High Resolution CT Reconstruction Parameters As Biomarkers Of Lung Structure Changes In Diesel Engine Testers

Objective:Currently,diesel engines are widely used in buses,trucks,tractors,ships and other mechanical equipment.With the increasing exposure of urban residents and professional people to diesel exhaust(DE),people are paying more and more attention to the adverse health effects of DE.Diesel exhaust particles(DEPs)can be suspended in the air and inhaled directly when people breathe.Because DEPs are nanoscale particles(particle size<100nm),so it is easy to penetrate into the terminal bronchioles,alveoli and other deep lungs and cause lung damage.In 2012,the International Agency for Research on Cancer(IARC)has classified DE human carcinogen(Ⅰ).Currently,studies on biomarkers of lung injury caused by DE exposure mainly focus on the molecular level,and the changes of lung structure behind the phenotypic changes are largely unknown.There is no effective parameters to evaluate the damage of lung structure caused by DE exposure.In this study,a set of imaging parameters related to lung structural changes were obtained by using high-resolution computed tomography(HRCT).The correlation between imaging parameters and carbon content in airway macrophages(CCAM),lung function parameters and markers of lung injury was studied to verify its feasibility as a biomarker of lung injury caused by DE exposure.Methods:1.This research team recruited 90 diesel engine testers(DETs)and 88 Non-DETs from the same city as the DETs in October 2018.We excluded 7 participants with missing smoking data and 17 participants who did not have CT scan or failed CT image reconstruction.Finally,78 DETs and 76 Non-DETs were included in the study.Demographic information,including smoking status,alcohol consumption,years of employment,occupational exposure history,dietary habits,and personal and family medical history,was obtained through standardized questionnaires,and venous blood and other biological samples were collected.2.All participants underwent oral inhalation of 4.5% ultrasonic-atomized hypertonic saline for sputum induction,and the sputum was stored in saccomanno.After standardized treatment and staining,the well-stained macrophages were observed by microscope and photographed by camera,and CCAM was quantitatively analyzed by Image J software.The CCAM was successfully measured in 53 participants in Non-DETs and DETs,respectively.3.Respiratory function test and HRCT scan of Non-DETs and DETs were performed by professional physicians.CT image post-processing software was used to analyze the tip of the right upper lobe bronchus(Right B1 to Carina,RB1),the lateral base segment of the right lower lobe bronchus(Right B9 to Carina,RB9),the posterior apex segment of the upper branch of the left upper lobe bronchus(Left B1+2 to Carina,LB1+2),and the lateral base segment of the left lower lobe bronchus(Left B9 to Carina,LB9),the airway size of grade 6 and grade 9,the total lung volume at the end of the inhalation phase,the mean lung density(MLD),the low attenuation area percentage(LAA%)were measured.4.Linear mixed effects(LME)model was used to analyze the correlation between the percentage of airway wall area and total airway area [ratio wall/airway area(%),WA%],DE exposure state and other functional parameters.The generalized linear model(GLM)was used to evaluate the relationship between lung density and DE exposure and other functional parameters.Spearman and pearson correlation analysis was used to test the correlation between lung density,lung injury markers and WA%.The association of WA%,surfactant protein A(SP-A)and MLD was evaluated after adjusting for covariates such as age,body mass index(BMI),smoking history,with GLM.Results:1.The results of environmental monitoring and CCAM showed that the particulate matter exposure was higher in DETs,which was related to the thickening of airway wall and the increase of WA% in grade 6.Compared with Non-DETs,no reduction in lumen area was found in DETs,indicating that the thickening of airway wall without lumen narrowing may be the main feature of airway remodeling in DETs.Compared with NonDETs,DETs had higher MLD and lower LAA%,but the difference between the two groups was not statistically significant.The effect of DE exposure on WA% did not vary with lung lobes or smoking status.2.There was significant negative correlation between WA% of grade 6 and grade 9and FEV1,FEV1/FVC,MMF,FEF50% and FEF75%.Mediation analysis found that part(about 20%)of the decrease in FEV1 caused by DE exposure could be explained by grade6 WA%.Pearson correlation analysis showed that MLD was significantly positively correlated with SP-A,grade 6 and grade 9 WA%,Spearman correlation analysis showed that LAA% was significantly positively correlated with s RAGE,and LAA% was significantly negatively correlated with grade 6 and grade 9 WA% and MLD.Using GLM,we found that WA% and the alveolar inflammation represented by SP-A jointly led to the elevation of MLD.Conclusion:1.In this study,HRCT demonstrated that long-term exposure to DE could lead to lung structural changes in occupational population.It was confirmed that airway wall thickening without lumen narrowing was an early pathological change in the lungs of DETs.The increase in lung density of DETs may be caused by the joint action of airway wall thickening and alveolar inflammation,and the inflammation may dissipate after the cessation of particulate matter exposure.2.In this study,we found that the degree of internal exposure to DE is closely related to the change of WA% of grade 6.The increase of WA% will lead to small airway obstruction(such as the decrease of FEF50% and FEF75%),which indicates that WA% can be used as a biomarker of lung tissue structure changes caused by DE exposure.This finding provides a strong basis for the development of health monitoring indicators for occupational DE exposed population and provides scientific evidence for improving the occupational quality of life of DE exposed population.