Characteristic Analysis,classification,evaluation And Predictive Value Of Quantitative CT In Chronic Obstructive Pulmonary Disease

BackgroupChronic obstructive pulmonary disease（COPD）is a common and frequently-occurring disease worldwide,which is also a chronic disease with the third highest global fatality rate reported by WHO in 2020,resulting in a huge economic and social burden.The main pathological changes are emphysema and airway stenosis.At present,the diagnosis of COPD mainly depends on pulmonary function examination,but it reflects the overall condition of the whole lung,can not reflect the existence of emphysema or airway lesions,and can not well reflect the heterogeneity of COPD,and requires a high degree of patient cooperation.Quantitative CT measurement is a hot research topic at present.More and more clinical studies related to COPD pay attention to the value of quantitative CT measurement.At present,quantitative measurement of COPD includes quantitative measurement of emphysema and airway,etc.CT scan has the advantages of speed,objectivity,high accuracy and easy coordination.Quantitative CT can describe and quantify the pathological changes of COPD in vivo,detect the changes of lung structure before the occurrence of abnormal lung function,and quantitatively describe the severity of the damage of COPD lung structure.Therefore,it has the potential to be an assessment or prognostic indicator of COPD.However,at present,the value of quantitative CT measurement in patients with COPD is still unknown,and most studies have been carried out abroad,lacking the results of Chinese COPD population,especially the prospective study of Chinese population.Objective1.To analyze the quantitative CT characteristics of COPD,and to explore the disease characteristics of different types based on the imaging classification of COPD by quantitative CT.2.To explore the value of quantitative CT in evaluating the severity of COPD and assisting the diagnosis of COPD.3.To explore the value of quantitative CT in evaluating and predicting the clinical outcomes of COPD（lung function,symptoms,acute exacerbation）.Subjects and MethodsA prospective observational cohort study was used in this study.Subjects of the study:All the subjects were from the CHEN-COPD cohort.Posters and outpatient referrals were used to recruit COPD subjects and normal subjects who were treated in the first affiliated Hospital of Guangzhou Medical University from August 2017 to October 2020.According to the inclusion and exclusion criteria,a total of 170 subjects with stable COPD and 50 normal subjects were included as the control group.Clinical data collection:The baseline data of the subjects（age,sex,CAT score,previous year aggravation,etc.）were collected,and pulmonary function and chest HRCT scanning were performed.The patients were followed up for 1 year after baseline,telephone follow-up every 3 months and on-the-spot follow-up every half a year.The aggravation and CAT score of COPD subjects were collected 1 year after baseline,and the pulmonary function test was reexamined.The aggravation of all COPD subjects was collected one year after baseline;90 COPD subjects and 28 normal subjects performed pulmonary function again after the median follow-up period of369.5（356.75-377.25）and 378（370.25-395）days,respectively;84 COPD subjects received CAT score after the median follow-up period of 371（370.25-378）days.Quantitative CT measurement:The end-inspiratory chest HRCT of the subjects was imported into the American VIDA Apollo Version 2.2 software in dicom format for quantitative CT measurement.The collected indexes included inspiratory lung volume（Vin）,the percentage of low-attenuation areas less than-950 Hounsfield units(%LAA_-950),the percentage of wall area（WA%）and thickness-diameter ratio（TDR）.Among them,the airway parameters WA%and TDR are calculated from the quantitative CT indexes of the midpoint cross section of five segments of bronchus,including the superior lingual segment of the left lung,the posterior basal segment of the left lower lung,the apical segment of the right upper lung,the lateral segment of the right middle lung and the posterior basal segment of the right lower lung.The calculation method is as follows:WA%=wall area/outer cross-sectional area*100%=（outer cross-sectional area-inner cross-sectional area）/outer cross-sectional area*100%.TDR=wall thickness/mean external diameter.The average values of WA%and TDR of the above five segments of bronchi were taken as the final results.Statistical analysis:Comparative analysis of quantitative CT indexes between COPD subjects and normal subjects.Referring to the previous literature,15%was used as the threshold of%LAA_-950 to divide COPD subjects into emphysema phenotype(%LAA_-950≥15%)and non-emphysema phenotype(%LAA_-950<15%),and the characteristic differences between the two groups were compared.Using ROC curve to evaluate the diagnostic value of quantitative CT index in COPD.Spearman test was used to analyze the correlation between quantitative CT indexes and lung function.The influencing factors of pulmonary function were analyzed by multiple linear regression.Binary Logistic regression was used to analyze the influencing factors of frequent exacerbation one year after baseline in patients with COPD.P<0.05 suggested that the difference was statistically significant.ResulesPart 1:The value of quantitative CT in classification and auxiliary diagnosis of stable chronic obstructive pulmonary disease1.Quantitative CT characteristics of COPD patients:There were pulmonary structural changes in normal smoking subjects,which was mainly characterized by the increase of Vin.With the decrease of pulmonary function,Vin and%LAA_-950increased gradually in COPD subjects.The thickening of proximal airway wall in grade 3-4 was mainly seen in GOLD3-4 COPD subjects,which was mainly characterized by the increase of WA%.2.Comparison of COPD characteristics between emphysema and non-emphysema phenotypes:Compared with the non-emphysema phenotype,the emphysema phenotype COPD subjects had smaller BMI,prediastolic FEV1%pred,MMEF,MEF50,MEF25,higher smoking load,higher proportion of Vin,GOLD3-4,CAT≥10 and frequent aggravation after 1-year follow-up（P<0.05）.There was no significant difference in age,acute aggravation risk and airway wall thickening index（WA%,TDR）between the two groups（P>0.05）.3.The value of quantitative CT index in the diagnosis of chronic obstructive pulmonary disease:ROC results showed that the AUC of%LAA_-950 was 0.929,P<0.0001,the diagnostic cut-off point for COPD was 1.07%,the sensitivity was 88.82%,and the specificity was 86%.The AUC of Vin was 0.739,P<0.0001,the diagnostic cut point for COPD was 5065.11mm³,the sensitivity was 76.47%,and the specificity was64%.The AUC of WA%was 0.595,P=0.0342,the diagnostic cut point of COPD was64.76%,the sensitivity was 64.71%,and the specificity was 58%.TDR had no diagnostic value for COPD.The pairwise comparison results showed that the diagnostic value of%LAA_-950,Vin and WA%in COPD had statistical significance（P<0.05）,among which,%LAA_-950 had the highest AUC,sensitivity and specificity in the diagnosis of COPD,so it had the highest auxiliary diagnostic value of COPD.Part 2:The value of quantitative CT in evaluating and predicting the clinical outcome of chronic obstructive pulmonary disease1.Correlation Analysis between quantitative CT index and pulmonary function:%LAA_-950 was negatively correlated with pre-diastolic FEV1%pred,post-diastolic FEV1/FVC,pre-diastolic PEF,MMEF,MEF50 and MEF25（P<0.01）,and the correlation coefficients were-0.679,-0.814,-0.614,-0.687,-0.746,-0.560.There was a weak negative correlation between other quantitative CT indexes and pulmonary function,but there was no correlation between WA%and TDR and small airway indexes（P>0.05）.2.Multiple linear regression analysis of quantitative CT index and pulmonary function FEV1%pred:After adjusting for the BMI,smoking package year,%LAA_-950,Vin,WA%,which is s significant in univariate analysis.The main factors affecting FEV1%pred were smoking package year（β=-0.082,P=0.049）,%LAA_-950（β=-0.978,P=0.000）,WA%（β=-2.246,P=0.000）.3.Comparative analysis of quantitative CT indexes of COPD patients with more symptoms and fewer symptoms:After using 1:1 tendency score matching method to correct the smoking pack years and pre-diastolic FEV1%pred of COPD,there was no significant difference in quantitative CT indexes(Vin,%LAA_-950,WA%,TDR)between the subjects with more symptoms and those with less symptoms（P>0.05）.4.Analysis of the changes of pulmonary function and/or CAT score one year after baseline in COPD patients with emphysema and non-emphysema phenotype and smokers with normal pulmonary function:Compared with the baseline,the FEV1 of the normal smoking control group decreased by 120ml after one year,and the difference was statistically significant（P=0.000）.Compared with the baseline,the FVE1 of the emphysema phenotype COPD subjects decreased by 30ml one year after the baseline,but the difference was not statistically significant（P=0.283）.The CAT score increased by 2.66 points compared with the baseline,and the difference was statistically significant（P=0.003）.Compared with the baseline,the median FEV1 of the non-emphysema phenotype COPD subjects decreased by 60ml one year after the baseline,and the difference was statistically significant（P=0.003）,CAT score had no significant difference between the baseline and the baseline（P=0.077）.5.Analysis of influencing factors of frequent exacerbation after one-year follow-up in patients with chronic obstructive pulmonary disease:Univariate analysis showed that smoking package,pre-diastolic FEV1%pred,CAT score,emphysema phenotype and high risk of acute exacerbation were the influencing factors of frequent exacerbation in patients with COPD after 1-year follow-up.After adjusting for confounding factors,emphysema phenotype was an independent risk factor for frequent aggravation in patients with COPD one year after baseline（OR 2.999;95%CI1.181-7.616%;P=0.021）.Conclusion1.Smokers with normal pulmonary function have pulmonary structural changes of GOLD1-2 COPD,which is characterized by an increase in lung volume,which may be a premorbid lesion of COPD.FEV1 decreased rapidly after 1 year of follow-up,suggesting the importance of prevention of diseases such as quitting smoking.2.With the decrease of lung function,the lung volume and emphysema level increased.The thickening of the proximal airway wall is mainly seen in patients in GOLD 3-4.3.Quantitative CT can classify COPD patients into emphysema and non-emphysema phenotypes.There are significant clinical differences between the two phenotypes in pulmonary function,symptom score and frequent exacerbation after 1-year follow-up.4.The quantitative CT index%LAA_-950 has a good correlation with pulmonary function,which can reflect the level of pulmonary function and has a certain auxiliary value in the diagnosis of COPD.5.The phenotype of emphysema based on quantitative CT can predict the changes of FEV1 and CAT scores and acute exacerbation at 1-year follow-up,which can be used as a good predictor of disease progression.