儿童鼻咽微生物群与哮喘严重恶化有关
2024/03/26
摘要
背景：呼吸道微生物组与哮喘的病因和疾病进展相关联。
目的：本研究评估了儿童严重哮喘急性加重时的鼻咽微生物组，并分析其与药物、空气质量和病毒感染的关联。
方法：对因哮喘加重而住进亚重症监护病房（MCU；人数=84）或重症监护病房（ICU；人数=78）的 2-18 岁儿童进行横断面研究。在病例对照分析中，我们将所有 2-6 岁的病例（n=87）与对照组按 1:2 的比例进行了配对。对照组为前瞻性病例对照研究或纵向出生队列的参与者（182 人）。通过 16S-rRNA 基因测序确定了鼻咽微生物组的特征。
结果：与对照组相比，病例显示出更高的Shannon多样性（ICU 和 MCU 合并；p=0.002）和独特的微生物群落组成（PERMANOVA R2=1.9%，p<0.001）。我们观察到，与对照组相比，病例中葡萄球菌和 "口腔 "类群（包括奈瑟氏菌、Veillonella 和链球菌属）的丰度明显较高，而懒惰狡诈菌、棒状杆菌和莫拉氏菌属的丰度较低（MaAsLin2，q<0.25）。此外，奈瑟氏菌的数量与疾病的严重程度有关（ICU 与 MCU MaAslin2 p=0.03，q=0.30）。奈瑟氏菌的数量还与微粒物质暴露有关，而嗜血杆菌和链球菌的数量则与近期吸入皮质类固醇有关。我们没有观察到与病毒感染的相关性。
结论：我们的研究结果表明，因哮喘加重而入院的儿童体内微生物群的特点是葡萄球菌和 "口腔 "微生物过度生长，而有益的、与生态位相适应的共生菌代表不足。虽然因果关系尚不明确，需要进一步调查，但（环境或医疗）暴露可能可以解释其中的一些关联。
Nasopharyngeal microbiota in children is associated with severe asthma exacerbations
van Beveren GJ, de Steenhuijsen Piters WAA, Boeschoten SA, Louman S, Chu ML, Arp K, Fraaij PL, de Hoog M, Buysse C, van Houten MA, Sanders EAM, Merkus PJFM, Boehmer AL, Bogaert D.
Abstract
Background:The respiratory microbiome has been associated with the etiology and disease course of asthma.
Objective:This study assessed the nasopharyngeal microbiota in children with a severe asthma exacerbation and their associations with medication, air quality and viral infection.
Methods:A cross-sectional study was performed among children aged 2-18 years admitted to the medium (MCU; n=84) or intensive care (ICU; n=78) with an asthma exacerbation. For case-control analyses, we matched all cases aged 2-6 years (n=87) to controls in a 1:2 ratio. Controls were participants of either a prospective case-control study or a longitudinal birth cohort (n=182). The nasopharyngeal microbiome was characterized by 16S-rRNA-gene sequencing.
Results:Cases showed higher Shannon diversity (ICU and MCU combined; p=0.002) and a distinct microbial community composition when compared to controls (PERMANOVA R2=1.9%, p<0.001). We observed significantly higher abundance of Staphylococcus and 'oral' taxa, including Neisseria, Veillonella and Streptococcus spp. and lower abundance of Dolosigranulum pigrum, Corynebacterium and Moraxella spp. (MaAsLin2, q<0.25) in cases versus controls. Furthermore, Neisseria abundance was associated with more severe disease (ICU vs MCU MaAslin2 p=0.03, q=0.30). Neisseria spp. abundance was also related with fine particulate matter exposure, whereas Haemophilus and Streptoccocus abundance was related with recent inhalation corticosteroid use. We observed no correlations with viral infection.
Conclusion:Our results demonstrate that children admitted with asthma exacerbations harbor a microbiome characterized by overgrowth of Staphylococcus and 'oral' microbes, and an underrepresentation of beneficial niche-appropriate commensals. Several of these associations may be explained by (environmental or medical) exposures, although cause-consequence relationships remain unclear and requires further investigations.
背景：呼吸道微生物组与哮喘的病因和疾病进展相关联。
目的：本研究评估了儿童严重哮喘急性加重时的鼻咽微生物组，并分析其与药物、空气质量和病毒感染的关联。
方法：对因哮喘加重而住进亚重症监护病房（MCU；人数=84）或重症监护病房（ICU；人数=78）的 2-18 岁儿童进行横断面研究。在病例对照分析中，我们将所有 2-6 岁的病例（n=87）与对照组按 1:2 的比例进行了配对。对照组为前瞻性病例对照研究或纵向出生队列的参与者（182 人）。通过 16S-rRNA 基因测序确定了鼻咽微生物组的特征。
结果：与对照组相比，病例显示出更高的Shannon多样性（ICU 和 MCU 合并；p=0.002）和独特的微生物群落组成（PERMANOVA R2=1.9%，p<0.001）。我们观察到，与对照组相比，病例中葡萄球菌和 "口腔 "类群（包括奈瑟氏菌、Veillonella 和链球菌属）的丰度明显较高，而懒惰狡诈菌、棒状杆菌和莫拉氏菌属的丰度较低（MaAsLin2，q<0.25）。此外，奈瑟氏菌的数量与疾病的严重程度有关（ICU 与 MCU MaAslin2 p=0.03，q=0.30）。奈瑟氏菌的数量还与微粒物质暴露有关，而嗜血杆菌和链球菌的数量则与近期吸入皮质类固醇有关。我们没有观察到与病毒感染的相关性。
结论：我们的研究结果表明，因哮喘加重而入院的儿童体内微生物群的特点是葡萄球菌和 "口腔 "微生物过度生长，而有益的、与生态位相适应的共生菌代表不足。虽然因果关系尚不明确，需要进一步调查，但（环境或医疗）暴露可能可以解释其中的一些关联。
(中日友好医院呼吸与危重症医学科 沈焜路 摘译 林江涛 审校)
(J Allergy Clin Immunol. 2024 Mar 9; DOI: 10.1016/j.jaci.2024.02.020)
(J Allergy Clin Immunol. 2024 Mar 9; DOI: 10.1016/j.jaci.2024.02.020)
Nasopharyngeal microbiota in children is associated with severe asthma exacerbations
van Beveren GJ, de Steenhuijsen Piters WAA, Boeschoten SA, Louman S, Chu ML, Arp K, Fraaij PL, de Hoog M, Buysse C, van Houten MA, Sanders EAM, Merkus PJFM, Boehmer AL, Bogaert D.
Abstract
Background:The respiratory microbiome has been associated with the etiology and disease course of asthma.
Objective:This study assessed the nasopharyngeal microbiota in children with a severe asthma exacerbation and their associations with medication, air quality and viral infection.
Methods:A cross-sectional study was performed among children aged 2-18 years admitted to the medium (MCU; n=84) or intensive care (ICU; n=78) with an asthma exacerbation. For case-control analyses, we matched all cases aged 2-6 years (n=87) to controls in a 1:2 ratio. Controls were participants of either a prospective case-control study or a longitudinal birth cohort (n=182). The nasopharyngeal microbiome was characterized by 16S-rRNA-gene sequencing.
Results:Cases showed higher Shannon diversity (ICU and MCU combined; p=0.002) and a distinct microbial community composition when compared to controls (PERMANOVA R2=1.9%, p<0.001). We observed significantly higher abundance of Staphylococcus and 'oral' taxa, including Neisseria, Veillonella and Streptococcus spp. and lower abundance of Dolosigranulum pigrum, Corynebacterium and Moraxella spp. (MaAsLin2, q<0.25) in cases versus controls. Furthermore, Neisseria abundance was associated with more severe disease (ICU vs MCU MaAslin2 p=0.03, q=0.30). Neisseria spp. abundance was also related with fine particulate matter exposure, whereas Haemophilus and Streptoccocus abundance was related with recent inhalation corticosteroid use. We observed no correlations with viral infection.
Conclusion:Our results demonstrate that children admitted with asthma exacerbations harbor a microbiome characterized by overgrowth of Staphylococcus and 'oral' microbes, and an underrepresentation of beneficial niche-appropriate commensals. Several of these associations may be explained by (environmental or medical) exposures, although cause-consequence relationships remain unclear and requires further investigations.
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哮喘及上皮的气道重塑:在一个新时代的边缘
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过敏性哮喘中人中性粒细胞一氧化氮的产生和细胞外捕获器的形成耦合作用
