COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital.
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, and.
Ann Am Thorac Soc. 2022 Dec;19(12):2031-2043. doi: 10.1513/AnnalsATS.202110-1152OC.
There is a major unmet need for improving the care of children and adolescents with severe asthma and wheeze. Identifying factors contributing to disease severity may lead to improved diagnostics, biomarkers, or therapies. The airway microbiota may be such a key factor. To compare the oropharyngeal airway microbiota of children and adolescents with severe and mild/moderate asthma/wheeze. Oropharyngeal swab samples from school-age and preschool children in the European U-BIOPRED (Unbiased BIOmarkers in the PREDiction of respiratory disease outcomes) multicenter study of severe asthma, all receiving severity-appropriate treatment, were examined using 16S ribosomal RNA gene sequencing. Bacterial taxa were defined as amplicon sequence variants. We analyzed 241 samples from four cohorts: A) 86 school-age children with severe asthma; B) 39 school-age children with mild/moderate asthma; C) 65 preschool children with severe wheeze; and D) 51 preschool children with mild/moderate wheeze. The most common bacteria were (mean relative abundance, 33.5%), (10.3%), (7.0%), (5.9%), and (5.5%). Age group (school-age vs. preschool) was associated with the microbiota in β-diversity analysis ( = 3.32, = 0.011) and in a differential abundance analysis (28 significant amplicon sequence variants). Among all children, we found no significant difference in the microbiota between children with severe and mild/moderate asthma/wheeze in univariable β-diversity analysis ( = 1.99, = 0.08, = 241), but a significant difference in a multivariable model ( = 2.66, = 0.035), including the number of exacerbations in the previous year. Age was also significant when expressed as a microbial maturity score (Spearman Rho, 0.39; = 4.6 × 10); however, this score was not associated with asthma/wheeze severity. There was a modest difference in the oropharyngeal airway microbiota between children with severe and mild/moderate asthma/wheeze across all children but not in individual age groups, and a strong association between the microbiota and age. This suggests the oropharyngeal airway microbiota as an interesting entity in studying asthma severity, but probably without the strength to serve as a biomarker for targeted intervention.
患有严重哮喘和喘息的儿童和青少年的护理存在重大未满足的需求。确定导致疾病严重程度的因素可能会导致改进的诊断，生物标志物或治疗方法。气道微生物组可能就是这样一个关键因素。 比较患有严重和轻度/中度哮喘/喘息的儿童和青少年的口咽气道微生物组。 使用 16S 核糖体 RNA 基因测序，对来自欧洲 U-BIOPRED（预测呼吸道疾病结局的无偏生物标志物）严重哮喘多中心研究的学龄和学龄前儿童的口咽拭子样本进行了研究，所有这些儿童均接受了适当的严重程度治疗。 细菌分类群被定义为扩增子序列变体。 我们分析了来自四个队列的 241 个样本：A）86 名患有严重哮喘的学龄儿童； B）39 名患有轻度/中度哮喘的学龄儿童； C）65 名患有严重喘息的学龄前儿童；和 D）51 名患有轻度/中度喘息的学龄前儿童。最常见的细菌是 （平均相对丰度，33.5％）， （10.3％）， （7.0％）， （5.9％）和 （5.5％）。β多样性分析（β=3.32，p=0.011）和差异丰度分析（28 个显着扩增子序列变体）表明，年龄组（学龄与学龄前）与微生物组相关。在所有儿童中，我们发现患有严重和轻度/中度哮喘/喘息的儿童之间的微生物组在单变量β多样性分析中没有差异（β=1.99，p=0.08，β=241），但在多变量模型中存在差异（β=2.66，p=0.035），包括前一年的加重次数。当表示为微生物成熟度评分时，年龄也是显着的（Spearman Rho，0.39；p=4.6×10）；但是，该评分与哮喘/喘息的严重程度无关。 在所有儿童中，患有严重和轻度/中度哮喘/喘息的儿童的口咽气道微生物组之间存在适度差异，但在各个年龄组中没有差异，并且微生物组与年龄之间存在很强的关联。这表明口咽气道微生物组是研究哮喘严重程度的一个有趣实体，但可能没有作为靶向干预的生物标志物的强度。
