Short-term Exposure To Air Pollutants Induces Adverse Respiratory Effects And Impact Of GSTT1-null Genotype: A Panel Study Of The Elderly

BackgroundAir pollution has always been an important environmental risk factor for public health worldwide,and its influence on the human health cannot be ignored.Studying the regulation of the effects of genetic factors on pollutants associated with respiratory systems is helps to understand its potential biological mechanisms,identify high-risk populations of respiratory diseases and provide targeted preventive measures.ObjectiveThis study aims to investigate acute adverse respiratory effects of air pollutants and to determine whether the glutathione S-transferase-theta（GSTT1）gene deficiency modifies those effects.MethodsRecruited the subjects from the health and retired staff of Xinxiang Medical College by questionnaire survey and inclusion criteria,and subsequently,the subjects were followed up five times（once every four weeks）from December 2018 to April 2019.The pulmonary indicators including fractional exhaled nitric oxide（FeNO）,forced vital capacity（FVC）,forced expiratory volume in one second（FEV1）,and peak expiratory flow（PEF）and the levels of 8-epi-prostaglandin F2alpha（8-epi-PGF2α）and interleukin 8（IL-8）,interleukin-1（IL-1β）,tumor necrosis factor（TNFα）in nasal samples were tested.Daily average concentration calculated by hourly concentration of air pollutants and meteorological factors as individual exposure concentration;Taking each pollutant concentration as the fixed effect and the object identify as the random effect parameter,and controlling the influence of covariables,such as age,body mass index（BMI）,sex,seasonal effect,meteorological factors（mean temperature,relative humidity）.A linear mixed-effect model was introduced to estimate the association between ambient PM_2.5 and acute respiratory effects of the healthy elderly,and to examine whether these associations are stronger among subjects with the GSTT1（Glutathione S-transferase theta1）gene polymorphism.ResultsA total of 32 subjects were enrolled,with an average BMI of（26.30±3.36）kg/m²,and mean age of（63.53±5.76）years respectively.（1）Lung functionSingle pollutant model found that both PM_2.5,PM₁₀,O₃,NO₂ and SO₂ concentrationswere negatively correlated with FVC,FEV1 and FEV1/FVC ratio;Negative statistical association was also observed between PM_2.5,PM₁₀ and NO₂ concentrations and PEF,PM₁₀ concentration and MV.Genetic stratification shows,Compared with GSTT1-sufficient population,PM₁₀,O₃,NO₂ and FVC;NO₂ and FEV1;NO₂ and ratio;PM_2.5,NO₂ and PEF were the stronger negative correlation in GSTT1-null populations,and the statistical difference between two genotypes was significant.（2）Fractional exhaled nitric oxide（FeNO）Single pollutant model showed that PM₁₀（lag03,lag04）,NO₂（lag1）,SO₂（lag2,lag05）,CO（lag1,lag02）concentration were positively associated with the increasement of FeNO level.Genetic stratification shows,the positive correlation between PM_2.5,CO and FeNO in GSTT1-null population is stronger compared to GSTT1-sufficient.Besides,in GSTT1-sufficient population,the increased effect on O₃,PM₁₀ and FeNO were significant among different genotypes.（3）Inflammatory biomarkersSingle pollutant model revealed that PM_2.5（lag2）,PM₁₀（lag2,lag02）,SO₂（lag1）and NO₂（lag1）concentrations were all significantly positively correlated with IL-8 levels,and the concentration of PM_2.5（lag2）was positively correlated with the IL-1βlevel,However,positive correlation was not found between other pollutants and IL-1β;In addition,it’s not found correlation among these pollutants and TNF-α.Genetic stratification shows that the positive correlation between O₃ and IL-8,IL-1βin GSTT1-null population are strong compared to GSTT1-sufficient population,and the difference between two groups was statistically significant.Intriguingly,the increased effects on PM_2.5,PM₁₀,CO and IL-8 were significant in GSTT1-sufficient population among different genotypes.（4）Oxidative stress biomarkers（8-epi-PGF2α）Single pollutant model presented that PM_2.5（lag2）,NO₂（lag1）and PM₁₀（lag2,lag02） concentrations were significantly positive correlated with 8-epi-PGF2αlevels.Compared with GSTT1-sufficient population,the positive associations of O₃ and 8-epi-PGF2αwere stronger in GSTT1-null and the difference was statistically significant.（5）Particulate matter compositionThe relationship between each component of particulate matter and each health effect index found that nitrate ion（NO₃^-）and lung function index,sulfate ion(SO₄^2-)and bromine ion（Br^-）were significantly negatively correlated with ratio,PEF levels,but no statistical correlation between other components and effect index was found.ConclusionThe findings from this study demonstrate that acute exposure to ambient air pollutants induce respiratory inflammation and oxidative stress,and decrement in lung functions in healthy elderly,which can be enhanced by GSTT1-null genotype.