呼出气一氧化氮诊断哮喘及哮喘患者呼出气一氧化氮与过敏原sIgE的相关性分析

发布时间：2018-06-20 16:24

本文选题：哮喘 + 呼出气一氧化氮　；参考：《第四军医大学》2013年硕士论文

【摘要】：第一部分：呼出气一氧化氮在哮喘诊断中的价值哮喘是由多种炎症细胞和细胞组分参与的气道慢性炎症性疾病。正是这种炎症的存在导致相关临床症状(咳嗽、喘息、气急、胸闷等)、可逆性气流受限、气道高反应性和气道结构的重塑[1,2]。目前公认的哮喘诊断和监测常常以症状、体征、气道阻塞程度、支气管舒张试验、支气管激发试验等结果为标准。但临床症状、体征和阳性肺功能指标都不能直接反应气道炎症状态。因此，直接测量气道炎症可能更适用于哮喘的诊断和监测。哮喘气道炎症测量法有：支气管镜下粘膜活检、支气管镜下肺泡灌洗液检查、诱导痰细胞分类学检查、呼出气冷凝物检测等。前两者属于侵入性检测，有一定风险，患者不易接受，因此不可能作为临床常规技术广泛开展；相对无创的诱导痰细胞分类学检查可导致肺功能暂时性下降，耗时、昂贵，需要专业技术人员来操作，而且大约有40%的哮喘患者诱导不出痰液[3,4]；呼出气冷凝物检测目前尚无统一的方法和标准。呼出气一氧化氮(fractional exhaled nitric oxide，FeNO)是一种公认的安全、无创、简单、重复性好、直接反应气道炎症的标志物。FeNO测量技术尚未在中国广泛开展，且因多种因素的影响，关于其诊断哮喘的准确性和最佳界值各个研究结果并不一致。目的：进一步明确FeNO诊断哮喘的准确性及其最佳界值。从而为哮喘诊断提供新的方法。方法：收集西京医院呼吸内科2012年6月至2012年12月就诊的具有喘息、胸闷、气急、咳嗽等症状，不吸烟，未使用激素治疗的疑似哮喘患者109例。使用FeNO测定仪（NIOXMINO Aerocrine AB瑞典）对109例疑似哮喘患者进行FeNO浓度测定，然后进行肺功能测定。以临床症状、肺功能舒张试验和（或）激发试验为诊断标准。通过接受者工作特征曲线图（receiver operating characteristic curves，ROC）来评价FeNO诊断哮喘的准确性。结果：109例患者中最终诊断哮喘患者47例，非哮喘患者62例，，两组患者FeNO中位数比较：70ppb vs16ppb,P＜0.001。ROC曲线下面积为0.808（95%可信区间：0.719，0.896)，在0.70～0.90之间表示诊断准确度为中等。FeNO诊断哮喘的最佳界值为41ppb，以41ppb为界诊断哮喘：Se：68.1%，Sp：83.9%，PV+：76.2%，PV_：77.6%，准确度：77.1%。但哮喘组中仍有15例（31.9%）患者的FeNO测量值≤41ppb，非哮喘组中有10例（16.1%）患者FeNO测量值＞41ppb。结论：FeNO诊断哮喘的准确度较高，可以作为哮喘诊断的辅助性工具。第二部分：哮喘患者呼出气一氧化氮与过敏原sIgE的相关性分析哮喘也被称为一种以嗜酸性粒细胞(Eosinophil,EOS)、肥大细胞反应为主的气道变应性炎症和气道高反应性(Airway hyperresponsiveness, AHR)为特征的疾病。目前认为哮喘发病和发展的危险因素除了遗传等内在因素外，环境因素是一个非常重要的外因。环境因素包括过敏原、感染、运动、气候变化、吸烟等，过敏原是环境因素中最主要的因素。哮喘患者常见过敏原有螨、户尘、粉尘、真菌、花粉、动物的毛屑、蛋白含量高的食物、药物等。过敏原通过抗原提呈细胞（antigen-presenting cells，APCs）激活辅助性T细胞，活化的T细胞产生炎症介质进一步激活B淋巴细胞，后者合成IgE结合于肥大细胞等细胞表面的IgE受体（FcεRI），当过敏原再次进入体内可与结合在细胞表面的IgE交联，产生炎症反应。 FeNO测量值是哮喘患者气道炎症的敏感指标，可作为客观依据支持哮喘诊断,可用于预测哮喘对激素治疗的敏感性[5,6]、监测哮喘气道炎症程度、评估哮喘激素治疗疗效、调整哮喘激素用量及判断哮喘患者激素治疗的依从性[7-9]。同时大量的研究证实FeNO与肺泡灌洗液、肺活检、诱导痰及外周血液中的EOS计数相关[10-12]。而到目前为止，FeNO与哮喘患者过敏原sIgE的相关性研究较少，且既往研究结果也不一致。目的：比较哮喘过敏者与非过敏者的FeNO。分析哮喘患者FeNO测量值与过敏原sIgE、总IgE的相关性。方法：收集2012年6月至2013年3月就诊于西京医院呼吸内科门诊的轻度哮喘患者125例。使用FeNO测试仪（NIOX MINO Aerocrine AB瑞典）和过敏原sIgE的AllergyScreen(敏筛)系统（德国默尔斯市Mediwiss公司出品）对125例哮喘患者进行FeNO、血清过敏原sIgE及总IgE测定。采用Pearson直线相关分析法对ln FeNO、ln血清过敏原sIgE进行相关分析。结果：125例哮喘患者中，血清过敏原sIgE阳性者73例，阴性者52例。血清过敏原sIgE阳性组FeNO几何均数(55ppb)明显高于阴性组(31ppb)，P＜0.001。ln FeNO测量值与ln户尘螨-sIgE浓度进行相关分析，证实两者呈中等正相关：r=0.7417,P＜0.001。ln FeNO测量值与ln真菌类-sIgE浓度的相关性分析结果显示成弱相关性：r=0.488, P＞0.05。同时得出FeNO测量值随着哮喘患者过敏原数量及血清总IgE浓度的增加而增高。结论：过敏原是FeNO测量值的一个重要因素，在哮喘患者中过敏原的暴露及致敏程度与气道炎症的敏感指标FeNO密切相关。
[Abstract]:Part I : Value of exhaled nitric oxide in diagnosis of asthma

Asthma is an airway chronic inflammatory disease involving multiple inflammatory cells and cellular components . It is the presence of this inflammation leading to associated clinical symptoms ( cough , asthma , shortness of breath , chest tightness , etc . ) , reversible airflow limitation , airway hyperresponsiveness , and remodeling of airway structures .

The airway inflammation measuring method of asthma is as follows : bronchoscopic submucous biopsy , bronchoscopic alveolar lavage fluid examination , induced sputum cell sorting examination , outgoing gas condensate detection , etc . Both of them belong to invasive detection , have a certain risk , the patient is not easy to accept , so it is not possible to be widely carried out as clinical routine technique ;
Relative non - invasive induced sputum cell taxonomy can lead to temporary decrease in lung function , time consuming and expensive , requiring professional technicians to operate , and about 40 % of patients with asthma can induce no sputum fluid , 3 , 4 hours ;
The detection of exhaled nitric oxide ( FeNO ) is a recognized safety , non - invasive , simple , reproducible and direct response to airway inflammation . FeNO measurement technology has not been widely developed in China , and the results of various factors have not been consistent .

Objective : To further clarify the accuracy and the best value of FeNO in diagnosis of asthma , and to provide a new method for diagnosis of asthma .

Methods : 109 cases of suspected asthma patients with asthma , chest distress , shortness of breath , cough and other symptoms were collected from June 2012 to December 2012 in Beijing Hospital . 109 cases of suspected asthma patients were treated with FeNO . The accuracy of FeNO was evaluated by receiver operating characteristic curves ( ROC ) .

Results : Among the 109 patients with asthma , 47 patients were diagnosed with asthma , 62 were non - asthmatic patients , the median of FeNO was 0.808 ( 95 % confidence interval : 0.719 , 0.896 ) . The diagnostic accuracy was 77.1 % . In the asthma group , there were 15 ( 31.9 % ) patients with asthma : Se : 68.1 % , Sp : 87.9 % , PV + : 76.2 % , PV _ : 77.6 % , accuracy : 77.1 % . Conclusion : The accuracy of FeNO in diagnosis of asthma is higher than that in asthma group , and it can be used as an auxiliary tool for diagnosis of asthma .

Part Two : Correlation between exhaled nitric oxide and allergen sIgE in patients with asthma

Asthma is also referred to as a disease characterized by airway hyperresponsiveness ( AHR ) , which is characterized by eosinophils and mast cell responses . Environmental factors include allergens , infections , sports , climate change , smoking , etc . The allergen is the most important factor in environmental factors . The allergens are allergen , infection , movement , climate change , smoking , etc . The allergen is an IgE receptor ( Fc.epsilon . RI ) that binds to the surface of cells such as mast cells . The allergen enters the body again to crosslink with IgE bound to the cell surface , producing an inflammatory response .

FeNO was a sensitive index of airway inflammation in patients with asthma , and can be used as an objective basis for the diagnosis of asthma . It can be used to predict the sensitivity of asthma to hormone therapy .

Objective : To compare the relationship between FeNO and IgE and total IgE in patients with asthma . Methods : 125 patients with asthma were collected from June 2012 to March 2013 .

Results : In 125 patients with asthma , the serum allergen sIgE positive group was 73 cases and negative group 52 cases . The serum allergen sIgE positive group FeNO geometric mean ( 55ppb ) was significantly higher than that in the negative group ( 31 ppb ) , P < 0.001 . ln ( P < 0.001 ) .

Conclusion : The allergen is an important factor in the measurement of FeNO , and the exposure and sensitization of allergen in patients with asthma is closely related to the sensitive index FeNO of airway inflammation .
【学位授予单位】：第四军医大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R562.25

【参考文献】