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Journal of Allergy and Clinical Immunology

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Airway microbiota and bronchial hyperresponsiveness in patients with suboptimally controlled asthma - 10/08/11

Doi : 10.1016/j.jaci.2010.10.048 
Yvonne J. Huang, MD a, Craig E. Nelson, PhD b, Eoin L. Brodie, PhD c, Todd Z. DeSantis, MS c, Marshall S. Baek, BS d, Jane Liu, MS a, Tanja Woyke, PhD e, Martin Allgaier, PhD d, Jim Bristow, MD e, Jeanine P. Wiener-Kronish, MD d, E. Rand Sutherland, MD, MPH f, Tonya S. King, PhD g, Nikolina Icitovic, MAS g, Richard J. Martin, MD f, William J. Calhoun, MD h, Mario Castro, MD i, Loren C. Denlinger, MD, PhD j, Emily DiMango, MD k, Monica Kraft, MD l, Stephen P. Peters, MD, PhD m, Stephen I. Wasserman, MD n, Michael E. Wechsler, MD o, Homer A. Boushey, MD a, Susan V. Lynch, PhD p, ⁎

National Heart, Lung, and Blood Institute’s Asthma Clinical Research Network

  Investigators of the Asthma Clinical Research Network are listed in Appendix E1 in this article’s Online Repository at www.jacionline.org.

a Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, San Francisco, Calif 
b Marine Science Institute, University of California, Santa Barbara, Calif 
c Earth Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, Calif 
d Department of Anesthesia and Perioperative Care, University of California, San Francisco, Calif 
e US Department of Energy, Joint Genome Institute, Walnut Creek, Calif 
f Division of Pulmonary and Critical Care Medicine, Department of Medicine, National Jewish Health, Denver, Colo 
g Division of Biostatistics, Department of Public Health Sciences, Pennsylvania State University, Hershey, Pa 
h Division of Allergy, Pulmonary, Immunology, Critical Care and Sleep, Department of Internal Medicine, University of Texas Medical Branch at Galveston, Galveston, Tex 
i Division of Pulmonary and Critical Care Medicine, Department of Medicine, Washington University, St Louis, Mo 
j Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Wisconsin Schools of Medicine and Public Health, Madison, Wis 
k Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 
l Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Duke University, Durham, NC 
m Section on Pulmonary, Critical Care, Allergy and Immunological Diseases, Department of Internal Medicine, Wake Forest University Health Sciences, Winston-Salem, NC 
n Allergy and Immunology Section, Department of Medicine, University of California San Diego, San Diego, Calif 
o Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass 
p Division of Gastroenterology, Department of Medicine, University of California, San Francisco, Calif 

Reprint requests: Susan V. Lynch, PhD, Colitis and Crohn’s Disease Center, Division of Gastroenterology, Department of Medicine, Box 0538, University of California, San Francisco, CA 94143.

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.
 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.


© 2010  American Academy of Allergy, Asthma & Immunology. Publié par Elsevier Masson SAS. Tous droits réservés.
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Vol 127 - N° 2

P. 372 - février 2011 Retour au numéro
Article précédent Article précédent
  • The burden of adult asthma in the United States: Evidence from the Medical Expenditure Panel Survey
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