title: Surfactant protein D and bronchial dysplasia in smokers at high risk of lung cancer.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, Division of Respirology, University of British Columbia, Vancouver, BC, Canada. Electronic address: dsin@mrl.ubc.ca.
authors.forename: Don D
authors.initials: DD
authors.lastname: Sin
authors.affiliation: Department of Medicine, Division of Respirology, University of British Columbia, Vancouver, BC, Canada.
authors.forename: S F Paul
authors.initials: SFP
authors.lastname: Man
authors.affiliation: Department of Medicine, Division of Respirology, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Annette
authors.initials: A
authors.lastname: McWilliams
authors.affiliation: Department of Medicine, Division of Respirology, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Stephen
authors.initials: S
authors.lastname: Lam
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D001980:Bronchi / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid; D002097:C-Reactive Protein / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005541:Forced Expiratory Volume; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008171:Lung Diseases / Q000378:metabolism*; D008175:Lung Neoplasms / Q000453:epidemiology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D037663:Pulmonary Surfactant-Associated Protein D / Q000378:metabolism*; D012307:Risk Factors; D012907:Smoking / Q000378:metabolism*; D014797:Vital Capacity
chemical_list: D015415:Biomarkers; D037663:Pulmonary Surfactant-Associated Protein D; D002097:C-Reactive Protein; D005978:Glutathione