Mayhew, David, Devos, Nathalie, Lambert, Christoph, Brown, James R., Clarke, Stuart, Kim, Viktoriya, Magid-Slav, Michal, Miller, Bruce E., Ostridge, Kristoffer, Patel, Ruchi, Sathe, Ganesh, Simola, Daniel F., Staples, Karl J., Sung, Ruby, Tal-Singer, Ruth M., Tuck, Andrew C., Van Horn, Stephanie, Weynants, Vincent, Williams, Nicholas, Devaster, Jeanne-Marie and Wilkinson, Tom M. (2018) Longitudinal profiling of the lung microbiome in the AERIS study demonstrates repeatability of bacterial and eosinophilic COPD exacerbations. Thorax, 73 (5), 422-430. (doi:10.1136/thoraxjnl-2017-210408).
Abstract
Background: Alterations in the composition of the lung microbiome associated with adverse clinical outcomes, known as dysbiosis, have been implicated with disease severity and exacerbations in chronic obstructive pulmonary disease (COPD).
Objective: To characterize longitudinal changes in the lung microbiome in the AERIS study (Acute Exacerbation and Respiratory Infections in COPD) and their relationship with associated COPD outcomes.
Methods: We surveyed 584 sputum samples from 101 COPD patients to analyze the lung microbiome at both stable and exacerbation time points over one year using highthroughput sequencing of the 16S ribosomal RNA gene. We incorporated additional lung microbiology, blood markers, and in-depth clinical assessments to classify COPD phenotypes.
Results: The stability of the lung microbiome over time was more likely to be decreased in exacerbations and within individuals with higher exacerbation frequencies. Analysis of exacerbation phenotypes using a Markov chain model revealed that bacterial and eosinophilic exacerbations were more likely to be repeated in subsequent exacerbations within a subject, whereas viral exacerbations were not more likely to be repeated. We also confirmed the association of bacterial genera, including Haemophilus and Moraxella, with disease severity, exacerbation events, and bronchiectasis.
Conclusions: Subtypes of COPD have distinct bacterial compositions and stabilities over time. Some exacerbation subtypes have non-random probabilities of repeating those subtypes in the future. This study provides insights pertaining to the identification of bacterial targets in the lung and biomarkers to classify COPD subtypes and to determine appropriate treatments for the patient.
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