Study identifies eight signals for asthma-COPD overlap

A new study identified eight signals for asthma-COPD overlap that researchers said appear to represent loci that predispose patients to type 2 inflammation and thus serious long-term consequences of asthma, researchers reported in Chest.

“Guidelines emphasize that asthma and COPD are different conditions, but may coexist in the same patient,” Catherine John, MBBChir, from the department of health sciences at the University of Leicester, England, and colleagues wrote. “People with features of both diseases risk being excluded from research that might provide evidence about the most effective treatment strategies.”

John and colleagues conducted a genome-wide association study that included 8,068 participants asthma-COPD overlap (mean age, 60 years; 48.2% women) and 40,360 controls without asthma or COPD (mean age, 57 years; 56.4% women) from the UK Biobank in stage 1. Researchers followed up promising signals that were still associated in analyses that compared asthma-COPD overlap vs. asthma-only controls and asthma-COPD overlap vs. COPD-only controls.

The researchers identified 31 independent variants to continue investigating in stage 2 of this study and identified eight novel signals for asthma-COPD overlap. These asthma-COPD overlap signals suggest that there is a spectrum of shared genetic influences in these patients, according to the researchers.

The following signals predominantly influenced asthma:

• FAM105A;
• GLB1;
• PHB; and
• TSLP.

The remaining signals predominantly influence fixed airflow obstruction:

• IL17RD;
• C5orf56; and
• HLA-DQB1.

There was one intergenic signal on chromosome 5 that was not previously associated with asthma, COPD or overall lung function, the researchers reported.

Researchers also conducted subgroup analyses that suggest that associations at all eight signals were not driven by smoking or age when diagnosed with asthma. In addition, phenome-wide scans, eosinophil counts, atopy and asthma traits were prominent.

According to the researchers, these findings contribute to the understanding of asthma-COPD overlap genetic architecture.

“We focus on variants that tend toward an intermediate phenotype with features of both asthma and fixed airflow obstruction, with pathways implicating innate and adaptive immunity and potentially bone development and signals for which the biology remains unclear,” the researchers wrote. “Further biological understanding is likely to be important for therapeutics to prevent the development of fixed airflow obstruction among people with asthma.”