Does Nonsteroidal Anti-inflammatory Drug Use Modify All-Cause and Cause-Specific Mortality Associated with PM_2.5 and Its Components? A Nationally Representative Cohort Study (2007–2017)

Several studies reported that nonsteroidal anti-inflammatory drug (NSAID) use could alleviate subclinical effects of short-term exposure to fine particulate matter (PM_2.5). However, whether chronic NSAID use could mitigate the long-term effects of PM_2.5 and its components on population mortality has been unknown. Based on a national representative survey of 47,086 adults (2007-2010) with follow-up information on the primary cause of death (until 2017), we investigated the long-term associations of PM_2.5 and its major components, including black carbon (BC), ammonium (NH₄ ⁺), nitrate (NO₃ ^-), organic matter (OM), and sulfate (SO₄ ^2-), with all-cause and cause-specific mortality using the Cox proportional hazards model. We also evaluated the effect modification by NSAID use (including broad NSAIDs, aspirin, or ibuprofen) on the associations using interaction models. Long-term exposures to PM_2.5 and its components were associated with increased risks of all-cause and cause-specific mortality, where BC, OM, and SO₄ ^2- showed stronger associations. Ibuprofen use could mitigate the associations of PM_2.5 and its components with mortality risks, while no significant modifying effects of aspirin were observed. For instance, along with per interquartile range increment in PM_2.5 concentration (34.8 μg/m³), the hazard ratios (HRs) of all-cause mortality were 1.21 (95% CI: 1.19, 1.22) and 1.10 (95% CI: 1.01, 1.19) in nonibuprofen and ibuprofen use groups (<i>P</i> for interaction = 0.026), respectively. Cause-specific analyses indicated that ibuprofen use could mainly mitigate risks of cardiovascular disease (CVD) especially ischemic heart disease (IHD) mortality attributable to PM_2.5 components. Stratified analyses found more apparent mitigating effects of ibuprofen use among participants without chronic diseases, participants ≤50 years, female participants, rural residents, and those with lower education levels. Our findings suggested potential implications in reducing population mortality caused by long-term exposures to PM_2.5 and its components through personalized interventions.