Independent And Joint Effects Of Long-term Exposure To Atmospheric PM_2.5 And O₃ On Mortality Ris

Background and objectiveAir pollution is a serious global public health problem and a serious health challenge to the population.Previous studies have shown that,in the settings of PM2.5 concentrations<35 μg/m3,long-term PM2.5 exposure increases the risk of mortality;however,in high exposure areas,the concentration-response(C-R)functions between long-term PM2.5 exposure and mortality are controversial.Also,the health effects of long-term O3 exposure are currently inconsistent,especially in low-and middle-income countries which have one of the highest total deaths from O3 pollution in the world;and the associations between long-term O3 exposure and all-cause mortality,cancer mortality,and respiratory disease mortality have not been reported.Identifying the synergistic health effects between pollutants can help refine the assessment of health effects of coordinated management,but no studies have reported the combined effect of long-term PM2.5 and O3 exposure on the risk of mortality.This study aims to explore the independent effects of long-term exposure to air pollution on all-cause,cardiovascular disease(CVD),cancer,and respiratory disease mortality,and to reveal the combined effect of PM2.5 and O3 on mortality.MethodsBased on the ChinaHEART(Health Evaluation And risk Reduction through nationwide Teamwork),this nationwide cohort study enrolled community residents aged 35-75 years who had lived in the region for at least 6 of the preceding 12 months from 143 counties(87 rural counties,56 urban districts)in all 31 provinces of the Chinese Mainland from November 2014 to December 2017.We collected the information on sociodemographic status,lifestyle information,medical history by standardized in-person interviews,and also measured height,weight,and blood pressure.The daily average PM2.5 concentrations and O3 daily maximum of 8 h average concentrations at a spatial resolution of 1 km×1 km were obtained from a random forest model.We matched 1-km grid-cell PM2.5 and O3 exposure to each participant by linking the residential address to the grid that residential address fall.The information on death and the underlying cause of death was obtained from the National Cause-of-death Surveillance System.The time of baseline survey of participants was considered as the time of entry into the cohort,and the outcomes included all-cause and cause-specific deaths up to 31 December 2021.We used Cox proportional hazards models to assess the associations between long-term exposure to air pollutants and mortality.We further investigated the C-R functions between air pollutants and mortality by fitting restricted cubic splines.Finally,we combined PM2.5 and O3 exposure levels to group participants to estimate the synergistic effects of PM2.5 and O3 on all-cause mortality and cause-specific mortality.ResultsThis study included 1,910,923 participants.In total,60,356 all-cause deaths occurred during a median follow-up period of 5·5 years,including 24,334 due to CVD,20,895 cancer,and 3,839 respiratory disease.Over a wide range of PM2.5 concentrations ranging from 17 to 102 μg/m3,each 10μg/m3 increase in long-term PM2.5 exposure was associated with a 2.0%,2.4%,3.7%,and 8.3%increase in the risk of death from all-cause,CVD,cancer,and respiratory disease,respectively,and the patterns of the C-R function varied by cause of death.The long-term PM2.5 exposure sub-linearly related to all-cause mortality(P for nonlinearity<0.001),with a 6%increase risk per 10 μg/m3 increase of PM2.5 concentrations at the level of≥50.4 μg/m3,but no significant association existed below 50.4 μg/m3.The risk of allcause death in this study was weaker than the results of studies in the settings of PM2.5 concentrations<35 μg/m3,and the effects in this study resulted mainly from the combined distinct C-R functions of the top three cause-specific mortalities.The C-R functions for CVD and cancer mortalities were nonlinear(P for nonlinearity<0.001),whereas the C-R function for respiratory diseases mortality was linear(P for nonlinearity=0.124).In addition,there were modifying effects of age,body mass index(BMI),drinking status,and urbanization on the associations between long-term PM2.5 exposure and mortality.Over a wide range of O3 concentrations ranging from 55 to 111 μg/m3,each 10μg/m3 increase in long-term O3 exposure was associated with a 3.1%,3.1%,and 8.3%increase in the risk of death from all-cause,CVD,and respiratory disease,respectively,and the patterns of the C-R function varied by cause of death.The long-term O3 exposure sub-linearly related to all-cause mortality(P for nonlinearity<0.001),with a steeper slope at higher concentrations.The nonlinear association resulted mainly from the combined distinct C-R functions of cause-specific mortalities.Specifically,the C-R function for CVD mortality was nonlinear(P for nonlinearity<0.001),whereas the C-R function for respiratory disease mortality was linear(P for nonlinearity=0.144).In addition,there were modifying effects of smoking status,drinking status,BMI,hypertension,diabetes,and CVD on the associations between long-term O3 exposure and mortality.High level of O3 exposure significantly increased the effects of PM2.5 on CVD mortality and respiratory disease mortality;and high level of PM2.5 exposure significantly increased the effect of O3 on CVD mortality.In addition,there was a synergistic effect of PM2.5 and O3 exposure on the risk of all-cause,CVD,and respiratory disease mortality,with a significantly higher risk of death from simultaneous exposure to high levels of PM2.5 and O3.ConclusionThis study found that long-term PM2.5 exposure increased the risk of all-cause,CVD,cancer,and respiratory diseases mortality;and long-term O3 exposure increased the risk of all-cause,CVD and respiratory diseases mortality.There was a synergistic effect of long-term exposure to the two air pollutants on the risk of mortality.These findings provide important evidence for assessing the burden of disease caused by air pollution and the health effects of coordinated management of pollutants,suggesting that active synergistic treatment of air pollution may significantly reduce the risk of air pollution-related mortality and improve health benefits.