Effects Of GSTM1 Gene Deficiency On Acute Respiratory Inflammatory Response And Lung Function Change In Healthy Volunteers Exposed To Haze

Objective To explore the effects of acute exposure to haze on respiratory tract and lung function in healthy volunteers and further to examine the differences in these respiratory effects between GSTM1 null and functional genotype subjects.Methods In the panel study,74 healthy college student volunteers with different GSTM1 genotypes were selected for the study,including 20 male and 54 female subjects.All of them were tested six times during September to December 2017.PM2.5 sampling and analysis for some of the metal constitutes were conducted on the day before each experiment.Major particulate matter and gaseous pollutants(PM2.5,PM10,SO2,NO2,NO,NOX,O3)and meteorological factors(temperature,relative humidity)daily concentrations for 24 hours were monitored.The upper respiratory inflammatory indicators(interleukin-8(IL-8),interleukin-6(IL-6),tumor necrosis factor-?(TNF-?))and oxidative stress indicator(8-epi-prostaglandin F2?,8-epi-PGF2?)were both measured by Enzyme-linked immunosorbent assay.Spirometer was used to examine lung function.Associations between pollutants and inflammatory indicators and lung function were investigated using mixed models.GSTM1 genotype stratificiation analysis to explore the effect of GSTM1 null genotype on pollutant-induced respiratory effects.Result1.Modification effects of GSTM1 gene deficiency on inflammatory responses in the upper respiratory tract exposed to major pollutants of haze: The levels of the upper respiratory inflammatory cytokines IL-6,TNF-? and IL-8 increased with elevating concentrations of particulate matter,which associations were more obvious with the growing exposure cumulative lag days(2-7d).For an IQR increase(127?g/m3)of PM10 at7-d moving averages,there was a 219.85%(95%CI:55.47~558.25%)increase in IL-6.Whereas,the levels of IL-6,TNF-?,and IL-8 decreased exposed of gaseous pollutants.The effects on IL-6 in the GSTM1 deletion genotype(GSTM1-)population were more pronounced than those in the GSTM1 functional genotype(GSTM1+)after PM10,NO2,NO,NOX,O3,and SO2 exposure,which also had a cumulative lag effect.In carriers of GSTM1 null genotype,for an IQR increase(127?g/m3)of PM10 at 5-d moving averages,there was a330.76%(P=0.0151)increase in IL-6;for a 10?g/m3 increase of NO2 at 7-d moving averages,there was a 72.09%(P=0.0345)decrease in IL-6;for a 10?g/m3 increase of NO at 3-d moving averages,there was a 45.21%(P=0.0019)decrease in IL-6;for a 10 ?g/m3 increase of NOX at 5-d moving averages,there was a 42.07%(P = 0.0327)decrease in IL-6;for a 10?g/m3 increase of O3 at 7-d moving averages,there was a 71.79%(P=0.00051)decrease in IL-6;for a 10?g/m3 increase of SO2 at 5-d moving averages,there was a81.44%(P=0.0264)decrease in IL-6.2.Modification effects of GSTM1 gene deficiency on oxidative stress in the upper respiratory tract exposed to major pollutants of haze: we observed an increase in8-epi-PGF2? exposed to particulate matter,especially for an IQR increase(127?g/m3)of PM10 at 5-d moving averages,there was a 59.57%(95% CI:4.55,143.48%)increase in8-epi-PGF2?.While a decrease in 8-epi-PGF2? exposed to gaseous pollutants.There was no significant difference effects between the GSTM1 deletion genotype and the GSTM1 functional genotype population.3.Modification effects of GSTM1 gene deficiency on lung function change exposed to major pollutants of haze:We found nonsignificant increase in lung function(FVC,FEV1,PEF,MVV,and MV)exposed to particulate matter,specifically for FVC and FEV1,there were a 2.081%(95% CI: 1.191,2.972)increase in FVC and a 2.031%(95% CI:1.178, 2.885%)increase in FEV1 for a 10 ?g/m3 increase of PM10 at 5-d moving averages.In the GSTM1 deletion genotype population,the statistically significant changes in FVC,FEV1,PEF,MVV,and MV exposed to particulate matter were more obvious than that of GSTM1 functional genotype population.With the concentration of gaseous pollutants increasing,there were decrease trends of the lung function indexes.In GSTM1-population,changes of lung function exposed to gaseous pollutants were more obvious than that of GSTM1+population,even though there were no statistical significance.4.Relationship between PM2.5 constitutes and inflammatory biomarkers,oxidative stress biomarkers,and lung function: Results showed that there were nonsignificant negative associations between most of the PM2.5 constitutes(including vanadium(V),chromium(Cr),copper(Cu),zinc(Zn),manganese(Mn),germanium(Ge),aluminum(Al),barium(Ba),strontium(Sr),lead(Pb),boron(B),arsenic(As))and IL-6,IL-8,8-epi-PGF2?,FVC,MVV and nonsignificant positive associations between these PM2.5 constitutes and TNF-?,PEF,MV and FEV1.The effect of the PM2.5 component on the health indicators in the GSTM1-population was not observed to be more pronounced than in the GSTM1+ group.5.The two-pollutants models showed that the effects of particulate matter(PM2.5 and PM10)on TNF-?,IL-6,IL-8,8-epi-PGF2? and lung function were found to be consistent with the single-pollutant models controlling the potential confounding gaseous pollutants.Conclusion1.Increased concentrations of PM2.5 and PM10 particles triggered upper respiratory tract inflammatory effects and oxidative stress elvating,while exposure to gaseous pollutants induced opposite effects and there is a clear dose-response relationship.The effects of PM10 and gaseous pollutant exposure on IL-6 in GSTM1-subjects were more pronounced than those of GSTM1+subjects.2.The effects of haze particulate matter and gaseous pollutant exposure on lung function had opposite effects,in which particulate pollutants increased lung function,and gaseous pollutants decreased lung function.The impact of particulate matter and gaseous pollutants on changes in lung function in GSTM1-subjects were more pronounced than in GSTM1+ subjects.3.With the increasing concentration of PM2.5 constitutes,there were nonsignificant decrease in IL-6,IL-8,8-epi-PGF2?,FVC,MVV,and no significant increase in FEV1,PEF,and MV.The modification of GSTM1-on these effects was not significantly different from GSTM1+.4.Generally,the results of two-pollutants models were consistent with the single pollutant models.