中性粒细胞增多型哮喘患者气道菌群特征分析及临床意义

杨睿; 张巧; 王彦; 李红; 任之栋; 马千里

doi:10.16016/j.2097-0927.202107009

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中性粒细胞增多型哮喘患者气道菌群特征分析及临床意义

临床医学 | 更新时间：2026-01-09

- 中性粒细胞增多型哮喘患者气道菌群特征分析及临床意义
- Features and clinical significance of airway microbiota in patients with neutrophilic asthma
- 陆军军医大学学报 2022年44卷第3期页码：231-240
- 作者机构：
  
  1.400037 重庆，陆军军医大学(第三军医大学)第二附属医院全军呼吸内科研究所，全军呼吸病研究重点实验室
  2.401121 重庆，北部宽仁医院慢性呼吸疾病管理与康复中心
- 作者简介：
  
  [ 马千里，E-mail：cqmql@163.com MA Qianli, E-mail: cqmql@163.com
- 基金信息：
  
  国家自然科学基金面上项目(81670012);国家自然科学基金面上项目(81670037)
- DOI：10.16016/j.2097-0927.202107009
  中图分类号： R562.2;R372
- 收稿：2021-07-01，
  
  修回：2021-08-09，
  
  纸质出版：2022-02-15
- 稿件说明：
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杨睿, 张巧, 王彦, 等. 中性粒细胞增多型哮喘患者气道菌群特征分析及临床意义[J]. 陆军军医大学学报, 2022,44(3):231-240.

Rui YANG, Qiao ZHANG, Yan WANG, et al. Features and clinical significance of airway microbiota in patients with neutrophilic asthma[J]. Journal of Army Medical University, 2022, 44(3): 231-240.
杨睿, 张巧, 王彦, 等. 中性粒细胞增多型哮喘患者气道菌群特征分析及临床意义[J]. 陆军军医大学学报, 2022,44(3):231-240. DOI： 10.16016/j.2097-0927.202107009.

Rui YANG, Qiao ZHANG, Yan WANG, et al. Features and clinical significance of airway microbiota in patients with neutrophilic asthma[J]. Journal of Army Medical University, 2022, 44(3): 231-240. DOI： 10.16016/j.2097-0927.202107009.

摘要

目的

探索稳定期中性粒细胞增多型哮喘患者的气道微生物群组特征及其临床意义。

方法

采集2019年8月至2020年1月就诊于陆军军医大学第二附属医院的44例临床稳定期中性粒细胞增多型哮喘患者的诱导痰标本，提取DNA后，采用PacBio SMRT测序技术对细菌16S rRNA和真菌ITS序列进行测序，通过对测序数据的层次聚类分析确定出2个亚组，分析组间细菌、真菌菌群及相关临床指标的差异。

结果

通过对44例受试者的细菌测序数据聚类分析鉴定出2组聚类簇，与较大的聚类簇(A1组，

=32)相比，较小的聚类簇(A2组，

=12)以嗜血杆菌处于其细菌菌群的优势地位为特征，展示出了更高的痰中性粒细胞百分比(

=-4.14，

0.001)和更低的FEV

% pred(

=2.15，

=0.037)。在细菌菌群结构上，2组聚类簇之间α多样性(Chao1指数和Simpson指数，

0.001)和β多样性(Adonis，

=0.290，

=0.001)差异都具有统计学意义；LEfSe分析提示在种水平上，A1组显著富集肺炎链球菌、副流感嗜血杆菌、具核梭杆菌、奇异劳特普罗菌、脑膜炎奈瑟氏菌、牙龈卟啉单胞菌、产黑色素普雷沃氏菌、苍白普雷沃氏菌、青枯劳尔氏菌，A2组则富集流感嗜血杆菌。在真菌菌群结构上，2组在α多样性上未观察到显著差异(Chao1指数，

=0.230；Simpson指数，

=0.097)，而在β多样性上两组差异显著(Adonis，

=0.068，

=0.002)；LEfSe分析提示在种水平上，A1组富集裂褶菌，而A2组则富集变色栓菌、白囊耙齿菌。进一步互作网络分析则提示A2组较A1组展现出了更多的菌属之间的相关关系，且A2组菌属之间的关联强度较A1组更强。

结论

在稳定期中性粒细胞增多型哮喘患者中，存在以流感嗜血杆菌作为其气道优势定植菌的亚组，该亚组在细菌及真菌菌群结构上与非流感嗜血杆菌优势组存在显著差异，并在临床上表现为更严重的气道炎症水平和更差的肺功能特征。

Abstract

Objective

To explore the characteristics and clinical significance of airway microbiota in the patients with neutrophilic asthma.

Methods

Induced sputum samples were collected from 44 patients with clinically stable neutrophilic asthma attending the second Affiliated Hospital of Army Medical University from August 2019 to January 2020. After DNA extraction

16S rRNA and internal transcribed space (ITS) sequencing were performed by PacBio Sequel Systems. Two subgroups were identified by hierarchical cluster analysis on sequencing data

and the differences in their bacterial and fungal microbiota and clinical characteristics were explored.

Results

Hierarchical clustering analysis of bacterial sequencing data from 44 subjects identified 2 clusters. Compared to the larger cluster (group A1

=32)

the smaller cluster (group A2

=12) was characterized by a predominance of

Haemophilus

in their bacterial microbiota

and the patients in this group demonstrated a higher percentage of sputum neutrophils (

=-4.14

0.001) and poorer FEV

% pred (

=2.15

=0.037). In bacterial microbiota

there were significant differences in both α-diversity (Chao1 and Simpson indexes

0.001) and β-diversity (Adonis

=0.290

=0.001) between the 2 groups. At the species level

LEfSe analysis revealed that the group A1 was significantly enriched in

Streptococcus pneumonia

Haemophilus parainfluenzae

Fusobacterium nucleatum

Lautropia mirabilis

Neisseria meningitides

Porphyromonas gingivalis

Prevotella melaninogenica

Prevotella pallens

and

Ralstonia solanacearum

while the group A2 was enriched in

Haemophilus influenzae

. In fungal microbiota

no significant differences were observed between the 2 groups in α-diversity (Chao1 index

=0.230; Simpson index

=0.097)

whereas significant differences were observed between their β-diversity (Adonis

=0.068

=0.002). At the species level

LEfSe analysis revealed that the group A1 was enriched in

Schizophyllum commune

and group A2 was enriched in

Trametes versicolor

and

Irpex lacteus

. Interaction network analysis indicated that group A2 showed more correlations between genus than group A1

and the strength of association between genus was more intense.

Conclusion

Among the patients with stable neutrophilic asthma

there is a subgroup characterized by the presence of

Haemophilus influenzae

as its airway predominant colonizing bacteria

which differs significantly from the non-

Haemophilus influenzae

dominant group in terms of bacterial and fungal microbiota

and presents clinical characteristics wi

th more severe airway inflammation and poorer lung function.

关键词

Keywords

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