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Surfactant Protein D and Bronchial Dysplasia in Smokers at High Risk of Lung Cancer

*From the Department of Medicine, Division of Respirology, University of British Columbia, Vancouver, BC, Canada.

Correspondence to: Don D. Sin, MD, MPH, FCCP, St. Paul's Hospital, 1081 Burrard St, Vancouver, BC, Canada V6Z 1Y6; e-mail: dsin{at}mrl.ubc.ca

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 FEV₁ 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 FEV₁/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.

Key Words: biomarker • bronchial dysplasia • surfactant protein D

Abbreviations: CI, confidence interval • CRP, C-reactive protein • OR, odds ratio • SP-D, surfactant protein D