Bronchodilator Responsiveness Predicts COPD Progression Better Than Genetic Risk: Study
USA: Researchers have discovered in a new research that bronchodilator responsiveness (BDR) shows a stronger association with progression to COPD and decline in FEV₁ than polygenic risk score (PRS). Additionally, part of the effect of polygenic risk score on disease progression appears to be mediated through BDR.
A new study published in Respiratory Medicine by Spyridon Fortis from the Center for Access & Delivery Research & Evaluation (CADRE), Iowa City VA Health Care System, and colleagues sheds light on how genetic susceptibility and physiological response to bronchodilators interact in shaping the risk and progression of chronic obstructive pulmonary disease (COPD). The findings suggest that BDR may be a more powerful early marker of disease progression than genetic risk alone, particularly among individuals with a history of smoking but normal lung function at baseline.
COPD is a progressive respiratory condition often linked to smoking, but not all smokers develop the disease. While polygenic risk scores aggregate multiple genetic variants associated with COPD risk, their relationship with early functional changes in the lungs has remained uncertain. The researchers aimed to clarify whether genetic risk is associated with BDR and how both factors influence lung function decline and progression to COPD.
The analysis drew on data from the COPDGene study, focusing on participants with a smoking history and normal spirometry at enrollment. The team examined associations between PRS and two measures of BDR—one based on change from pre-bronchodilator values and another relative to predicted lung function. They also assessed how PRS and BDR related to future COPD development and longitudinal decline in forced expiratory volume in one second (FEV₁), adjusting for key demographic and clinical factors.
The following were the key findings:
• The analysis showed clear ancestry-related differences, with higher polygenic risk scores significantly associated with greater bronchodilator responsiveness among non-Hispanic White participants, while no meaningful association between PRS and BDR was observed in African American participants.
• Non-Hispanic White individuals who exhibited bronchodilator responsiveness had higher genetic risk scores compared with those without bronchodilator responsiveness.
• Bronchodilator responsiveness proved to be a stronger predictor of lung function decline than polygenic risk score.
• Models that included BDR more accurately predicted progression to COPD and long-term decline in FEV₁ than models based solely on polygenic risk score, a finding consistent across both ancestry groups.
• Mediation analysis indicated that approximately one-third of the effect of polygenic risk on lung function decline in non-Hispanic White participants was mediated through bronchodilator responsiveness, suggesting a biological pathway linking genetic susceptibility to airway response.
"Overall, the study highlights bronchodilator responsiveness as a key intermediate marker connecting genetic risk to COPD progression. The findings support the potential value of incorporating BDR assessment into early risk stratification strategies, especially for smokers with normal spirometry, to better identify individuals at higher risk of developing COPD," the authors concluded.
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