Distinguishing the associations between daily mortality and hospital admissions and nitrogen dioxide from those of particulate matter: a systematic review and meta-analysis

Objectives: To quantitatively assess time-series studies of daily nitrogen dioxide (NO2) and mortality and hospital admissions which also controlled for particulate matter (PM) to determine whether or to what extent the NO2 associations are independent of PM. Design: A systematic review and meta-analysis. Methods: Time-series studies-published in peer-reviewed journals worldwide, up to May 2011-that reported both single-pollutant and two-pollutant model estimates for NO2 and PM were ascertained from bibliographic databases (PubMed, EMBASE and Web of Science) and reviews. Random-effects summary estimates were calculated globally and stratified by different geographical regions, and effect modification was investigated. Outcome measures: Mortality and hospital admissions for various cardiovascular or respiratory diseases in different age groups in the general population. Results: 60 eligible studies were identified, and meta-analysis was conducted on 23 outcomes. Two-pollutant model study estimates generally showed that the NO2 associations were independent of PM mass. For all-cause mortality, a 10 mu g/m(3) increase in 24-hour NO2 was associated with a 0.78% (95% CI 0.47% to 1.09%) increase in the risk of death, which reduced to 0.60% (0.33% to 0.87%) after control for PM. Heterogeneity between geographical region-specific estimates was removed by control for PM (I-2 from 66.9% to 0%). Estimates of PM and daily mortality assembled from the same studies were greatly attenuated after control for NO2: from 0.51% (0.29% to 0.74%) to 0.18% (-0.11% to 0.47%) per 10 mu g/m(3) PM10 and 0.74% (0.34% to 1.14%) to 0.54% (-0.25% to 1.34%) for PM2.5. Conclusions: The association between short-term exposure to NO2 and adverse health outcomes is largely independent of PM mass. Further studies should attempt to investigate whether this is a generic PM effect or whether it is modified by the source and physicochemical characteristics of PM. This finding strengthens the argument for NO2 having a causal role in health effects.