Nickel in ambient particulate matter and respiratory or cardiovascular outcomes: A critical review

Exposure to ambient particulate matter (PM) has been associated with respiratory and cardiovascular outcomes, and nickel has been more frequently associated with these outcomes than other metal constituents of ambient PM. Because of this, we evaluated whether the evidence to date supports causal relationships between exposure to nickel in ambient PM and respiratory or cardiovascular outcomes. We critically reviewed 38 studies in human populations published between 2012 and 2022. Although a large variety of respiratory and cardiovascular outcomes were examined, data were sparse for many. As a result, we focused our evaluation on seven respiratory outcomes and three cardiovascular outcomes that were each examined in ≥3 studies. Of these health outcomes, exposure to nickel in ambient PM has been statistically significantly associated with respiratory mortality, respiratory emergency hospital visits, asthma, lung function (i.e., forced expiratory volume in 1 s, forced vital capacity), cardiovascular mortality, and ischemic heart disease mortality. Studies of the health outcomes of focus are subject to multiple methodological limitations, primarily ecological fallacy (short-term exposure studies), exposure measurement error, confounding, model misspecification, and multiple comparisons issue. While some statistically significant associations were reported, they were not strong, precise, or consistent. Statistically significant findings for long-term exposure to nickel in PM were largely reported in studies that could not establish temporality, despite their cohort study design. Statistically significant findings for short-term exposure to nickel in PM were largely reported in studies that could establish temporality, although this cannot inform causal inference at the individual level due to the aggregate level data used. The biological plausibility of the associations is only supported at high concentrations not relevant to ambient exposures. Overall, the literature to date does not provide adequate support for a causal relationship between nickel in ambient PM and respiratory or cardiovascular outcomes.