Cystatin C and chronic obstructive pulmonary disease (COPD): Results from the National Health and Nutrition Examination Survey (NHANES 1999-2002)

Evidence about CysC's role in COPD is scarce. CysC is a potent cysteine protease inhibitor and may contribute to elastolysis by protease-antiprotease imbalance.

Methods Cross sectional data from NHANES 1999- 2002 were used. The outcome COPD was determined using standardized questionnaires asking about emphysema, active bronchitis or past history of bronchitis. Active smoking was defined by self report or measured serum cotinine >10ng/mL. Data were pooled using standard methods and 4 year combined weights were calculated. Survey statistics traditionally used to analyze complex semi-random survey designs were employed.

Results The prevalence (95% CI) of COPD was 6.8% (6.1 – 7.5%). The mean CysC level in the COPD group was significantly higher than the non-COPD group (p=0.001). When stratified by COPD category, the emphysema group had significantly higher CysC levels compared to the non-COPD group (p<0.001). Using multivariate regression analysis adjusting for demographic and clinical variables, the mean CysC levels in the emphysema group were significantly higher than the non-COPD group (p<0.001). Stratifying the emphysema group by smoking status, the active-smokers had 115.4 (24.2 – 206.6) μg/L higher CysC levels than non-COPD group (p<0.001).

Conclusions In a large representative noninstitutionalized US population, the mean CysC level in the COPD group was higher than the non-COPD group, primarily influenced by the emphysema group. Stratifying the emphysema group by smoking status, the active-smoker subgroup had significantly higher CysC levels. The persistence of this association after adjustment C reactive protein suggests that mechanisms other than inflammation may be involved in the pathogenesis of emphysema.