Bacterial Colonization and Airway Inflammation Relationship with COPD Examined

Chronic obstructive pulmonary disease (COPD) is linked to both airway inflammation and bacterial colonization, but it is unknown whether the airway microbiome is associated with systemic protein levels.

A team, led by Mohammadali Yavari Ramsheh, University of Leicester, investigated the relationship between the COPD sputum microbiome and contemporaneous proteome profile in a poster presented at the European Respiratory Society International Congress 2020 (ERS 2020).

The investigators examined 31 patients with COPD at the stable stage as part of the COPD-BEAT study and obtained microbial profile from sputum and proteomic profile from plasma through 16S rDNA sequencing and mass spectrophotometry respectively.

Of the 31 COPD patients, 24 (77%) were male with a median age of 68.23 years old.

Proteomic profiles were investigated all identified bacterial genera exceeding 1% of the cumulative microbiome with bacterial abundance dichotomized by high and low expression against the median.

A total 377 proteins were significantly differentially expressed between high and low abundance of the bacterial genera were included and pathway analysis of these proteins showed the complement and coagulation cascades pathway was most frequently correlated with specific bacterial genera.

Notably, Moraxella and Veillonella were positively and negatively associated, respectively.

In addition, the investigators found a reciprocal relationship between the abundances of these genera (r = -0.38; P = 0.03), with no significant correlation between proteins identified in this pathway and clinical characteristics.

“The complement and coagulation cascades pathway was up-regulated in response to airway presence of Moraxella genera that might suggest an activation of systemic innate immunity in response to Moraxella rather than impaired systemic immunity driving airway colonization,” the authors wrote.

Recently, investigators discovered how polygenic risk scores could be used to help high risk patients for COPD.

An international team of investigators—led by Martin D. Tobin, PhD, of the University of Leicester, and Michael H. Cho, MD, of Brigham and Women’s Hospital—a polygenic risk score comprised of genome-wide association study of lung function helped predict individuals at increased risk of moderate-to-severe COPD, cigarette smoking-associated emphysema, and reduced lung growth.

The risk score could help inform future COPD mechanism research, eventually benefitting preventive and prognostic developments into a chronic pulmonary condition which is still little-understood and limitedly treated.

Tobin, Cho and colleagues created a polygenic risk score using metrics of lung function—including FEV1 and FEV1/FVC—from the UK Biobank and SpiroMeta. As investigators noted, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) definition for COPD entails the presence of persistent respiratory symptoms with airflow obstruction based on a low FEV1/FVC ration, and a graded spirometry based on predicted FEV1 percentage.

The team tested the polygenic risk score in 9 cohorts of multiple ethnicities for an association with moderate-to-severe COPD as per FEV1/FVC <.07 and FEV1 <80% predicted.

Polygenic risk scores were superior to previously described genetic risk scores, and when combined with clinical risk factors of patient age, sex, and smoking pack-years, showed improved COPD prediction versus a model using just clinical factors.

The study, “Association between microbiome and plasma proteome profile in COPD,” was published online by ERS 2020.