Relationship between cadmium exposure in metal mixtures and preserved ratio impaired spirometry: A combined cohort and experimental study - PubMed

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Cadmium (Cd) exposure increases the risk of Preserved Ratio Impaired Spirometry (PRISm), an early abnormal phenotype in COPD development.
Analysis of 6585 U.S. adults from NHANES (2007-2012) showed elevated Cd levels linked to higher PRISm risk (OR:1.35, 95% CI: 1.10–1.65).
Metal mixture exposure, particularly Cd, significantly affects PRISm incidence in females, with Cd identified as the primary contributor (PIP = 0.9996).
A nonlinear relationship was found for blood Cd, with a risk threshold at logCd = -0.673 (Cd = 0.510 μg/L).
Mediation analysis revealed albumin, HRR, and RAR mediate 5.06%, 3.59%, and 11.11% of the logCd-PRISm association, respectively.
Mouse models exposed to CdCl₂ via drinking water or inhalation showed lung inflammation, histopathological damage, and increased EMT-related and matrix degradation-related mRNA expression.
RNA-seq KEGG pathway analysis enriched four pathways (ECM-receptor interaction, IL-17, TNF, hematopoietic cell lineage) consistent with phenotypic and mediation data.
Findings highlight Cd's critical role in PRISm pathogenesis, warranting further prospective and mechanistic investigation.

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