沙美特罗替卡松治疗支气管扩张并不可逆气流受限患者的疗效与安全性研究

发布时间：2018-04-28 22:34

本文选题：支气管扩张症 + 氟替卡松/沙美特罗　；参考：《山东大学》2012年硕士论文

【摘要】：背景：支气管扩张症是由于各种微生物的反复感染或慢性感染引起的慢性支气管炎症导致永久气道扩张,首次由Rene Theophile Laennec在1819年描述。支气管扩张症的特点是支气管局部管腔扩张、粘液分泌、粘膜炎症,导致痰量增多和慢性咳嗽。支气管扩张症分为非纤维化支气管扩张症(NCFB,以下简称支扩)和纤维化伴发支气管扩张症,其中后者为继发,不属于本课题范围。支扩的病因是复杂的,但有共同的病理生理过程,其中包含三个主要因素[2-31：炎症,感染和破坏(酶的作用)。由于各种病因,机体不能及时清除呼吸道局部微生物的定植,从而导致感染,进一步导致炎症反应。炎症可以抵御外来物的侵袭,但这种反应未能及时正确消除外来物时,可能会变成慢性炎症,从而诱发支气管壁破坏和不可逆的扩张。出现这种由细菌感染引起的呼吸道炎症反应过度,甚至在细菌感染控制后仍持续存在,从而导致促炎因子和／或不受控制的活化效应细胞持续存在。支气管扩张症的炎性细胞是单核细胞和中性粒细胞,单核细胞和中性粒细胞也是导致气流受限的慢性支气管阻塞和频繁的支气管高反应性的炎性细胞。有统计显示[4],支气管扩张患者大约有50%存在气流受限。而肺功能改变与病变的范围及性质有密切的关系。病变局限者,肺功能一般无改变；柱状扩张对肺功能影响轻微,囊状扩张的支气管破坏严重,可并发阻塞性肺气肿。资料显示,支气管扩张症患者的肺功能变化以阻塞性通气功能障碍为多见(80%患者),少数为混合性通气功能障碍,33%-76%患者存在气道高反应性。目前,关于支气管扩张稳定期的治疗没有一个明确有效的长期治疗方案。研究显示[7-8],高剂量糖皮质激素(ICS)应用能改善支气管扩张病人的临床症状和生活质量,减轻支气管粘膜的炎症,但是它不能完全清除气道炎症,而副作用的出现如咳嗽、口干、发声困难、口腔溃疡、喷嚏及口腔念珠菌感染等却令人担心；而小剂量吸入激素(500μ g/天氟替卡松),副作用小,但不能明显改善临床症状和生活质量。ICS+LABA[9]联合吸入治疗降低了激素用量,表现出一个良好的临床安全性和有效性,国外已有小样本研究的报道,发现在症状、运动耐量、生活质量等方面较治疗前明显改善,但肺功能改善无统计学意义。我国支扩发病率高,病因分布与国外也有较大的不同,ICS+LABA长期应用是否对我国支扩稳定期患者有效未见报道。目的：评价氟替卡松/沙美特罗(F/S)在治疗非纤维化(NCFB)支气管扩张症合并不可逆的气流受限患者吸入治疗的疗效和安全性。材料与方法：这项临床试验是一项6个月的随机、对照、前瞻性研究,收集的患者从2010年6月至2011年8月。60例支气管扩张症、有不可逆的气流受限患者都要经过高分辨率CT、肺功能检查确诊。随机分为两组：A组接受F/S联合治疗(50/250u g吸入BID)+常规治疗；B组接受常规治疗(按需应用沙丁胺醇、抗菌药物、祛痰药)。在研究期间,所有的患者在需要时都允许应用吸入沙丁胺醇治疗。分别于治疗3个月、6个月观察临床状况、健康相关生活质量(HRQL)、急性发作次数、肺功能、β2-肾上腺素能激动剂(沙丁胺醇)使用量、病原微生物(PPMs)的菌株、药物副作用等,对以上指标应用SPSS13.0软件进行统计分析,以P0.05为统计学意义。结果：(1)接受F/S的综合治疗的A组在呼吸困难评分、咳嗽次数、不使用β2-肾上腺素受体激动剂的天数方面与对照组有显著性差异。(2)HRQL的改善方面有显著性差异。(3)两组肺功能、PPMs的分离无统计学差异,虽然A组在肺功能方面有一定的改善。(4)A组急性发作次数明显少于对照组。(5)两组不良反应无显著性差异。结论：对非囊性纤维化支气管扩张症合并不可逆的气流受限患者,联合吸入F/S治疗是有效和安全的。
[Abstract]:Background: bronchiectasis is a chronic bronchitis caused by repeated infection of various microbes or chronic bronchitis caused by chronic bronchitis, resulting in permanent airway dilatation. It is first described in 1819 by Rene Theophile Laennec. Bronchiectasis is characterized by localized bronchiectasis, mucus secretions, mucous inflammation, increased phlegm and chronic cough. Cough.
Bronchiectasis is divided into non fibrotic bronchiectasis (NCFB, hereinafter referred to as bronchiectasis) and fibrosis associated bronchiectasis. The latter is secondary and does not belong to the subject. The etiology of the bronchiectasis is complex but has a common pathophysiological process, including three main factors, [2-31: inflammation, infection and destruction (enzyme action). Because of various causes, the body can not remove the colonization of the local microorganism in the respiratory tract in time, which leads to infection and further causes the inflammatory response. The inflammation can resist the invasion of foreign objects, but this reaction may become chronic inflammation when it fails to eliminate foreign objects correctly in time, which induces the destruction of the bronchial wall and the irreversible expansion. The inflammation of the respiratory tract caused by bacterial infection is excessive and even persists after the bacterial infection control, which leads to the persistence of pro-inflammatory and / or uncontrolled activated cells. The inflammatory cells of bronchiectasis are mononuclear cells and neutrophils, monocytes and neutrophils also lead to gas. Flow limited chronic bronchial obstruction and frequent bronchial hyperresponsiveness of inflammatory cells.
Statistics show that about 50% of the patients with bronchiectasis have airflow limitation, and the changes in pulmonary function are closely related to the range and nature of the lesion. The pulmonary function is generally not changed in those with localized lesions; the pulmonary function is slightly affected by the columnar dilatation, and the cystic dilatation of the bronchiectus is severe, which can be complicated by obstructive pulmonary emphysema. Data display, bronchiectasis, and bronchiectasis. The pulmonary function changes in patients with tracheal dilatation are more common in obstructive ventilation dysfunction (80% patients), a few are mixed ventilation dysfunction, and 33%-76% patients have airway hyperresponsiveness.
At present, there is no clear and effective long-term treatment for the treatment of bronchiectasis. The study shows that [7-8], high dose glucocorticoid (ICS) application can improve the clinical symptoms and quality of life of bronchiectasis patients and reduce the inflammation of bronchial mucosa, but it can not completely eliminate airway inflammation and side effects. Such as coughing, dry mouth, dysporia, oral ulcers, sneezing and oral Candida infection, but small dose inhaled hormone (500 g/ days fluticasone), with small side effects, can not significantly improve the clinical symptoms and quality of life.ICS+LABA[9] combined inhalation treatment to lower the hormone dosage, showing a good clinical safety and clinical safety. It has been reported that the symptoms, the exercise tolerance, the quality of life and other aspects are obviously improved, but the improvement of lung function is not statistically significant. The incidence of bronchiectasis in China is high and the distribution of the etiology is different from that of foreign countries. The long-term application of ICS+LABA has not been reported effectively for patients with stable period of Chinese bronchiectasis. Avenue.
Objective: To evaluate the efficacy and safety of fluticasone / Shah Mette Lo (F/S) in the treatment of patients with non fibrosis (NCFB) bronchiectasis with irreversible airflow limitation.
Materials and methods: This clinical trial was a 6 month randomized, controlled, prospective study of bronchiectasis in.60 cases from June 2010 to August 2011. Patients with irreversible airflow were diagnosed with high resolution CT and lung function examination. The patients were randomly divided into two groups: group A received F/S combined therapy (50/250u g inhaled BI). D) + routine treatment; group B received routine treatment (using salbutamol, antibacterials, expectorant). During the study, all patients were allowed to use inhaled salbutamol for 3 months, 6 months of clinical observation, health related life quality (HRQL), acute attack times, lung function, beta 2- adrenaline The dosage of the agonist (salbutamol), the strain of the pathogenic microorganism (PPMs), the side effects of the drug, and so on. The above index was statistically analyzed with the SPSS13.0 software, and P0.05 was statistically significant.
Results: (1) the A group receiving F/S comprehensive treatment had significant difference with the control group in the score of dyspnea, the number of coughing times and the number of days without beta 2- adrenergic receptor agonist. (2) there were significant differences in the improvement of HRQL. (3) there was no statistical difference between the two groups of lung function and the separation of PPMs, although the A group had some changes in the lung function. Good. (4) the number of acute attacks in group A was significantly less than that in control group. (5) there was no significant difference in adverse reactions between the two groups.
Conclusion: combined inhalation of F/S is effective and safe for patients with non cystic fibrosis bronchiectasis and irreversible airflow limitation.

【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R562.22

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