Effect And Mechanism Of Coal Burning On Air Pollution And Asthma Hospitalization

Part One The Effect and Burden Modification of Heating on Adult Asthma Hospitalization in ShijiazhuangObjective: This study was aimed to evaluate the effect and burden modification of heating season on short-term associations between asthma hospitalizations and main ambient air pollutants among adults in the north China city of Shijiazhuang during 2013²016.Methods: From January 1,2013 to December 31,2016,daily air pollution concentration data and daily meteorological data（temperature and humidity）in Shijiazhuang urban area were obtained from Hebei meteorological bureau.The hospitalization data of daily asthma patients came from Shijiazhuang medical insurance center.The inclusion criteria for asthma patients were:（1）Local resident patients hospitalized in all secondary and tertiary hospitals in urban Shijiazhuang during the study period.（2）The main discharge diagnosis was an acute attack of asthma（ICD-9: J45.000,J45.003,J45.007,J45.100,J45.800,J45.900,J45.902,J45.903,J45.904,j46.x00）.（3）Age ≥18 years old.Generalized additive models combined with penalized distributed lag nonlinear models were used to model associations between daily asthma hospitalizations and ambient air pollutants,adjusting for long-term and seasonality trend,day of week,statutory holiday,daily mean air pressure and temperature.Linear and nonlinear exposure-effect model was established for heating season and non-heating season,and the exposure-lag-effect curves were compared to evaluate the possible effect of heating on the admission of asthma.Attributable risks were calculated to evaluate the burden of asthma hospitalizations due to air pollutants exposure.The effect of pollutants on hospitalization and the attributable measures were estimated in heating and non-heating season separately and the comparisons between the two seasons were conducted.Results: All pollutants(PM_2.5,PM₁₀,SO₂,NO₂,CO,O₃)demonstrated positive and significant impacts on asthma hospitalizations both in heating season and non-heating season,except for O₃ in heating season where a negative association was observed.The cumulative effect of the lag of 7 days was higher in the non-heating season than in heating season,but the difference between the two seasons was not statistically significant.SO₂ and NO₂ exposure were associated with the heaviest burden among all pollutants in heating season.The ANs were 169.392（95%CI: 97.695,247.563）and 182.028（95%CI: 106.111,257.134）,and the AFs were 9.3%（95%CI: 5.2,12.7%）and 10%（95%CI: 5.8,13.7%）,respectively.Meanwhile,PM₁₀and PM_2.5were associated with the heaviest burden in heating season.The ANs were 252.334（95%CI: 121.342,380.115）and 186.101（95%CI: 73.435,293.414）,and the AFs were 11.3%（95%CI: 4.9,17%）and 8.3%（95%CI: 3.1,13.2%）,respectively.Except that the AN of PM₁₀in non-heating season was significantly higher than that in heating season（P=0.039）,there was no significant statistical difference in other attributable measures in the two seasons（P>0.05）.Conclusions: In conclusion,this study confirmed that there was a significant correlation between air pollutants and admission for acute asthma attack in Shijiazhuang urban area from 2013 to 2016.Of the six major air pollutants,SO₂ and NO₂ had the strongest associations with hospitalization of asthma in both the heating season and the non-heating season.The 7-day cumulative relative risk of pollutants in non-heating season was higher than that in heating season,but the difference was not statistically significant.Exposure to SO₂ and NO₂ caused the highest hospital admission burden for asthmatics during the heating season,while PM₁₀and PM_2.5were the top two pollutants that caused hospital admission burden for asthma during the non-heating season.The results of this study are of positive significance for the formulation of scientific and reasonable management suggestions for asthma patients and air pollution control strategies to reduce the social burden.Part Two The Mechanism of Hypersensitivity Reaction Disease due to PM_2.5 Exposure Induced Differential Gene Expression in Human Airway Epithelial CellsObjective: To investigate the effect of PM_2.5 on gene expression in human airway epithelial cells.The possible lung diseases caused by PM_2.5 exposure and their molecular mechanisms were analyzed to provide possible target selection for the treatment of diseases.Methods: The gene expression data were obtained from the GEO database GSE108134 data set.The GSE108134 data set included 29 healthy non-smoking subjects and 129 smoking subjects（including 71 healthy smokers and 58 COPD patients）.Bronchial epithelial cells were collected via bronchoscopy brush biopsy at the time of enrollment,3,6 and 12 months after enrollment for each patient,and RNA gene sequencing analysis was performed.Meanwhile,mean atmospheric PM_2.5 concentration in the month before sample collection was recorded and its influence on gene expression was analyzed.The software packages of "limma","clusterprofiler" and "GEOquery" in R language environment were used to screen differentially expressed genes.Enrichment analysis of GO,KEGG and DO were carried out respectively.The differentially expressed genes related to allergic diseases in DO analysis were analyzed again by GO and KEGG enrichment analysis.Protein interaction network analysis was conducted using STRING platform.MCODE plug-in in Cytoscape software was used to extract key genes and visualize the network.Results: In this study,a total of 2846 differentially expressed genes related to PM_2.5 exposure were identified,including 1640 up-regulated genes and 1206 down-regulated genes.The GO gene overexpression analysis showed that the differentially expressed genes mainly enriched in the epithelial tube formation and the covalent chromatin modification.Analysis of the KEGG pathway showed that the differentially expressed genes were mainly enriched in the vasopressin regulatory pathway and the longevity regulatory pathway.DO disease analysis showed that differentially expressed genes were mainly related to hypersensitivity reaction disease and neoplastic diseases.Fifty differentially expressed genes were related to hypersensitivity reaction disease,mainly enriched in stress response,immune regulation and apoptosis pathways.JUN,ATM,EP300,CASP3 and HSPA4 were the key genes for PM_2.5 causing hypersensitivity reaction disease.Conclusions: PM_2.5 exposure can significantly change the gene expression of human airway epithelial cells,which mainly affects the epithelial tube formation and the biological processes regulated by vasopressin regulatory.These gene expression changes are mainly related to hypersensitivity reaction disease and neoplastic diseases,mainly through the impact on immune response and stress response to cause hypersensitivity reaction disease.JUN,ATM,EP300,CASP3 and HSPA4 are the key genes of PM_2.5 causing hypersensitivity reaction disease and may become the therapeutic targets of such disease.