Airway Angiogenesis And basement Membrane Remodeling In Smokers And Chronic Obstructive pulmonary Disease: cross-sectional And Longitudinal Studies

RATIONALE: Airway remodeling complicates the course of chronic inflammatory airway diseases and angiogenesis is one of its main features. Published data on angiogenesis in bronchial biopsies (BB) from subjects with chronic obstructive pulmonary disease (COPD) is limited, and especially so for effects of medication. METHODS: BB from current-smoker COPD (S-COPD), ex-smoker COPD (ES-COPD) and smokers with normal lung function (S-N) were stained with collagen IV and vascular endothelial growth factor (VEGF) antibodies and compared with healthy non-smokers (H-N). Then COPD subjects entered a double blind controlled trial comparing fluticasone propionate (FP, 0.5 mg/twice daily) with placebo (2:1 randomization) for 6 months and their BB were compared before and after treatment. RESULTS: (Table 1). 66 subjects were recruited in the cross-sectional study and 22 mild to moderate COPD patients had enough pair tissues for the clinical trial (FP, n=15 and placebo, n=7). The intervention groups were well matched at baseline. The Rbm was significantly fragmented in all 3 clinical groups compared with H-N; fragmentation was measured as length of splits (Figure 1 A). The Rbm was also hypervascular (Figure 1 A) but the lamina propria (LP) in contrast was hypovascular in both current smoker groups but not in ES-COPD. Staining for VEGF in the Rbm was significantly greater in the three clinical groups compared with H-N. Rbm splitting regressed significantly with FP (p<0.03) but not with placebo (p=0.7) (Figure 1 B). Vessels in the Rbm and LP and VEGF staining did not change with either treatment. Vessels in the Rbm and LP did not change with FP in S-COPD group when analyzed separately. CONCLUSIONS: Smokers, with or without COPD, had unique Rbm changes in BB, including fragmentation which responded to FP. Rbm fragmentation has been reported as a hallmark of the effects of matrix metalloproteinase involved in active epithelial-mesenchymal transition (EMT). This needs specific confirmatory studies. The Rbm is also hypervascular while the LP is hypovascular in smokers but these effects are not influenced by FP, nor is VEGF expression. Studies of the activity of other angiogenic factors are needed as well as VEGF receptor system.