呼出气一氧化氮预测稳定期COPD患者吸入糖皮质激素治疗疗效的价值

发布时间：2017-12-27 08:58

本文关键词：呼出气一氧化氮预测稳定期COPD患者吸入糖皮质激素治疗疗效的价值　出处：《山东大学》2016年硕士论文　论文类型：学位论文

【摘要】：研究背景慢性组塞性肺疾病(chronic obstructive pulmonary disease,COPD)是一种常见的慢性炎症性呼吸系统的疾病,是世界范围内患病率与病死率较高的疾病之一,其特点是不完全可逆的气流受限并呈进行性发展,主要表现为慢性的咳嗽、咳痰、气短、胸闷、喘息及呼吸困难等症状。COPD的实质为气道和肺组织的慢性非特异性炎症反应,与患者吸入香烟烟雾及有害颗粒等刺激有关,其中主要的炎症细胞为中性粒细胞、肺泡巨噬细胞及CD8+T细胞,另外肺的结构细胞如肺泡上皮细胞和内皮细胞等均参与了气道炎症的发生与发展。近年来有较多研究显示嗜酸性粒细胞及肥大细胞等炎症细胞也参与了COPD的气道炎症反应的过程,尤其是在COPD急性加重期的患者中表现更为明显。呼出气一氧化氮(fraction of exhaled nitric oxide, FENO)是目前研究较多的一种气道炎症标志物,在呼吸系统的炎症反应及氧化应激等方面均发挥了重要作用,尤其是在支气管哮喘诊治中的作用已逐渐受到重视,并得到了国内外专家的肯定和广泛的应用。国内外较多研究也显示FENO能够反应支气管哮喘、过敏性咳嗽、COPD慢性嗜酸性肺炎等慢性气道炎症性疾病的气道炎症水平,尤其是气道内嗜酸性粒细胞增多的气道炎症,此类气道炎症对糖皮质激素类药物治疗效果的反应性较好,因此临床上可以用FENO检测手段来指导患有气道炎症性疾病的患者应用糖皮质激素类药物治疗。COPD患者的慢性气道炎症能加重气道壁的损伤、修复及重构,因此延缓COPD患者病情持续性进展及肺功能进行性减退的关键是控制慢性气道炎症的发展。糖皮质激素在控制气道炎症方面起到了尤为重要的作用,其机制为直接抑制中性粒细胞、嗜酸性粒细胞、肺泡巨噬细胞等炎症细胞的活化,并能抑制白三烯、前列环素等炎症介质的合成与释放,从而舒张支气管,改善患者的肺功能和预后。但也有研究表明,COPD患者应用糖皮质激素类药物治疗时能加重肺炎等并发症的发生率,因此,临床上迫切需要能指导COPD患者使用糖皮质激素治疗的辅助检查方法。FENO作为一种有用的气道炎症标志物,其操作简单、重复性好、有较高的灵敏度和特异度,因此可以用来指导COPD患者应用糖皮质激素治疗。研究目的探讨应用FENO测定技术预测稳定期COPD患者应用ICS治疗疗效的价值。研究方法1.选取2015年3-7月就诊于山东省立医院呼吸内科门诊,确诊为稳定期COPD(稳定期COPD是指患者咳嗽、咳痰、气短等症状稳定或轻微)的患者31例；2.进行单组、开放性的试验研究,试验前测定FENO值(将呼气流速定为50mL/s),并行肺功能、支气管舒张试验检查,肺功能测定前患者应静坐十分钟,在测定过程患者中保持坐位。3.检查后确诊为COPD的患者,给予布地奈德/福莫特罗粉(信必可)吸入剂160ug/4.5ug,每天2次、每次1吸,并给予化痰、止咳等基础治疗,同时督促患者戒烟及指导患者康复锻炼等治疗,4周以后重复上述检查。4.分别记录患者用药前后FENO值及相关的肺功能指标(包括FEV1.FEV1％. FVC.FEV1/FVC%等).研究结果31例稳定期COPD患者中,其中1人因吸入布地奈德/福莫特罗粉药物过程中出现咽部瘙痒干涩、刺激性咳嗽等不良反应而中途停止用药并退出本试验研究,余30例稳定期COPD患者顺利地完成了本试验研究。1.受试者的一般资料、吸烟及肺功能分级与FENO的关系基线水平FENO在不同的性别组、年龄组、体重指数组、有无吸烟史组、肺功能分级组之间差异无统计学意义(P均0.05)；2.基线水平FENO值与相关肺功能指标的关系基线FENO值与基线FEV1直无明显相关性(r=0.203,P=0.281),然而,基线FENO水平与使用ICS治疗后第1秒用力呼气容积(forced expiratory volume in one second, FEV1)改善值却有着显著地相关性(r=0.865,P0.05)；3.吸入布地奈德/福莫特罗粉吸入剂后FENO值的变化趋势基线FENO的值越高,使用ICS治疗4周后FENO值的下降幅度越大,反之亦然。4.基线水平FEN0对稳定期COPD患者吸入糖皮质激素治疗的预测价值对ICS治疗有反应者(FEV1增加的绝对值≥200mL)较对ICS治疗无反应者(FEV1增加的绝对值200ml)的FENO基线值明显增高(P0.05),利用基线FENO值诊断有反应者与无反应者的AUC为0.931,切点值定为29. lppb。研究结论1.基线水平FENO值与稳定期COPD的肺功能损伤的严重程度无明显的相关性,FENO并不能代表COPD患者的严重程度分级；2.基线水平FENO的值越高,COPD患者的气道炎症程度越重,治疗效果越好,因此FENO能反应稳定期COPD患者的气道类型及炎症的严重程度；3.在稳定期COPD患者中,FENO是一个能较好的预测其吸入糖皮质激素治疗疗效的指标。
[Abstract]:Background: chronic obstructive pulmonary disease (chronic obstructive pulmonary disease, COPD) is a chronic inflammatory disease of the common respiratory system, is one of the worldwide high prevalence and mortality of the disease, which is characterized by airflow limitation that is not fully reversible and progressive development, mainly for chronic cough, expectoration, shortness of breath, chest pain, breathing and breathing difficulties and other symptoms. The essence of COPD is chronic nonspecific inflammation of airway and lung tissue, and patients with inhalation of cigarette smoke and harmful particles and other stimuli, including inflammatory cells of neutrophils and alveolar macrophages and CD8+T cells, another cell lung structure such as alveolar epithelial cells and endothelial cells are involved in the occurrence and development of airway inflammation. In recent years, many studies have shown that inflammatory cells such as eosinophils and mast cells are also involved in the process of airway inflammation in COPD, especially in patients with acute exacerbation of COPD. Exhaled nitric oxide (fraction of exhaled nitric oxide, FENO) is at present. A marker of airway inflammation, has played an important role in the respiratory system inflammation and oxidative stress, especially in the diagnosis and treatment of bronchial asthma in the role has been gradually paid attention to, and obtained the domestic and foreign experts affirmed and widely used. The domestic and foreign research also showed that FENO reaction of bronchial asthma, allergic cough, COPD chronic eosinophilic pneumonia and chronic airway inflammatory disease of the airway inflammation, especially airway inflammation in the airway eosinophilia, airway inflammatory reaction of the glucocorticoid treatment effect is better, with glucocorticoid therapy in clinical FENO can be used to guide the detection means with airway inflammatory diseases. Chronic airway inflammation in patients with COPD can aggravate the damage, repair and reconstruction of airway wall. Therefore, the key to delay the progression of COPD's disease and the progressive decline of lung function is to control the development of chronic airway inflammation. Glucocorticoid in controlling airway inflammation plays a particularly important role, its mechanism is direct inhibition of neutrophils, eosinophils, macrophages and other inflammatory cell activation, and can inhibit the synthesis and release of leukotrienes, prostacyclin and other inflammatory mediators, thereby relaxing bronchia, improve lung function and prognosis of patients the. However, there are studies showing that glucocorticoid therapy can aggravate the incidence of complications such as pneumonia in COPD patients. Therefore, there is an urgent need for an auxiliary examination method that can guide COPD patients to use glucocorticoids. As a useful marker of airway inflammation, FENO is simple, reproducible, and has high sensitivity and specificity, so it can be used to guide glucocorticoid therapy in COPD patients. Objective to explore the value of using FENO technique to predict the efficacy of ICS in the treatment of stable COPD patients. Research methods 1. 3-7 month 2015 in Shangdong Province-owned Hospital from respiratory medicine clinic, diagnosed with stable COPD (stable COPD refers to patients with cough, expectoration, shortness of breath and other symptoms of stable or slight) in 31 cases of patients; 2. tests were performed on single group, open the test before the determination of FENO value (the expiratory flow rate constant 50mL/s), pulmonary function, bronchial dilation test, patients should sit for ten minutes before the lung function testing, to keep the seat in the determination of the patients. 3. diagnosed COPD patients, treated with budesonide / formoterol (Symbicort) inhalation powder 160ug/4.5ug, 2 times a day, and give 1 suction, phlegm, cough and other basic treatment, while urging patients to stop smoking and guide the patients to rehabilitation treatment, 4 weeks later, repeat the above check. 4. patients were recorded before and after treatment FENO value and related indexes of pulmonary function (including FEV1.FEV1%. FVC.FEV1/FVC%). The results of 31 patients with stable COPD patients, 1 of them due to inhaled budesonide / formoterol powder drug during the dry throat itching, irritating cough and other adverse reactions and stop medication and quit the study and more than 30 stable COPD patients successfully completed the study. 1. subjects of general information, smoking and lung function and the relationship between the FENO baseline levels of FENO in different gender groups, age groups, BMI group, smoking history, lung function between groups was not statistically significant (P < 0.05); the relationship between baseline FENO 2. baseline FENO value and correlation lung function index value had no significant correlation with baseline FEV1 (r=0.203, P=0.281), however, the baseline level of FENO and ICS after the treatment of forced expiratory volume in one second (forced expiratory volume in one second, FEV1) to improve the value has significant correlation (r=0.865, P0.05); 3. inhaled budesonide / trend the baseline FENO FENO value of formoterol fumarate powder for inhalation after the higher the value, the use of ICS after 4 weeks of treatment, the FENO value decreased, and vice versa. The value of 4. FEN0 baseline forecast of inhaled corticosteroids in the treatment of patients with stable COPD treatment responders to ICS (absolute value is more than 200mL increased FEV1) than on ICS nonresponders (absolute value of 200ml increased FEV1) FENO baseline values were significantly higher (P0.05), using the base line FENO diagnosis value responders and non responders to AUC 0.931, cut-off value was 29. lppb. Conclusion 1. baseline FENO values had no significant correlation with the severity of pulmonary function in COPD stable stage of injury, FENO does not represent the severity of COPD in patients with grade 2. at baseline; the higher the value of FENO, COPD in patients with airway inflammation severity, the treatment effect is better, so FENO can type and severity of airway the inflammatory reaction of COPD patients in the stable period; in 3. patients with stable COPD, FENO is a better prediction of the
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R563.9

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