气道过敏反应测试系统在慢性咳嗽诊断中的意义

发布时间：2018-10-12 10:25

【摘要】：背景随着空气污染日益严重,河南省豫北地区咳嗽患者门诊量逐年上升。咳嗽(Cough)是清除气道内分泌物,防止外来异物进入机体的反射性防御动作。但是,频繁咳嗽可引起胸腔压力增高,加重心脏负担,引起呕吐,胸痛,从而进一步影响患者夜间睡眠质量,造成白天嗜睡和疲乏,影响生活质量。再加上花粉、粉尘过敏原和炎症因子等刺激,使得咳嗽成为临床上最常见呼吸系统疾病症状。慢性咳嗽的诊断标准:以咳嗽为主要或唯一症状(持续时间8周),而胸部影像学检查无明显异常[2]。患者仅表现为咳嗽,而胸部X光及CT检查均无异常,常被误诊为慢性支气管炎,无法给予正确有效的治疗,延误病情且严重影响生活质量。致使临床上常应用抗生素进行对症治疗和进行多种非必要的检查,浪费大量医疗资源。因此,早期明确诊断慢性咳嗽的病因对其进行有效治疗具有重要意义。咳嗽变异性哮喘(Cough variant asthma,CVA)、嗜酸性粒细胞性支气管炎、胃食管反流和鼻后滴漏综合征、应用血管紧张素转换酶抑制剂是引起慢性咳嗽的常见原因。尽管引起慢性咳嗽的病因很多,包括独立病因和多发病因,但是咳嗽变异性哮喘是慢性咳嗽最重要的原因。咳嗽变异性哮喘是一种临床上非典型表现的隐匿性哮喘,慢性咳嗽是首发或唯一表现,主要多发于夜间,吸入糖皮质激素或支气管舒张剂治疗有效,因其没有喘息、发作性呼吸困难等临床症状且双肺无哮鸣音,临床医师常诊断为支气管炎,进行大量的无效的治疗,引起药物相关并发症。气道高反应性和炎症引起的气道重构是支气管哮喘的主要病理生理特征。当前研究显示支气管激发试验是检测各种类型哮喘的有效手段(包括咳嗽变异性哮喘)。近期研究表明,Th17细胞产生白介素17(Interleukin-17,IL-17)、IL-22及IL-23等细胞因子促使中性粒细胞活化和趋化,从而加重气道敏感性和炎症反应,慢性咳嗽患者气道中IL-17表达与中性粒细胞浸润数量和疾病严重程度密切相关。干扰素调节因子4(Interferon regulatory factor 4,IRF4),主要调控Th17细胞分化。当CD4+T细胞在转化生长因子β(transforming growth factor beta,TGF-β)和IL-6并存时,如果IRF4缺陷,即使存在TGF-β、IL-6及抗原刺激,Th0细胞不分化为Th17细胞,成熟Th17细胞分泌IL-17、IL-21也受限。IRF4还可控制IL-6诱导CD11b树突状细胞(dendritic cell,DC)的分化发育来影响Th17细胞分化。因此在气道过敏反应中,IRF4可以通过调节Th17细胞的分化而参与慢性咳嗽的发病机制。慢性咳嗽发病危险因素中最重要的是遗传和环境因素能通过IRF4对Th17细胞分化及功能起到重要的调节作用。为进一步明确气道过敏反应测试系统(支气管激发试验)在慢性咳嗽诊断中的应用价值及IRF4在慢性咳嗽发生过程中的作用机制,以期为慢性咳嗽防治提供新思路和理论依据,分析2016年2月至2017年2月在新乡市第一人民医院呼吸内科门诊就诊的298例慢性咳嗽患者,均进行气道过敏反应检测,现报告如下。目的探讨气道过敏反应测试系统在慢性咳嗽诊断中的意义。方法1.选取新乡市第一人民医院呼吸内科2016年2月至2017年2月期间慢性咳嗽患者298例为本研究对象,其中男性患者162例,女性患者136例,并对患者依据年龄进行分组。2.采用全自动气道过敏反应检测仪(ASTOGRAPH J-21)对慢性咳嗽患者进行支气管激发试验检查。3.分析慢性咳嗽患者中诊断为咳嗽变异性哮喘与年龄和性别的关系。4.Real-time PCR检测受试者炎症指标的表达:ICAM-1,TNF-α,TGF-β、IL-17。5.应用SPSS 17.0统计软件包,根据资料类型分别采用χ2检验和t检验进行统计学处理,以P0.05为具有统计学意义。结果1.298例慢性咳嗽患者中,气道过敏反应检测、炎症指标诊断咳嗽变异性哮喘在各年龄组之间差异有统计学意义。2.气道过敏反应检测、炎症指标诊断咳嗽变异性哮喘在性别之间差异无统计学意义。3.气道过敏反应检测阳性157例(52.68%),阴性141例(47.32%),FEV1、FEV1/FVC、PEF及MMEF在激发阳性、阴性患者间差异均有统计学意义(P0.05),FVC在激发阳性、阴性患者间比较差异无统计学意义(P0.05)。4.气道过敏反应检测阳性157例,阴性141例,炎症指标在激发阳性、阴性患者间差异均有统计学意义(P0.05)。结论1.在298例慢性咳嗽中,支气管激发试验阳性在不同年龄组中有显著差异,而男女两组阳性率无显著差异,最终确诊CVA患者的支气管激发试验阳性率为47.31%。支气管激发阳性与过敏相关因素、年龄、性别、咳嗽症状总积分、诱导痰嗜酸性粒细胞、血清ICAM-1、TNF-α、TGF-β、IL-17和FeNO因素显著相关。2.气道过敏反应检测系统在慢性咳嗽的诊断中有明确意义,应用气道过敏反应测试系统在慢性咳嗽患者中筛查CVA患者,早期诊断、正确治疗,有助于防止其发展为典型哮喘。
[Abstract]:Background As the air pollution becomes more and more serious, the outpatient quantity of cough patients in Henan Province is increasing year by year. Coughing is a reflex defense that removes secretions from the airways and prevents foreign bodies from entering the body. However, frequent cough can cause elevated chest pressure, increase heart burden, cause vomiting, chest pain, and further affect night sleep quality in patients, resulting in daytime sleepiness and fatigue, affecting quality of life. Add pollen, dust allergen and inflammatory factors to make the cough become the most common symptom of respiratory disease in clinic. Diagnostic criteria for chronic cough: major or unique symptoms of cough (8 weeks duration) and no significant abnormalities in chest imaging[2]. The patient only showed cough, while chest Xray and CT examination were not abnormal, often misdiagnosed as chronic bronchitis, unable to give correct and effective treatment, delay the condition and seriously affect the quality of life. so that the clinical application of antibiotics for symptomatic treatment and multiple unnecessary examinations is carried out, and a large amount of medical resources are wasted. Therefore, the early diagnosis of chronic cough is of great significance for effective treatment of chronic cough. Cough variant asthma (CVA), eosinophilic bronchitis, transesophageal reflux and post-nasal drip syndrome, the use of angiotensin converting enzyme inhibitors is a common cause of chronic cough. Cough variant asthma is the most important cause of chronic cough despite the many causes of chronic cough, including independent etiology and multiple morbidity. Cough variant asthma is a clinically atypical allergic asthma, chronic cough is the first or only manifestation, mostly at night, inhaled corticosteroids or bronchodilators are effective because they are not breathing, There are clinical symptoms such as paroxysmal dyspnea, and the double lungs do not have any symptoms, and the clinician is often diagnosed as bronchitis, and a large number of ineffective treatments are carried out, resulting in drug-related complications. Airway remodeling caused by high airway hyperresponsiveness and inflammation is the main pathophysiological feature of bronchial asthma. The current study shows that the bronchial provocation test is an effective means of detecting various types of asthma (including cough variant asthma). Recent studies have shown that Th17 cells produce IL-17 (Interleukin-17, IL-17), IL-22 and IL-23, which promote the activation and chemotaxis of neutrophils, thus increasing airway sensitivity and inflammatory response, and the expression of IL-17 in the airway of chronic cough is closely related to the number of neutrophils and the severity of the disease. An interferon regulatory factor 4 (IRF4) was used to regulate the differentiation of Th17 cells. When CD4 + T cells coexist in transforming growth factor beta (IL-6) and IL-6, if IRF4 is deficient, even if there are IL-6, IL-6 and IL-6, Th0 cells are not differentiated into Th17 cells, and mature Th17 cells secrete IL-17, and IL-21 is also restricted. IRF4 may also control the differentiation development of IL-6-induced CD11b dendritic cells (DC) to affect Th17 cell differentiation. Therefore, IRF4 may be involved in the pathogenesis of chronic cough by modulating the differentiation of Th17 cells in airway allergic reactions. The most important factor in the risk factors of chronic cough is that genetic and environmental factors play an important role in the differentiation and function of Th17 cells by IRF4. To further clarify the application value of airway allergic reaction test system (bronchial provocation test) in the diagnosis of chronic cough and the mechanism of IRF4 in the course of chronic cough, so as to provide new ideas and theoretical basis for the prevention and cure of chronic cough. From February 2016 to February 2017, 298 patients with chronic cough in the respiratory department of the First People's Hospital of Xinxiang City were analyzed, and airway allergic reaction was detected. The report is as follows. Objective To investigate the significance of airway allergy test system in diagnosis of chronic cough. Method 1. 298 cases of chronic cough were selected from February 2016 to February 2017 for the first People's Hospital of Xinxiang City from February 2016 to February 2017. Among them, 162 were male, 136 were female, and the patient was grouped according to age. Bronchial provocation test was performed in patients with chronic cough with a full-automatic airway allergy tester (ASTM OGRAPH J-21). To analyze the relationship between cough variant asthma and age and sex in patients with chronic cough. Statistical processing was carried out using SPSS 17. 0 statistical software package according to the type of data, respectively. The statistical significance was found in P0.05. Results One hundred and twenty-eight patients with chronic cough, airway allergic reaction, inflammation index and cough variant asthma had statistical significance between age groups. There was no significant difference in gender between the diagnosis of airway hypersensitivity and the diagnosis of cough variant asthma. There were 157 cases (52. 68%) positive airway allergy test, 141 cases negative (47. 32%), FEV1, FEV1/ FVC, FEV1 and MMEF were statistically significant (P0.05), and there was no significant difference in FVC between positive and negative patients (P0.05). There were 157 cases of positive airway allergy test, 141 cases were negative, and there was statistical difference between the positive and negative patients (P0.05). Conclusion 1. In 298 cases of chronic cough, the positive rate of bronchial provocation test was significantly different in different age groups, while there was no significant difference between the two groups. The positive rate of bronchial provocation test in the patients with CVA was 47. 31%. The positive and allergy-related factors, age, sex, cough symptom and total score of bronchial provocation, induced sputum eosinophil, serum ICAM-1, TNF-CoV, IL-17, IL-17 and FeNO were significantly correlated. The airway allergy test system has definite meaning in the diagnosis of chronic cough, and the application of the airway allergic reaction test system to screen CVA patients in chronic cough patients, early diagnosis, correct treatment, and help prevent it from developing into typical asthma.
【学位授予单位】：新乡医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R56

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