Department of Paediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, The Netherlands; Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands; Department of Paediatrics, Spaarne Hospital, Haarlem, The Netherlands.
Department of Paediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, The Netherlands; Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
J Allergy Clin Immunol. 2024 Jun;153(6):1574-1585.e14. doi: 10.1016/j.jaci.2024.02.020. Epub 2024 Mar 10.
The respiratory microbiome has been associated with the etiology and disease course of asthma.
We sought to assess the nasopharyngeal microbiota in children with a severe asthma exacerbation and their associations with medication, air quality, and viral infection.
A cross-sectional study was performed among children aged 2 to 18 years admitted to the medium care unit (MCU; n = 84) or intensive care unit (ICU; n = 78) with an asthma exacerbation. For case-control analyses, we matched all cases aged 2 to 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 microbiota was characterized by 16S-rRNA-gene sequencing.
Cases showed higher Shannon diversity index (ICU and MCU combined; P = .002) and a distinct microbial community composition when compared with controls (permutational multivariate ANOVA R = 1.9%; P < .001). We observed significantly higher abundance of Staphylococcus and "oral" taxa, including Neisseria, Veillonella, and Streptococcus spp. and a 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 = .03; q = 0.30). Neisseria spp. abundance was also related with fine particulate matter exposure, whereas Haemophilus and Streptococcus abundances were related with recent inhaled corticosteroid use. We observed no correlations with viral infection.
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 require further investigations.
呼吸道微生物群与哮喘的病因和病程有关。
我们旨在评估患有严重哮喘加重的儿童的鼻咽微生物群，并评估其与药物、空气质量和病毒感染的关系。
对因哮喘加重而入住中级护理病房（MCU；n=84）或重症监护病房（ICU；n=78）的 2 至 18 岁儿童进行了一项横断面研究。为了进行病例对照分析，我们将所有 2 至 6 岁的病例（n=87）与年龄在 1:2 比例的对照进行匹配。对照组是前瞻性病例对照研究或纵向出生队列的参与者（n=182）。鼻咽微生物群通过 16S-rRNA 基因测序进行描述。
与对照组相比，病例组的香农多样性指数（ICU 和 MCU 合并；P=0.002）和微生物群落组成明显更高（置换多元方差分析 R=1.9%；P<0.001）。我们观察到病例组中葡萄球菌和“口腔”分类群（包括奈瑟菌、韦荣球菌和链球菌属）的丰度显著更高，而多尔西格兰姆菌、棒状杆菌和莫拉菌属的丰度显著更低（MaAsLin2；q<0.25）。此外，奈瑟菌的丰度与更严重的疾病相关（ICU 与 MCU MaAsLin2，P=0.03；q=0.30）。奈瑟菌的丰度与细颗粒物暴露有关，而嗜血杆菌和链球菌的丰度与近期吸入皮质类固醇的使用有关。我们没有观察到与病毒感染的相关性。
我们的研究结果表明，因哮喘加重而住院的儿童的微生物组特征是葡萄球菌和“口腔”微生物过度生长，以及有益的适居性共生体代表性不足。其中一些关联可能是由（环境或医疗）暴露引起的，尽管因果关系尚不清楚，需要进一步研究。
