Airway microbiota and bronchial hyperresponsiveness in patients with suboptimally controlled asthma - 10/08/11
National Heart, Lung, and Blood Institute’s Asthma Clinical Research Network
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.
Le texte complet de cet article est disponible en PDF.Key words : Microbiome, bacteria, asthma, 16S ribosomal RNA, PhyloChip
Abbreviations used : ICS, iNKT, MIA, MRPP, NMDS, Q-PCR, 16S rRNA
Plan
Supported by the National Heart, Lung, and Blood Institute (NHLBI; U10 HL 074204) and by the Strategic Asthma Basic Research Center at the University of California, San Francisco, supported by the Sandler Family Foundation. Y.J.H. was funded by National Institutes of Health (NIH)/NHLBI grant T32 HL007185 and by a University of California Tobacco-related Disease Research Program award (17FT-0040). C.E.N. is funded by NSF 0709975 (to C.E.N. and J.M. Melack). S.V.L. is funded by NIH/National Institute of Allergy and Infectious Diseases (NIAID) grant U01 AI075410. E.L.B., T.Z.D., and J.B. are funded under the auspices of the University of California under contract number DOE DE-AC02-05CH11231. |
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Disclosure of potential conflict of interest: T. Z. DeSantis is a part-time employee of PhyloTech, Inc. J. Bristow receives research support from the DOE Joint Genome Institute. J. P. Weiner-Kronish is a board member of the Foundation of Anesthesia Education and Research. E. R. Sutherland is an advisor and DSMB member for GlaxoSmithKline, is an advisor for Dey, is a DSMB member for Merck, and receives research support from the National Institutes of Health, Novartis, and Boehringer-Ingelheim. R. J. Martin receives research support from the National Heart, Lung, and Blood Institute of the National Institutes of Health. M. Castro is a consultant for NKT Therapeutics, Schering-Plough, Asthmatx, and Cephalon; is on the Advisory Board for Genentech; is on the speakers’ bureau for Astra-Zeneca, Boehringer-Ingelheim, Pfizer, Merck, and GlaxoSmithKline; has received grant support from Asthmatx, Amgen, Ception, Genentech, MedImmune, Merck, Novartis, the National Institutes of Health, GlaxoSmithKline, and the American Lung Association; and has received royalties from Elsevier. L. C. Denlinger receives research support from the National Institutes of Health (NIH)–National Heart, Lung, and Blood Institute (NHLBI). M. Kraft has received research support from GlaxoSmithKline, Merck, Asthmatx, GE Healthcare, Novartis, and Genentech. S. P. Peters receives grant support from the NIH-NHLBI. S. I. Wasserman has provided legal consultation services/expert witness testimony in cases related to mold toxicity and transfer factor and is president of the American Board of Allergy and Immunology. M. E. Wechsler receives research support from the NHLBI. H. A. Boushey is an ad-hoc consultant for Kalobios, is on the advisory committee for Pharmaxis, is on ad-hoc advisory committees for Glaxo-SmithKline and Merck, and receives research support from GlaxoSmithKline. S. V. Lynch receives research support from the National Institutes of Health. The rest of the authors have declared that they have no conflict of interest. |
Vol 127 - N° 2
P. 372 - février 2011 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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