Abstract
Background and Objectives: The 2023 GOLD report introduced seven etiological categories, known as etiotypes, to better reflect the heterogeneity of chronic obstructive pulmonary disease (COPD). However, the clinical, functional, radiological, and psychosocial characteristics associated with these etiologies remain insufficiently defined. This study aimed to explore the differences among GOLD 2023 etiotypes in a stable COPD cohort. Materials and Methods: This prospective, observational, cross-sectional study included 315 stable outpatients with COPD from a tertiary clinic between June and July 2025. Etiological classification was based on predefined criteria, including genetic predisposition, impaired lung development, exposure-related mechanisms, infection-related mechanisms, and asthma-like characteristics. Patients were evaluated using clinical instruments (mMRC and CAT), psychological assessments (LCQ, BDI, BAI, and CAFS), pulmonary function tests, and thoracic CT scans. Results: COPD due to environmental exposure (COPD-E) was the most common type (98.7%), followed by infection-related (COPD-I, 13.3%), asthma-related (COPD-A, 9.8%), and combined forms (COPD-D and COPD-G, each 2.5%). Participants with COPD-A were younger (median 54 vs. 66 years; p < 0.001), reported less tobacco exposure (36 vs. 50 pack-years; p < 0.001), and showed less CT-detected emphysema (31.6% vs. 78.3%; p < 0.001). COPD-G exhibited more severe airflow obstruction (FEV(1) 25.5% predicted; p < 0.001), higher symptom burden (CAT score 21 vs. 6; p < 0.001), and lower oxygen saturation (p = 0.001). Eosinophil counts and psychosocial measures did not significantly differ by etiology. Conclusions: The GOLD 2023 COPD etiotypes demonstrated distinct clinical and functional profiles, reflecting diverse underlying mechanisms of the disease. Recognizing these etiological differences can help clinicians tailor diagnostic evaluations, guide individualized treatment strategies, and ultimately improve patient outcomes. Understanding disease etiology remains a cornerstone for accurate diagnosis, personalized management and optimized therapeutic decisions in COPD.