本文選題：哮喘 + 呼出氣一氧化氮��； 參考：《第四軍醫(yī)大學(xué)》2013年碩士論文

【摘要】：第一部分：呼出氣一氧化氮在哮喘診斷中的價(jià)值 哮喘是由多種炎癥細(xì)胞和細(xì)胞組分參與的氣道慢性炎癥性疾病。正是這種炎癥的存在導(dǎo)致相關(guān)臨床癥狀(咳嗽、喘息、氣急、胸悶等)、可逆性氣流受限、氣道高反應(yīng)性和氣道結(jié)構(gòu)的重塑[1,2]。目前公認(rèn)的哮喘診斷和監(jiān)測常常以癥狀、體征、氣道阻塞程度、支氣管舒張?jiān)囼?yàn)、支氣管激發(fā)試驗(yàn)等結(jié)果為標(biāo)準(zhǔn)。但臨床癥狀、體征和陽性肺功能指標(biāo)都不能直接反應(yīng)氣道炎癥狀態(tài)。因此，直接測量氣道炎癥可能更適用于哮喘的診斷和監(jiān)測。 哮喘氣道炎癥測量法有：支氣管鏡下粘膜活檢、支氣管鏡下肺泡灌洗液檢查、誘導(dǎo)痰細(xì)胞分類學(xué)檢查、呼出氣冷凝物檢測等。前兩者屬于侵入性檢測，有一定風(fēng)險(xiǎn)，患者不易接受，因此不可能作為臨床常規(guī)技術(shù)廣泛開展；相對無創(chuàng)的誘導(dǎo)痰細(xì)胞分類學(xué)檢查可導(dǎo)致肺功能暫時(shí)性下降，耗時(shí)、昂貴，需要專業(yè)技術(shù)人員來操作，而且大約有40%的哮喘患者誘導(dǎo)不出痰液[3,4]；呼出氣冷凝物檢測目前尚無統(tǒng)一的方法和標(biāo)準(zhǔn)。呼出氣一氧化氮(fractional exhaled nitric oxide，F(xiàn)eNO)是一種公認(rèn)的安全、無創(chuàng)、簡單、重復(fù)性好、直接反應(yīng)氣道炎癥的標(biāo)志物。FeNO測量技術(shù)尚未在中國廣泛開展，且因多種因素的影響，關(guān)于其診斷哮喘的準(zhǔn)確性和最佳界值各個(gè)研究結(jié)果并不一致。 目的：進(jìn)一步明確FeNO診斷哮喘的準(zhǔn)確性及其最佳界值。從而為哮喘診斷提供新的方法。 方法：收集西京醫(yī)院呼吸內(nèi)科2012年6月至2012年12月就診的具有喘息、胸悶、氣急、咳嗽等癥狀，不吸煙，未使用激素治療的疑似哮喘患者109例。使用FeNO測定儀（NIOXMINO Aerocrine AB瑞典）對109例疑似哮喘患者進(jìn)行FeNO濃度測定，然后進(jìn)行肺功能測定。以臨床癥狀、肺功能舒張?jiān)囼?yàn)和（或）激發(fā)試驗(yàn)為診斷標(biāo)準(zhǔn)。通過接受者工作特征曲線圖（receiver operating characteristic curves，ROC）來評價(jià)FeNO診斷哮喘的準(zhǔn)確性。 結(jié)果：109例患者中最終診斷哮喘患者47例，非哮喘患者62例，，兩組患者FeNO中位數(shù)比較：70ppb vs16ppb,P＜0.001。ROC曲線下面積為0.808（95%可信區(qū)間：0.719，0.896)，在0.70～0.90之間表示診斷準(zhǔn)確度為中等。FeNO診斷哮喘的最佳界值為41ppb，以41ppb為界診斷哮喘：Se：68.1%，Sp：83.9%，PV+：76.2%，PV_：77.6%，準(zhǔn)確度：77.1%。但哮喘組中仍有15例（31.9%）患者的FeNO測量值≤41ppb，非哮喘組中有10例（16.1%）患者FeNO測量值＞41ppb。結(jié)論：FeNO診斷哮喘的準(zhǔn)確度較高，可以作為哮喘診斷的輔助性工具。 第二部分：哮喘患者呼出氣一氧化氮與過敏原sIgE的相關(guān)性分析 哮喘也被稱為一種以嗜酸性粒細(xì)胞(Eosinophil,EOS)、肥大細(xì)胞反應(yīng)為主的氣道變應(yīng)性炎癥和氣道高反應(yīng)性(Airway hyperresponsiveness, AHR)為特征的疾病。目前認(rèn)為哮喘發(fā)病和發(fā)展的危險(xiǎn)因素除了遺傳等內(nèi)在因素外，環(huán)境因素是一個(gè)非常重要的外因。環(huán)境因素包括過敏原、感染、運(yùn)動、氣候變化、吸煙等，過敏原是環(huán)境因素中最主要的因素。哮喘患者常見過敏原有螨、戶塵、粉塵、真菌、花粉、動物的毛屑、蛋白含量高的食物、藥物等。過敏原通過抗原提呈細(xì)胞（antigen-presenting cells，APCs）激活輔助性T細(xì)胞，活化的T細(xì)胞產(chǎn)生炎癥介質(zhì)進(jìn)一步激活B淋巴細(xì)胞，后者合成IgE結(jié)合于肥大細(xì)胞等細(xì)胞表面的IgE受體（FcεRI），當(dāng)過敏原再次進(jìn)入體內(nèi)可與結(jié)合在細(xì)胞表面的IgE交聯(lián)，產(chǎn)生炎癥反應(yīng)。 FeNO測量值是哮喘患者氣道炎癥的敏感指標(biāo)，可作為客觀依據(jù)支持哮喘診斷,可用于預(yù)測哮喘對激素治療的敏感性[5,6]、監(jiān)測哮喘氣道炎癥程度、評估哮喘激素治療療效、調(diào)整哮喘激素用量及判斷哮喘患者激素治療的依從性[7-9]。同時(shí)大量的研究證實(shí)FeNO與肺泡灌洗液、肺活檢、誘導(dǎo)痰及外周血液中的EOS計(jì)數(shù)相關(guān)[10-12]。而到目前為止，F(xiàn)eNO與哮喘患者過敏原sIgE的相關(guān)性研究較少，且既往研究結(jié)果也不一致。 目的：比較哮喘過敏者與非過敏者的FeNO。分析哮喘患者FeNO測量值與過敏原sIgE、總IgE的相關(guān)性。方法：收集2012年6月至2013年3月就診于西京醫(yī)院呼吸內(nèi)科門診的輕度哮喘患者125例。使用FeNO測試儀（NIOX MINO Aerocrine AB瑞典）和過敏原sIgE的AllergyScreen(敏篩)系統(tǒng)（德國默爾斯市Mediwiss公司出品）對125例哮喘患者進(jìn)行FeNO、血清過敏原sIgE及總IgE測定。采用Pearson直線相關(guān)分析法對ln FeNO、ln血清過敏原sIgE進(jìn)行相關(guān)分析。 結(jié)果：125例哮喘患者中，血清過敏原sIgE陽性者73例，陰性者52例。血清過敏原sIgE陽性組FeNO幾何均數(shù)(55ppb)明顯高于陰性組(31ppb)，P＜0.001。ln FeNO測量值與ln戶塵螨-sIgE濃度進(jìn)行相關(guān)分析，證實(shí)兩者呈中等正相關(guān)：r=0.7417,P＜0.001。ln FeNO測量值與ln真菌類-sIgE濃度的相關(guān)性分析結(jié)果顯示成弱相關(guān)性：r=0.488, P＞0.05。同時(shí)得出FeNO測量值隨著哮喘患者過敏原數(shù)量及血清總IgE濃度的增加而增高。 結(jié)論：過敏原是FeNO測量值的一個(gè)重要因素，在哮喘患者中過敏原的暴露及致敏程度與氣道炎癥的敏感指標(biāo)FeNO密切相關(guān)。
[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 .
【學(xué)位授予單位】：第四軍醫(yī)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2013
【分類號】：R562.25

【參考文獻(xiàn)】

相關(guān)期刊論文 前2條

1 孫寶清;韋妮莉;李靖;鐘南山;;三種不同方法檢測常見過敏原的對比分析[J];現(xiàn)代醫(yī)院;2006年10期

2 任旭斌;劉春濤;黃玉芳;朱濤;;呼出氣一氧化氮檢測對支氣管哮喘的診斷價(jià)值[J];中國呼吸與危重監(jiān)護(hù)雜志;2009年04期

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