Environmental Cadmium and Mortality from Influenza and Pneumonia in US Adults

BACKGROUND: Environmental cadmium exposure is widespread. In humans, cadmium is poorly excreted, triggers pulmonary inflammation, reduces pulmonary function, and enhances lung injury by respiratory syncytial virus. OBJECTIVES: We examined the association of cadmium burden with mortality related to influenza or pneumonia. METHODS: This prospective analysis of the National Health and Nutrition Examination Survey (NHANES) included 7,173 and 8,678 participants >= 45 years of age enrolled in NHANES-III and NHANES 1999-2006, respectively. Associations were evaluated between cadmium and mortality from influenza or pneumonia during a median follow-up of 17.3 y (NHANES-III, based on creatinine-corrected urine cadmium) and 11.4 y (NHANES 1999-2006, based on blood cadmium). Survey-weighted Cox proportional hazard models were used to compute hazard ratios (HRs) comparing the mortality of individuals at the 80th vs. the 20th percentile of cadmium concentrations. RESULTS: In NHANES-III, after adjustment for sex, race/ethnicity, education, body mass index, serum cholesterol, hypertension, and NHANES phase (or cycle), the HR comparing influenza or pneumonia mortality among participants with creatinine-corrected urinary cadmium in the 80th vs. 20th percentile was 1.15 (95% CI: 1.05, 1.26; p = 0.002) in the population as a whole and 1.27 (95% CI: 1.12, 1.43; p = 0.002) among never smokers. In NHANES 1999-2006, adjusted HRs for the 80th vs. 20th percentile of blood cadmium were 1.14 (95% CI: 0.96, 1.36; p = 0.15) for the overall population and 1.71 (95% CI: 0.95, 3.09; p = 0.07) in never smokers. DISCUSSION: Among middle-aged and older adults in the United States, higher cadmium burdens are associated with higher mortality from influenza or pneumonia. This raises the possibility that cadmium may worsen outcomes from COVID-19 infections.