COPD
Aiya Almogaber, PharmD
A major update to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines includes a more personalized approach to inhaled therapy in patients with stable COPD.
Published in JAMA on June 23, 2025, as a synopsis of the 2025 GOLD report, the guidance outlines stepwise treatment strategies that emphasize inhaled combinations, escalation based on blood eosinophil counts, and de-escalation of corticosteroids when appropriate.
The clinical challenge
COPD affects more than 10% of adults worldwide and is marked by persistent airflow obstruction leading to chronic symptoms and periodic exacerbations. Stable COPD refers to disease that is not currently in an acute exacerbation. The goals of treatment include reducing daily symptoms, lowering the risk of future flare-ups, and improving quality of life.
To classify patients, the 2025 GOLD report introduced the ABE system, replacing the prior ABCD scheme. Patients with two or more moderate exacerbations or one hospitalization per year are now grouped as category E, reflecting highest exacerbation risk. Those with fewer events are grouped as A or B based on symptom severity, measured by the COPD Assessment Test or the modified Medical Research Council dyspnea scale.
Initiation of pharmacotherapy
All patients should be offered a short-acting bronchodilator for immediate relief of symptoms, according to the guidelines. For patients in group A, long-acting bronchodilator monotherapy, either a muscarinic antagonist (LAMA) or b-agonist (LABA), is preferred over short-acting options. Evidence from large trials, such as INVIGORATE and POET-COPD, demonstrated that LAMAs like tiotropium reduced exacerbation rates compared with LABAs, such as indacaterol or salmeterol, although both classes improved lung function with similar safety profiles.
For patients in groups B and E, who either have greater symptom burden or higher exacerbation risk, dual therapy with a LABA and a LAMA is recommended as the starting regimen.
Clinical trials and meta-analyses consistently show that LABA–LAMA combinations provide better symptom control and reduce exacerbations more effectively than monotherapy or LABA–inhaled corticosteroid (ICS) combinations.
Escalation and de-escalation
If symptoms persist despite correct inhaler use, therapy should be escalated, said the guideline authors. Patients with uncontrolled dyspnea on monotherapy should be switched to LABA–LAMA dual therapy. If exacerbations continue on dual therapy, the guidelines recommend checking the blood absolute eosinophil count (AEC) to guide whether to add an ICS.
Evidence shows that patients with higher eosinophil counts benefit most from ICS-containing regimens, with greater reductions in exacerbations seen as AEC rises above 100–300 cells/μL. The ETHOS trial further demonstrated that triple therapy (LABA–LAMA–ICS) reduced all-cause mortality compared with dual bronchodilator therapy.
The 2025 guidelines also highlight when to scale back therapy. Patients on LABA–ICS without frequent exacerbations or with eosinophil counts below 100 cells/μL should be transitioned to LABA–LAMA. ICS withdrawal may also be appropriate for patients experiencing adverse effects, such as recurrent pneumonia or oral candidiasis, though caution is advised in those with very high eosinophil counts where withdrawal increased exacerbation risk.
Balancing benefits and harms
While guideline-based inhaled therapies improve symptoms and reduce exacerbations, they carry potential risks.
LABAs may cause tachycardia, arrhythmias, or tremors in older adults. LAMAs are commonly associated with dry mouth. ICS use may also increase pneumonia risk, particularly at higher doses. A network meta-analysis showed pneumonia was diagnosed more often in patients using ICS compared with placebo, an effect largely linked to high-dose corticosteroid exposure.
The new GOLD report also emphasizes the importance of nondrug measures. Smoking cessation, vaccination, and pulmonary rehabilitation remain essential pillars of COPD management. The guidelines additionally note future directions, including the development of digital inhalers that track adherence and new therapies such as ensifentrine, a dual phosphodiesterase inhibitor currently under investigation.
Implications for care
The 2025 GOLD report underscores a more individualized approach to COPD therapy. Treatment choices now hinge not only on symptoms and exacerbation history, but also on biomarkers such as eosinophil counts. This shift allows clinicians to match therapy intensity more closely with patient needs, balancing benefits against risks like pneumonia.
With more than 30 available inhaled products, cost, device type, and patient ability to use the inhaler correctly also play a role. Regular assessment of response, adherence, and inhaler technique is recommended before declaring therapy failure.
Together, these updates encourage clinicians to see inhaled therapy not as a one-size-fits-all approach, but as a tailored plan that should evolve with the patient’s disease course. ■