Airway microbiota and bronchial hyperresponsiveness in patients with suboptimally controlled asthma

被引:536
作者
Huang, Yvonne J. [2 ]
Nelson, Craig E. [3 ]
Brodie, Eoin L. [4 ]
DeSantis, Todd Z. [4 ]
Baek, Marshall S. [5 ]
Liu, Jane [2 ]
Woyke, Tanja [6 ]
Allgaier, Martin [5 ]
Bristow, Jim [6 ]
Wiener-Kronish, Jeanine P. [5 ]
Sutherland, E. Rand [7 ]
King, Tonya S. [8 ]
Icitovic, Nikolina [8 ]
Martin, Richard J. [7 ]
Calhoun, William J. [9 ]
Castro, Mario [10 ]
Denlinger, Loren C. [11 ]
DiMango, Emily [12 ]
Kraft, Monica [13 ]
Peters, Stephen P. [14 ]
Wasserman, Stephen I. [15 ]
Wechsler, Michael E. [16 ]
Boushey, Homer A. [2 ]
Lynch, Susan V. [1 ,17 ]
机构
[1] Univ Calif San Francisco, Colitis & Crohns Dis Ctr, Div Gastroenterol, Dept Med, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Div Pulm & Crit Care Med, Dept Med, San Francisco, CA 94143 USA
[3] Univ Calif Santa Barbara, Inst Marine Sci, Santa Barbara, CA 93106 USA
[4] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Earth Sci, Berkeley, CA 94720 USA
[5] Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA
[6] US DOE, Joint Genome Inst, Walnut Creek, CA USA
[7] Natl Jewish Hlth, Div Pulm & Crit Care Med, Dept Med, Denver, CO USA
[8] Penn State Univ, Div Biostat, Dept Publ Hlth Sci, Hershey, PA USA
[9] Univ Texas Med Branch Galveston, Div Allergy Pulm Immunol Crit Care & Sleep, Dept Internal Med, Galveston, TX USA
[10] Washington Univ, Div Pulm & Crit Care Med, Dept Med, St Louis, MO 63130 USA
[11] Univ Wisconsin, Div Pulm & Crit Care Med, Dept Med, Sch Med & Publ Hlth, Madison, WI 53706 USA
[12] Columbia Univ Coll Phys & Surg, Div Pulm Allergy & Crit Care Med, Dept Med, New York, NY 10032 USA
[13] Duke Univ, Div Pulm Allergy & Crit Care Med, Dept Med, Durham, NC 27706 USA
[14] Wake Forest Univ Hlth Sci, Sect Pulm Crit Care Allergy & Immunol Dis, Dept Internal Med, Winston Salem, NC USA
[15] Univ Calif San Diego, Allergy & Immunol Sect, Dept Med, San Diego, CA 92103 USA
[16] Brigham & Womens Hosp, Div Pulm & Crit Care Med, Dept Med, Boston, MA 02115 USA
[17] Harvard Univ, Sch Med, Boston, MA 02115 USA
基金
美国国家科学基金会; 美国国家卫生研究院;
关键词
Microbiome; bacteria; asthma; 16S ribosomal RNA; PhyloChip; OBSTRUCTIVE PULMONARY-DISEASE; KILLER T-CELLS; EXHALED NITRIC-OXIDE; EOSINOPHILIC INFLAMMATION; INHALED CORTICOSTEROIDS; PSEUDOMONAS-AERUGINOSA; COMAMONAS-TESTOSTERONI; CHLAMYDIA-PNEUMONIAE; BACTERIAL DIVERSITY; CLUSTER-ANALYSIS;
D O I
10.1016/j.jaci.2010.10.048
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
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 2011;127:372-81.)
引用
收藏
页码:372 / U689
页数:13
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