Researchers at the GOLD 2026 COPD International Conference in Philadelphia presented new findings on November 5, 2026, regarding how type 2 biologics affect mucus plugs and airway inflammation in chronic obstructive pulmonary disease and asthma.
Corticosteroids Fail to Prevent Goblet Cell Replacement in Asthma
Airway biopsies from the Severe Asthma Research Program showed that goblet cells nearly replaced the epithelium even when patients received high-dose inhaled and systemic corticosteroids, according to presentations at the conference.
We know this pathway is not modified by corticosteroids,
Castro
Researchers suggested this limitation helps explain why patient responses to targeted therapies vary. Adding dupilumab, which blocks the IL-4 receptor alpha to inhibit both IL-4 and IL-13 signaling, partially restored ciliary beating frequency at increasing concentrations.
Mucus Plug Changes Correlate with Declining Lung Function
Mucus plugs persist longitudinally but change in structure over time, shifting from short, stubby forms under 12 mm to longer, stringy forms that span multiple airway branches. Higher mucus scores were linked over time to declines in both forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), with the FVC decline potentially reflecting airway closure reaching from proximal airways to distal small airways.
History from the patient is not sufficient to help us detect this mucus phenotype. What we need really is quantitative technology,
Castro
Quantitative computed tomography and hyperpolarized xenon magnetic resonance imaging serve as tools to measure airway dimensions, lung density, mucus plugs, and ventilation defects. Experts called for clinical trials to establish the minimal clinically important difference for each measure.
Clinical Trial Results in Asthma and COPD
Within the CASCADE study of individuals suffering from poorly controlled moderate to severe asthma, treatment with the anti-thymic stromal lymphopoietin antibody tezepelumab lowered mucus plug scores by a mean of 1.7, which was a markedly greater decrease than what was observed with the placebo.
Separately, the VESTIGE trial randomized 109 patients with moderate to severe asthma, blood eosinophils of 300 cells/µL or higher, and fractional exhaled nitric oxide of 25 ppb or higher to receive dupilumab or placebo for 24 weeks. About two-thirds of dupilumab-treated patients achieved fractional exhaled nitric oxide levels below 25 ppb from baselines ranging between 50 and 60 ppb.
When applying asthma biologics to COPD, clinical trials have yielded mixed results. Effect sizes tend to be smaller in COPD due to fundamental biological differences, since type 2 inflammation represents one component of COPD but serves as the dominant process in most asthma cases.
Real-World Evidence and Regulatory Context for Mepolizumab in COPD
Chronic obstructive pulmonary disease affects approximately 14.2 million adults in the United States, causing over 130,000 deaths annually and carrying a substantial economic burden. Insured individuals accounted for roughly 1.8 million COPD-related hospitalizations and 1.4 million emergency department visits in 2021. Mepolizumab reduces exacerbations in adult patients with inadequately controlled chronic obstructive pulmonary disease and an eosinophilic phenotype.
The US Food and Drug Administration originally approved mepolizumab in 2015 for severe eosinophilic asthma. Subsequent approvals followed for eosinophilic granulomatosis with polyangiitis in 2017, hypereosinophilic syndrome in 2020, and chronic rhinosinusitis with nasal polyps in 2021. Regulatory approval for mepolizumab as an add-on treatment for COPD with an eosinophilic phenotype (blood eosinophil count [BEC] ≥150 cells/µL) was granted by the FDA in the year 2025.
A retrospective, longitudinal analysis evaluated real-world data from the US Komodo Research claims database covering the period from January 2016 to June 2024. Prior to the official clearance of mepolizumab as a COPD therapy by US regulators in May 2025, investigators evaluated the drug’s real-world effectiveness among 470 COPD patients utilizing insurance information retrieved from a major American health database.
After starting mepolizumab in the pre-post analysis population, the rate of moderate or severe COPD exacerbations fell. Relative reductions of 26% and 33% in rates of OCS dispensing and bursts were also observed.
This study complied with the Health Insurance Portability and Accountability Act.
Earlier coverage: GOLD 2027 Report Refines COPD Diagnosis and Management
