Study On Association Between PM_2.5 Exposure And The Expression Of Inflammatory Biomarkers In Human Plasma

Objective:Concentrations of fine particular matter(PM_2.5)exposure have been associated with adverse effects on human health.A cross-sectional study was conducted to investigate the association between PM_2.5.5 exposure and the expression of inflammatory biomarkers in the six districts from September to November 2017.It can provide scientific support for clarifying the physiological mechanism of the acute health effects of the cardiopulmonary diseases caused by PM_2.5,assesing and predictiong the health risk of the cardiopulmonary diseases in the population.Methods:Data of questionnaire,health examination,and air pollution exposure in the strengthening research area in the autumn was obtained from the project of"China Short-Term Health Effect of Air Pollution Study（China SHEAP Study）"led by National Institute of Environmental Health,Chinese Center for Disease Control and Prevention.This study based on the above data was applied to explore the association between PM_2.5.5 short and medium term outdoor exposure and inflammatory biomarkers401 respondents who aged 40 to 89 years old from the strengthening research areas were involved in the research.According to the research object’s home address,the data of the nearest environmental protection and meteorological monitoring stations are matched.According to the research object’s physical examination time,we matched the PM_2.5.5 and meteorological factors with different lag and cumulative exposure levels in short and medium terms.Multiple linear regression model was adopted to investigate the relationship between PM_2.5.5 short-term outdoor exposure and Tumor Necrosis Factor–α（TNF-α）,Interleukin-1β（IL-1β）,Interleukin-6（IL-6）and Interleukin-8（IL-8）after adjusting for confounding factors such as age,gender,temperature,and relative humidity.Furthermore,stratified analysis was applied to explore the modified effects of gender,age,obesity,disease,and geography on the study.Statistical significance was achieved with a two-tailed value of P<0.05.In order to evaluate the accuracy of the research results,three parts of sensitivity analysis were conducted in this study.Firstly,binary association analysis between PM_2.5.5 and different inflammatory biomarkers.Secondly,other risk factors,such as whether to engage in dust exposure occupation,were added to the main model one by one to determine whether the results were stable.Finally,Ozone（O₃）and Nitrogen Dioxide（NO₂）in the same exposure period of PM_2.5.5 were included in the main model separately to determine whether the results were stable.Results:（1）The study was conducted in 6 counties of China,including Daoli in Harbin,Xinji in Shijiazhuang,Guangyang in Langfang,Binhu and Jiangyin in Wuxi.The average age of the 401 objects was 64.35 years old,with 198 males（49.38%）.The inflammatory factors in the plasma showed skewed distribution.The median value of TNF-α,IL-1β,IL-6 and IL-8 were 11.24 pg/ml,1.66 pg/ml,1.86 pg/ml,and 4.7 pg/ml,respectively.（2）The outdoor daily average concentration of PM_2.5,NO₂,and O₃ on the day prior to the physical examination were lower than the secondary concentration limits of China’s ambient air quality standards.The outdoor levels of PM_2.5,NO₂,O₃,temperature,and relative humidity were 59.17μg/m³,61.58μg/m³,39.46μg/m³,12.80°C,and 68.66%,respectively.（3）This study analyzed the relationships between the lag and cumulative exposure of PM_2.5.5 and TNF-αin short and medium term The short-term cumulative effect of PM_2.5.5 for the 6-day average（Lag06）was the most obvious,with a 10μg/m³ increasing of PM_2.5,a 4.73%（P<0.05）increase of TNF-α.And the medium term cumulative effect of the 180-day average（Lag0180）PM_2.5.5 was the most obvious,with a 10μg/m³ increasing of PM_2.5,a 9.22%（P<0.05）increase of TNF-α.（4）In this study,significant associations were only found between effect of 3-day lag（Lag3）and cumulative effect of 30-day average（Lag030）of PM_2.5and IL-1β,a 10μg/m³ increase of which correspond to a increase of 2.88%（P<0.05）and 9.27%（P<0.05）in the levels of IL-1β,respectively.（5）The short term exposure to PM_2.5.5 was associated with IL-6.The greatest effect on IL-6 was observed for Lag6 and Lag010 PM_2.5,increase of8.67%（P<0.05）and 13.74%（P<0.05）.And the medium term cumulative effect of Lag0180 PM_2.5.5 was the greastest effect,with a 10μg/m³ increasing of PM_2.5,a26.13%（P<0.05）increase of IL-6.（6）PM_2.5.5 for different lag patterns was associated with IL-8.The greatest effect on IL-8 was observed for lag 12 PM_2.5.5 increase of 9.27%（P<0.05）.Over the exposure time of PM_2.5,the effect on IL-8 was gradually greater,the greatest short term effect of PM_2.5.5 occurred in 9-day average,with increase of 12.19%（P<0.05）in IL-8.And in the cumulative 180-day exposure period of PM_2.5,the significant association between PM_2.5.5 and IL-8 was strongest,a 10μg/m³increase in the exposure to PM_2.5.5 was associated with increases of 34.42%（P<0.05）in IL-8.（7）The stratified analysis on the associations between PM_2.5（averaged over lags 4¹4）and expression level of inflammatory biomarkers suggested that there was no statistically significant difference in the effect of gender in short and medium term.It was found that per 10μg/m³ increase in PM_2.5concentration resulted in a 16.39%increase in IL-8 expression in women（P<0.05）.For people who was less than 60 years old,when the concentration of PM_2.5.5 increased by 10μg/m³,the levels of IL-6 and IL-8 increased by 11.80%（P<0.05）and 11.94%（P<0.05）,respectively.It was found that per 10μg/m³increase in PM_2.5.5 concentration resulted in a 13.46%increase in IL-6 expression in non-obese（P<0.05）.It was found that per 10μg/m³ increase in PM_2.5.5 leaded to a 23.39%increase in IL-8 in objects with cardiovascular diseases（P<0.05）,and the levels of TNF-αand IL-6 in objects without cardiovascular diseases increased by 6.03%（P<0.05）and 15.16%（P<0.05）,respectively.And also,a 10μg/m³ increase in PM_2.5.5 concentration can result in a 9.18%increase in the level of IL-8 in objects who live in the northern region（P<0.05）.Conclusions:1、There is a positive correlation between PM_2.5.5 exposure concentration and inflammatorybiomarkers,suggestingthatincreasedPM_2.5exposure concentration may increase inflammatory responses in the human,and further increase the risk of cardiopulmonary disease.2、The correlation between PM_2.5.5 and inflammatory biomarkers has lag effect and cumulative effect,suggesting that this effect should be considered in the early warning and prediction of the health risks of cardiopulmonary diseases.