US researchers have shown that patients with both chronic obstructive pulmonary disease (COPD) and asthma have more exacerbations, less emphysema and more airway disease than patients with COPD alone.
The 450 overlap patients, who were all non-Hispanic White or African American with a current or previous smoking history, also had several genetic variants that approached genome-wide significance that were not present to such a degree in the 3120 individuals with COPD alone.
These included a variant in the CSMD1 gene, which has previously been associated with emphysema, and another within the SOX5 gene, which has been associated with COPD. Both may play a role in lung development that is specific to non-Hispanic White patients.
Meta-analysis of the non-Hispanic White and African–American patients also highlighted six single nucleotide polymorphisms in GPR65 that were associated with COPD–asthma overlap. The protein encoded by this gene “is a member of the G2A G protein-coupled receptor family and plays an important role in eosinophil activation during asthma and extracellular inhibition of proinflammatory cytokines”, the researchers note in the European Respiratory Journal.
The team found that patients with COPD and asthma were significantly younger (60 versus 64 years) and had a significantly higher body mass index (BMI; 28.2 vs 27.9 kg/m2) and fewer pack–years of smoking (mean 45.7 vs 54.2) than those with COPD alone. The overlap patients were also more likely to be female (56 vs 43%) and African American (37 vs 20%) than those with COPD only.
After adjustment for age, race, gender and pack–years of smoking, the overlap patients had significantly worse measures of disease severity than the COPD patients including higher BODE (BMI, airflow obstruction, dyspnoea and exercise capacity; mean 3.1 vs 2.9) and St George’s Respiratory Questionnaire scores (47.4 vs 39.7).
Overlap patients also had more exacerbations per year (1.2 vs 0.7) and more severe exacerbations resulting in an emergency room visit or hospital stay in the previous year (34 vs 21%).
Volumetric chest computed tomography images showed less emphysema but thicker airways in the COPD patients than in the overlap patients, suggesting that “the airflow limitation in the overlap subjects may be the result [of] different pathological changes in the small airways”.
Commenting on their findings, Megan Harding (Brigham and Women’s Hospital, Boston, Massachusetts, USA) and colleagues say that “COPD and asthma overlap is an important syndrome and may require distinct clinical management.”
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