title: Ageing and smoking contribute to plasma surfactant proteins and protease imbalance with correlations to airway obstruction.
abstract: BACKGROUND
  A significant number of young people start smoking at an age of 13-15, which means that serious smoking-evoked changes may have been occurred by their twenties. Surfactant proteins (SP) and matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) have been linked to cigarette smoke induced lung remodelling and chronic obstructive pulmonary disease (COPD). However, the level of these proteins has not been examined during ageing or in young individuals with short smoking histories.
  
  
  METHODS
  Plasma levels of SP-A, SP-D, MMP-9, and TIMP-1 were measured by EIA/ELISA from young (18-23 years) non-smoking controls (YNS) (n = 36), smokers (YS) (n = 51), middle aged/elderly (37-77 years) non-smoking controls (ONS) (n = 40), smokers (OS) (n = 64) (FEV1/FVC >0.7 in all subjects) and patients with COPD (n = 44, 35-79 years).
  
  
  RESULTS
  Plasma levels of SP-A increased with age and in the older group in relation to smoking and COPD. Plasma SP-D and MMP-9 levels did not change with age but were elevated in OS and COPD as compared to ONS. The TIMP-1 level declined with age but increased in chronic smokers when compared to ONS. The clearest correlations could be detected between plasma SP-A vs. age, pack years and FEV1/FVC. The receiver operating characteristic (ROC) curve analysis revealed SP-A to be the best marker for discriminating between patients with COPD and the controls (area under ROC curve of 0.842; 95% confidence interval, 0.785-0.899; p < 0.001).
  
  
  CONCLUSIONS
  Age has a significant contribution to potential markers related to smoking and COPD; SP-A seems to be the best factor in differentiating COPD from the controls.
authors.affiliation: Department of Medicine, Division of Pulmonary Medicine, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. helen.ilumets@helsinki.fi
authors.forename: Helen
authors.initials: H
authors.lastname: Ilumets
authors.forename: Witold
authors.initials: W
authors.lastname: Mazur
authors.forename: Tuula
authors.initials: T
authors.lastname: Toljamo
authors.forename: Noora
authors.initials: N
authors.lastname: Louhelainen
authors.forename: Pentti
authors.initials: P
authors.lastname: Nieminen
authors.forename: Hideo
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Ishikawa
authors.forename: Vuokko L
authors.initials: VL
authors.lastname: Kinnula
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000097:blood*; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism* / Q000503:physiopathology; D037662:Pulmonary Surfactant-Associated Protein A / Q000097:blood; D037663:Pulmonary Surfactant-Associated Protein D / Q000097:blood; D011663:Pulmonary Surfactants / Q000097:blood*; D012372:ROC Curve; D012907:Smoking / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D014797:Vital Capacity / Q000502:physiology; D055815:Young Adult
chemical_list: D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants; D019715:Tissue Inhibitor of Metalloproteinase-1; D010447:Peptide Hydrolases; D020780:Matrix Metalloproteinase 9