title: Serum cystatin C and emphysema: results from the National Health and Nutrition Examination Survey (NHANES).
abstract: BACKGROUND
  Cystatin C (CysC) is a potent nonorgan-specific cysteine protease inhibitor and may contribute to elastolysis and tissue destruction by a mechanism of protease–antiprotease imbalance. Given the prevalence of CysC in the serum of smokers and its role in tissue destruction, we aimed to evaluate the association between CysC and emphysema.
  
  
  METHODS
  Pooled cross-sectional data from the National Health and Nutrition Examination Survey 1999–2002 were used. Emphysema and chronic bronchitis were defined by a self-reported history ascertained using standardized questionnaires. Active smokers were defined as self-reported current smokers or measured serum cotinine ≥10 ng/mL. Nonactive smokers with a serum cotinine level >0.05 ng/mL were defined as environmental tobacco smoke (ETS)-exposed.
  
  
  RESULTS
  The prevalence (95% CI) of emphysema was 1.3% (range = 0.9–1.8%). The mean (SE) CysC level in the emphysema group was significantly higher than in normal controls [1,139 (22) vs. 883 (8) μg/L; p = 0.001]. Upon stratification of the study population by C-reactive protein (CRP) concentrations, we demonstrated a progressive increase in the mean serum CysC level with serially increasing CRP concentrations. Active smokers with emphysema had 115.4 (46.5) μg/L higher mean (SE) CysC levels than the normal controls (p < 0.001). Upon adjusted analysis, we observed that nonactive smokers with significant ETS exposure had 31.2 (15.2) μg/L higher mean (SE) serum CysC levels as compared to ETS unexposed nonactive smokers (p = 0.04).
  
  
  CONCLUSIONS
  In a large representative noninstitutionalized US population, we demonstrated an association between emphysema and serum CysC. Active smokers with emphysema had significantly higher CysC levels. These findings suggest that CysC may play a role in the pathogenesis of smoking-related emphysema.
authors.affiliation: Department of Internal Medicine, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Haala K
authors.initials: HK
authors.lastname: Rokadia
authors.forename: Shikhar
authors.initials: S
authors.lastname: Agarwal
mesh_terms: D000328:Adult; D000368:Aged; D029481:Bronchitis, Chronic / Q000097:blood / Q000453:epidemiology; D002097:C-Reactive Protein / Q000378:metabolism; D055316:Cystatin C / Q000097:blood*; D004646:Emphysema / Q000097:blood* / Q000453:epidemiology* / Q000209:etiology; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009749:Nutrition Surveys; D015995:Prevalence; D012907:Smoking / Q000009:adverse effects; D014028:Tobacco Smoke Pollution / Q000009:adverse effects; D014481:United States
chemical_list: D055316:Cystatin C; D014028:Tobacco Smoke Pollution; D002097:C-Reactive Protein