Potential joint association between urinary metal mixtures and adult asthma: A matched case-control study in China

Exposure to multi-metal mixtures is a public health concern, but their joint association with adult asthma remains insufficiently characterized, particularly in Asian populations. This study aimed to investigate the joint association between urinary multi-metal mixtures and adult asthma and to identify the metals contributing to this association. We conducted a case-control study including 551 adults with asthma and 551 age- and sex-matched controls in China. Urinary concentrations of 23 metals were measured by ICP-MS. Principal component analysis (PCA), weighted quantile sum regression (WQS), quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR) were used to evaluate mixture associations. Across the mixture models, the 23-metal mixture showed a positive joint association with adult asthma. Titanium (Ti), uranium (U), and molybdenum (Mo) showed relatively consistent positive contributions, whereas iron (Fe), manganese (Mn), and nickel (Ni) showed inverse contributions. Although larger positive point estimates were observed among females and participants aged ≤ 40 years, formal interaction tests did not indicate statistically significant heterogeneity. BKMR suggested potential nonlinear and pairwise patterns involving multiple metals, particularly U, Ti and vanadium (V), but these findings were exploratory and do not establish synergistic toxicity. Overall, these findings suggest an association between urinary multi-metal mixtures and adult asthma but do not establish causality. Prospective studies are needed to clarify the temporal sequence and underlying biological pathways.