气道流感嗜血杆菌相对丰度过高的严重哮喘表型与痰中性粒细胞增多相关
2024/10/29
摘要
背景：严重哮喘（SA）包括几种具有异质性气道微生物组的临床表型。我们确定了与低α多样性微生物组相关的表型。
方法: 对SA参与者的痰样本进行宏基因组测序。使用低于轻度-中度哮喘和健康对照受试者的α-多样性平均值2个标准差的阈值来定义那些具有异常丰度阈值的相对优势种（RDS）。
结果: 97份SA样本中有51份被归类为RDS，其中流感嗜血杆菌RDS最常见（n=16），其次是未分类的放线杆菌（n=10），未分类的韦荣氏菌（n=9），埃及嗜血杆菌（n=9），假肺炎链球菌（n=7），痤疮丙酸杆菌（n=5），卡他莫拉菌（n=5）和惠氏滋养菌（n=5）。流感嗜血杆菌RDS的病程最长，前一年恶化更多，每日口服皮质类固醇的数量最多。RDS分层聚类显示，C2集群（n = 9）具有最高的流感嗜血杆菌RDS相对丰度，其病程较长，痰中性粒细胞计数较高，与MAPK、NF-κB、TNF、mTOR和坏死性凋亡的富集途径相关，而C1集群（42个RDS中有7个流感嗜血杆菌RDS）则相反。与C1 RDS相比，C2簇的痰转录组学显示中性粒细胞胞外诱捕途径（NETosis）、IL - 6转导信号和中性粒细胞活化的表达更高。
结论: 我们描述了与中性粒细胞炎症和NETosis相关的相对丰度最高的流感嗜血杆菌簇，表明宿主对细菌有反应。这种严重哮喘的表型可能对特定抗生素有反应。
A severe asthma phenotype of excessive airway Haemophilus influenzae relative abundance associated with sputum neutrophilia.
Ali, Versi; Adnan, Azim; Fransiskus Xaverius, Ivan;
Abstrast
Background: Severe asthma (SA) encompasses several clinical phenotypes with a heterogeneous airway microbiome. We determined the phenotypes associated with a low α-diversity microbiome.
Methods: Metagenomic sequencing was performed on sputum samples from SA participants. A threshold of 2 standard deviations below the mean of α-diversity of mild-moderate asthma and healthy control subjects was used to define those with an abnormal abundance threshold as relative dominant species (RDS).
Results: Fifty-one out of 97 SA samples were classified as RDSs with Haemophilus influenzae RDS being most common (n = 16), followed by Actinobacillus unclassified (n = 10), Veillonella unclassified (n = 9), Haemophilus aegyptius (n = 9), Streptococcus pseudopneumoniae (n = 7), Propionibacterium acnes (n = 5), Moraxella catarrhalis (n = 5) and Tropheryma whipplei (n = 5). Haemophilus influenzae RDS had the highest duration of disease, more exacerbations in previous year and greatest number on daily oral corticosteroids. Hierarchical clustering of RDSs revealed a C2 cluster (n = 9) of highest relative abundance of exclusively Haemophilus influenzae RDSs with longer duration of disease and higher sputum neutrophil counts associated with enrichment pathways of MAPK, NF-κB, TNF, mTOR and necroptosis, compared to the only other cluster, C1, which consisted of 7 Haemophilus influenzae RDSs out of 42. Sputum transcriptomics of C2 cluster compared to C1 RDSs revealed higher expression of neutrophil extracellular trap pathway (NETosis), IL6-transignalling signature and neutrophil activation.
Conclusions：We describe a Haemophilus influenzae cluster of the highest relative abundance associated with neutrophilic inflammation and NETosis indicating a host response to the bacteria. This phenotype of severe asthma may respond to specific antibiotics.
背景：严重哮喘（SA）包括几种具有异质性气道微生物组的临床表型。我们确定了与低α多样性微生物组相关的表型。
方法: 对SA参与者的痰样本进行宏基因组测序。使用低于轻度-中度哮喘和健康对照受试者的α-多样性平均值2个标准差的阈值来定义那些具有异常丰度阈值的相对优势种（RDS）。
结果: 97份SA样本中有51份被归类为RDS，其中流感嗜血杆菌RDS最常见（n=16），其次是未分类的放线杆菌（n=10），未分类的韦荣氏菌（n=9），埃及嗜血杆菌（n=9），假肺炎链球菌（n=7），痤疮丙酸杆菌（n=5），卡他莫拉菌（n=5）和惠氏滋养菌（n=5）。流感嗜血杆菌RDS的病程最长，前一年恶化更多，每日口服皮质类固醇的数量最多。RDS分层聚类显示，C2集群（n = 9）具有最高的流感嗜血杆菌RDS相对丰度，其病程较长，痰中性粒细胞计数较高，与MAPK、NF-κB、TNF、mTOR和坏死性凋亡的富集途径相关，而C1集群（42个RDS中有7个流感嗜血杆菌RDS）则相反。与C1 RDS相比，C2簇的痰转录组学显示中性粒细胞胞外诱捕途径（NETosis）、IL - 6转导信号和中性粒细胞活化的表达更高。
结论: 我们描述了与中性粒细胞炎症和NETosis相关的相对丰度最高的流感嗜血杆菌簇，表明宿主对细菌有反应。这种严重哮喘的表型可能对特定抗生素有反应。
(中日友好医院呼吸与危重症医学科 万静萱 摘译 林江涛 审校)
(Clin Transl Med 2024 Sep;14(9):e70007 DOI: 10.1002/ctm2.70007.IF: 7.919)
(Clin Transl Med 2024 Sep;14(9):e70007 DOI: 10.1002/ctm2.70007.IF: 7.919)
A severe asthma phenotype of excessive airway Haemophilus influenzae relative abundance associated with sputum neutrophilia.
Ali, Versi; Adnan, Azim; Fransiskus Xaverius, Ivan;
Abstrast
Background: Severe asthma (SA) encompasses several clinical phenotypes with a heterogeneous airway microbiome. We determined the phenotypes associated with a low α-diversity microbiome.
Methods: Metagenomic sequencing was performed on sputum samples from SA participants. A threshold of 2 standard deviations below the mean of α-diversity of mild-moderate asthma and healthy control subjects was used to define those with an abnormal abundance threshold as relative dominant species (RDS).
Results: Fifty-one out of 97 SA samples were classified as RDSs with Haemophilus influenzae RDS being most common (n = 16), followed by Actinobacillus unclassified (n = 10), Veillonella unclassified (n = 9), Haemophilus aegyptius (n = 9), Streptococcus pseudopneumoniae (n = 7), Propionibacterium acnes (n = 5), Moraxella catarrhalis (n = 5) and Tropheryma whipplei (n = 5). Haemophilus influenzae RDS had the highest duration of disease, more exacerbations in previous year and greatest number on daily oral corticosteroids. Hierarchical clustering of RDSs revealed a C2 cluster (n = 9) of highest relative abundance of exclusively Haemophilus influenzae RDSs with longer duration of disease and higher sputum neutrophil counts associated with enrichment pathways of MAPK, NF-κB, TNF, mTOR and necroptosis, compared to the only other cluster, C1, which consisted of 7 Haemophilus influenzae RDSs out of 42. Sputum transcriptomics of C2 cluster compared to C1 RDSs revealed higher expression of neutrophil extracellular trap pathway (NETosis), IL6-transignalling signature and neutrophil activation.
Conclusions：We describe a Haemophilus influenzae cluster of the highest relative abundance associated with neutrophilic inflammation and NETosis indicating a host response to the bacteria. This phenotype of severe asthma may respond to specific antibiotics.
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度普利尤单抗的疗效和度普利尤单抗诱导的重症哮喘嗜酸性粒细胞增多的危险因素：来自中国的初步研究
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