Role of heavy metals in chronic obstructive pulmonary disease (COPD): Results from National Health and Nutrition Examination Survey (NHANES) 1999-2008

Cigarette smoke is the primary mechanisms of exposure to heavy metals. We aim to assess the role of lead and cadmium as partial mediators in the association between smoking and COPD.

Methods Cross-sectional data from NHANES 1999-2008 were used. The outcome of COPD was determined using standardized questionnaires regarding a history of emphysema and active and past chronic bronchitis. Active smoking was defined by self-report or measured serum cotinine > 10 ng/mL. Serum lead and cadmium levels were measured by mass spectrometry. Survey statistics were employed to analyze the complex semi-random survey design. Data were pooled using standard methods and 10 year combined weights were calculated.

Results After adjusted analysis, odds ratios (OR) (95%CI) for COPD in former and active smokers relative to never smokers was 1.79 (1.49-2.15) and 2.44 (2.07-2.88) respectively. These ORs were unchanged when adjusted for lead levels, however significantly reduced when adjusted for cadmium to 1.66 (1.39-1.99 and 1.72 (1.34-2.19), respectively. On adjusted analysis, higher levels of serum cadmium were associated with higher risk of COPD (p for trend <0.001). This trend was primarily driven by emphysema group; ORs (95%CI) for COPD by cadmium quintiles 2 to 5 compared to lowest quintile were 0.88 (0.35-2.24), 1.69 (0.77-3.69), 3.27 (1.59-6.70), 5.26 (2.28-12.11).

Conclusions The relationship of smoking and COPD may be partially mediated through cadmium. COPD is increasing with higher levels of serum cadmium and emphysema is primarily driving that trend. The risk of COPD was significantly higher despite cadmium levels lower than the current safety standard.