Study Title:

Asthma Linked to Inappropriate Bacteria Inhabiting Airways

Study 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.

From press release:

Asthma may have a surprising relationship with the composition of the species of bacteria that inhabit bronchial airways, a finding that could suggest new treatment or even potential cures for the common inflammatory disease, according to a new UCSF-led study.

Using new detection methods, researchers learned that the diversity of microbes inside the respiratory tract is far vaster than previously suspected -- creating a complex and inter-connected microbial neighborhood that appears to be associated with asthma, and akin to what has also been found in inflammatory bowel disease, vaginitis, periodontitis, and possibly even obesity.

Contrary to popular belief, the scientists also learned that the airways are not necessarily entirely sterile environments, even in healthy people, while the airways of asthmatics are infected by a richer, more complex collection of bacteria. These findings could improve understanding of the biology of asthma, and potentially lead to new and much-needed therapies.

"People thought that asthma was caused by inhalation of allergens but this study shows that it may be more complicated than that -- asthma may involve colonization of the airways by multiple bacteria,'' said study co-author Homer Boushey, MD, a UCSF professor of medicine in the division of Pulmonary and Critical Care Medicine.

The study is published online in the Journal of Allergy and Clinical Immunology.

Asthma is one of the most common diseases in the world, with approximately 300 million asthmatics globally, including 24 million in the United States, according to the Centers for Disease Control. The disease has been on the rise for the last 60 years.

"It has gone from 3 percent of the population to slightly more than 8 percent of the population in the U.S.,'' said Boushey. "It is most prevalent in western, developed nations -- and we don't know why.''

In recent years, scientists began studying communities of mixed-species microorganisms (microbiome) found in both diseased and healthy people to better understand their role in a variety of diseases. But research on the microbiome in respiratory disease is relatively uncharted terrain.

"We know fairly little about the diversity, complexity and collective function of bacteria living in the respiratory tract, and how they might contribute to diseases like asthma,'' said Yvonne J. Huang, MD, the paper's first author. She is a research fellow and clinical instructor in the UCSF Pulmonary Division.

"Traditionally, the airways have been thought to be sterile. However, this study suggests this is not the case. Certain asthma patients who require inhaled corticosteroid therapy possess a great abundance of bacteria compared to healthy individuals, and have an increased relative abundance of specific organisms that is correlated with greater sensitivity of their airways.''

In their three-year pilot project, the scientists collected samples from the airway linings of 65 adults with mild to moderate asthma and 10 healthy subjects. Then, using a tool that can identify approximately 8,500 distinct groups of bacteria in a single assay, the scientists profiled the organisms present in each sample to look for relationships between bacterial community composition and clinical characteristics of the patients' asthma.

The researchers found that bronchial airway samples from asthmatic patients contained far more bacteria than samples from healthy patients. The scientists also found greater bacterial diversity in the asthmatic patients who had the most hyper-responsive or sensitive airways (a feature of asthma).

"People have viewed asthma as a misdirected immune reaction to environmental exposures, but few have thought of it in the context of airway microbiota composition,'' said senior author Susan Lynch, PhD, an assistant professor of medicine and director of the UCSF Colitis and Crohn's Disease Microbiome Research Core in the division of gastroenterology.

"We took an ecological approach, considering the bacteria in the context of their microbial neighborhoods to identify relationships between characteristics of these communities and features of the disease…This new approach will help us to better understand the microbiota-host relationships that define human health.''

The authors say that further studies are needed to determine how these specific bacteria identified in the study may influence the cause and development of asthma.

Study Information

Yvonne J. Huang, Craig E. Nelson, Eoin L. Brodie, Todd Z. DeSantis, Marshall S. Baek, Jane Liu, Tanja Woyke, Martin Allgaier, Jim Bristow, Jeanine P. Wiener-Kronish.
Airway microbiota and bronchial hyperresponsiveness in patients with suboptimally controlled asthma
Journal of Allergy and Clinical Immunology
2011 February
University of California - San Francisco.

Full Study

http://www.jacionline.org/article/S0091-6749(10)01760-4/fulltext