Biological exacerbation clusters demonstrate asthma and chronic obstructive pulmonary disease overlap with distinct mediator and microbiome profiles

Abstract

BackgroundExacerbations of asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous.ObjectiveWe sought to investigate the sputum cellular, mediator, and microbiome profiles of both asthma and COPD exacerbations.MethodsPatients with severe asthma or moderate-to-severe COPD were recruited prospectively to a single center. Sputum mediators were available in 32 asthmatic patients and 73 patients with COPD assessed at exacerbation. Biologic clusters were determined by using factor and cluster analyses on a panel of sputum mediators. Patterns of clinical parameters, sputum mediators, and microbiome communities were assessed across the identified clusters.ResultsThe asthmatic patients and patients with COPD had different clinical characteristics and inflammatory profiles but similar microbial ecology. Three exacerbation biologic clusters were identified. Cluster 1 was COPD predominant, with 27 patients with COPD and 7 asthmatic patients exhibiting increased blood and sputum neutrophil counts, proinflammatory mediators (IL-1β, IL-6, IL-6 receptor, TNF-α, TNF receptors 1 and 2, and vascular endothelial growth factor), and proportions of the bacterial phylum Proteobacteria. Cluster 2 had 10 asthmatic patients and 17 patients with COPD with increased blood and sputum eosinophil counts, type 2 mediators (IL-5, IL-13, CCL13, CCL17, and CCL26), and proportions of the bacterial phylum Bacteroidetes. Cluster 3 had 15 asthmatic patients and 29 patients with COPD with increased type 1 mediators (CXCL10, CXCL11, and IFN-γ) and proportions of the phyla Actinobacteria and Firmicutes.ConclusionsA biologic clustering approach revealed 3 subgroups of asthma and COPD exacerbations, each with different percentages of patients with overlapping asthma and COPD. The sputum mediator and microbiome profiles were distinct between clusters.

Blood eosinophil count and airway epithelial transcriptome relationships in COPD versus asthma

“…Our study was cross‐sectional, and the stability of the eosinophilic phenotype and the associated gene expression profile cannot be determined in this study. Although previous reports suggest the stability of the eosinophilic phenotype is moderate‐to‐good suggesting our findings are valid . A number of possible confounders could have influenced our study.…”

The Role of Lung and Gut Microbiota in the Pathology of Asthma

“…Within asthmatic inflammatory phenotypes, patients with neutrophilic asthma, usually receiving high doses of inhaled corticosteroids (ICSs), demonstrate a less diverse bacterial load with relative enrichment in Haemophilus and Moraxella species, members of Proteobacteria phylum, and a reduction in the relative abundance of Streptococcus, Gemella, and Porphyromonas taxa compared with patients with eosinophilic asthma (Taylor et al, 2019;Simpson et al, 2016;Green et al, 2014). In patients with severe asthma, a Th17 cell epithelial gene signature representing the non-type 2 asthma has been associated with increased representation of the phylum Proteobacteria, which further correlates with worsening of asthma control (Huang et al, 2015) and neutrophilic exacerbations of asthma (Ghebre et al, 2018). Klebsiella is one genus of bacteria within the Proteobacteria phylum enriched specifically in patients with severe asthma, whereas the phylum Actinobacteria correlates with improvement or no change is asthma control.…”

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

“…The recent analysis of a cohort of patients with asthma or COPD demonstrated the relationship between airway inflammation and lower airway microbiology . Sputum microbiota composition, assessed during exacerbation, was found to cluster principally according to inflammatory phenotype (eosinophilic, neutrophilic or viral‐associated inflammatory markers), rather than according to the disease group .…”