Serum Cystatin C and Emphysema: Results from the National Health and Nutrition Examination Survey (NHANES)

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. 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 a parts per thousand yen10 ng/mL. Nonactive smokers with a serum cotinine level > 0.05 ng/mL were defined as environmental tobacco smoke (ETS)-exposed. 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) mu g/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) mu g/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) mu g/L higher mean (SE) serum CysC levels as compared to ETS unexposed nonactive smokers (p = 0.04). 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.