Effects Of Smoking,Heavy Metal And Nickel Exposure On The Occurrence Of COPD And Its Effect Indicators

Purpose: Through this study,we mainly explored the role of smoking and heavy metal exposure in the occurrence and development of COPD and its related mechanisms,and further understood whether smoking and heavy metal exposure have synergistic effects on the pathogenesis of COPD,in order to provide relevant evidence for the prevention and treatment of COPD in the future.Methods: This study is mainly divided into two parts: population study and animal experiment.First,a nested case-control study was conducted using the Jinchang cohort population data.Cases included all patients newly diagnosed with COPD among members of Jin-chang cohort during the first follow up,Controls were selected from Jinchang cohort members free of COPD and other respiratory diseases during the same study period,were matched to cases（4:1）by age（±3years）and sex.The Logistic regression model was used to understand the risk factors affecting the incidence of COPD,and the interaction multiplication model was used to analyze whether there was an interaction between smoking and occupational heavy metal exposure on the incidence of COPD.Secondly,a simple smoke exposure mouse model,a simple nickel sulfate aerosol exposure mouse model,and a smoke combined nickel sulfate aerosol exposure mouse model were established.Compare the results of each model with the results of the control group,to verify the causal relationship between smoking or nickel exposure and lung injury.Then,the results of the mice in the smoke combined nickel sulfate aerosol exposure mouse model were compared with the results of the mice exposed to simple smoke exposure mouse model and their corresponding simple nickel sulfate aerosol exposure mouse model to further explore the interaction between smoking and nickel exposure.Finally,the pathological HE staining sections of mouse lung tissue were used to observe the lung damage of mice in each group.The levels of interleukin 13（IL-13）,tumor necrosis factor（TNF-α）,and Mucin-5AC（MUC5AC）in the bronchoalveolar lavage fluid of mice in each group were detected by enzyme-linked immunosorbent assay（ELISA）to explore smoking mechanisms of nickel exposure in the development and progression of COPD.Results: Population study: 1.Educational level and occupation were important factors affecting the incidence of COPD in the Jinchang cohort（P <0.05）.2.With the increase of the cigarette smoked daily,smoking years,and pack years,the incidence of COPD in the Jinchang cohort showed an upward trend（P for trend <0.05）.Smoking started earlier than 30 years old was associated with an increased risk of COPD（P <0.05）.3.High occupational heavy metal exposure is a risk factor for COPD（P<0.05）,but there is no trend correlation between the increasing occupational heavy metal exposure and the incidence of COPD（P for trend>0.05）.4.Smoking and heavy metal exposure had an interaction effect on the pathogenesis of COPD（P-interaction<0.01）.Pack years≥20,with the aggravation of metal exposure level,OR（95%CI）increased sequentially,and the risk of COPD increased,and the difference between smoking and heavy metal exposure was statistically significant（P<0.05）.5.Occupational heavy metal exposure was constant,with the increase of pack years,the risk of COPD increased,and the trend was statistically significant（P for trend<0.01）.Animal experiments: 1.Pulmonary function data showed that compared with the blank control,the PIF,PEF,and TV of the mice exposed to cigarettes were significantly reduced,and the f,Penh,and EF50 were significantly increased（P <0.05）;in the simple nickel sulfate aerosol exposure mouse model,the PIF,PEF and TV of the mice in the 0.6Ni and 1.2Ni group decreased significantly,but f,Penh increased significantly（P <0.05）.In the smoke combined nickel sulfate aerosol exposure mouse model,compared with the blank control,PIF,PEF,TV were decreased,and f,Penh,and EF50 were increased.Compared with the simple smoke exposure mouse model,PEF and TV were increased,and f,Penh and EF50 were decreased.Compared with simple nickel sulfate aerosol exposure mouse model,the PIF and TV of mice in CS+0.15 Ni,CS+0.3Ni and CS+0.6Ni groups all decreased,while f and Penh increased.2.The results of pathological sections and emphysema showed that compared with the blank control,the average alveolar lining interval of the simple smoke exposure model mice increased（P <0.05）,and the blood vessels and alveolar walls were congested,and the bullae and alveolar walls were necrotic and shed.Phenomenon;In the simple nickel sulfate aerosol exposure mouse model,with the increase of nickel sulfate aerosol exposure concentration,the lung injury in mice gradually increased,and the average alveolar lining interval increased（P <0.05）;In the smoke combined nickel sulfate aerosol exposure mouse model,compared with the blank control group,with the increase of nickel sulfate aerosol exposure concentration,the average alveolar lining interval decreased after increased.The difference of emphysema was statistically significant（P<0.05）.Compared with the simple smoke exposure group,the mean alveolar lining interval was smaller,and the difference was statistically significant in the CS+0.15 Ni and CS+0.3Ni groups（P <0.05）.Compared with the simple nickel sulfate aerosol exposure mouse model,the mean alveolar lining interval of mice in CS+0.15 Ni,CS+0.3Ni and CS+0.6Ni groups increased,while the mean alveolar lining interval of CS+1.2Ni group decreased,and the difference was statistically significant（P <0.05）.3.Compared with the blank control group,the IL-13 and MUC5 AC levels of mice in the simple smoke exposure model group were significantly increased（P <0.05）;In the simple nickel sulfate aerosol exposure model group,the levels of IL-13,TNF-α and MUC5 AC were significantly increased in the 0.6Ni group and 1.2Ni group（P <0.05）;In the smoke combined nickel sulfate aerosol exposure mouse model,compared with the blank control,the levels of TNF-α,IL-13 and MUC5 AC in the CS+0.3Ni group and CS+0.6Ni group were significantly increased（P <0.05）,and compared with the simple smoke exposure mouse model and simple nickel sulfate aerosol exposure mouse model,the TNF-α level in the CS+1.2 Ni group was significantly lower（P <0.05）.Conclusion: 1.Low educational level,smoking,occupation（workers,service staff）and high heavy metals exposure are risk factors for COPD in the Jinchang cohort,and there is an interaction between smoking and occupational exposure to heavy metals on the occurrence of COPD.2.Long-term smoking and high nickel exposure can induce the decline of lung function,the formation of emphysema,the aggravation of inflammatory response and the increase of airway mucin expression in mice.3.There is a synergistic effect of smoking and nickel exposure on the pathogenesis of COPD.