The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2026 update revised COPD combined assessment and recommends dual long-acting β2-agonist/long-acting muscarinic antagonist (LABA/LAMA) therapy as initial inhaled maintenance for patients in GOLD assessment groups B and E. Despite this recommendation, some patients continue to experience exacerbations while receiving dual bronchodilator therapy. The authors conducted a retrospective cohort study to identify baseline risk factors associated with future exacerbations in patients with COPD treated with dual LABA/LAMA.
This study used a retrospective cohort design. Baseline data collected included demographic characteristics, pulmonary function, symptom scores (clinical COPD questionnaire), GOLD grades and GOLD groups, the number of exacerbations and hospitalizations in the prior year, the specific use of LABA/LAMA, and comorbidities. Patients were followed for one year and the number of future exacerbations during that period was recorded. The primary analytic approach was logistic regression to identify independent risk factors associated with experiencing an exacerbation during follow-up.
A total of 1,076 patients with COPD were included in the analysis. During one year of follow-up, 284 patients (26.4%) experienced exacerbations while on dual LABA/LAMA therapy.
Patients who experienced exacerbations during follow-up differed from those who did not in several baseline features: they were older, had higher clinical COPD questionnaire scores indicating greater symptom burden, had a greater number of exacerbations and hospitalizations in the previous year, and a higher proportion had GOLD grades 3–4 (more severe airflow limitation).
In multivariable logistic regression analyses of the full cohort, the following baseline factors were independently associated with increased odds of experiencing an exacerbation during follow-up:
These findings indicate that more severe airflow obstruction and a history of prior exacerbations were associated with a higher risk of future exacerbation despite treatment with dual bronchodilators.
Because GOLD 2026 recommends LABA/LAMA as initial therapy for groups B and E, the investigators performed subgroup logistic regression analyses within these assessment groups.
In GOLD group B, independent risk factors for experiencing an exacerbation during follow-up were GOLD grades 3–4 (OR = 1.808, 95% CI = 1.096–2.981) and a comorbid diagnosis of hypertension (OR = 3.400, 95% CI = 1.712–6.752).
In GOLD group E, having two or more exacerbations in the prior year (≥2) was an independent predictor of future exacerbation (OR = 1.426, 95% CI = 1.021–1.993).
These subgroup results suggest heterogeneity in risk profiles: airflow limitation severity and cardiovascular comorbidity were prominent drivers in group B, while prior exacerbation burden remained important in group E.
In this cohort of 1,076 patients with COPD treated with dual LABA/LAMA, more than one-quarter (26.4%) experienced exacerbations during one year of follow-up. The study identifies GOLD grades 3–4 and prior-year exacerbation history as independent risk factors for future exacerbation in patients receiving dual bronchodilator therapy. Subgroup analysis showed that hypertension emerged as an additional independent risk factor in GOLD group B, while recurrent prior exacerbations (≥2) predicted recurrence in group E.
These findings underscore that treatment with guideline-recommended LABA/LAMA does not eliminate exacerbation risk, and clinicians should pay particular attention to patients with advanced airflow limitation and those with recent exacerbations. The data support close monitoring and consideration of individualized management strategies for these higher-risk patients while on dual bronchodilator therapy.
Note: The provided source abstract presents study design, baseline variables, main outcomes, and multivariable results. Additional methodological details, such as exact definitions of exacerbation used, exclusion criteria, specific LABA/LAMA agents, and other potential confounders, were not reported in the abstract text supplied here.