Quantitative Study Of COPD About Emphysema And Airway Remodeling By Imaging

Part?Establishment and Evaluation of Rat Model of ChronicObstructive Pulmonary Disease Objective To establish rat models of COPD with smoking,protease instillation and the combination of them,and to evaluate the model in terms of inflammation,imaging and pathology.Methods Rat models of COPD were established with smoking,protease instillation and a combination of the two methods.There were 60 rats in the smoked group,30 rats in the protease group and 30 rats in the protease + smoke group.At the same time,the control group containing 20 rats was set.Rats' body weight was measured every week.In the smoked group and the control group,5 rats and 2 rats were executed respectively at the 24 th hour,the 1st,2nd,4th,8th,12 th,16th,20 th,and 24 th week after modeling,and in the protease group and the protease + smoke group,5 rats were executed respectively at the 24 th hour,the 1st,2nd,4th,8th,and 12 th week.The executed rats were respectively subjected to cytokines detection,Micro-CT examination and pathological examination.Results The weight gain of rats in the smoked group and the protease+smoke group was significantly slower than the control group since the 7th week(P<0.05).The levels of IL-10 at the 24 th hour,the 1st,2nd and 4th week were significantly lower in the protease group and the protease + smoke group than in the control group(P<0.05).The concentration of MMP-9 at the 24 th hour was significantly higher in the protease group and the protease + smoke group than the control group(P<0.05).Emphysema were observed on both of the Micro-CT images and pathological images in the protease group at the 4th week,proteinase+smoke group at the 4th week,and the smoked group at the 8th week.Conclusion The rat models of COPD can be successfully established using the methods of smoking,protease instillation and the combination of them.Micro-CT can reflect the changes of lung with high sensitivity and validity.Part? Quantitative Study of Emphysema and Airway Remodeling in COPD Rat Model by Micro-CT Objective To analyze the dynamic changes of COPD by quantitatively measuring emphysema and trachea related parameters with Micro-CT.Methods There were 8 rats in control group,9 in smoked group and 9 in protease group.The control group underwent Micro-CT examinations and pathological examinations at the 4th,8th,12 th and 24 th week after modeling.The smoking group and the protease group underwent Micro-CT examinations and pathological examinations at the 4th,12 th,24th week and the 4th,8th,12 th week respectively.Micro-CT quantitative parameters included lung density,air volume to total lung volume radio,bronchial lumen diameter and wall thickness.Pathological quantitative parameters included(tracheal area-lumen area)/tracheal area(MA%),wall thickness/radius of the trachea(MT%),mean alveolar area,and mean liner intercept.Results In the 12 th week,the lung density in smoke group and protease group was significantly lower(P<0.001,P<0.001),and LAA%-928 was significantly higher(P=0.031,P=0.013)than the control group.In the 24 th week,the lung density in the smoke group was significantly lower(P=0.001),and LAA%-928 was significantly higher than the control group(P=0.028).The bronchial wall of the 4th grade bronchus in the 12 th week and the 3rd,4th grade in the 24 th week of rats in the smoked group were significantly thicker than those in the control group(P=0.04,P=0.033,P=0.008).Lung density negatively correlated with mean alveolar area and mean liner intercept(P = 0.001,R =-0.838;P = 0.043,R =-0.592).LAA%-928 positively correlated with mean alveolar area and mean liner intercept(P <0.001,R = 0.926;P = 0.029,R = 0.629).The bronchial wall thickness measured by Micro-CT was positively correlated with MT%(P=0.026,r=0.638).Conclusion The results of Micro-CT can reflect the real condition of the rat lung.Emphysema and bronchial remodeling exist in rats with COPD in the 12 th week after modeling.Part III Quantitative Analyses of Emphysema and Air Trapping at Inspiratory and Expiratory Phase MDCT Scan in Smokers: Correlation with Pulmonary Function Test Objective Quantify emphysema and air trapping at inspiratory and expiratory phase multi-detector computed tomography(MDCT)scanning in smokers without respiratory symptom,and analyze the correlation between the CT quantifiable parameters and lung function parameters.Methods 72 smokers enrolled in this research were divided into two groups: 24 smokers with COPD and 48 smokers without COPD.Besides,39 non-smokers with normal pulmonary function were enrolled as the controls.All subjects underwent double phase MDCT scanning and pulmonary function tests.CT quantifiable parameters of emphysema included the low attenuation area below a threshold of-950 Hounsfield Units(HU)(LAA%-950),the lowest 15 th percentile of the histogram of end-inspiratory attenuation values(P15-IN),the lowest 15 th percentile of the histogram of end-expiratory attenuation values(P15-EX),relative volume change(RVC)and the expiratory to inspiratory ratio of mean lung density(E/IMLD).Pulmonary function parameters included forced expiratory volume in 1 second expressed as percent predicted(FEV1%),forced expiratory volume in one second to forced vital capacity ratio(FEV1/FVC),residual volume to total lung capacity ratio(RV/TLC)and carbon monoxide diffusion capacity corrected for alveolar volume(DLCO/VA).The differences of CT quantifiable parameters and pulmonary function parameters among the three groups were analyzed using one-way analysis of variance or Kruskal–Wallis H test.The correlation between CT quantifiable parameters and pulmonary function parameters was analyzed using Spearman's correlation analysis.Results The differences of LAA%-950,P15-IN,FEV1%,FEV1/FVC,DLCO/VA and RV/TLC among the three groups were statistically significant(p<0.05).In the control group,LAA%-950 negatively correlated with FEV1/FVC and DLCO/VA(r=-0.32,P=0.04;r=-0.69,p=0.00)and neither did P15-IN with FEV1%(r=-0.14,p=0.02).Inversely,P15-IN positively correlated with DLCO/VA(r=0.55,p=0.00).In the group of smokers without COPD,LAA%-950 negatively correlated with FEV1/FVC and DLCO/VA(r=-0.31,p=0.04;r=-0.42,p=0.00),and P15-IN positively correlated with FEV1/FVC and DLCO/VA(r=0.33,p=0.02;r=0.30,p=0.04).In the group of smokers with COPD,LAA%-950 negatively correlated with DLCO/VA(r=-0.62,p=0.00),but positively correlated with RV/TLC(r=0.59,p=0.00).And P15-IN positively correlated with DLCO/VA(r=0.53,p=0.01).Conclusion Smokers emphysema and air trapping can be effectively evaluated by double phase MDCT.Moreover,two of the CT quantifiable parameters,LAA%-950 and P15-IN,were highly sensitive to changes in pulmonary function.