Ratio-preserved, spirometry-defined small airway dysfunction is associated with COPD: evidence from CT quantification and pathological assessments

This study investigated the radiologic and pathologic features of spirometry-defined small airway dysfunction (SAD) in patients with a preserved forced expiratory volume in one second to forced vital capacity ratio (FEV 1 /FVC > 0.7), providing evidence that SAD may be associated with chronic obstructive pulmonary disease (COPD). Patients enrolled at the First Affiliated Hospital of Guangzhou Medical University between August and December 2023 were classified into control, SAD, and COPD groups based on spirometry results. Low attenuation area (LAA) and large airway wall thickness were quantified using chest computed tomography. Thickness of small airways and vessels and alveolar structure were analyzed through histopathological evaluation of lung tissue specimens. Among 103 participants (31 controls, 32 SAD, 40 COPD), patients with SAD exhibited cough symptoms comparable to those with COPD. In addition to reduced small airway flow parameters, large airway flow rates (e.g., FEV 1 /FVC) were significantly lower in SAD than in controls. LAA values were elevated in severe COPD but not in SAD or mild-to-moderate COPD. Histologic analysis included 30 airways and 34 vessels in controls, 45 airways and 88 vessels in SAD, and 53 airways and 70 vessels in COPD. SAD patients showed significantly increased wall area percentages and narrowing indices of small airways (< 2 mm) and wall area percentages of small vessels (≤ 500 μm), similar to COPD, along with greater interstitial thickening and macrophage infiltration. Ratio-preserved, spirometry-defined SAD demonstrated functional and pathological alterations resembling COPD, supporting its role correlated with COPD pathogenesis.