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16S rRNA PhyloChip Analysis of Bacterial Communities in COPD

Institution: University of California, San Francisco
Investigator(s): Yvonne Huang, M.D.
Award Cycle: 2008 (Cycle 17) Grant #: 17FT-0040 Award: $75,000
Subject Area: Pulmonary Disease
Award Type: Postdoctoral Fellowship Awards

Initial Award Abstract
Chronic obstructive pulmonary disease (COPD) is an important health problem that is a primary consequence of long-term tobacco smoke exposure. Two major features often found in the respiratory tract of individuals with COPD are evidence of inflammation, and the presence of bacteria in the airways. These features have also been detected in some smokers, whether or not they have developed COPD. Some smokers also have symptoms of chronic cough and phlegm production. It is not entirely clear what all the important factors are that drive the development of COPD in a subset of smokers. Furthermore, in individuals who already have COPD, the pathologic processes involved in the occurrence of acute episodes of worsening disease (described as exacerbations) are also incompletely understood. The presence of bacteria in the respiratory tract along with persistent inflammation in COPD is increasingly well-recognized, but further research is needed to determine the importance of these findings and how they may relate to the development and worsening of COPD.

To date, research on the role of bacteria in COPD has mostly relied on performing cultures of respiratory samples (e.g. sputum or phlegm) in the laboratory to detect and identify organisms. However, only a small percentage of all bacteria which exist are able to be grown and identified by culture. As a consequence only a similar range of bacterial species have been detected across the majority of studies, and the potential importance of difficult to culture bacteria in COPD may be overlooked. For example, in the study of other diseases using newer lab methods which do not rely on cultures, such as gum disease in the mouth and inflammatory diseases of the gut, complex communities of bacteria have been identified in these areas, and shifts or differences in these bacterial communities relate to these conditions. Recently our research team has applied a novel, non-culture-based tool, called the 16S rRNA “PhyloChip”, to demonstrate the existence and importance of complex bacterial populations in exacerbations of lung disease associated with cystic fibrosis, as well as in patients with COPD who required ICU hospitalization for respiratory failure.

The PhyloChip is the most advanced tool in microbiology currently available to conduct streamlined and efficient detection of over 9,000 known bacterial species. In this research we will use the PhyloChip in two complementary studies with the overall aim to investigate the presence and potential role of different bacterial populations in the development of COPD among smokers as well as in the development of disease exacerbations among individuals who have established COPD. In the first study we will analyze, by PhyloChip, sputum obtained from smokers with and without COPD and with and without symptoms of chronic cough and sputum production. We hypothesize that differences in bacterial populations exist in the airways which may delineate smokers who do and do not have COPD and among those who do and do not experience symptoms of chronic cough and sputum production. In a second study investigating exacerbations of COPD, we will perform comparative analyses of sputum obtained from COPD patients during periods when they are stable medically, followed by when they develop an exacerbation and then as they recover from an exacerbation. Using the PhyloChip we will analyze how the types, complexity and abundance of different bacterial populations alter through these periods. Our hope is that the advanced capabilities of the PhyloChip will bring an innovative approach to studying the role of bacteria found in the respiratory tract of smokers and those with COPD and shed insight into their contribution and importance in this all-too-common disease.

A persistent and diverse airway microbiota present during chronic obstructive pulmonary disease exacerbations.
Periodical: Journal of Intergative Biology Index Medicus:
Authors: Huang,YJ; Kim, E; Cox, MJ; Brodie, EL; Brown, R; Wiener-Kronish, JP; Lynch, SV ART
Yr: 2010 Vol: 14 Nbr: 1 Abs: Pg: 9 - 59