Increased epithelial thickness and luminal narrowing in the small airways of smokers with Preserved Ratio Impaired Spirometry (PRISm)

<bold>Title:</bold> Increased epithelial thickness and luminal narrowing in the small airways of smokers with Preserved Ratio Impaired Spirometry (PRISm) <bold>Background:</bold> Studies have shown increased risk of COPD and mortality in patients with PRISm. Small airways (SA) are the primary site of pathophysiology in COPD but have yet to be investigated in PRISm. <bold>Methods:</bold> Analysis of SA histology was performed using H&E-stained sections of peripheral lung tissue from smokers without airflow obstruction (FEV1/FVC >0.7) separated into two groups: >100 FEV1% predicted (controls n=41) and <90 FEV1% predicted (PRISm n=48). In airways <2mm diameter we measured epithelial thickness, luminal narrowing, airway wall thickness and alveolar attachment numbers (AA). <bold>Results:</bold> In all airways, epithelial thickness was significantly greater in the PRISm group compared to controls (p=0.0361). When airways were separated into tertiles based on airway diameters (<337mm, 337-756mm, >756mm) epithelial thickness (p=0.0023) and luminal narrowing (p=0.0377) were greater in PRISm compared to controls in the smallest airways; in <337.2mm tertile only. There were no significant differences in wall thickness and AA between groups. <bold>Conclusions:</bold> Luminal narrowing and epithelial thickness are increased in airways with the smallest diameters in smokers with PRISM, despite no airflow obstruction. These changes indicate the early stages of SA disease in PRISM.