Longitudinal profiling of the lung microbiome in the AERIS study demonstrates repeatability of bacterial and eosinophilic COPD exacerbations

Abstract

BackgroundAlterations in the composition of the lung microbiome associated with adverse clinical outcomes, known as dysbiosis, have been implicated with disease severity and exacerbations in COPD.ObjectiveTo characterise longitudinal changes in the lung microbiome in the AERIS study (Acute Exacerbation and Respiratory InfectionS in COPD) and their relationship with associated COPD outcomes.MethodsWe surveyed 584 sputum samples from 101 patients with COPD to analyse the lung microbiome at both stable and exacerbation time points over 1 year using high-throughput sequencing of the 16S ribosomal RNA gene. We incorporated additional lung microbiology, blood markers and in-depth clinical assessments to classify COPD phenotypes.ResultsThe 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.ConclusionsSubtypes 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.Trial registration numberResults, NCT01360398.

The contribution of respiratory microbiome analysis to a treatable traits model of care

“…This microbiota composition during bacterial exacerbations was characterized by a higher relative abundance of members of either the Haemophilus or Moraxella genera . Similar findings were reported in the AERIS study; a second large longitudinal study in COPD …”

“…Patients who suffer exacerbations more frequently than would be predicted based on established risk factors are at a higher risk of serious complications . Results from the AERIS study showed that eosinophilic and bacterial exacerbations in COPD were more likely to be recurring, compared to viral exacerbations . Pre‐exacerbation microbiota diversity was also found to be lower in those experiencing more frequent exacerbations .…”

“…However, other more complex relationships between the respiratory microbiome and airway diseases also exist. Airway pathophysiology, including mucociliary dysfunction, increased airway secretions and changes in immune function, represents a group of selective pressures that influence the types and abundance of microorganisms that are present within lower airways . In the latter description, the characteristics of the respiratory microbiota reflect the conditions of the lower airway and can inform disease indirectly …”

Blood eosinophil count correlates with severity of respiratory failure in life‐threatening asthma and predicts risk of subsequent exacerbations

“…9,10,32 However, it cannot simply be assumed that thresholds for pharmacodynamic re- 35,36 and eosinophilic respiratory exacerbations portend a higher likelihood of subsequent eosinophilic exacerbation. 37 Taken together, these data suggest that high blood eosinophils could be taken as a biomarker of eosinophilic asthma, and by corollary a biomarker of response to treatments targeted at eosinophilic asthma. Our data demonstrated an obvious divergence of long-term disease trajectory at the threshold BEC of 1.2 × 10 9 cells/L, suggesting that this group may exhibit the severe eosinophilic phenotype characterized by frequent exacerbations.…”

Beneficial Effect of Early Intervention with Garenoxacin for Bacterial Infection-Induced Acute Exacerbation of Bronchial Asthma and Chronic Obstructive Pulmonary Disease

“…Recent studies utilizing specific bacterial 13S-rRNA screening showed bacterial colonization, including colonization of quinolone- or GRNX-sensitive bacteria, in both upper and lower airways of patients with asthma and COPD [22-25]. Exacerbation of CRDs were also related to microbial dysbiosis in lower airways, suggesting antibiotics may play a role in these settings [24, 26].…”