Comparison Of The Quantitative Evaluation In High-resolution CT And Pulmonary Function Tests In Chronic Obstructive Pulmonary Disease

BackgroundChronic obstructive pulmonary disease (COPD) is a harmful disease to the human beings that causes death and disability, which is one of the prominent obstructive lung diseases, but it can be treated. COPD is progressive and poorly reversible. Characteristics in pathological changes of COPD are found in the central and peripheral airways, lung parenchyma and pulmonary vasculature. The airflow limitation in COPD patients is caused by small airways disease and parenchymal destruction primarily. The pathological changes of the peripheral airways are characterized by the presence of inflammatory exudates in the wall and lumen, reduced lumen, structural reorganization of the airway wall, increased smooth muscle and deposition of peribronchial connective tissue. Changes of the lung parenchyma are characterized by pulmonary tissue injury, elastic recoil force decreases. Pulmonary emphysema and airway disease coexists to various degrees in any given patient. Some patients show severe emphysema, while others show partial reversibility of airflow limitation. Therefore, COPD is not a simple homogenous disease defined only as irreversible airflow limitation. CT appears to be an effective and sensitive noninvasive tool to assess the change of airway wall morphology, lung density and the whole lung volume. The percentage of total lung area occupied by low attenuation area reflect the tissue destruction (pulmonary emphysema). High resolution computed tomography (HRCT) reflects the small airway changes by direct measurement of bronchus. CT can quantify pulmonary emphysema and airway disease.Part1 The correlation between HRCT quantitative evaluation and PFT value for chronic obstructive pulmonary diseaseObjectiveTo analyse the Correlation between the high-resolution CT (1024x1024) measurements (T, D, PA, T/PA, TDR, WA%, Ai%, LAA%) and PFTs (Z5, R5, FEV1/FVC, FEV1%pred, MMEF, MEF50, MEF25) at all levels of chronic obstructive pulmonary disease patients (COPD) and healthy patients with smoking.Materials and Methods1. SubjectsPatients with COPD and healthy patients with smoking underwent HRCT examination and PFT. COPD patients condition for Lung Disease (Global Initiative for Chronic Obstructive Lung Diseases, GOLD) criteria that forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) ratio less than 0.7. All patients fulfilled the following criteria:no concomitant pulmonary disease (eg pulmonary infection, tuberculosis, bronchiectasis), no pulmonary resection, and no malignancy of any organ.2. CT examinationsLow kV CT examination and the upper lobe of the right lung target amplification scanning were performed by using Philips Brilliance 256 slice spiral CT at 100KV and Automatic milliamperemeter. The scanning collimation 128 x 0.625mm, pitch 0.915, bed scanning speed 146.4mm/s, rotation time of 0.5s, FOV 35 x35cm. Low KV scanning were reconstructed with 1mm thick sections, while the upper lobe of the right lung target amplification scanning sequential acquisitions of lmm thick sections. Low KV scanning images were reconstructed by using standard algorithm, and target amplification scanning images were reconstructed by using sharp-Y algorithm. Before the CT examination, each patient was instructed to breathe and perform respiratory maneuvers while lying on the CT table. The dimensions of subsubsegmental apical bronchi of right upper lobes in the target amplification scanning images were measured by multiplanar reformation (MPR) method. Found the cross-sectional of subsubsegmental apical bronchi of right upper lobes before the measurement. The measurements included the following parameters:airway wall thickness (T), total airway diameter (D), and pulmonary artery (PA), the airway wall thickness to total airway diameter ratio (T/PA), thickness diameter ratio (TDR), percentage of wall area (WA%) and percentage of airway luminal area (Ai%) were Calculated by formula. The percentage of total lung area occupied by low attenuation area (LAA%) was measured by Philips lung Density software in Low KV scanning images.3. Pulmonary Function TestPFTs were performed by using a constant-volume body plethysmograph (Jaeger company, Germany). First Impulse oscillometry system (IOS) inspection was completed in the basic state, then the pulmonay ventilation test was underway. The patients inhaled 400μg of ventolin from a metered dose inhaler in 15 minutes before the pulmonay ventilation test. PFTs were performed with the patient in the seated position. Lung function index including:ratio of the first second forced expiratory volume to forced vital capacity (FEV1/FVC), ratio of measurement to prediction of forced expiratory volume to the first second (FEV1%pred),total respiratory impedance (Z5), total airway resistance (R5), central airway resistance (R20), R5-R20, maximal mid expiratory flow (MMEF), Maximum expiratory flow at 50% of the FVC (MEF50), Maximum expiratory flow at 50% of the FVC (MEF25). Then according to Global Initiative for Chronic Obstructive Lung Diseases (GOLD) revised 2011 version of the standard, namely on the basis of FEV1%pred COPD were divided into four grades. Grade 1:FEV1%pred>80%; 2:50%< FEV1%pred<80%; 3: 30%< FEV1%pred<50%; 4:FEV1%pred<30%:Statistical MethodSPSS 19.0 software package was applied to deal with the data of the study. Measurement datas were expressed as x±SD. Compare HRCT measurements, PFT indexes between the control group and COPD groups using Kruskal-Wallis H test, pairwise comparison using Mann-Whitney U test. Analysis the correlation of HRCT measurements, PFT indexes between the control group and COPD groups using Spearman correlation test. Statistical tests were two-tailed test method using side, a significant level of statistical significance test P<0.05.ResultsTotal 91 subjects,81 cases of which were COPD patients (mild in 13, moderate in 30, severe in 26, very severe in 12), and 10 cases were normal patients.1. Comparison among normal group and COPD groups.① The age had no significant difference in each group (P>0.05), that was not an interference factor; ② The differences of T and D had no statistical significances in each group (P>0.05); ③ PA, D, MEF25, Z5, R5, R20 and R5-R20 had no statistical significance differences between the normal and COPD I patients (P>0.05); ④ There were no statistical significances differences in PA, D, Z5, R5, R20, R5-R20 between the normal and COPD II patients (P>0.05); ⑤ R5 and R20 had no statistical significances difference between the normal and COPⅢ patients (P>0.05); ⑥ R20 showed statistical significance difference between the normal and CQPD IV patients (P<0.05).2. Comparison in COPD Ⅰ-Ⅳ① LAA%showed statistical significance difference between COPD I and COPD II (P<0.05); Z5, R5, R20 and R5-R20 had no statistical significance differences between two groups (P>0.05); ② T、PA、T/PA、D had no statistical significances difference between COPD I and COPDIII (P>0.05); R20 had no statistical significances difference between two groups (P>0.05)③T and D had no statistical significances difference between COPD I and COPD IV (P>0.05); R20 had no statistical significance difference between two groups (P>0.05); ④Only LAA% had statistical significance difference between COPD Ⅱ and COPDⅢ (P<0.05); Z5, R5 and R20 had no statistical significance differences between two groups (P>0.05); ⑤ and D had no statistical significance differences in COPD Ⅱ and COPD Ⅳ (P> 0.05); Most measurements of lung function had statistical significance differences between two groups except R20 (P>0.05); ⑥ LAA% and T/PA had statistical significance differences between COPD Ⅲ and COPDⅣ (P<0.05); MEF25 and R20 had no statistical significance differences between two groups (P>0.05); On the contrary BMI showed statistical significance difference between two groups (P<0.05).3. The correlation between HRCT index and PFT index① The correlation between T and PFT parameters had no statistical significance (P>0.05); ② There were positive correlation between PA and FEV1%, FEV1/FVC, MMEF, MEF75, MEF50, MEF25 (r=0.302,0.335,0.289,0.324,0.290,0.229,0.029, 0.065, P< 0.05); There were negative correlation between T/PA and these index (r=-0.420,-0.429,-0.359,-0.448,-0.384,-0.314, P<0.05); ③ There were negative correlation between LAA% and FEV1%, FEV1/FVC, MMEF, MEF75, MEF50, MEF25 (r=-0.880,-0.875,-0.824,-0.883,-0.860,-0.670, P<0.05) and positive correlation with Z5, R5 and R5-R20 (r=0.377、0.341,0.653, P<0.05). ④ There were positive correlation between D, Ai% and FEV1%, FEV1/FVC, MMEF, MEF75, MEF50, MEF25 respectively (r= 0.372,0.331,0.403,0.367,0.369,0.339 and 0.493, 0.421,0.458,0.486,0.447,0.406, independently, P<0.05), and negative correlation with Z5, R5, R20, R5-R20 respectively (r=-0.357,-0.353,-0.225,-0.305 and r= 0.477,-0.480,-0.327,-0.336, independently, P<0.05). ⑤ There were negative correlation between WA%, TDR and FEV1%, FEV1/VC, MMEF, MEF75, MEF50, MEF25 (r=-0.493,-0.421,-0.458,-0.486,-0.447,-0.406, P<0.05) and positive correlation with Z5, R5, R20, R5-R20 (r= 0.477,0.480,0.327,0.336, P<0.05).Conclusion1. With the increase of COPD grade, the number of discrepant indexes was increased between COPD group and the normal group.2. The closer the two levels (such as COPD Ⅰ and COPD II, COPD II and COPDIII, COPDIII and COPD Ⅳ), the less the difference indicators. There are differences of LAA% in normal group and COPD Ⅰ-Ⅳgrades patients. Comparison of BMI shows no difference in all levels COPD patients.3. Although total respiratory impedance, total airway resistance, central airway resistance had no statistically significant between two groups, but Peripheral airway resistance would have statistically significant.4. LAA% is Most indicators correlated with PFT indexes among all groups. HRCT are correlated with PFT indexes.CT is a valuable tool for COPD patients that can be used to evaluate pulmonary function.Part2 The analysis of characteristics of pulmonary function among COPD patients with different CT phenotypesObjectiveTo evaluate the characteristics of pulmonary function tests (PFT) in chronic obstructive pulmonary disease (COPD) patients with different CT phenotypes. The characteristics of PFTs (FEV1/FVC, FEV,%pred, Z5, R5, MMEF, MEF50, MEF25, BMI and CAT) in different CT phenotypes were analyzed.Materials and Methods1. Subjects81 patients with COPD underwent HRCT examination and PFT. COPD patients condition for Global Initiative for Chronic Obstructive Lung Diseases (GOLD) criteria that ratio of the first second forced expiratory volume to forced vital capacity (FEV1/FVC) less than 0.7. All subjects fulfilled the following conditions:no concomitant pulmonary disease (eg bronchiectasis, tuberculosis, pulmonary infection), no pulmonary resection, and malignancy of any organ.2. CT examinationsCT scanning were performed at Philips Brilliance 256 slice spiral CT including low kV CT examinations and the upper lobe of the right lung target amplification. The scanning condition was 100KV and Automatic milliamperemeter. The bed scanning speed 146.4mm/s, rotation time of 0.5s, scanning collimation 128 x 0.625mm, pitch 0.915, FOV 35 ×35cm. Low KV scanning images were reconstructed with lmm thick sections and using standard algorithm, while the upper lobe of the right lung target amplification scanning images sequential acquisitions of lmm thick sections when the time of scanning and reconstructed by using sharp-Y algorithm. Measured airway wall thickness (T), total airway diameter (D) and pulmonary artery (PA) of subsubsegmental apical bronchi of right upper lobes in the target amplification scanning images. The airway wall thickness to total airway diameter ratio (T/PA), thickness diameter ratio (TDR), percentage of wall area (WA%) and percentage of airway luminal area (Ai%) were Calculated by formula. Found the cross-sectional of subsubsegmental apical bronchi of right upper lobes with multiplanar reformation (MPR) method before the measurement. The percentage of total lung area occupied by low attenuation area (LAA%) was measured by Philips lung Density software in Low KV scanning images.3. CT Phenotypes of COPDThe patients were classified into three phenotypes based on the presence of emphysema or bronchial wall thickening evaluated by HRCT. Phenotype A:absence of emphysema, with little emphysema, with or without bronchial wall thickening (LAA%<25%). Phenotype E:emphysema without bronchial wall thickening (LAA%≥25% and T/PA<30%). Phenotype M:emphysema with bronchial wall thickening (LAA%>25% and T/PA>30%)4. Pulmonary Function TestPFTs were performed by using a constant-volume body plethysmograph (Jaeger, Germany). First Impulse oscillometry system (IOS) inspection was completed in the basic state, index including:total respiratory impedance (Z5), total airway resistance (R5), R20, Peripheral airway resistance (R5-R20). Then the pulmonay ventilation test was underway, index including:FEV1/FVC, ratio of measurement to prediction of forced expiratory volume to the first second (FEV1%pred), maximal mid expiratory flow (MMEF), Maximum expiratory flow at 50% of the FVC (MEF50), Maximum expiratory flow at 50% of the FVC (MEF25) and Body Mass Index (BMI). The patients inhaled 400μg of salbutamol from a metered dose inhaler in 15 minutes before the pulmonay ventilation test. All subjects were investigated for COPD Assessment Test (CAT) after the pulmonary function tests.Statistical MethodSPSS 19.0 software package was applied to deal with the data of the study. Measurement datas were expressed as x+SD. Compare PFT indexes among the different Phenotypes of COPD using Kruskal-Wallis H test, pairwise comparison using Mann-Whitney U test. Statistical tests were two-tailed test method using side, a significant level of statistical significance test P<0.05.ResultsTotal 81 subjects of COPD.35 patients were phenotype A,20 patients were Phenotype E, and 26 were Phenotype M.1. Comparison among different CT phenotype groups① Age had no significant difference in each groups (P>0.05); ②FEV1/FVC、 FEV1%pred, MMEF, MEF50, MEF25 and R5-R20 all had statistical significance differences in each groups (P<0.05); Measurements in A, E and M were respectively (56.19±11.40,45.27±9.37,37.01±9.14), (70.74±19.49,50.89±15.73,36.24±11.15), (26.33±14.73,14.26±5.76,10.81±4.53), (30.69±18.04,14.50±6.71,9.98±3.85), (21.11±11.47,13.72±6.63,12.88±6.16), (0.29±1.36,2.43±5.92,2.60±7.02); Z5, R5 and R20 had no statistical significance differences in each groups (P>0.05); ③CAT, BMI and GOLD had statistical significance differences in each groups (P<0.05).2. Comparison among A, E, M groups① Z5, R5, R20 and of PFT indexes had no statistical significance differences in phenotype A and phenotype E (P>0.05), but R5-R20 showed statistical significance difference in two groups (P<0.05); CAT and BMI had no statistical significance differences in two groups (P>0.05), but GOLD showed statistical significance difference between them (P<0.05); ② Z5, R5, R20 and R5-R20 had no statistical significance differences between phenotype A and phenotype M (P>0.05); CAT, BMI and GOLD had significant differences in two groups (P<0.05); ③Z5, R5, R20, R5-R20 and MEF25 had no statistical significance differences between phenotype E and phenotype M (P>0.05); BMI, CAT and GOLD had significant difference differences between phenotype E and phenotype M (P<0.05).Conclusion1. Different CT phenotype of COPD patients with different lung function indicators. FEV1%, FEV1/FVC, MMEF, MEF50 and MEF25 between phenotype A and phenotype E, phenotype A and phenotype M, phenotype E and phenotype M.2. Different CT phenotype of COPD patients with different clinical manifestations. BMI and CAT are different in three groups basically.3. The difference of R5-R20 in small airway indexes was more obviously, the increase of peripheral airway resistance will be caused by severe inflammation of the airway and lung tissue damage.4. M phenotype with the worst PFT indicators in the three.COPD patients that with the same level of GOLD and different CT phenotypes have obvious differences of pulmonary function and general situation.