咳嗽高敏感綜合征：不明原因慢性咳嗽的新概念

賴克方，方章福，姚紅梅

咳嗽高敏感綜合征：不明原因慢性咳嗽的新概念

賴克方，方章福，姚紅梅

賴克方，教授，博士研究生導(dǎo)師。廣州醫(yī)學(xué)院第一附屬醫(yī)院、廣州呼吸疾病研究所、呼吸疾病國(guó)家重點(diǎn)實(shí)驗(yàn)室臨床研究部主任，中華醫(yī)學(xué)會(huì)呼吸病學(xué)分會(huì)哮喘學(xué)組副組長(zhǎng)，歐洲呼吸協(xié)會(huì)(ERS)特邀會(huì)員，港澳胸科協(xié)會(huì)聯(lián)合會(huì)員，《咳嗽診治通訊》主編，《中華哮喘雜志》常務(wù)編委，《中華肺部疾病雜志》、《國(guó)際呼吸雜志》和《中國(guó)臨床醫(yī)生》雜志編委。從事呼吸內(nèi)科臨床、科研與教學(xué)工作20余年，研究方向?yàn)槁钥人耘c支氣管哮喘的診治及發(fā)病機(jī)制。負(fù)責(zé)國(guó)家“863”重大科技計(jì)劃、國(guó)家“十一五”攻關(guān)課題、國(guó)家自然科學(xué)基金、教育部重點(diǎn)攻關(guān)課題等課題10余項(xiàng)。在國(guó)內(nèi)率先開展了不明原因慢性咳嗽的病因診斷、治療及發(fā)病機(jī)制的系統(tǒng)研究，建立了誘導(dǎo)痰、咳嗽激發(fā)試驗(yàn)、食管pH值監(jiān)測(cè)等慢性咳嗽檢查方法；提出了適合我國(guó)國(guó)情的慢性咳嗽診斷程序；調(diào)查國(guó)內(nèi)慢性咳嗽的病因分布，發(fā)現(xiàn)嗜酸細(xì)胞性支氣管炎、胃食管反流等是慢性咳嗽的常見病因；是我國(guó)首部《咳嗽的診斷與治療指南》的起草者。在國(guó)內(nèi)外期刊發(fā)表論文100余篇，主編專著《慢性咳嗽》，參編呼吸內(nèi)科學(xué)和支氣管哮喘等相關(guān)專著10部。獲省級(jí)科技進(jìn)步二等獎(jiǎng)1項(xiàng)、三等獎(jiǎng)2項(xiàng)，市級(jí)科技進(jìn)步一等獎(jiǎng)1項(xiàng)。

慢性咳嗽是患者就醫(yī)最常見的原因之一。多數(shù)慢性咳嗽患者可以獲得明確的病因診斷。然而，有一部分慢性咳嗽患者在進(jìn)行了全面檢查后，病因仍無(wú)法明確。這類慢性咳嗽患者主要表現(xiàn)為咳嗽敏感性的增高，既往稱為慢性特發(fā)性咳嗽或者不明原因慢性咳嗽，是慢性咳嗽治療的難點(diǎn)。最近，有學(xué)者提出咳嗽高敏感綜合征的概念以定義這一類慢性咳嗽患者。本文主要綜述咳嗽高敏感綜合征的病理生理與神經(jīng)生理機(jī)制、診斷及治療方法的研究進(jìn)展。

咳嗽高敏感綜合征；咳嗽敏感性；神經(jīng)生理機(jī)制；診斷；治療

咳嗽是呼吸系統(tǒng)重要的防御反射，具有防止異物誤吸及清除氣道分泌物的作用，其功能受損或敏感性增高都會(huì)對(duì)人體造成傷害[1]?？人允桥R床上最常見的病癥之一。一項(xiàng)針對(duì)中國(guó)大學(xué)生的咳嗽流行病學(xué)調(diào)查結(jié)果顯示，咳嗽的總患病率為11%[2]；在西方國(guó)家，社區(qū)咳嗽的患病率為9%～33%[3-4]。Irwin等[5]學(xué)者在1981年首次應(yīng)用解剖學(xué)程序?qū)β钥人曰颊哌M(jìn)行病因診斷，此后咳嗽的病因?qū)W研究在國(guó)內(nèi)及國(guó)外相繼展開[6-10]。這些研究結(jié)果顯示，慢性咳嗽的常見病因包括上氣道咳嗽綜合征(upper airway cough syndrome)[11]、嗜酸性粒細(xì)胞性支氣管炎(eosinophilic bronchitis)[12]、咳嗽變異性哮喘(cough variant asthma)[13]及胃食管反流性咳嗽(gastroesophageal reflux-related cough)。病因明確的患者經(jīng)過(guò)病因治療均能得到有效緩解。但是，有一部分患者經(jīng)過(guò)全面檢查后仍未能明確病因，既往稱為慢性特發(fā)性咳嗽(chronic idiopathic cough)或不明原因慢性咳嗽(unexplained chronic cough)[14-16]，這類患者是目前慢性咳嗽治療的難點(diǎn)，而咳嗽敏感性增高是此類患者的重要臨床與病理生理特征。近年來(lái)提出咳嗽高敏感綜合征(cough hypersensitivity syndrome，CHS)的概念來(lái)描述此類慢性咳嗽患者[17-20]。本文對(duì)CHS的定義、臨床特征、病理生理學(xué)機(jī)制及治療研究進(jìn)展進(jìn)行綜述。

1 CHS的定義和臨床特征

咳嗽敏感性(cough re fl ex sensitivity)是指機(jī)體在接受外界刺激(包括化學(xué)、機(jī)械、溫?zé)?時(shí)，表現(xiàn)出來(lái)的咳嗽難易程度。目前CHS的主要定義為咳嗽敏感性升高、全面檢查仍不能歸于已知病因的一些特發(fā)性慢性咳嗽患者[20-21]。與此相類似，Chung[18]將CHS定義為咳嗽時(shí)間持續(xù)超過(guò)8周，伴典型的刺激癥狀或感覺，并表現(xiàn)出咳嗽敏感性增高，其中咳嗽高敏感性是CHS定義中最主要的特征。CHS的臨床特征主要表現(xiàn)為慢性刺激性干咳，對(duì)一種或者多種咳嗽激發(fā)物如冷空氣、講話及氣味等敏感，咽喉部存在咳嗽沖動(dòng)，并嚴(yán)重影響患者生活質(zhì)量[20]。另外，CHS患者以中年女性較為常見[22]，經(jīng)常以上呼吸道感染作為起病的首發(fā)因素[14]。

2 咳嗽高敏感性的評(píng)估及病理生理學(xué)機(jī)制

咳嗽敏感性增高及其相關(guān)通路改變是CHS的主要發(fā)病機(jī)制。每一次自主咳嗽反射都是由完整的咳嗽反射弧參與完成的，該反射弧的組成包含咳嗽外周感受器、迷走傳入神經(jīng)、咳嗽高級(jí)中樞、傳出神經(jīng)及效應(yīng)器(膈肌、喉、胸部和腹肌群等)，所以咳嗽反射的任意一個(gè)環(huán)節(jié)出現(xiàn)異常均可能引起咳嗽敏感性的增高，從而引發(fā)CHS。

2.1 評(píng)估 目前臨床應(yīng)用最廣泛的是化學(xué)物質(zhì)激發(fā)的咳嗽敏感性檢測(cè)，常見的激發(fā)物包括辣椒素、檸檬酸，均以定量的方式吸入[23]；其在方法學(xué)上與支氣管激發(fā)試驗(yàn)相似，目前已被寫進(jìn)中國(guó)[24]及歐洲[25]咳嗽診治指南。吸入化學(xué)物質(zhì)的咳嗽激發(fā)試驗(yàn)主要反映特定的外周化學(xué)感受器介導(dǎo)的咳嗽反射，不能有效檢測(cè)其他通路介導(dǎo)的咳嗽敏感性。有報(bào)道利用吸入氨水引起的聲門閉合反射(glottic-stop reflex)來(lái)評(píng)估咳嗽敏感性，該方法還能區(qū)分慢性咳嗽患者與正常人的敏感性，其聲門閉合反射的敏感性與辣椒素咳嗽敏感性具有顯著相關(guān)性[26]。此外，日本學(xué)者報(bào)道了機(jī)械性刺激頸部氣管激發(fā)咳嗽評(píng)估患者咳嗽敏感性的方法[27]。但后兩種方法在臨床中的應(yīng)用經(jīng)驗(yàn)有限，還需要進(jìn)一步評(píng)估。

2.2 咳嗽敏感性的影響因素 Choudry等[28]的研究結(jié)果表明，伴鼻后滴流癥狀的慢性咳嗽患者辣椒素C2(刺激咳嗽次數(shù)≥2次時(shí)的辣椒素濃度)、C5(刺激咳嗽次數(shù)≥5次時(shí)的辣椒素濃度)顯著高于支氣管哮喘患者、服用ACEI藥物者及胃食管反流患者。Nieto等[29]的研究則表明伴支氣管哮喘以及胃食管反流的慢性咳嗽患者辣椒素咳嗽敏感性顯著高于正常組和鼻后滴流組。馬千里等[30]觀察了108例慢性咳嗽患者的辣椒素咳嗽敏感性，結(jié)果表明胃食管反流組患者的咳嗽敏感性顯著高于咳嗽變異性哮喘組和上氣道咳嗽綜合征組。Birring等[19-20]將咳嗽高敏感性分為可逆性與持續(xù)性，可逆性咳嗽高敏感性見于感冒后咳嗽、ACEI類咳嗽、咳嗽變異性哮喘及嗜酸細(xì)胞性支氣管炎，持續(xù)性咳嗽高敏感性則主要見于不明原因的慢性咳嗽。Kastelik等[31]觀察了慢性咳嗽患者的檸檬酸及辣椒素咳嗽敏感性，結(jié)果發(fā)現(xiàn)女性慢性咳嗽患者檸檬酸及辣椒素的C2、C5均顯著低于男性慢性咳嗽患者，同樣，Kelsall等[32]的研究也顯示不明原因慢性咳嗽患者檸檬酸咳嗽敏感性在女性中明顯高于男性。這些結(jié)果在一定程度上解釋了CHS以中年女性為主的原因。

2.3 病理生理學(xué)機(jī)制 目前咳嗽高敏感性的機(jī)制尚未完全明確，瞬時(shí)受體電位(transient receptor potential，TRP)通路激活、氣道炎癥及咳嗽中樞易化被認(rèn)為參與了咳嗽高敏感性的發(fā)生發(fā)展過(guò)程。

2.3.1 TRP通路激活 TRP通道蛋白首次從果蠅體內(nèi)分離獲得，由于其對(duì)強(qiáng)光反應(yīng)表現(xiàn)為瞬時(shí)性，因此被命名為瞬時(shí)受體電位通道[33]。TRP通道由6個(gè)跨膜多肽亞單位組成，大部分細(xì)胞都有此類通道蛋白的表達(dá)，主要感受細(xì)胞內(nèi)外的信號(hào)如化學(xué)刺激、機(jī)械刺激、溫度變化及滲透壓等[34]。目前發(fā)現(xiàn)哺乳動(dòng)物TRP家族有28個(gè)成員，根據(jù)氨基酸序列同源性分為6個(gè)亞家族，包括TRPC、TRPV、TRPM、TRPA、TRPP及TRPML[35]。有些TRP通道與感官知覺相關(guān)[36]，亦有研究發(fā)現(xiàn)TRP通道參與了呼吸系統(tǒng)疾病如慢性阻塞性肺疾病、支氣管哮喘、肺纖維化等的發(fā)病[37-39]。

瞬時(shí)受體電位香草酸亞型1(transient receptor potential vaniloid 1，TRPV1)為非選擇性陽(yáng)離子通道，是首個(gè)被證實(shí)能夠介導(dǎo)豚鼠咳嗽反射的TRP通道[40]。隨后TRPV1被成功克隆[36]，上述觀點(diǎn)進(jìn)一步得到驗(yàn)證。TRPV1的主要激發(fā)物包括辣椒素、熱、酸以及內(nèi)源性大麻素等[36,41-42]，是目前研究最多的咳嗽相關(guān)TRP通道。Watanabe等[43]利用免疫組織化學(xué)技術(shù)定位TRPV1豚鼠在氣道中的分布，結(jié)果顯示其主要分布于氣管、支氣管及肺泡的神經(jīng)軸突。Groneberg等[44]利用免疫熒光方法檢測(cè)慢性咳嗽患者及正常人支氣管鏡活檢標(biāo)本中TRPV1的表達(dá)，發(fā)現(xiàn)慢性咳嗽患者支氣管上皮中TRPV1陽(yáng)性熒光表達(dá)量顯著高于健康對(duì)照者，且與辣椒素咳嗽敏感性顯著相關(guān)。

與TRPV1類似，另外一個(gè)TRP通道瞬時(shí)受體電位錨蛋白1 (transient receptor potential ankyrin 1，TRPA1)為非選擇性鈣離子通道。TRPA1首先在人類肺成纖維細(xì)胞中分離[45]，廣泛分布于感覺神經(jīng)元細(xì)胞[46-47]。TRPA1的主要激發(fā)物包括丙烯醛、肉桂醛、冷空氣、機(jī)動(dòng)車尾氣及香煙煙霧等[48]。Andre等[49]利用TRPA1激動(dòng)劑肉桂醛、異硫氰酸烯丙酯吸入激發(fā)豚鼠咳嗽敏感性增高，該效應(yīng)能被TRPA1選擇性拮抗劑HC-030031抑制。Birrell等[50]發(fā)現(xiàn)吸入TRPA1激動(dòng)劑丙烯醛、肉桂醛能夠分別在豚鼠和健康人類志愿者中引發(fā)咳嗽，而且豚鼠的咳嗽效應(yīng)能被拮抗劑HC-030031抑制。

參與咳嗽敏感性的TRP通道還包括TRPM8。作為溫度感受器，當(dāng)溫度＜15℃或接觸涼味劑如薄荷醇、Icilin時(shí)，TRPM8可被激活，從而降低咳嗽敏感性[51]。Millqvist等[52]開展了一項(xiàng)吸入薄荷醇的隨機(jī)雙盲實(shí)驗(yàn)，共納入對(duì)環(huán)境刺激敏感的慢性咳嗽患者14例，結(jié)果顯示吸入薄荷醇組患者辣椒素咳嗽敏感性顯著低于吸入安慰劑組，提示薄荷醇能通過(guò)TRP通道降低咳嗽敏感性。最近Plevkova等[53]報(bào)道豚鼠經(jīng)口給予薄荷醇(100mg/kg)后能顯著抑制檸檬酸激發(fā)的咳嗽敏感性，該效應(yīng)與豚鼠鼻部三叉神經(jīng)的TRPM8表達(dá)升高相關(guān)。在哺乳動(dòng)物中，TRP家族包含了至少28個(gè)通道[34]，其余通道與咳嗽敏感性的關(guān)系還有待進(jìn)一步研究。

2.3.2 氣道炎癥 Birring等[54-55]發(fā)現(xiàn)慢性特發(fā)性咳嗽患者中伴有器官特異性自身免疫性疾病的比例(59%)明顯高于對(duì)照組(12%)，且慢性特發(fā)性咳嗽患者支氣管肺泡灌洗液(BALF)中淋巴細(xì)胞的比例(10%)顯著高于正常對(duì)照組(6.3%)及咳嗽病因明確組(5.2%)。Mund等[56]進(jìn)一步研究發(fā)現(xiàn)，在以干咳為主的慢性原發(fā)性咳嗽女性患者中，BALF中CD3+、CD4+淋巴細(xì)胞總數(shù)顯著高于健康對(duì)照組。然而這種特異性氣道炎癥提高咳嗽敏感性的機(jī)制尚有待進(jìn)一步研究。Boulet等[57]發(fā)現(xiàn)非哮喘性慢性咳嗽患者BALF中的炎癥細(xì)胞數(shù)目顯著增加，支氣管活檢可見支氣管上皮脫落及以單核細(xì)胞浸潤(rùn)為主的炎癥。此外，當(dāng)氣道存在非特異性炎癥時(shí)，機(jī)體可分泌內(nèi)源性炎性介質(zhì)如前列腺素(PG)及血管舒張肽。既往研究證實(shí)PGE2及緩激肽能夠敏化咳嗽反射，致使辣椒素咳嗽敏感性增高[58]，其機(jī)制與PGE2、緩激肽激活了蛋白激酶C，從而敏化TRPV1通道有關(guān)[59-60]。Grace等[61]進(jìn)一步證實(shí)PGE2及緩激肽作為激發(fā)物能引起TRPV1及TRPA1通路誘導(dǎo)的豚鼠咳嗽敏感性增高。暴露于大氣污染物引起的氣道炎癥與咳嗽敏感性的關(guān)系亦有報(bào)道，如McLeod等[62]將豚鼠暴露于二氧化硫(1000ppm，3h/d，連續(xù)4d)，結(jié)果顯示豚鼠的辣椒素咳嗽敏感性增高，而該效應(yīng)能被地塞米松抑制。

2.3.3 咳嗽中樞易化 目前觀點(diǎn)認(rèn)為，延髓孤束核(nucleus tractus solitarius)參與了咳嗽中樞反射的調(diào)節(jié)。Lindsey等[63]和Shannon等[64]的研究發(fā)現(xiàn)外界刺激信號(hào)經(jīng)迷走神經(jīng)傳入，經(jīng)由靠近或位于孤束核內(nèi)的不同亞核二級(jí)神經(jīng)元處理、整合并輸出。最近腦功能核磁共振顯像技術(shù)已用于檢測(cè)與人類咳嗽控制相關(guān)的大腦區(qū)域。Mazzone等[65]的研究中將10例正常人以偽隨機(jī)的方式分別納入吸入辣椒素組或吸入生理鹽水組(對(duì)照組)，記錄各組咳嗽沖動(dòng)并進(jìn)行功能性腦顯像，結(jié)果顯示辣椒素能穩(wěn)定地誘導(dǎo)咳嗽沖動(dòng)，并與大腦皮層的激活相關(guān)，提示皮層神經(jīng)網(wǎng)絡(luò)可能參與了人類咳嗽的調(diào)控。當(dāng)機(jī)體處于應(yīng)激狀態(tài)或者暴露于環(huán)境污染物時(shí)，孤束核神經(jīng)元細(xì)胞可出現(xiàn)神經(jīng)可塑性改變[66-67]。Joad等[68]使豚鼠暴露于香煙(1mg/m3，6h/d，5d/周)環(huán)境，暴露5周后豚鼠檸檬酸咳嗽敏感性顯著增高，第6周分別注射P物質(zhì)拮抗劑SR140333(拮抗神經(jīng)激肽1受體)，結(jié)果顯示SR140333能顯著抑制香煙暴露的豚鼠咳嗽敏感性，提示孤束核通過(guò)釋放P物質(zhì)，引起咳嗽敏感性增高。

3 CHS的治療

目前CHS的治療選擇仍然有限，根據(jù)其定義以及病理生理學(xué)特征，在處理時(shí)主要以降低咳嗽敏感性為目的，包括藥物治療手段及非藥物治療手段。

3.1 藥物治療選擇

3.1.1 神經(jīng)調(diào)節(jié)因子類藥物 神經(jīng)調(diào)節(jié)因子類藥物是指神經(jīng)遞質(zhì)γ-氨基丁酸(GABA)受體激動(dòng)劑，主要包括加巴噴丁(gabapentin)、阿米替林(amitriptyline)、巴氯芬(baclofen)等。Ryan等[69]的隨機(jī)、雙盲、對(duì)照研究中納入62例難治性慢性咳嗽患者，觀察到加巴噴丁能顯著改善慢性咳嗽患者咳嗽相關(guān)生活質(zhì)量，咳嗽頻率及咳嗽嚴(yán)重程度(VAS評(píng)分)均較安慰劑組顯著下降，而且患者能較好耐受加巴噴丁的副作用。Jeyakumar等[70]在另外一項(xiàng)隨機(jī)對(duì)照試驗(yàn)中納入28例慢性咳嗽患者，分為阿米替林治療組及可待因/愈創(chuàng)甘油醚組，結(jié)果顯示阿米替林治療組咳嗽相關(guān)生活質(zhì)量改善率明顯高于可待因/愈創(chuàng)甘油醚組。此外在Dicpinigaitis等[71]的報(bào)道中，2例難治性慢性患者在使用巴氯芬后咳嗽頻率及嚴(yán)重程度均下降，辣椒素咳嗽敏感性顯著下降；與此類似，國(guó)內(nèi)Xu等[72]報(bào)道了3例胃食管反流引起的難治性慢性咳嗽患者，在嘗試抗反流治療無(wú)效后，給予巴氯芬(20mg，3次/d)口服代替抗反流藥物，1～4周后咳嗽癥狀明顯緩解，咳嗽癥狀積分及辣椒素咳嗽敏感性均顯著下降。

3.1.2 其他鎮(zhèn)咳藥物 目前已知效果最好的中樞性鎮(zhèn)咳藥物如可卡因、嗎啡等因具有成癮性，在臨床的應(yīng)用受到限制[73]。Lim等[74]回顧性分析了165例成年患者霧化吸入利多卡治療難治性咳嗽的療效，結(jié)果顯示治療后咳嗽癥狀VAS積分顯著降低，在完成治療的92例患者中，49%的患者咳嗽癥狀得到緩解。

3.1.3 正在研制的藥物 一些分子靶向藥物如TRPV1受體拮抗劑、選擇性大麻素受體激動(dòng)劑(CB2 agonist)、鉀離子通道開放劑(maxi-K channel)等被證實(shí)能起到一定的鎮(zhèn)咳作用[75]。Smith等[76]在一項(xiàng)雙盲、對(duì)照試驗(yàn)中應(yīng)用口服TRPV1受體拮抗劑SB705498治療不明原因慢性咳嗽患者，初步結(jié)果顯示用藥組2h后辣椒素C5閾值是安慰劑組的4倍，而用藥組與安慰劑組的24h咳嗽次數(shù)無(wú)明顯差異。

3.2 非藥物治療選擇 非藥物治療手段包括語(yǔ)言病理治療及咳嗽抑制性生理治療，統(tǒng)稱為咳嗽抑制性治療(cough suppression therapy，CST)。CST在改善患者咳嗽相關(guān)生活質(zhì)量、降低咳嗽敏感性及咳嗽頻率方面顯示出一定效果。根據(jù)病情需要，CST治療分為2～4期[77]，主要內(nèi)容包括教育患者何為咳嗽敏感性、咳嗽高敏感性以及反復(fù)大量咳嗽的危害；注意喉部衛(wèi)生如盡量用鼻子呼吸，減少環(huán)境刺激物的吸入以及增加水的攝入頻率及攝入量；控制咳嗽發(fā)生如辨認(rèn)咳嗽的激發(fā)物，善于利用抑制咳嗽沖動(dòng)的技巧以及學(xué)會(huì)改變呼吸的方式；提供心理教育輔導(dǎo)如鼓勵(lì)自主性咳嗽，樹立治療目標(biāo)以及排除心理壓力等[78-81]。Vertigan等[78]在一項(xiàng)隨機(jī)對(duì)照試驗(yàn)中納入87難治性慢性咳嗽患者，隨機(jī)分為語(yǔ)言病理治療組及安慰劑對(duì)照組，治療周期為2個(gè)月，結(jié)果顯示語(yǔ)言病理治療組患者的咳嗽、呼吸、發(fā)聲及上氣道積分改善程度顯著高于安慰劑對(duì)照組。隨后，Ryan等[80-81]報(bào)道難治性咳嗽患者接受語(yǔ)言康復(fù)療法治療后，咳嗽相關(guān)生活質(zhì)量(LCQ積分)顯著提高，而辣椒素咳嗽敏感性以及咳嗽頻率顯著下降。Patel等[79]在一項(xiàng)前瞻性研究中觀察了23例難治性慢性咳嗽患者接受咳嗽抑制性生理治療2個(gè)月前后的健康狀況變化，結(jié)果顯示治療后患者咳嗽相關(guān)生活質(zhì)量積分(LCQ)顯著升高，咳嗽頻率顯著下降。

4 總 結(jié)

CHS概念的提出對(duì)認(rèn)識(shí)慢性咳嗽的病理生理機(jī)制及促進(jìn)咳嗽新藥開發(fā)有重要意義?？人悦舾行栽龈呤荂HS患者的主要臨床和病理生理學(xué)特征。臨床上咳嗽敏感性的檢測(cè)方法目前仍主要依賴于吸入TRPV1激動(dòng)劑如辣椒素或檸檬酸誘導(dǎo)咳嗽反射，對(duì)于其他通道介導(dǎo)的咳嗽敏感性尚不能有效檢測(cè)。未來(lái)的研究方向主要在于進(jìn)一步完善臨床咳嗽敏感性激發(fā)方法，使咳嗽敏感性的檢查結(jié)果更具臨床價(jià)值，并在認(rèn)識(shí)咳嗽敏感性增高機(jī)制的前提下，進(jìn)一步開發(fā)新型的、副作用小的分子靶向藥物，以滿足臨床需要。

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Cough hypersensitivity syndrome: a new concept for chronic idiopathic cough

LAI Ke-fang, FANG Zhang-fu, YAO Hong-mei State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Diseases, First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China

Chronic cough is one of the most common conditions that patients seek medical consultation, and the causes of chronic cough can be determined in most patients according to diagnostic algorithm. Whereas, there is still the etiology of chronic cough in some patients remained unexplained despite detailed investigations, and it was referred to as 'chronic idiopathic cough' or'unexplained chronic cough' previously. Cough reflex hypersensitivity is an underlying feature of those patients, a new term 'cough hypersensitivity syndrome' has been put forward to define those patients with chronic cough recently. This article reviews the pathophysiological and neurophysiological mechanisms of cough hypersensitivity syndrome and progress in diagnosis and treatment.

cough hypersensitivity syndrome; cough reflex sensitivity; neurophysiological mechanisms; diagnosis; treatment

R441.5

A

0577-7402(2014)05-0343-07

10.11855/j.issn.0577-7402.2014.05.02

510120 廣州 廣州醫(yī)科大學(xué)附屬第一醫(yī)院廣州呼吸疾病研究所，呼吸疾病國(guó)家重點(diǎn)實(shí)驗(yàn)室(賴克方、方章福、姚紅梅)

2014-01-04；

2014-03-02)

沈?qū)?