Combined Effects Of Air Pollutants And Temperature On Asthma

ObjectiveTo identify the combined effects of air pollutants and temperture on asthma.On the one hand,time series analysis were used to detect the relationship between concentration of SO₂,NO₂,PM₁₀,PM_2.5,O₃,CO,temparture and children asthma outpatients in hospital.On the other hand,the animal model was used to explore the aggravating effect and mechanism of PM_2.5and cold temperature on asthmatic mice.MethodsCollect asthma clinic data of children aged 0-14 in a children’s hospital,air pollution variables and meteorological data of Shanghai from 2013 to 2017.GAM was used to construct time series models of SO₂,NO₂,PM₁₀,PM_2.5,O₃,CO and total asthma outpatients,boys outpatients,girls outpatients.We also examined lag effects of air pollutants with single-day lag（lag1 to lag7）and moving average lag（lag01 to lag07）.The interactive effects of pollutants and temperature were incorporated into models to analyze whether the pollutants and temperature had interactive effects on asthma outpatients.Finally,three-dimensional maps of pollutants,temperature and asthma outpatients were constructed by bivariate response models to describe the spatial distribution characteristics.Ovalbumin was used to establish the allergic asthmatic mice.25 male8-week-old C57BL/6J mice were randomly divided into 5 groups,control group,asthma group,asthma+PM_2.5group,asthma+cold temperature group and asthma+PM_2.5+cold temperature group（n=5）.The mice were exposed to PM_2.5and cold temperature by meteorological and environmental animal exposure system.After the last OVA/PBS sensitization,anesthetized mice with pentobarbital and collected BALF,blood and lung tissue within 24 hours.CAT,GSH,SOD,MDA in BALF;Th1cytokines IL-2 and IFN-γ,Th2 cytokines IL-4,IL-6 and IL-13,Th17 cytokine IL-17A and Treg cytokine TGF-β;the m RNA expression levels of IFN-γ,IL-4,IL-13,TGF-β,Th17 transcription factor ROR-γt and Treg transcription factor Fox P3 were detected.Results1.Time series analysis of air pollutants and temperature on asthma clinics visits in children aged 0-14（1）Characteristics of asthma outpatients visits for 0-14 years old in a children’s hospital and air pollution in Shanghai.Children asthma outpatients increased each year from 2013 to 2017,boys outpatients are twice as many as girls outpatients.Shanghai’s air quality is generally good,while there are still excessive concentrations of PM_2.5,PM₁₀and O₃.（2）The impact of pollutants on the total children asthma outpatients.Asthma outpatients were signifificantly associated with increase of air pollutants（P<0.05）.Every 10μg/m~3increase in SO₂,NO₂and PM₁₀,children asthma outpatients increased by 2.64%（95%CI:0.09%,4.20%）,1.07%（95%CI:0.39%,1.75%）and 0.36%（95%CI:0.02%,0.69%）,respectively.Significant relationships were observed for asthma outpatients with SO₂at lag day 2 and 01 to 07;with NO₂at lag day 1 to 7 and01 to 07;with PM₁₀at lag day 2,3,5 and 01 to 07;and with PM_2.5at lag day 03 to07（P<0.05）.No association was found between O₃,CO and asthma patients at any other lag periods.（3）The impact of pollutants on boys asthma outpatients.SO₂,NO₂,PM₁₀and PM_2.5were significantly correlated with the increase of boys outpatients except for O₃and CO（P<0.05）.Every 10μg/m~3increase in SO₂and NO₂,boys asthma outpatients increased by 2.38%（95%CI:0.28%,1.70%）and 1.10%（95%CI:0.39%,1.80%）.Statistically significant relationships were observed for boys outpatients with SO₂at lag day 01 to 07;with NO₂at lag day 2 to 7 and 01 to 07;with PM₁₀at lag day 5 and03 to 07;and with PM_2.5at lag day 05,06（P<0.05）.（4）The impact of pollutants on girls asthma outpatients.Girls outpatients were signifificantly associated with increase of air pollutants（P<0.05）.Every 10μg/m~3increase in SO₂,NO₂and PM₁₀,girls outpatients increased by 3.15%（95%CI:1.26%,5.07%）,1.02%（95%CI:0.19%,1.86%）and 0.45%（95%CI:0.05%,0.86%）,respectively（P<0.05）.Statistically significant relationships were observed for girls outpatients with SO₂at lag day 1,2 and 01 to 07;with NO₂at lag 1 to 7 and 01 to 07;with PM₁₀at lag day 2,3 and 01 to 07;and with PM_2.5at lag day 2,3 and 02 to07（P<0.05）.We didn’t find relationship between O₃,CO and girls patients at any lag structures.（5）Analysis of interaction between air pollutants and temperature on children asthma patients.There was no significant interaction between pollutants and temperature on asthma outpatients except PM_2.5.The PM_2.5concentration of lag3 and temperature had an interactive effect on total asthma outpatients,boys and girls（P<0.05）.Three-dimensional models showed that the higher the concentration of PM_2.5at low temperature,the more children asthma outpatients,boys and girls.2.Effects of combined exposure of PM_2.5and low temperature on Th1/Th2 and Th17/Treg in asthmatic mice（1）Effects of PM_2.5and cold temperature on oxidative damage,Th1,Th2cytokines in asthmatic mice.The levels of CAT,GSH and SOD in asthma+PM_2.5group,asthma+cold temperature group and asthma+PM_2.5+cold temperature group were decreased compared with control group and asthma group,while MDA was increased significantly（P<0.05）.The levels of Th1 cytokines IFN-γand IL-2 and the m RNA level of IFN-γwere decreased;the levels of Th2 cytokines IL-4,IL-6 and IL-13 and the m RNA levels of IL-4 and IL-13 were increased（P<0.05）.Expression levels of CAT,IFN-γ,IL-2 and the m RNA level of IFN-γin asthma+PM_2.5+cold temperature group were lower than that of asthma+PM_2.5group and asthma+cold temperature group;the levels of MDA,IL-4,IL-6,IL-13 and the m RNA levels of IL-4and IL-13 were higher than that of asthma+PM_2.5group and asthma+cold temperature group with statistical significance（P<0.05）.（2）Effects of PM_2.5and cold temperature on Th17 and Treg cytokines in asthmatic mice.The concentration of IL-17A and TGF-βand the m RNA level of ROR-γt in asthma+PM_2.5group,asthma+cold temperature group and asthma+PM_2.5+cold temperature group were increased compared with control group and asthma group,while the m RNA level of Fox P3 was decreased（P<0.05）.The levels of IL-17A,ROR-γt and TGF-βin asthma+PM_2.5+cold temperature group were higher than that of asthma+PM_2.5group and asthma+cold temperature group,Fox P3was lower than that of asthma+PM_2.5group and asthma+cold temperature group（P<0.05）.Conclusion1.Children asthma outpatients aged 0-14 in Shanghai are increasing year by year,boys patients are twice that of girls patients.Air quality in Shanghai has improved from 2013,but PM_2.5,PM₁₀and O₃concentrations still exceeded air quality standard sometimes.2.The concentrations of SO₂,NO₂,PM₁₀and PM_2.5were interacted with the increase of asthma outpatients aged 0-14 in Shanghai,with single-day and moving average lag effects.The higher the concentration of PM_2.5at low temperature,the more the children asthma outpatients,boys and girls.3.PM_2.5and cold temperature can aggravate asthma in mice,the possible mechanism is that PM_2.5and cold temperature play a synergistic role in aggravating oxidative damage and inflammatory response in asthmatic mice,promote the levels of Th2 cytokines and inhibit Th1 cytokines,promote the levels of Th17 cytokines and inhibit Treg cytokines,resulting in imbalance of Th1/Th2 and Th17/Treg,leading to asthma exacerbation.