哮喘联盟

   摘要
   背景：哮喘是异质的，轻中度哮喘患者气道的微生物失调与其临床特征是相关的，但在重症哮喘患者中是否存在类似的关系是未知的。
   目的：我们试图评估支气管微生物与重症哮喘特征之间的关系。
   方法：用以16s核糖体RNA为基础的方法评估了40例参加了糖皮质激素抵抗性哮喘生物标志物（BOBCAT）的支气管镜探索性研究患者的支气管刷检结果。对支气管存在微生物的患者进行了微生物与临床特征及炎症特点关系的分析。其次，比较了重症哮喘患者和之前研究的健康对照者（n=7）及轻中度哮喘患者（n=41）的细菌组成分布。
   结果：在重症哮喘患者中，支气管细菌组成与几个疾病相关特征有关，这些疾病相关特征包括身体质量指数（P<0.05，布雷-柯蒂斯距离排列多元方差分析，PERMANNOVA）、哮喘控制问卷（ACQ）评分的改变（P<0.01）、痰液白细胞总数（P=0.06）和支气管活检嗜酸性粒细胞数目（每平方毫米，P=0.07）。与日益恶化的ACQ评分和痰液白细胞总数相关的菌群（主要是变形菌）显著不同于与身体质量指数相关的菌群（拟杆菌/厚壁菌）。相反地，改善的/稳定的ACQ评分和支气管上皮细胞FK506结合蛋白（FKBP5）的基因表达（对糖皮质激素有反应的一个指标），与放线菌相关。活检嗜酸性粒细胞数目和变形菌大多呈负相关。没有菌群与TH2相关上皮基因表达信号相关，但TH17相关基因的表达与变形菌相关。与健康对照者或轻中度哮喘患者相比，重症哮喘患者有显著增多的放线菌，尽管观察到的最大差异为肺炎克雷伯菌属（重症哮喘患者增加了7.8倍，校正后p<0.001）。
   结论：特定的微生物群与重症哮喘患者及其相关表型相关，并可能调节炎症过程。重症患者的气道微生物失调似乎不同于使用吸入糖皮质激素的轻度哮喘患者。
 

（杨冬 审校）
JAllergyClinImmunol. 2015Jul25.pii:S0091-6749(15)00838-6.doi:10.1016/j.jaci.2015.05.044. [Epub ahead of print]

 

The airway microbiome in patients with severe asthma: Associations with disease features and severity.
 

Huang YJ1, Nariya S2, Harris JM3, Lynch SV4, Choy DF3, Arron JR3, Boushey H2.
 

Abstract
BACKGROUND:Asthma is heterogeneous, and airway dysbiosis is associated with clinical features in patients with mild-to-moderate asthma. Whether similar relationships exist among patients with severe asthma is unknown.
OBJECTIVE:We sought to evaluate relationships between the bronchial microbiome and features of severe asthma.
METHODS:Bronchial brushings from 40 participants in the Bronchoscopic Exploratory Research Study of Biomarkers in Corticosteroid-refractory Asthma (BOBCAT) study were evaluated by using 16S ribosomal RNA-based methods. Relationships to clinical and inflammatory features were analyzed among microbiome-profiled subjects. Secondarily, bacterial compositional profiles were compared between patients with severe asthma and previously studied healthy control subjects (n = 7) and patients with mild-to-moderate asthma (n = 41).
RESULTS:In patients with severe asthma, bronchial bacterial composition was associated with several disease-related features, including body mass index (P < .05, Bray-Curtis distance-based permutational multivariate analysis of variance; PERMANOVA), changes in Asthma Control Questionnaire (ACQ) scores (P < .01), sputum total leukocyte values (P = .06), and bronchial biopsy eosinophil values (per square millimeter, P = .07). Bacterial communities associated with worsening ACQ scores and sputum total leukocyte values (predominantly Proteobacteria) differed markedly from those associated with body mass index (Bacteroidetes/Firmicutes). In contrast, improving/stable ACQ scores and bronchial epithelial gene expression of FK506 binding protein (FKBP5), an indicator of steroid responsiveness, correlated with Actinobacteria. Mostly negative correlations were observed between biopsy eosinophil values and Proteobacteria. No taxa were associated with a TH2-related epithelial gene expression signature, but expression of TH17-related genes was associated with Proteobacteria. Patients with severe asthma compared with healthy control subjects or patients with mild-to-moderate asthma were significantly enriched in Actinobacteria, although the largest differences observed involved a Klebsiella genus member (7.8-fold increase in patients with severe asthma, adjusted P < .001).
CONCLUSIONS:Specific microbiota are associated with and may modulate inflammatory processes in patients with severe asthma and related phenotypes. Airway dysbiosis in patients with severe asthma appears to differ from that observed in those with milder asthma in the setting of inhaled corticosteroid use.
 

JAllergyClinImmunol. 2015Jul25.pii:S0091-6749(15)00838-6.doi:10.1016/j.jaci.2015.05.044. [Epub ahead of print]