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Background: Although FEV1 remains the gold standard for staging COPD, the association between airway remodeling and airflow limitation remains unclear. Endobronchial optical coherence tomography (EB-OCT) was performed to assess the association between disorders of large and medium to small airways and COPD staging. We also evaluated small airway architecture in heavy smokers with normal FEV1 (SNL) and healthy never-smokers.Methods: We recruited 48 patients with COPD (stage I, n = 14; stage II, n = 15; stage, III-IV, n = 19), 21 SNL, and 17 healthy never-smokers. A smoking history inquiry, as well as spirometry, chest CT, bronchoscopy, and EB-OCT were performed. Mean luminal diameter (Dmean), inner luminal area (Ai), and airway wall area (Aw) of third- to ninth-generation bronchi were measured using EB-OCT.Results: Patients with more advanced COPD demonstrated greater abnormality of airway architecture in both large and medium to small airways, followed by SNL and never-smokers. Abnormality of airway architecture and EB-OCT parameters in SNL were comparable to those in stage I COPD. FEV1% predicted correlated with Dmean and Ai of seventh- to ninth-generation bronchi in COPD; however, neither Dmean nor Ai of third- to sixth-generation bronchi correlated with FEV1% in stage I and stage II COPD and in SNL.Conclusions: FEV1-based COPD staging partially correlates with small airway disorders in stage II-IV COPD. Small airway abnormalities detected by EB-OCT correlate with FEV1-based staging in COPD and identify early pathologic changes in healthy heavy smokers. [ABSTRACT FROM AUTHOR]