Environmental chemical-wide associations with immune biomarkers in US adults: A cross-sectional analysis

Environmental chemical exposures influence immune system functions, and humans are exposed to a wide range of chemicals, termed the chemical “exposome”. A comprehensive, discovery analysis of the associations of multiple chemical families with immune biomarkers is needed. In this study, we tested the associations between environmental chemical concentrations and immune biomarkers. We analyzed the United States cross-sectional National Health and Nutrition Examination Survey (NHANES 1999-2018). Chemical biomarker concentrations were measured in blood or urine (196 chemicals, 17 chemical families). Immune biomarkers included counts of lymphocytes, neutrophils, monocytes, basophils, eosinophils, red blood cells, white blood cells, and mean corpuscular volume. We conducted separate survey-weighted, multivariable linear regressions of each log2-transformed chemicals on immune measures, adjusted for relevant covariates. We accounted for multiple comparisons using a false discovery rate (FDR). Among 45,528 adult participants, the mean age was 45.7 years, 51.4% were female, and 69.3% were Non-Hispanic White. 71 (36.2%) chemicals were associated with at least one of the eight immune biomarkers. The most chemical associations (FDR<0.05) were observed with mean corpuscular volume (36 chemicals) and red blood cell counts (35 chemicals). For example, a doubling in the concentration of cotinine was associated with 0.16 fL (95% CI: 0.15, 0.17; FDR<0.001) increased mean corpuscular volume, and a doubling in the concentration of blood lead was associated with 61,736 increased red blood cells per μL (95% CI: 54,335, 69,138; FDR<0.001). A wide variety of chemicals, such as metals and smoking-related compounds, were highly associated with immune system biomarkers. This environmental chemical-wide association study identified chemicals from multiple families for further toxicological, immunologic, and epidemiological investigation.