title: Chronic obstructive pulmonary disease and inhaled steroids alter surfactant protein D (SP-D) levels: a cross-sectional study.
abstract: BACKGROUND
  Surfactant protein D (SP-D), an innate immune molecule, plays an important protective role during airway inflammation. Deficiency of this molecule induces emphysematous changes in murine lungs, but its significance in human COPD remains unclear.
  
  
  METHODS
  We collected bronchoalveolar lavage fluid from 20 subjects with varying degrees of COPD (8 former smokers and 12 current smokers) and 15 asymptomatic healthy control subjects (5 never smokers, 3 remote former smokers, and 7 current smokers). All subjects underwent a complete medical history and pulmonary function testing. SP-D was measured by Enzyme-Linked ImmunoSorbent Assay. Statistical analysis was performed using nonparametric methods and multivariable linear regression for control of confounding. The effect of corticosteroid treatment on SP-D synthesis was studied in vitro using an established model of isolated type II alveolar epithelial cell culture.
  
  
  RESULTS
  Among former smokers, those with COPD had significantly lower SP-D levels than healthy subjects (median 502 and 1067 ng/mL, respectively, p = 0.01). In a multivariable linear regression model controlling for age, sex, race, and pack-years of tobacco, COPD was independently associated with lower SP-D levels (model coefficient -539, p = 0.04) and inhaled corticosteroid use was independently associated with higher SP-D levels (398, p = 0.046). To support the hypothesis that corticosteroids increase SP-D production we used type II alveolar epithelial cells isolated from adult rat lungs. These cells responded to dexamethasone treatment by a significant increase of SP-D mRNA (p = 0.041) and protein (p = 0.037) production after 4 days of culture.
  
  
  CONCLUSIONS
  Among former smokers, COPD is associated with lower levels of SP-D and inhaled corticosteroid use is associated with higher levels of SP-D in the lung. Dexamethasone induced SP-D mRNA and protein expression in isolated epithelial cells in vitro. Given the importance of this molecule as a modulator of innate immunity and inflammation in the lung, low levels may play a role in the pathogenesis and/or progression of COPD. Further, we speculate that inhaled steroids may induce SP-D expression and that this mechanism may contribute to their beneficial effects in COPD. Larger, prospective studies are warranted to further elucidate the role of surfactant protein D in modulating pulmonary inflammation and COPD pathogenesis.
authors.affiliation: Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA. michael.sims@uphs.upenn.edu
authors.forename: Michael W
authors.initials: MW
authors.lastname: Sims
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Tal-Singer
authors.forename: Sonja
authors.initials: S
authors.lastname: Kierstein
authors.forename: Ali I
authors.initials: AI
authors.lastname: Musani
authors.forename: Michael F
authors.initials: MF
authors.lastname: Beers
authors.forename: Reynold A
authors.initials: RA
authors.lastname: Panettieri
authors.forename: Angela
authors.initials: A
authors.lastname: Haczku
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000378:metabolism*; D037663:Pulmonary Surfactant-Associated Protein D / Q000032:analysis*; D051381:Rats; D013256:Steroids / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D037663:Pulmonary Surfactant-Associated Protein D; D013256:Steroids