Association between gaseous air pollutants and biomarkers of systemic inflammation: A systematic review and meta-analysis

Studies have linked gaseous air pollutants to multiple health effects via inflammatory pathways. Several major inflammatory biomarkers, including C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) have also been considered as predictors of cardiovascular disease. However, there has been no meta-analysis to evaluate the associations between gaseous air pollutants and these typical biomarkers of inflammation to date. To evaluate the overall associations between short-term and long-term exposures to ambient ozone (O 3 ), nitrogen dioxide (NO 2 ), sulfur dioxide (SO 2 ), carbon dioxide (CO) and major inflammatory biomarkers including CRP, fibrinogen, IL-6 and TNF-α. A meta-analysis was conducted for publications from PubMed, Web of Science, Scopus and EMBASE databases up to Feb 1st, 2021. The meta-analysis included 38 studies conducted among 210,438 participants. Generally, we only observed significant positive associations between short-term exposures to gaseous air pollutants and inflammatory biomarkers. For a 10 μg/m 3 increase in short-term exposure to O 3 , NO 2 , and SO 2 , there were significant increases of 1.05% (95%CI: 0.09%, 2.02%), 1.60% (95%CI: 0.49%, 2.72%), and 10.44% (95%CI: 4.20%, 17.05%) in CRP, respectively. Meanwhile, a 10 μg/m 3 increase in NO 2 was also associated with a 4.85% (95%CI: 1.10%, 8.73%) increase in TNF-α. Long-term exposures to gaseous air pollutants were not statistically associated with these biomarkers, but the study numbers were relatively small. Subgroup analyses found more apparent associations in studies with better study design, higher quality, and smaller sample size. Meanwhile, the associations also varied across studies conducted in different geographical regions. Short-term exposure to gaseous air pollutants is associated with increased levels of circulating inflammatory biomarkers, suggesting that a systemic inflammatory state is activated upon exposure. More studies on long-term exposure to gaseous air pollutants and inflammatory biomarkers are warranted to verify the associations. • The first meta-analysis on gaseous pollutants and systematic inflammation biomarkers. • Short-term exposures to O 3 , NO 2 , and SO 2 were associated with increased CRP. • Short-term exposure to NO 2 was associated with increased TNF-α.