Researchers Use Genetic Risk Score, CT of Lungs to Personalize Risk of COPD

A genetic risk score (GRS) related to chronic obstructive pulmonary disease (COPD) susceptibility was found to be associated to lung structure measured by computed tomography (CT), indicating the possible use of lung structure data to determine COPD risk, according to a study published this week in the American Journal of Respiratory and Critical Care Medicine.

Genetic variants associated with COPD have been found to provide a significant benefit toward distinguishing risk for specific patients. Researchers sought to examine the extent to which genetic risk is associated to variations in lung structure, which has yet to be examined. The study assessed the link between a GRS associated with COPD susceptibility and CT-measured lung structure through data derived from 2517 participants of the Multi-Ethnic Study of Atherosclerosis Lung Study (MESA Lung), and 2339 participants of the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS):

• Weighted GRS calculated from 83 single nucleotide polymorphisms previously associated with lung function
• Lung density, spatially matched airway dimensions, and airway counts were assessed on full-lung CT
• Generalized linear models adjusted for age, age squared, sex, height, principal components of genetic ancestry, smoking, pack-years, CT model, milliamperes, and total lung volume

Data unveiled a higher GRS associated with lower lung function, lower lung density, smaller airway lumens, and fewer small airways toward increased COPD risk, without effect modification by smoking. “Adjustment for CT lung structure, particularly small airway measures, attenuated associations between GRS and FEV₁/FVC by 100% and 60% in MESA and SPIROMICS,” said the authors.

The significant correlation found in both data sets, chiefly in MESA Lung, reveals the stark impact of lung structure on COPD susceptibility through related GRS scores. Researchers further highlighted the potential of lung structure in measured COPD risk as it alone showed improved discrimination of moderate-to-severe COPD cases relative to clinical factors, while GRS did not (P <.0001 vs P >.10).

Utilizing lung structure as a potential indicator of COPD risk can improve preventative treatment of at-risk patients. Based off the US general population-based cohort, these findings will continue research into genetic variants associated with COPD. “Lung structure may be an important mediator of heritability and determinant of personalized COPD risk,” said the authors.

Reference

Oelsner EC, Ortega VE, Smith BM, et al. A genetic risk score associated with chronic obstructive pulmonary disease susceptibility and lung structure on computed tomography. [published online September 15, 2019]. American Journal of Respiratory and Critical Care Medicine. doi: 10.1164/rccm.201812-2355OC.