慢性阻塞性肺疾病稳定期患者小气道改变及其对吸入剂的治疗反应评价
发布时间：2018-09-08 16:34
【摘要】：慢性阻塞性肺疾病(Chronic obstructive pulmonary disease, COPD,简称慢阻肺)是以持续存在的气流受限为特征的疾病,气流受限呈进行性发展,伴有气道和肺组织对有害气体或颗粒的炎症反应的增加。慢阻肺是呼吸系统的常见病和多发病,患病率、病死率居高不下,在影响患者的劳动力和生活质量的同时,也将带来沉重的社会和经济负担。预计2020年慢阻肺将占世界疾病经济负担的第五位,2030年其病死率将位居第三位,致残率则升至第七位。小气道疾病(SAD)和肺实质的破坏(肺气肿)是慢阻肺重要的发病机制,也是气流受限的主要原因。小气道是指直径小于2mm,没有软骨的气道,通常位于气管支气管树的第8-23级。在慢阻肺患者,长期的慢性炎症刺激使小气道管壁增厚、管腔狭窄阻塞,气道阻力明显增加,小气道成为气流受限的主要部位。了解小气道结构和功能变化,对于分析慢阻肺的严重程度、了解疾病进展、评价治疗疗效和预后均有重要意义。肺通气功能检查(PFT)是诊断慢阻肺并进行疾病严重程度分级的金标准。但是肺功能分级相同的患者肺气肿和小气道改变程度存在差异,PFT并不能反映患者的病理改变特征和病变程度。脉冲振荡检查(IOS)是近年来研究较多的气道阻力评价方法,可分析气道总阻力、中心气道和外周小气道阻力。IOS指标比肺通气功能指标FEV1更敏感,可用于评价慢阻肺患者早期的小气道改变,并评估吸入治疗药物的疗效。高分辨率CT(HRCT)可定量分析气道和肺组织结构改变,由于中等大小的气道可以代表小气道,并反映小气道组织病理改变程度,因而可通过HRCT分析大中气道来反映小气道功能。目前,HRCT已成为临床研究中远端肺组织评价的重要的手段。稳定期慢阻肺的治疗以缓解患者症状,提高运动耐量,改善肺功能及降低急性加重的风险为目标。吸入性糖皮质激素和长效的β2受体激动剂联合治疗(ICS/LABA)对改善患者临床症状和生活质量、减少住院次数和降低急性加重风险均有重要意义。小气道为慢阻肺患者气流受限的主要部位,以小气道改变为主的慢阻肺患者对短效β2受体激动剂有较大的反应性。因此,治疗小气道或是了解小气道的治疗反应,有望更好地控制疾病。吸入性丙酸倍氯米松/福莫特罗提供的超细颗粒药物(1.4-1.5um)有较高的肺部沉积,可改善整个气道的炎症和支气管收缩反应。已有研究表明,丙酸倍氯米松/福莫特罗治疗可改善慢阻肺患者的气体限闭,但其对气道阻力和气道、肺组织结构的影响尚不明确,同时也很少有研究比较其与传统治疗药物的疗效差异。第一部分慢性阻塞性肺疾病患者小气道结构和功能评价目的分析小气道改变在慢阻肺发生、发展中的作用,探讨高分辨率CT和脉冲振荡在慢阻肺小气道评价中的应用价值。方法以2014年9月至2015年12月期间就诊于南方医科大学珠江医院门诊的稳定期慢阻肺患者为研究对象(慢阻肺组),均符合2013年中华医学会呼吸病学分会慢性阻塞性肺疾病学组关于慢阻肺的诊断标准,并排除其它呼吸道急慢性疾病者。以同期门诊健康体检者为对照组,要求经查体、近期胸片和肺通气功能检查均未见异常。采用德国耶格公司MasterScreen肺功能仪对所有受试者依次进行IOS和肺通气功能检查,分析响应频率(Fres)、小气道阻力(R5-R20)与PFT指标相关性。并在同一天内使用Philips Brilliance 256层iCT对慢阻肺患者进行HRCT检查,测定右肺上叶尖段支气管第3级分支气管壁径线(WT)、伴行肺动脉直径(BWT),同时予肺气肿定量(LAA%),分析气道壁增厚、肺气肿与PFT、IOS指标相关性。结果1.一般资料：入选慢阻肺患者132例,其中男性117例,女性15例,平均年龄为(67.9±9.7)岁。根据2013版慢阻肺全球防治策略(GOLD)对气流受限严重程度的分级标准,GOLD1级28例,GOLD 2级42例,GOLD3级42例,GOLD4级20例。对照组92名,其中男性78名,女性14名,平均年龄(65.49±9.8)岁。两组受试者在年龄、性别、身高、体重方面的差别均无统计学意义。慢阻肺组吸烟指数较对照组明显增高(t=4.960,P0.01)。2.慢阻肺组和对照组肺功能比较：慢阻肺组FEV1%pred和FEV1/FVC明显低于对照组,肺通气功能小气道指标FEF25%-75%pred、FEF50%pred、 FEF75%pred也较对照组明显降低,组间差别有统计学意义(P0.01)。慢阻肺组Z5、R5、Fres、R5-R20均较对照组增高(P0.01),慢阻肺患者X5绝对值增大(P0.01),两组间R20差别无统计学意义(P=0.754)。3.慢阻肺GOLD1～4级患者IOS指标比较：慢阻肺患者随气流受限程度加重(GOLD1～4级),Z5、R5、Fres、R5-R20均逐渐增大,组间差别有统计学意义(P0.01)。X5绝对值随阻塞程度加重逐渐增大(P0.01),但中心气道阻力指标R20的变化不明显(P=0.662)。4.慢阻肺组IOS与PFT指标相关性分析：Z5、R5、Fres、R5-R20与肺通气功能各指标均存在负相关(P0.01)。X5与FEV1%pred、FEV1/FVC、 FEF25%-75%pred、FEF50%pred等指标存在正相关(P0.01)。Fres与通气功能各指标FVC、FEV1、FEV1%pred、FEV1/FVC、FEF25%-75%pred、FEF50%pred的相关性均较强,且与FEV1相关性最强(r=-0.715,P0.01)。R5-R20与FEV1%pred、FEF25%-75%pred、FEF50%pred也有较强的相关性(P0.01)。5.IOS指标ROC曲线及曲线下面积：以132名慢阻肺患者和92名健康对照组为分析人群建立ROC曲线。以IOS各指标各临界点对应的敏感度(Sensitivity)为纵坐标,以误判率(1-specificity)为横坐标绘制曲线。IOS各指标对应的曲线下面积取值大小依次是:FresR5-R20Z5R50.5.同时,以正确诊断指数(Youden指数)最大值对应点为各指标的最佳分界点,Fres、R5-R20诊断慢阻肺的最佳分界点分别为13.93和0.055。6.HRCT结果分析：慢阻肺组GOLD 1～4级HRCT测定指标分析结果：WT：(1.39±0.20)mm；BWT:(4.09±0.76)mm；WT/BWT:(35.1±7.31)%:LAA%: (7.14%±8.49)%。WT随气流受限程度加重而增加,但组间差别无统计学意义(P0.05)。随气流受限程度增加,WT/BWT逐渐增大(F=4.859,P0.01),LAA%亦增大(F=9.792,P0.01)。WT/BWT与FEV1%pred存在负相关性(r=-0.329,P0.01),与IOS指标Fres、R5-R20存在正相关(P0.05)；LAA% 与FEV1%pred、FEF25%-75%pred、FEF50%pred存在负相关,其中与FEV1%pred的相关性最强,相关系数为-0.566(P0.01)。LAA%与Fres、R5-R20正相关,相关系数分别为0.466(P0.01)、0.340(P0.05)。结论1.慢阻肺患者小气道管壁增厚,气道阻力增加,其增加程度可反映疾病的严重程度。2.脉冲振荡检查可较准确地测定小气道阻力,反映小气道功能,并对慢阻肺有一定的诊断价值。3.高分辨率CT图像直观,可定性定量分析气道和肺组织结构改变,并反映疾病的病理基础和严重程度。4.HRCT和IOS与肺通气检查结果相关,可更全面评估小气道结构和功能改变,对慢阻肺的早期诊断和综合评估有重要意义。第二部分慢性阻塞性肺疾病患者小气道对吸入剂的治疗反应评价目的了解ICS/LABA联合治疗对慢阻肺患者小气道的影响,探讨HRCT和1OS在慢阻肺吸入剂治疗中的评价价值,比较两种吸入治疗药物(丙酸倍氯米松/福莫特罗、布地奈德/福莫特罗)的疗效。方法本研究为一项随机对照研究,以2015年4月至2016年3月期间符合条件的稳定期慢阻肺患者为研究对象。受试者经2周的洗脱期之后,随机分成2组,分别以丙酸倍氯米松/福莫特罗(100/6ug,2吸/次,2/日)、布地奈德/福莫特罗(160/4.5ug,2吸/次,2/日)治疗3月。于入组时、2周后(洗脱期结束时)、治疗1月、治疗3月对受试者进行共4次随访。每次随访时行脉冲振荡、肺通气功能、弥散功能、支气管舒张试验、6分钟步行试验,并完成呼吸困难评分(mMRC评分)、CAT评分、圣乔治调查问卷(SGRQ)。第2、4次随诊时完成HRCT。评价2组治疗后小气道气道结构和功能改变的差异,比较2组疗效。结果1.一般资料：本研究共筛选出符合条件的稳定期慢阻肺患者42例,其中,2例患者在洗脱期失访,共有40例慢阻肺患者进入随机分组,其中男性36例,女性4例。分别接受丙酸倍氯米松/福莫特罗和布地奈德/福莫特罗治疗,每组20例患者。两组受试者在性别、年龄、体重指数、吸烟史方面差别无统计学意义(P0.05)。两组治疗前肺通气功能指标FVC%pred、FEV1%pred、FEV1/FVC、 DLCO%pred及6分钟步行距离6MWD无差别(P0.05)。2.症状评分和6分钟步行距离：治疗前两组患者症状评分、6分钟步行距离差别无统计学意义(P0.05)。两种药物治疗3月后,患者的症状评分mMRC评分、CAT评分、圣乔治调查问卷评分均较治疗前明显降低(P0.05)。两组治疗后6分钟步行距离均较治疗前增加(P0.05)。各指标治疗前后改变量在两组间差别无统计学意义(P0.05)。3.肺功能检查结果分析：两种药物治疗后肺通气功能指标FVC、FVC%pred、 YEV1、FEV1%pred、FEV1/FVC等较治疗前有所增加,但各指标治疗前后差别无统计学意义(P0.05)。两药治疗后气道阻力指标Z5、R5、20、R5-R20均较治疗前降低(P0.01), Fres较治疗前明显降低(P0.01),X5绝对值较治疗前减小(P0.01)。FVC、FEV1、Z5、R5、X5等指标治疗前后改变量在两个药物组间差别无统计学意义(P0.05)。尽管丙酸倍氯米松/福莫特罗组治疗前后R5-R20、Fres改变量较布地奈德/福莫特罗组更大,但两组差别无统计学意义(P=0.506,0.766)。丙酸倍氯米松/福莫特罗组治疗后DLCO%pred较治疗前增加(P0.01),布地奈德/福莫特罗组治疗后DLCO%pred无明显改变(P=0.152)。4.HRCT检查结果分析：治疗前LAA%与mMRC评分、CAT评分、SGRQ评分均有明显的相关性,相关系数分别为0.645,0.601,0.596(P0.01)。同时,LAA%与FEV1%pred、DLCO%pred也存在较强的相关性(r=-0.708,-0.664,0.01)。两组治疗前WT、BWT、WT/BWT及LAA%均无差别(P0.05)。尽管两种药物治疗后WT、WT/BWT指标均较治疗前有所降低,但治疗前后差别无统计学意义(P0.05)。两药治疗前后LAA%均无明显差别(P0.05)。结论1.ICS/LABA吸入治疗可降低慢阻肺患者小气道阻力,改善患者生活质量和呼吸困难症状。2.IOS气道阻力指标较肺通气功能指标更敏感,能更好地评价慢阻肺患者吸入治疗的疗效。3.较小剂量的丙酸倍氯米松/福莫特罗的疗效并不亚于布地奈德/福莫特罗。4. HRCT对于吸入治疗疗效的评价作用及小颗粒药物丙酸倍氯米松/福莫特罗对慢阻肺的治疗作用有待进一步研究。
[Abstract]:Chronic obstructive pulmonary disease (COPD) is a chronic obstructive pulmonary disease characterized by persistent airflow restriction. Airflow restriction develops progressively, accompanied by an increase in airway and lung tissue inflammation response to harmful gases or particles. COPD is a common and frequently-occurring disease of the respiratory system, and its prevalence is high. It is expected that COPD will be the fifth largest economic burden in the world by 2020, the third highest in mortality by 2030, and the seventh highest in disability. Small airway disease (SAD) and lung parenchymal destruction (lung qi) Swelling is an important pathogenesis of COPD and a major cause of airflow limitation. Small airways refer to airways less than 2 mm in diameter and without cartilage, usually located in grades 8-23 of the tracheobronchial tree. The main site of airflow limitation. Understanding the structural and functional changes of small airways is of great significance to the analysis of the severity of COPD, the understanding of disease progression, the evaluation of therapeutic efficacy and prognosis. Impulse oscillation test (IOS) is a widely studied method of airway resistance evaluation in recent years. It can analyze total airway resistance, central airway resistance and peripheral airway resistance. IOS is more sensitive than lung ventilation function index FEV1 and can be used for evaluation. High resolution computed tomography (HRCT) can quantitatively analyze the changes of airway and pulmonary tissue. Since the medium-sized airway can represent the small airway and reflect the degree of pathological changes of small airway tissue, the large and medium airway can be analyzed by HRCT to reflect the function of small airway. At present, HRCT has become an important means of evaluating the distal lung tissue in clinical research. The treatment of stable COPD aims to relieve symptoms, improve exercise tolerance, improve lung function and reduce the risk of acute exacerbation. Inhaled glucocorticoids combined with effective beta 2 receptor agonists (ICS/LABA) can improve the clinical symptoms of patients. Small airways are the main site of airflow restriction in patients with COPD, and patients with small airway changes are more responsive to short-acting beta-2 receptor agonists. Previous studies have shown that beclomethasone propionate/formoterol therapy can improve airway obstruction and airway resistance in patients with COPD. The effect of airway and pulmonary tissue structure on COPD is not clear, and there are few studies comparing it with traditional treatment. Part I: Evaluation of small airway structure and function in patients with COPD Objective To analyze the role of small airway changes in the occurrence and development of COPD, and to explore the role of high resolution CT and pulse oscillation in COPD. Methods Patients with chronic obstructive pulmonary disease (COPD) in the outpatient clinic of Zhujiang Hospital of Southern Medical University from September 2014 to December 2015 were selected as the study subjects. All patients met the diagnostic criteria of COPD in the Society of Respiratory Diseases, Chinese Medical Association, in 2013, and were excluded. Patients with acute or chronic respiratory diseases were examined with Master Screen Pulmonary Function Instrument (Master Screen), a German company, to analyze the response frequency (Fres), small airway resistance (R5-R20) and pulmonary ventilation function. In the same day, Philips Brilliance 256-slice iCT was used to examine the tracheal wall diameter (WT) of the third-grade branch of the right upper lobe apical bronchus, accompanied by pulmonary artery diameter (BWT), and quantitative pulmonary emphysema (LAA%). The correlation between the airway wall thickening, emphysema and PFT, IOS was analyzed. General data: 132 patients with COPD were enrolled, including 117 males and 15 females, with an average age of (67.9 The smoking index in COPD group was significantly higher than that in control group (t = 4.960, P 0.01). 2. Comparison of lung function between COPD group and control group: FEV1% PRED and FEV1 / FVC in COPD group were significantly lower than those in control group, and the small airway index FEF in pulmonary ventilation function was significantly lower than those in COPD group. The levels of Z5, R5, Fres and R5-R20 in COPD group were higher than those in control group (P 0.01). The absolute value of X5 in COPD patients increased (P 0.01). There was no significant difference in R20 between the two groups (P = 0.754). 3. COPD patients with GOLD grade 1-4 had no significant difference in IOS index: COPD patients with COPD grade 1-4: COPD The absolute value of X5 increased with the degree of obstruction (P 0.01), but the change of central airway resistance index R20 was not significant (P = 0.662). 4. Correlation analysis of IOS and PFT in COPD group: Z5, R5, Fres, R5-R20 and PFT All indexes of pulmonary ventilation function were negatively correlated (P 0.01). X5 was positively correlated with FEV1% pred, FEV1 / FVC, FEF25% - 75% pred, FEF50% pred, etc. (P 0.01). Fres was strongly correlated with FVC, FEV1, FEV1% pred, FEV1 / FVC, FEF 25% - 75% pred, FEF 50% pred, and had the strongest correlation with FEV1 (r = - 0.715, P 0.01). The ROC curve and area under the curve of IOS index were established in 132 COPD patients and 92 healthy controls. The sensitivity of each critical point of IOS index was used as ordinate, and the error rate was used as abscissa. The best dividing points for each index were FresR5-R20Z5R50.5. The best dividing points for Fres and R5-R20 were 13.93 and 0.055.6 respectively. HRCT results analysis: GOLD 1-4 HRCT analysis in COPD group Results:WT:(1.39+0.20)mm; BWT:(4.09+0.76)mm; WT/BWT:(35.1+7.31)%:LAA%:7.14%+8.49%. WT increased with the severity of airflow limitation, but there was no significant difference between groups (P 0.05). WT/BWT gradually increased with the degree of airflow limitation (F=4.859, P 0.01), LAA% increased (F=9.792, P 0.01). WT was negatively correlated with TFEV1%. LAA% was negatively correlated with FEV 1% pred, FEF 25% - 75% pred, FEF 50% pred, and the correlation coefficient with FEV 1% PRED was the strongest, and the correlation coefficient was - 0.566 (P 0.01). LAA% was positively correlated with Fres and R5-R20, and the correlation coefficients were 0.466 (P 0.01), 0.340 (P 0). Pulse oscillation test can accurately determine the small airway resistance, reflect the small airway function, and has a certain diagnostic value for COPD. 3. High resolution CT image is intuitive, can qualitative and quantitative analysis of airway and lung tissue structure changes, and reflect the disease. Pathological basis and severity. 4. HRCT and IOS are correlated with the results of pulmonary ventilation, and can be used to evaluate the changes of small airway structure and function more comprehensively. It is important for early diagnosis and comprehensive evaluation of COPD. To investigate the effect of HRCT and 1OS on small airway in patients with COPD and to compare the efficacy of two inhalation therapies (beclomethasone propionate/formoterol, budesonide/formoterol). Methods A randomized controlled study was conducted to compare the eligible stable phase between April 2015 and March 2016. Patients with obstructive pulmonary disease were randomly divided into two groups after 2 weeks of elution. They were treated with beclomethasone propionate/formoterol (100/6 ug, 2 inhalation/time, 2/day), budesonide/formoterol (160/4.5 ug, 2 inhalation/time, 2/day) for 3 months. Interview. Pulse oscillation, pulmonary ventilation, diffusion function, bronchodilation test, 6-minute walking test, dyspnea score (mMRC score), CAT score and St. George's Questionnaire (SGRQ) were performed at each follow-up. HRCT was performed at the 2nd and 4th follow-up. The differences of airway structure and function between the two groups were evaluated, and the effects of the two groups were compared. General data: 42 patients with stable COPD were selected in this study. Among them, 2 patients were lost in elution phase and 40 patients were randomly divided into two groups, 36 males and 4 females. They were treated with beclomethasone propionate / formoterol and budesonide / formoterol respectively, 20 patients in each group. There was no significant difference in gender, age, body mass index, smoking history between the two groups (P 0.05). Before treatment, the lung ventilation function index FVC% pred, FEV1% pred, FEV1 / FVC, DLCO% PRED and 6-minute walking distance 6MWD had no difference between the two groups (P 0.05). 2. Symptom score and 6-minute walking distance: Symptom score before treatment, 6-minute walking distance difference between the two groups. There was no significant difference between the two groups (P 0.05). After 3 months of treatment, the symptoms scores of the patients, such as mMRC score, CAT score and St. George's questionnaire score, were significantly lower than those before treatment (P 0.05). The 6-minute walking distance of the two groups increased after treatment (P 0.05). The results of pulmonary function test showed that FVC, FVC% pred, YEV1, FEV1% PRED and FEV1 / FVC were increased after treatment, but there was no significant difference between before and after treatment (P 0.05). FVC, FEV1, Z5, R5, X5 and other indicators before and after treatment had no significant difference between the two drug groups (P 0.05). 766). DLCO% PRED in beclomethasone propionate / formoterol group increased after treatment (P 0.01). There was no significant change in DLCO% PRED in budesonide / formoterol group after treatment (P = 0.152). 4. HRCT analysis showed that LAA% was significantly correlated with mMRC score, CAT score and SGRQ score before treatment, and the correlation coefficients were 0.645, 0.601, 0.596 (P 0.01). There was no significant difference in WT, BWT, WT / BWT and LAA% between the two groups before and after treatment (P Conclusion 1. ICS / LABA inhalation therapy can reduce the small airway resistance and improve the quality of life and dyspnea symptoms in COPD patients. 2.
【学位授予单位】：南方医科大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R563.9
本文编号：2231078
[Abstract]:Chronic obstructive pulmonary disease (COPD) is a chronic obstructive pulmonary disease characterized by persistent airflow restriction. Airflow restriction develops progressively, accompanied by an increase in airway and lung tissue inflammation response to harmful gases or particles. COPD is a common and frequently-occurring disease of the respiratory system, and its prevalence is high. It is expected that COPD will be the fifth largest economic burden in the world by 2020, the third highest in mortality by 2030, and the seventh highest in disability. Small airway disease (SAD) and lung parenchymal destruction (lung qi) Swelling is an important pathogenesis of COPD and a major cause of airflow limitation. Small airways refer to airways less than 2 mm in diameter and without cartilage, usually located in grades 8-23 of the tracheobronchial tree. The main site of airflow limitation. Understanding the structural and functional changes of small airways is of great significance to the analysis of the severity of COPD, the understanding of disease progression, the evaluation of therapeutic efficacy and prognosis. Impulse oscillation test (IOS) is a widely studied method of airway resistance evaluation in recent years. It can analyze total airway resistance, central airway resistance and peripheral airway resistance. IOS is more sensitive than lung ventilation function index FEV1 and can be used for evaluation. High resolution computed tomography (HRCT) can quantitatively analyze the changes of airway and pulmonary tissue. Since the medium-sized airway can represent the small airway and reflect the degree of pathological changes of small airway tissue, the large and medium airway can be analyzed by HRCT to reflect the function of small airway. At present, HRCT has become an important means of evaluating the distal lung tissue in clinical research. The treatment of stable COPD aims to relieve symptoms, improve exercise tolerance, improve lung function and reduce the risk of acute exacerbation. Inhaled glucocorticoids combined with effective beta 2 receptor agonists (ICS/LABA) can improve the clinical symptoms of patients. Small airways are the main site of airflow restriction in patients with COPD, and patients with small airway changes are more responsive to short-acting beta-2 receptor agonists. Previous studies have shown that beclomethasone propionate/formoterol therapy can improve airway obstruction and airway resistance in patients with COPD. The effect of airway and pulmonary tissue structure on COPD is not clear, and there are few studies comparing it with traditional treatment. Part I: Evaluation of small airway structure and function in patients with COPD Objective To analyze the role of small airway changes in the occurrence and development of COPD, and to explore the role of high resolution CT and pulse oscillation in COPD. Methods Patients with chronic obstructive pulmonary disease (COPD) in the outpatient clinic of Zhujiang Hospital of Southern Medical University from September 2014 to December 2015 were selected as the study subjects. All patients met the diagnostic criteria of COPD in the Society of Respiratory Diseases, Chinese Medical Association, in 2013, and were excluded. Patients with acute or chronic respiratory diseases were examined with Master Screen Pulmonary Function Instrument (Master Screen), a German company, to analyze the response frequency (Fres), small airway resistance (R5-R20) and pulmonary ventilation function. In the same day, Philips Brilliance 256-slice iCT was used to examine the tracheal wall diameter (WT) of the third-grade branch of the right upper lobe apical bronchus, accompanied by pulmonary artery diameter (BWT), and quantitative pulmonary emphysema (LAA%). The correlation between the airway wall thickening, emphysema and PFT, IOS was analyzed. General data: 132 patients with COPD were enrolled, including 117 males and 15 females, with an average age of (67.9 The smoking index in COPD group was significantly higher than that in control group (t = 4.960, P 0.01). 2. Comparison of lung function between COPD group and control group: FEV1% PRED and FEV1 / FVC in COPD group were significantly lower than those in control group, and the small airway index FEF in pulmonary ventilation function was significantly lower than those in COPD group. The levels of Z5, R5, Fres and R5-R20 in COPD group were higher than those in control group (P 0.01). The absolute value of X5 in COPD patients increased (P 0.01). There was no significant difference in R20 between the two groups (P = 0.754). 3. COPD patients with GOLD grade 1-4 had no significant difference in IOS index: COPD patients with COPD grade 1-4: COPD The absolute value of X5 increased with the degree of obstruction (P 0.01), but the change of central airway resistance index R20 was not significant (P = 0.662). 4. Correlation analysis of IOS and PFT in COPD group: Z5, R5, Fres, R5-R20 and PFT All indexes of pulmonary ventilation function were negatively correlated (P 0.01). X5 was positively correlated with FEV1% pred, FEV1 / FVC, FEF25% - 75% pred, FEF50% pred, etc. (P 0.01). Fres was strongly correlated with FVC, FEV1, FEV1% pred, FEV1 / FVC, FEF 25% - 75% pred, FEF 50% pred, and had the strongest correlation with FEV1 (r = - 0.715, P 0.01). The ROC curve and area under the curve of IOS index were established in 132 COPD patients and 92 healthy controls. The sensitivity of each critical point of IOS index was used as ordinate, and the error rate was used as abscissa. The best dividing points for each index were FresR5-R20Z5R50.5. The best dividing points for Fres and R5-R20 were 13.93 and 0.055.6 respectively. HRCT results analysis: GOLD 1-4 HRCT analysis in COPD group Results:WT:(1.39+0.20)mm; BWT:(4.09+0.76)mm; WT/BWT:(35.1+7.31)%:LAA%:7.14%+8.49%. WT increased with the severity of airflow limitation, but there was no significant difference between groups (P 0.05). WT/BWT gradually increased with the degree of airflow limitation (F=4.859, P 0.01), LAA% increased (F=9.792, P 0.01). WT was negatively correlated with TFEV1%. LAA% was negatively correlated with FEV 1% pred, FEF 25% - 75% pred, FEF 50% pred, and the correlation coefficient with FEV 1% PRED was the strongest, and the correlation coefficient was - 0.566 (P 0.01). LAA% was positively correlated with Fres and R5-R20, and the correlation coefficients were 0.466 (P 0.01), 0.340 (P 0). Pulse oscillation test can accurately determine the small airway resistance, reflect the small airway function, and has a certain diagnostic value for COPD. 3. High resolution CT image is intuitive, can qualitative and quantitative analysis of airway and lung tissue structure changes, and reflect the disease. Pathological basis and severity. 4. HRCT and IOS are correlated with the results of pulmonary ventilation, and can be used to evaluate the changes of small airway structure and function more comprehensively. It is important for early diagnosis and comprehensive evaluation of COPD. To investigate the effect of HRCT and 1OS on small airway in patients with COPD and to compare the efficacy of two inhalation therapies (beclomethasone propionate/formoterol, budesonide/formoterol). Methods A randomized controlled study was conducted to compare the eligible stable phase between April 2015 and March 2016. Patients with obstructive pulmonary disease were randomly divided into two groups after 2 weeks of elution. They were treated with beclomethasone propionate/formoterol (100/6 ug, 2 inhalation/time, 2/day), budesonide/formoterol (160/4.5 ug, 2 inhalation/time, 2/day) for 3 months. Interview. Pulse oscillation, pulmonary ventilation, diffusion function, bronchodilation test, 6-minute walking test, dyspnea score (mMRC score), CAT score and St. George's Questionnaire (SGRQ) were performed at each follow-up. HRCT was performed at the 2nd and 4th follow-up. The differences of airway structure and function between the two groups were evaluated, and the effects of the two groups were compared. General data: 42 patients with stable COPD were selected in this study. Among them, 2 patients were lost in elution phase and 40 patients were randomly divided into two groups, 36 males and 4 females. They were treated with beclomethasone propionate / formoterol and budesonide / formoterol respectively, 20 patients in each group. There was no significant difference in gender, age, body mass index, smoking history between the two groups (P 0.05). Before treatment, the lung ventilation function index FVC% pred, FEV1% pred, FEV1 / FVC, DLCO% PRED and 6-minute walking distance 6MWD had no difference between the two groups (P 0.05). 2. Symptom score and 6-minute walking distance: Symptom score before treatment, 6-minute walking distance difference between the two groups. There was no significant difference between the two groups (P 0.05). After 3 months of treatment, the symptoms scores of the patients, such as mMRC score, CAT score and St. George's questionnaire score, were significantly lower than those before treatment (P 0.05). The 6-minute walking distance of the two groups increased after treatment (P 0.05). The results of pulmonary function test showed that FVC, FVC% pred, YEV1, FEV1% PRED and FEV1 / FVC were increased after treatment, but there was no significant difference between before and after treatment (P 0.05). FVC, FEV1, Z5, R5, X5 and other indicators before and after treatment had no significant difference between the two drug groups (P 0.05). 766). DLCO% PRED in beclomethasone propionate / formoterol group increased after treatment (P 0.01). There was no significant change in DLCO% PRED in budesonide / formoterol group after treatment (P = 0.152). 4. HRCT analysis showed that LAA% was significantly correlated with mMRC score, CAT score and SGRQ score before treatment, and the correlation coefficients were 0.645, 0.601, 0.596 (P 0.01). There was no significant difference in WT, BWT, WT / BWT and LAA% between the two groups before and after treatment (P Conclusion 1. ICS / LABA inhalation therapy can reduce the small airway resistance and improve the quality of life and dyspnea symptoms in COPD patients. 2.
【学位授予单位】：南方医科大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R563.9
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