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Relationships between bronchodilator responsiveness, a COPD polygenic risk score, and COPD progression
Spyridon Fortis1, Alejandro P Comellas2, Russell P Bowler3
1Center for Access & Delivery Research & Evaluation (CADRE), Iowa City VA Health Care System, Iowa City, IA, USA; Division of Pulmonary, Critical Care and Occupational Medicine, University of Iowa Hospital and Clinics, Iowa City, IA, USA.
Respiratory Medicine
|January 11, 2026
Summary
Bronchodilator responsiveness (BDR) is a stronger predictor of COPD progression and lung function decline than genetic risk scores (PRS). BDR partially mediates the effect of PRS on lung function decline.
Area of Science:
- Pulmonary Medicine
- Genetics
- Respiratory Research
Background:
- Bronchodilator responsiveness (BDR) is linked to Chronic Obstructive Pulmonary Disease (COPD) progression.
- Polygenic risk scores (PRS) predict COPD and reduced lung function.
- The relationship between genetic predisposition, BDR, and COPD development remains unclear.
Purpose of the Study:
- To investigate the association between PRS and BDR in individuals at risk for COPD.
- To determine if PRS and BDR together influence lung function decline.
- To compare the predictive power of PRS and BDR for COPD progression and FEV1 decline.
Main Methods:
- Analysis of data from the COPDGene study participants with smoking history and normal baseline spirometry.
- Cross-sectional examination of PRS association with BDR (FEV1% change).
- Longitudinal analysis of PRS, BDR, and FEV1 decline, adjusted for covariates.
Main Results:
- PRS correlated with BDR in non-Hispanic Whites (NHW) but not African Americans (AA).
- BDR models showed higher accuracy than PRS models for predicting COPD progression and FEV1 decline in both AA and NHW.
- Mediation analysis indicated BDR explains approximately one-third of the PRS effect on FEV1 decline in NHW.
Conclusions:
- BDR is a more significant predictor of COPD progression and FEV1 decline than PRS.
- BDR partially mediates the impact of genetic predisposition (PRS) on lung function decline.
- Findings highlight the clinical relevance of BDR in managing COPD risk.
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