Don D Sin1, S F Paul Man2, Annette McWilliams2, Stephen Lam2. 1. Department of Medicine, Division of Respirology, University of British Columbia, Vancouver, BC, Canada. Electronic address: dsin@mrl.ubc.ca. 2. Department of Medicine, Division of Respirology, University of British Columbia, Vancouver, BC, Canada.
Abstract
BACKGROUND: Surfactant dysfunction has been implicated in both lung cancer and COPD. This study evaluated the relationship between surfactant protein D (SP-D) and the progression of bronchial dysplasia in heavy smokers. METHODS: SP-D and oxidized glutathione levels were determined in samples of BAL fluid from 71 ex-smokers and current heavy smokers who participated in a lung cancer chemoprevention study with inhaled budesonide therapy. Bronchoscopy with biopsies was performed at baseline and was repeated at 6 months. The primary end point was the progression of bronchial dysplasia over 6 months. RESULTS: Log-normalized SP-D levels in BAL fluid were significantly associated with the progression of bronchial dysplasia. A 1-U decrease in log-normalized SP-D levels at baseline was associated with a 3.2-fold increase (95% confidence interval, 1.24 to 8.26) in the risk for progression. Reduced FEV(1) also predicted the progression of bronchial dysplasia (p < 0.05). Additional reductions in BAL fluid SP-D levels over the 6 months further increased the risk of progression (odds ratio, 1.76 for a 1-U decrease in log-normalized SP-D levels in BAL fluid; p = 0.023). Thirty-seven percent of the variation in SP-D levels in BAL fluid was related positively to the subject's FEV(1)/FVC ratio, and inversely to their plasma C-reactive protein levels and number of pack-years of smoking. CONCLUSION: Reduced SP-D expression in BAL fluid was associated with the progression of bronchial dysplasia. SP-D levels in BAL fluid may serve as a potential biomarker to identify smokers who are at risk of early lung cancer.
BACKGROUND: Surfactant dysfunction has been implicated in both lung cancer and COPD. This study evaluated the relationship between surfactant protein D (SP-D) and the progression of bronchial dysplasia in heavy smokers. METHODS:SP-D and oxidized glutathione levels were determined in samples of BAL fluid from 71 ex-smokers and current heavy smokers who participated in a lung cancer chemoprevention study with inhaled budesonide therapy. Bronchoscopy with biopsies was performed at baseline and was repeated at 6 months. The primary end point was the progression of bronchial dysplasia over 6 months. RESULTS: Log-normalized SP-D levels in BAL fluid were significantly associated with the progression of bronchial dysplasia. A 1-U decrease in log-normalized SP-D levels at baseline was associated with a 3.2-fold increase (95% confidence interval, 1.24 to 8.26) in the risk for progression. Reduced FEV(1) also predicted the progression of bronchial dysplasia (p < 0.05). Additional reductions in BAL fluid SP-D levels over the 6 months further increased the risk of progression (odds ratio, 1.76 for a 1-U decrease in log-normalized SP-D levels in BAL fluid; p = 0.023). Thirty-seven percent of the variation in SP-D levels in BAL fluid was related positively to the subject's FEV(1)/FVC ratio, and inversely to their plasma C-reactive protein levels and number of pack-years of smoking. CONCLUSION: Reduced SP-D expression in BAL fluid was associated with the progression of bronchial dysplasia. SP-D levels in BAL fluid may serve as a potential biomarker to identify smokers who are at risk of early lung cancer.
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