| Background: Heavy metals can enter the human body through the digestive tract,respiratory tract and skin.Long-term exposure to high levels of heavy metals can damage lung function.At present,most studies focus on the effects of single heavy metal exposure on lung function,but human body is often exposed to multiple heavy metals at the same time.Moreover,most of the current studies only focus on the level in vitro or in vivo.And it can not well reflect the accurate level of heavy metal exposure according to the heavy metal in a single biological sample.Objective:(1)To assess the heavy metal exposure levels in urine,blood and household dust samples and lung function levels of residents in typical rural areas of Gansu province.(2)To explore the effect of single heavy metal exposure on lung function based on exposome methods.(3)To explore the damaging effect of co-exposure to heavy metals on lung function and identify the heavy metals that contribute the most based on exposome evaluation.(4)To explore the possible role of immune molecules in the process of lung function damage caused by heavy metals.Methods: This study enrolled 382 permanent residents in rural areas of Gansu province who participated in the survey from September to December 2019 as the research objects.A face-to-face interview was conducted to collect the basic demographic and sociological information,living habits,disease history and other information of the subjects.At the same time,the physical examination including height,weight and the lung function test was carried out.Lung function indicators included: forced vital capacity(FVC),forced expiratory volume in the first second(FEV1),the ratio of forced expiratory volume to forced vital capacity in the first second(FEV1/FVC),forced expiratory capacity/prediction(FVC%),forced expiratory volume in one second/prediction(FEV1%).Pulmonary ventilation dysfunction(PVD)was defined as FVC% < 80% or FEV1% < 80% or FEV1/FVC <70%.The fasting blood samples and morning urine samples of the subjects were collected,and the household dust samples for each subjects were collected at the same time.The concentrations of Co,Ni,Mo,Cd,Sb,Cu,Zn,Hg,Pb,and Mn were determined by inductively coupled plasma mass spectrometry digestion.The levels of Interleukin-2(IL-2),Interleukin-4(IL-4),Interleukin-6(IL-6),Interleukin-8(IL-8),Interleukin-10(IL-10),Immunoglobin G(IgG),Immunoglobin A(IgA),Immunoglobin M(IgM),Interferon-γ(IFN-γ)and tumor necrosis factor-α(TNF-α)in urine were determined by enzyme-linked immunosorbent assay.First,the linear regression model and restricted cubic spline model were used to analyze the relationship between the single exposure of heavy metals in urine,blood and household dust samples and FVC%,FEV1%,FEV1/FVC.Then,bayesian kernel machine regression(BKMR)was used to analyze the relationship between co-exposure to heavy metals in urine,blood and household dust samples and lung function.And the posterior inclusion probability(PIP)was used to confirm the heavy metal that contributed the most.Then,the interaction between immune molecules and heavy metals on lung function damage was analyzed to find out the possible mechanism of lung function damage caused by heavy metals.Finally,the differences in the relationship between heavy metals and lung function among subjects of different genders and addresses were analyzed.Results:(1)A total of 382 subjects were included in this study,of which 142(37.17%)were males and 230(60.21%)were diagnosed with PVD.The lung function of residents in typical rural areas of Gansu was poor.The mean and standard deviation of FVC,FVC%,FEV1,FEV1% and FEV1/FVC were 2283.11 ± 630.46 m L,72.93 ±17.12 %,2082.51 ± 519.26 m L,84.37 ± 19.47 %,92.14 ± 8.08 %,respectively.There were 218 blood samples,of which 118(54.1%)were males and 134(61.47%)were diagnosed with PVD.Among 85 subjects with household dust samples,48(56.5%)were males and 61(71.76%)were diagnosed with PVD.(2)About the single pollutant model of heavy metal.In urine,Sb(β=-4.714),Hg(β=-10.150),Mn(β=-8.477)were negatively correlated with FVC%,and Sb(β=-5.603),Hg(β=-10.935),Mn(β=-8.783)were negatively correlated with FEV1%.In blood,Co(β=-10.029),Ni(β=-5.784),and Pb(β=-10.185)were negatively correlated with FVC%,while Co(β=-10.066),Zn(β=-36.851),Pb(β=-13.373)were negatively correlated with FEV1%.In household dust samples,Pb(β=11.499)was positively correlated with FEV1%.(3)BKMR model was used to analyze the combined effects of heavy metals on lung function.The results showed that lung function gradually decreased with the increase of the level of heavy metal mixture in urine,and the largest contributions to FVC%,FEV1%,FEV1/FVC were Cd(PIP=1.0000),Cd(PIP=1.0000),Cu(PIP=0.4244),respectively.The co-exposure of heavy metals in blood was negatively correlated with FVC% and FEV1%,and the largest contribution to both FVC% and FEV1% was Pb(FVC%: PIP=0.9410,FEV1%: PIP=0.7838),respectively.However,the co-exposure of heavy metals in household dust samples had no significant relationship with lung function.(4)By analyzing the relationship between the level of immune molecules and lung function,it was found that IL-2,IL-4,IL-6,IL-8,IL-10,IgG,IgA,IFN-γ,TNF-αwere negatively correlated with FVC%,FEV1%,FEV1/FVC,especially IL-10 and IgG.It was found that IL-10 had a multiplicative interaction with Cd(β=0.639),Sb(β=-0.459),Hg(β=-0.672),Pb(β=0.450),and Mn(β=-0.667)on FVC%.IL-10 had a multiplicative interaction with Co(β=-0.715),Cd(β=0.536),Sb(β=-0.694),Zn(β=-0.549),Hg(β=-0.848),and Mn(β=-0.822)on FEV1%.IL-10 had a multiplicative interaction with Co(β=-0.288),Ni(β=-0.303),Mo(β=-0.205),Cd(β=-0.225),Sb(β=-0.202),and Pb(β=-0.228)on FEV1/FVC.IgG had a multiplicative interaction with Mo(β=0.521),Cd(β=0.911),Pb(β=0.746)and Mn(β=-0.428)on FVC%.IgG had a multiplicative interaction with Cd(β=0.934),Sb(β=-0.504),Hg(β=-0.675),Pb(β=0.649),and Mn(β=-0.627)on FEV1%.IgG had a multiplicative interaction with Co(β=-0.380),Ni(β=-0.349),Mo(β=-0.346),Cd(β=-0.346),Sb(β=-0.306),Cu(β=-0.272),Pb(β=-0.245),and Mn(β=-0.245)on FEV1/FVC.(5)The results of the relationship between heavy metals and lung function in different characteristic populations showed that there was no significant correlation between heavy metals and lung function in men,while Mo,Cd,Sb,Hg,Pb,Mn and FVC%,FEV1% showed different degrees of correlation in women.Conclusion:(1)The proportion of residents with pulmonary ventilation dysfunction is high in a typical rural area of Gansu Province,and local residents are exposed to different levels of heavy metal pollution.(2)Both single and combined exposure to heavy metals were associated with lung function impairment,especially Co,Ni,Cd,Sb,Zn,Hg,Pb,and Mn,while the contribution of Cd and Pb may be greater,particularly in females.(3)Heavy metals may cause lung function damage by disturbing the levels of immune molecules. |
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