The metal mixture inflammatory index has been associated with an increased prevalence of chronic obstructive pulmonary disease and higher all-cause mortality.

Chronic obstructive pulmonary disease (COPD) is a common respiratory condition with increasing prevalence and mortality worldwide. The Metal Mixture Inflammation Index (MMII) is a novel metric designed to quantify the potential impact of mixed heavy metal exposure on systemic low-grade inflammation. The weight-adjusted waist index (WWI) has emerged as a new anthropometric indicator of obesity. This study aimed to investigate the association between MMII and COPD, assess the mediating role of WWI, and evaluate the relationship between MMII and both all-cause and cardiovascular mortality among individuals with COPD. A study was conducted using data from the 2005-2018 National Health and Nutrition Examination Survey (NHANES). Logistic regression, subgroup analysis, and restricted cubic spline (RCS) models were employed to examine the association between MMII and COPD prevalence. Mediation analysis was performed to explore the potential mediating effect of WWI on the relationship between MMII and COPD. Additionally, Cox proportional hazards models were used to assess the associations between MMII and all-cause and cardiovascular mortality in individuals with and without COPD. A total of 11,577 participants were included, comprising 550 individuals with COPD and 11,027 without COPD. After adjustment for known confounders in multivariable logistic regression models, each unit increase in MMII and WWI was associated with a 5.85-fold (OR = 5.85, 95% CI: 3.41-10.03) and 1.30-fold (OR = 1.30, 95% CI: 1.06-1.59) increase in the odds of COPD, respectively. Similar results were observed when MMII and WWI were categorized into tertiles, with a significant dose-response trend (P for trend < 0.05). RCS models revealed a linear positive association between both MMII and WWI with COPD prevalence. Mediation analysis indicated that WWI exerted significant direct and indirect effects, accounting for 2.40% of the association between MMII and COPD. Moreover, higher MMII levels were associated with increased all-cause mortality in the general population (HR = 2.41, P < 0.001), COPD population (HR = 2.62, P = 0.033), and non-COPD population (HR = 2.04, P < 0.001). No significant association was found between MMII and cardiovascular mortality. MMII was positively and linearly associated with COPD prevalence. Elevated MMII levels were independently associated with increased all-cause mortality among the overall, COPD, and non-COPD populations, but no significant relationship was observed with cardiovascular mortality. In addition, WWI partially mediated this association, suggesting a role for obesity in the pathway linking metal mixture exposure to COPD.