Independent and combined associations of multiple-heavy-metal exposure with lung function: a population-based study in US children

Abstract

Previous research has found relationships between some single metals and lung function parameters. However, the role of simultaneous multi-metal exposure is poorly understood. The crucial period throughout childhood, when people are most susceptible to environmental dangers, has also been largely ignored. The study aimed to evaluate the joint and individual associations of 12 selected urinary metals with pediatric lung function measures using multi-pollutant approaches. A total of 1227 children aged 6-17 years from the National Health and Nutrition Examination Survey database of the 2007-2012 cycles were used. The metal exposure indicators were 12 urine metals adjusted for urine creatinine, including arsenic (As), barium (Ba), cadmium (Cd), cesium (Cs), cobalt (Co), mercury (Hg), molybdenum (Mo), lead (Pb), antimony (Sb), thallium (Tl), tungsten (Tu), and uranium (Ur). The outcomes of interest were lung function indices, including the 1st second of a forceful exhalation (FEV₁), forced vital capacity (FVC), forced expiratory flow between 25 and 7% of vital capacity (FEF_25-75%), and peak expiratory flow (PEF). Multivariate linear regression, quantile g-computation (QG-C), and Bayesian kernel machine regression models (BKMR) were adopted. A significantly negative overall effect of metal mixtures on FEV₁ (β = - 161.70, 95% CI - 218.12, - 105.27; p < 0.001), FVC (β = - 182.69, 95% CI - 246.33, - 119.06; p < 0.001), FEF_25-75% (β = - 178.86 (95% CI - 274.47, - 83.26; p < 0.001), and PEF (β = - 424.17, 95% CI - 556.55, - 291.80; p < 0.001) was observed. Pb had the largest negative contribution to the negative associations, with posterior inclusion probabilities (PIPs) of 1 for FEV₁, FVC, and FEF_25-75%, and 0.9966 for PEF. And Pb's relationship with lung function metrics showed to be nonlinear, with an approximate "L" shape. Potential interactions between Pb and Cd in lung function decline were observed. Ba was positively associated with lung function metrics. Metal mixtures were negatively associated with pediatric lung function. Pb might be a crucial element. Our findings highlight the need for prioritizing children's environmental health to protect them from later respiratory disorders and to guide future research into the toxic mechanisms of metal-mediated lung function injury in the pediatric population.

Keywords: Bayesian kernel machine regression; Lung function; Metal; Mixture; NHANES.