Spyridon Fortis, MD, from the division of pulmonary, critical care, and occupational medicine at the University of Iowa Hospital and Clinics.

Spyridon Fortis, MD

Bronchodilator Response Predicts COPD Risk, With Spyridon Fortis, MD

Bronchodilator responsiveness has traditionally been associated with 

, often leading clinicians to consider asthma-COPD overlap when airflow limitation is observed. However, in 

, 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 

 is associated with bronchodilator responsiveness and whether these factors independently or jointly influence lung function decline among individuals at risk for COPD.

 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.

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

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

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Fortis discusses new data that challenge the use of bronchodilator response as a tool for distinguishing asthma from COPD.

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.

“Bronchodilator Response includes every type of pathology, while genetic risk scores only this one genetically predisposed to have 

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 

. “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 

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..

https://www.hcplive.com/view/bronchodilator-response-outperforms-genetic-risk-predicting-copd-progression 

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. 

COPDGene data show bronchodilator response more accurately predicts FEV₁ decline and disease progression than polygenic risk scores, including among smokers with preserved spirometry.

Spyridon Fortis, MD

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