Lung microbiome and inflammatory changes associated with increased COPD mortality

Published online: April 27, 2020

The symptoms and disease progression experienced by patients with the lung disease Chronic Obstructive Pulmonary Disease (COPD) can vary greatly, yet it is only relatively recently that therapies have moved away from “one size fits all” treatments to a personalised approach using, for example, blood eosinophil counts to direct treatment with inhaled corticosteroids. Bacteria are thought to play a key role in disease pathogenesis, both during disease stability and at periods of worsening symptoms (exacerbations); recent molecular studies investigating the bacteria (microbiome) present in the lungs of COPD patients have shown that as the disease becomes more severe, loss of microbial diversity (dysbiosis) increases. If dysbiosis is related to more severe disease and different immune profiles, it is plausible that the lung microbiome may associate with long term mortality and be a tool to aid in personalising treatments. No studies to date have assessed the association of the stable sputum microbiome profile with different inflammatory and clinical profiles in COPD.

In a recent study published in The Journal of Allergy and Clinical Immunology (JACI), Dicker et al report the results from a group of COPD patients. Using 16S rRNA gene sequencing on sputum from 253 clinically stable COPD patients, they compared the lung microbiome with clinical phenotypes, including blood eosinophil counts, and long-term outcomes such as mortality. 78 patient samples subsequently underwent label free liquid chromatography/ mass spectrometry followed by integration of clinical, microbiome and proteomic data to identify whether the sputum microbiome was related to different inflammatory patterns which could link to personalized treatment decisions.

The study found that patients with a microbiome dominated by Proteobacteria were more likely to have frequent exacerbations, to have more severe disease symptoms and a reduced lung function. The authors also showed that blood eosinophil counts were positively related with the percentage of Firmicutes and Streptococcus sequences in sputum. On studying mortality rates in a four year follow up period, a significantly increased mortality rate was shown in those patients with Proteobacteria dysbiosis compared to those with Firmicutes dysbiosis or a balanced microbiome. When comparing the clinical, microbiome and proteomic data, the authors were able to show that an airway dominated with Proteobacteria was associated with proteins linked to neutrophilic inflammation.

This study demonstrates for the first time that the sputum microbiome in stable COPD patients is associated with long term survival and that, for patients with a microbiome dominated with Proteobacteria, they are characterized by eosinopenia and worse disease symptoms. Whether these microbiome differences are linked to response to treatments such as inhaled corticosteroids remains to be established, but this study gives further weight to a personalized medicine approach in COPD.

The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.