Pathology of small airways in non-COPD smokers with low diffusion capacity and patients with COPD

Abstract

Background: Impaired diffusing capacity for carbon monoxide (D_LCO) is an early physiological abnormality in smokers with normal spirometry who subsequently develop COPD. Thus, exploring lung pathology of this subtype of smokers could help uncover the pathogenesis of early COPD. This study aimed to histologically compare small airway pathology in non-COPD smokers with low D_LCO to that in non-COPD smokers with normal D_LCO and patients with mild to moderate COPD.

Methods: Lung specimens were obtained from smokers who underwent lung lobectomy for tumor resection at Kyoto University Hospital. Hemoglobin-adjusted D_LCO was measured using the single-breath method prior to surgery. Wall thickness and the number of alveolar attachments to the airway’s wall per basement membrane length (AAs) were measured on histological sections.

Results: Non-COPD smokers with and without <70% of predicted D_LCO (n=17 and 12) and patients with mild to moderate COPD (n=34) were enrolled. Age, sex, and smoking status did not differ between the 3 groups. The number of AAs was significantly lower in non-COPD smoker with reduced DLco than those without, whereas wall thickness did not differ between smokers with and without reduced D_LCO. Moreover, decreased AAs in non-COPD smokers was associated with reduced D_LCO (ρ=0.68, p<0.01), but not with % forced expiratory volume in 1 sec (%FEV₁) (ρ=-0.18, p=0.35), whereas decreased AAs in COPD was associated with reduced D_LCO (ρ=0.36, p=0.03) and %FEV₁ (ρ=0.43, p=0.01).

Conclusion: Loss of alveolar attachments without increased wall thickness might be a pathological feature of the small airways in early COPD.