Association of exposure to environmental heavy metals with markers of sepsis susceptibility: a population-based study from NHANES.

BACKGROUND

Sepsis is a life-threatening syndrome of immune dysregulation; preexisting lymphopenia and an elevated neutrophil-to-lymphocyte ratio (NLR) heighten host susceptibility. Chronic low-dose exposure to lead (Pb), cadmium (Cd), and mercury (Hg) is immunotoxic, but its association with these pre-sepsis markers in the general population remains unclear.

METHODS

We analyzed 12,580 adults from NHANES 2011-2018. Outcomes were lymphopenia (absolute lymphocyte count <1.0 × 109/L) and high NLR (top quartile). Survey-weighted logistic and Weighted Quantile Sum (WQS) regressions evaluated individual and joint mixture effects. Restricted cubic splines modeled dose-response relationships. Continuous exposure models were also constructed to minimize information loss.

RESULTS

Fully adjusted models showed higher quartiles of Pb, Cd, and Hg were each associated with greater odds of lymphopenia and high NLR. Comparing highest to lowest quartiles, ORs for lymphopenia were 1.85 (95% CI 1.42-2.41) for Pb, 1.66 (95% CI 1.28-2.15) for Cd, and 1.52 (95% CI 1.15-2.01) for Hg. Continuous models confirmed that each log2-fold increase in blood metals was associated with significantly reduced absolute lymphocyte counts and elevated NLR (all p < 0.05). The WQS index was positively associated with lymphopenia (OR 1.63) and high NLR (OR 1.48).

CONCLUSION

In a nationally representative sample, chronic low-level exposure to Pb, Cd, and Hg was independently associated with an immune profile linked to sepsis susceptibility, suggesting environmental metal reduction as a potential population-level strategy to reduce sepsis risk.