重度COPD患者的双侧鼻孔进行鼻腔吸附来采集鼻黏膜液。所有40个样本,加上4个阴性对照,进行DNA提取,并进行16S V4核糖体RNA(rRNA)(细菌)和核糖体内部转录间隔区2(ITS2)(真菌)测序。我们使用PERMANOVA检验对Bray-Curtis差异进行分析,考虑样本的个体内相关性,测量由临床因素解释的β多样性中的方差比例(R),这些临床因素包括年龄、性别、体重指数(BMI)、COPD治疗、疾病严重程度(1秒用力呼气量[FEV]、症状/急性加重频率)、外周嗜酸性粒细胞水平(≥150对<150个细胞/μL)和采样季节。我们使用微生物组多变量线性模型关联(MaAsLin2)软件包评估鼻腔群落中微生物特征的相对丰度及其与临床特征的关联。

结果

鼻液中最丰富的细菌类群是 、 、 、 和 ,真菌类群是 、 、 、 和 。细菌微生物组组成与使用短效毒蕈碱拮抗剂有关(R 11.8%, =0.002)、性别(R 8.3%, =0.044)、使用鼻用类固醇(R 7.7%, =0.064)以及较高的嗜酸性粒细胞水平(R 7.6%, =0.084)。真菌微生物组组成与较高的嗜酸性粒细胞水平(R 14.4%, =0.004)和低FEV有关(R 7.5%, =0.071)。在多变量逐个特征分析中,没有特定的细菌或真菌在相对丰度上因临床特征而有显著差异。

结论

COPD患者鼻腔微生物群系的分类组成是异质性的,并且可能部分由临床特征来解释。

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