Bronchodilator Response Predicts COPD Risk, With Spyridon Fortis, MD

Bronchodilator responsiveness has traditionally been associated with asthma, often leading clinicians to consider asthma-COPD overlap when airflow limitation is observed. However, in an interview with HCPLive, Spyridon Fortis, MD, of the University of Iowa Hospital and Clinics, said that this perspective may overlook the broader prognostic value of bronchodilator response, particularly in smokers with preserved spirometry.

“A lot of people…use the bronchodilator response stimulus as a [criterion]… to say, ‘Oh, my patient has asthma,’ or ‘My patient has…COPD.’ Bronchodilator responsiveness [is] actually [a] diagnostic [criterion] to demonstrate lung function viability in asthma. In COPD, [it] has no role, and it should not be used to distinguish the two diseases,” Fortis said. “It's very common to have bronchodilator responsiveness [in both] COPD and asthma…it shouldn't play any role to say my patient has asthma-COPD, asthma-COPD overlap. I don't even like the term [of asthma-COPD overlap]. Every year, [I] teach medical students, [it is] very difficult [for them] to accept that bronchodilator responsiveness cannot distinguish the two diseases.”

Fortis and colleagues conducted the COPDGene analysis, a cross-sectional study evaluating whether genetic predisposition to COPD is associated with bronchodilator responsiveness and whether these factors independently or jointly influence lung function decline among individuals at risk for COPD.^1,2 The study included 4824 adults aged 45 to 80 years with ≥ 10 pack-year smoking history and normal baseline spirometry. Bronchodilator responsiveness, measured as the percent change in forced expiratory volume in 1 second (FEV₁) after bronchodilator administration, was compared with polygenic risk scores to determine which better predicted long-term lung function decline and COPD development.

Across racial groups, bronchodilator responsiveness consistently outperformed genetic risk scores, demonstrating higher predictive accuracy for FEV₁ decline and progression to COPD. Genetic risk was correlated with bronchodilator response only in non-Hispanic White participants, not in African American participants.

During the interview, Fortis emphasized that bronchodilator responsiveness should not be used to distinguish asthma from COPD. While it remains a diagnostic criterion for asthma, in COPD it primarily reflects airway pathology. such as inflammation and smooth muscle constriction, rather than disease classification. The study supports this view, showing that even among individuals with normal spirometry, bronchodilator responsiveness identifies subclinical airway disease that may signal future lung function decline.

The analysis also highlighted the challenges of applying rigid thresholds for bronchodilator response. Historical guidelines define responsiveness using different criteria, but no single cutoff reliably stratifies long-term risk. Responsiveness can vary over time, influenced by disease activity and airway inflammation. Nevertheless, greater responsiveness consistently correlated with faster FEV₁ decline, underscoring its value as a prognostic marker rather than a diagnostic test.

Fortis noted that interventional studies are needed to determine whether early treatment in individuals with preserved lung function and significant bronchodilator responsiveness could slow or prevent COPD progression. If successful, such studies could shift clinical practice toward earlier risk identification and proactive intervention, moving COPD care beyond traditional diagnostic frameworks and leveraging bronchodilator responsiveness as a tool for prevention rather than classification.

“If we test and prove…that existing treatment in people with bronchodilator response [and] normal spirometry can prevent them [from losing] lung function, that can change [our] practice…and that will be a new focus,” Fortis said.

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