The Role of Interleukin-13 in Chronic Airway Diseases: A Cross-Sectional Study in COPD and Asthma–COPD Overlap

Background: Distinguishing chronic obstructive pulmonary disease (COPD) from asthma–COPD overlap (ACO) remains challenging due to shared clinical and inflammatory features. Interleukin-13 (IL-13) is implicated in airway inflammation and remodeling and may represent a potential treatable trait. This study aimed to evaluate whether serum IL-13 could differentiate between COPD and ACO or define ACO subtypes and to explore its relationship with clinical and phenotype parameters. Materials and Methods: We conducted a cross-sectional bicentric study in 215 COPD and ACO patients recruited from outpatient clinics. The study measured blood IL-13 levels in COPD vs. ACO patients, across five ACO subtypes, and evaluated IL-13’s ability to predict ACO. Additionally, correlations were explored among endotype (IL-13) and different phenotype traits (e.g., fractional exhaled nitric oxide (FeNO), sputum eosinophilia, serum total immunoglobulin E (tIgE) levels, blood eosinophilia, and neutrophilia) and clinical outcomes (annualized exacerbation rate, symptom scores, and pulmonary function parameters). Results: No significant differences in IL-13 levels were found between COPD and ACO patients or among ACO subtypes. IL-13 did not predict ACO occurrence. We observed a weak correlation between IL-13 and tIgE levels in the entire cohort. Additionally, there was a weak correlation between IL-13 and FeNO in patients with eosinophil counts exceeding 300 cells/μL, as well as between IL-13 and age in the COPD cohort. No correlation was found between IL-13 and other phenotypic features or clinical outcomes in the overall cohort, including within both COPD and ACO groups. Conclusions: IL-13 cannot differentiate between COPD and ACO or ACO’s subtypes.