The relation of cigarette smoking to increased extracellular matrix in the layer of airway smooth muscle

Reduced FEV 1 in smokers may be due to the combined effects of pre-existing airway remodeling and/or progressive loss of lung function (due to emphysema or airway remodeling). We have previously observed an inverse relationship between FEV 1 and the volume fraction of extracellular matrix (V VECM ) in the layer of airway smooth muscle (ASM). Given the increased decline in FEV 1 in smokers, we hypothesized that this relationship reflects progressive remodeling of the ASM in smokers. Aim: To examine the relationship between smoke exposure and V VECM within the ASM layer in smokers and non-smokers undergoing lung resection. Methods: Prior to surgery, FEV 1 was measured and smoking history was recorded. Post-operative tissue was obtained from current smokers (n=10), ex-smokers (n=20) and never smokers (n=9). Transverse sections (0.5μm thick) of large and small airway were stained with the Masson9s trichrome technique. V VECM within the ASM layer was estimated and related to age, duration of smoking and number cigarettes smoked per week. Results: Mean pack-years of smoking was 49±39 (range 4-160). V VECM was increased in current (p=0.001) and ex-smokers (p=0.016) compared with non-smokers in the large airways. V VECM was not related to pack years (r 2 =0.036, p=0.38), duration of smoking (r 2 =0.035, p=0.41), number of cigarettes smoked (r 2 =0.008, p=0.69) or age (r 2 =0.007, p=0.68) in large or small airways. Conclusion: Although increase V VECM in the ASM layer is related to FEV 1 and current smoking, we could not detect a dose effect of smoking. This suggests a non-progressive effect of smoking and the presence of pre-existing remodeling of the ASM layer or a threshold effect of cigarette smoking.