Why Bronchodilator Response Matters in COPD Risk, With Spyridon Fortis, MD

Bronchodilator responsiveness may offer clinicians a more clinically actionable signal of chronic obstructive pulmonary disease (COPD) risk than genetic profiling, according to recent findings from the COPDGene study.1,2

“Bronchodilator Response includes every type of pathology, while genetic risk scores only this one genetically predisposed to have FEV₁ decline or obstruction,” Spyridon Fortis, MD, from the division of pulmonary, critical care, and occupational medicine at the University of Iowa Hospital and Clinics, told HCPLive. “Bronchodilator Response is used in clinical practice…only to help you to diagnose asthma. It does have prognostic values in COPD…almost every single study that has studied bronchodilator response shows that it is associated with FEV₁ decline, so that's very well established.”

COPD remains underdiagnosed in its early stages, particularly among smokers whose spirometry appears normal. Identifying individuals at heightened risk before irreversible lung damage occurs is a persistent challenge. These results suggest that bronchodilator responsiveness, a readily available clinical measure, may help fill that gap by identifying subclinical airway disease that genetics alone may miss.

While bronchodilator responsiveness has established prognostic value, its role in guiding treatment decisions remains limited. Fortis and colleagues conducted a cross-sectional analysis of 4824 adults aged 45 to 80 years enrolled in the multicenter COPDGene study. All participants had a smoking history of at least 10 pack-years and normal spirometry at baseline. The cohort included both non-Hispanic White (n = 3378) and African American (n = 1446) participants. Bronchodilator responsiveness was defined by the percent change in forced expiratory volume in 1 second (FEV₁) following bronchodilator administration, while polygenic risk scores were used to estimate inherited COPD risk.

The study suggests that airway responsiveness better predicts lung function decline and progression to COPD than polygenic risk scores, even among individuals with preserved spirometry. Across models, bronchodilator responsiveness consistently outperformed genetic risk in predicting FEV₁ decline.

The analysis found that genetic risk was not correlated with bronchodilator response in African American individuals (P =.82) but had a slight, weak correlation in non-Hispanic White participants (P <.001). Non-Hispanic White participants with a bronchodilator response versus those without displayed greater polygenic risk scores.

“This is a limitation of the polygenic risk score that we use because the polygenic risk score that we use was primarily developed [using] people of European ancestry,” Fortis said. “I don't know for sure, but I believe that polygenic score that [was] developed or derived using…African American or African ancestry population will show us the same results. This is just a limitation of this specific polygenic risk score that we used.

Disclosures for Fortis include AstraZeneca Pharmaceuticals LP and GlaxoSmithKline, LLC..

References

1. Derman C. Bronchodilator Response Outperforms Genetic Risk in Predicting COPD Progression. HCPLive. Published on January 14, 2026. Accessed on January 22, 2026. https://www.hcplive.com/view/bronchodilator-response-outperforms-genetic-risk-predicting-copd-progression

2. Fortis S, Comellas AP, Bowler RP, et al. Relationships between bronchodilator responsiveness, a COPD polygenic risk score, and COPD progression. Respir Med. Published online January 9, 2026. doi:10.1016/j.rmed.2026.108636