Comment on “Environmental Cadmium and Mortality from Influenza and Pneumonia in U.S. Adults”

Abstract

Park et al. (2020) conducted a prospective study on the association between cadmium (Cd) exposure and subsequent mortality associatedwith influenza and pneumonia. The adjusted hazard ratio (HR) of participants with creatinine-corrected urinary Cd (U-Cd) in the 80th vs. 20th percentiles for influenzaor pneumonia-associated mortality was 1.15 (95% confidence interval: 1.05, 1.26), and the significance was maintained among never-smokers. In contrast, no significant association was reported between blood Cd levels and influenzaor pneumonia-associated mortality, which raises some questions about their study. First, the level of Cd exposure was low, presenting a mean value of 0:58 lg=g of creatinine in the urine, suggesting that participants lived in non-Cd–polluted areas (Chaumont et al. 2013). The background level of Cd exposure is important for considering the mechanism of association between Cd and influenzaor pneumonia-associated mortality. The effects of Cd on the kidney cannot be observed in this population, and the association with influenza is less likely to be related to Cd nephrotoxicity. Second, I speculate that the discrepancy between the associations of U-Cd and blood Cd with influenzaor pneumoniaassociated mortality is important. Huang et al. (2013) reported that mean U-Cd in men was significantly higher in current and former smokers than in never-smokers. Cd has a shorter half-life in blood than in urine, and blood Cd more likely reflects recent exposure, including smoking (Lauwerys et al. 1994; Adams and Newcomb 2014). Therefore, middleto long-term Cd exposure can be monitored based on urine samples. I suggest that future studies of Cd and lung tissue should paymore attention toU-Cd than to bloodCd. Third, Park et al. (2020) used Cox regression analysis to predict influenzaor pneumonia-associated mortality by Cd exposure. U-Cd concentrations varied widely by age, and there are different results of the adjusted HRs for mortality in each age class. Adjustment of sociodemographic and socioeconomic data, such as race, ethnicity, income, education, and occupational position, could provide insight into whether the association of Cd exposure with influenza and pneumoniamight vary by age. Although a statistically significant association was observed in this study using a sufficiently large sample, sensitivity analysis showed that the significance was observed in participants ages 65–84 y. Further studies are needed to elucidate age-related factors affecting the relationship between Cd exposure and influenzaor pneumonia-associated mortality.