在哮喘未达到最佳控制的患者中的气道微生物群和支气管高反应性
2011/03/28
摘要
背景：大环内酯类抗生素治疗后肺功能改善，可能与降低支气管细菌感染有关。然而，支气管内定植有多种生物群，哮喘的临床特征可能与气道微生物群的特征相关。
目的：采用不依赖培养的方法，检测大多数已知细菌及其丰度，研究气道细菌微生物群与哮喘临床症状之间是否存在相关性。
方法：在本项初步研究中，对来自研究克拉霉素对哮喘控制影响的多中心试验中的65名哮喘控制未达到最佳的成人患者，和10名健康对照，刷取支气管上皮细胞。联合高密度16S核糖体RNA基因芯片分析和平行克隆文库测序分析，研究微生物群及其与临床检测指标之间的关系。
结果：与健康对照者相比，哮喘患者的16S核糖体RNA扩增子浓度（细菌负担的一个指标）和细菌多样性显著增加。多变量分析显示，气道微生物群组成和多样性与支气管高反应性显著相关。特别是，某些种系型（包括丛毛单胞菌科、鞘脂单胞菌科、草酸杆菌科和其他细菌家族）相对丰度，与支气管高反应性程度显著相关。
结论：在哮喘未达到最佳控制的患者中，支气管微生物群组成与支气管高反应性程度相关。因此，有必要进行功能学试验，研究这些气道微生物群成员在哮喘致病中的作用。
（陈欣 审校）
J Allergy Clin Immunol. 2010 Dec 30. [Epub ahead of print]
Airway microbiota and bronchial hyperresponsiveness in patients with suboptimally controlled asthma.
Huang YJ, Nelson CE, Brodie EL, Desantis TZ, Baek MS, Liu J, Woyke T, Allgaier M, Bristow J, Wiener-Kronish JP, Sutherland ER, King TS, Icitovic N, Martin RJ, Calhoun WJ, Castro M, Denlinger LC, Dimango E, Kraft M, Peters SP, Wasserman SI, Wechsler ME, Boushey HA, Lynch SV; for the National Heart, Lung, and Blood Institute’s Asthma Clinical Research Network.
Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Francisco, Calif.
Abstract
BACKGROUND: Improvement in lung function after macrolide antibiotic therapy has been attributed to reduction in bronchial infection by specific bacteria. However, the airway might be populated by a more diverse microbiota, and clinical features of asthma might be associated with characteristics of the airway microbiota present.
OBJECTIVE: We sought to determine whether relationships exist between the composition of the airway bacterial microbiota and clinical features of asthma using culture-independent tools capable of detecting the presence and relative abundance of most known bacteria.
METHODS: In this pilot study bronchial epithelial brushings were collected from 65 adults with suboptimally controlled asthma participating in a multicenter study of the effects of clarithromycin on asthma control and 10 healthy control subjects. A combination of high-density 16S ribosomal RNA microarray and parallel clone library-sequencing analysis was used to profile the microbiota and examine relationships with clinical measurements.
RESULTS: Compared with control subjects, 16S ribosomal RNA amplicon concentrations (a proxy for bacterial burden) and bacterial diversity were significantly higher among asthmatic patients. In multivariate analyses airway microbiota composition and diversity were significantly correlated with bronchial hyperresponsiveness. Specifically, the relative abundance of particular phylotypes, including members of the Comamonadaceae, Sphingomonadaceae, Oxalobacteraceae, and other bacterial families were highly correlated with the degree of bronchial hyperresponsiveness.
Conclusion: The composition of bronchial airway microbiota is associated with the degree of bronchial hyperresponsiveness among patients with suboptimally controlled asthma. These findings support the need for further functional studies to examine the potential contribution of members of the airway microbiota in asthma pathogenesis.
J Allergy Clin Immunol. 2010 Dec 30. [Epub ahead of print]
背景：大环内酯类抗生素治疗后肺功能改善，可能与降低支气管细菌感染有关。然而，支气管内定植有多种生物群，哮喘的临床特征可能与气道微生物群的特征相关。
目的：采用不依赖培养的方法，检测大多数已知细菌及其丰度，研究气道细菌微生物群与哮喘临床症状之间是否存在相关性。
方法：在本项初步研究中，对来自研究克拉霉素对哮喘控制影响的多中心试验中的65名哮喘控制未达到最佳的成人患者，和10名健康对照，刷取支气管上皮细胞。联合高密度16S核糖体RNA基因芯片分析和平行克隆文库测序分析，研究微生物群及其与临床检测指标之间的关系。
结果：与健康对照者相比，哮喘患者的16S核糖体RNA扩增子浓度（细菌负担的一个指标）和细菌多样性显著增加。多变量分析显示，气道微生物群组成和多样性与支气管高反应性显著相关。特别是，某些种系型（包括丛毛单胞菌科、鞘脂单胞菌科、草酸杆菌科和其他细菌家族）相对丰度，与支气管高反应性程度显著相关。
结论：在哮喘未达到最佳控制的患者中，支气管微生物群组成与支气管高反应性程度相关。因此，有必要进行功能学试验，研究这些气道微生物群成员在哮喘致病中的作用。
（陈欣 审校）
J Allergy Clin Immunol. 2010 Dec 30. [Epub ahead of print]
Airway microbiota and bronchial hyperresponsiveness in patients with suboptimally controlled asthma.
Huang YJ, Nelson CE, Brodie EL, Desantis TZ, Baek MS, Liu J, Woyke T, Allgaier M, Bristow J, Wiener-Kronish JP, Sutherland ER, King TS, Icitovic N, Martin RJ, Calhoun WJ, Castro M, Denlinger LC, Dimango E, Kraft M, Peters SP, Wasserman SI, Wechsler ME, Boushey HA, Lynch SV; for the National Heart, Lung, and Blood Institute’s Asthma Clinical Research Network.
Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Francisco, Calif.
Abstract
BACKGROUND: Improvement in lung function after macrolide antibiotic therapy has been attributed to reduction in bronchial infection by specific bacteria. However, the airway might be populated by a more diverse microbiota, and clinical features of asthma might be associated with characteristics of the airway microbiota present.
OBJECTIVE: We sought to determine whether relationships exist between the composition of the airway bacterial microbiota and clinical features of asthma using culture-independent tools capable of detecting the presence and relative abundance of most known bacteria.
METHODS: In this pilot study bronchial epithelial brushings were collected from 65 adults with suboptimally controlled asthma participating in a multicenter study of the effects of clarithromycin on asthma control and 10 healthy control subjects. A combination of high-density 16S ribosomal RNA microarray and parallel clone library-sequencing analysis was used to profile the microbiota and examine relationships with clinical measurements.
RESULTS: Compared with control subjects, 16S ribosomal RNA amplicon concentrations (a proxy for bacterial burden) and bacterial diversity were significantly higher among asthmatic patients. In multivariate analyses airway microbiota composition and diversity were significantly correlated with bronchial hyperresponsiveness. Specifically, the relative abundance of particular phylotypes, including members of the Comamonadaceae, Sphingomonadaceae, Oxalobacteraceae, and other bacterial families were highly correlated with the degree of bronchial hyperresponsiveness.
Conclusion: The composition of bronchial airway microbiota is associated with the degree of bronchial hyperresponsiveness among patients with suboptimally controlled asthma. These findings support the need for further functional studies to examine the potential contribution of members of the airway microbiota in asthma pathogenesis.
J Allergy Clin Immunol. 2010 Dec 30. [Epub ahead of print]
上一篇：
同卵双生子呼吸道合胞病毒所致毛细支气管炎与哮喘的因果关联研究
下一篇：
基于诱导痰液样本的基因表达谱，定义哮喘的转录表型
