CVA的诊断与治疗进展ppt课件.pptx
CVA的诊断与治疗进展The Diagnosis and Treatment Progress of CVA,主要内容 Content,CVA的流行病学 The Epidemiology of CVA,CVA的诊断进展 The Progress on Treatment of CVA,CVA的治疗现状 The Present Situation of Treatment on CVA,CVA的早期描述The Early Description of CVA,1979年，美国罗德岛医院的Corrao WM和Irwin RS等人提出一种哮喘的变异形式，即以咳嗽为惟一临床表现。这种咳嗽在给予支气管舒张剂治疗后消失，但停药后又复发。,Corrao WM,et al.N Engl J Med.1979;300(12):633-7,咳嗽可以是哮喘的惟一症状Cough might be the only symptom of asthma,In 1979,Corrar WM and Irwin RS from Rhode Island hospital USA,proposed a variation form of asthma with cough as the only clinical manifestation.This cough may resolve after administration of bronchodilators,but may relapse after drug discontinuance.,CVA的定义The Definition of CVA,中华医学会呼吸病学分会哮喘学组.中华结核和呼吸杂志2009;32(6):407-413GINA 2014,咳嗽变异性哮喘（Cough Variant Asthma，CVA）,CVA is a special type of asthma with cough as the only or main clinical manifestation.There is no obvious symptoms or signs like wheezing or shortness of breath,but bronchial hyperresponsiveness.,Patients with(CVA)present with a chronic cough as the sole symptom,along with bronchial hyperreactivity.,慢性咳嗽患病情况The Prevalence of Chronic Cough,Lai K,et al.Cough 2013;9(1):18,尽管调查人群和慢性咳嗽定义不同，但大多数流调结果显示，慢性咳嗽的患病率10%，在7.2%-33%之间。Although the responses from the surveys are different from the definition of chronic cough,most results of epidemiological sampling survey showed that the prevalence of chronic cough is between 7.2%and 33%,generally over 10%.,成人慢性咳嗽患病情况The Prevalence of Chronic Cough in Adults,Ford AC,et al.Thorax.2006;61(11):975-9陈如冲,等.中华流行病学杂志2006;27(2):123-126,CVA在中国成人慢性咳嗽患者中的比例The Proportion of CVA in Chinese Adult Patients with Chronic Cough,赖克方等.中华结核和呼吸杂志2006;29(2):96-99牛瑞等.中华流行病学杂志,2009;30(5):511-513何智敏等.中国医药指南2011;9(25):302-303Lai K,et al.Chest 2013;143(3):613-20,CVA是中国慢性咳嗽患者的主要病因，约占30%左右3,4。CVA is the leading cause to Chinese patients with chronic cough and accounts for about 30%.,赖克方等.中华结核和呼吸杂志2006;29(2):96-99,通过观察慢性咳嗽的病因分布，为建立中国慢性咳嗽病因诊断程序奠定基础Observing the constituent ratio of causes to chronic cough lay a foundation for etiological diagnostic procedure for chronic cough in China,PNDS：鼻后滴流综合征；CVA：咳嗽变异性哮喘；EB：嗜酸粒细胞性支气管炎；GERC：胃食管反流性咳嗽；AC：变应性咳嗽。,慢性咳嗽病因构成：中国不明原因慢性咳嗽的病因分布（2006）The Etiology of Chronic Cough:the constituent ratio of causes to chronic cough with unknown causes in China(2006),共收集慢性咳嗽患者194例，平均年龄4112岁。对于入选的慢性咳嗽（咳嗽超过3周，胸部X线检查无明显异常）患者，在询问病史和查体的基础上，进行诱导痰、肺通气功能+气道高反应性、X线胸片、鼻窦X线片或CT、24h食管PH 值监测等检查，根据检查结果和治疗反应，最后确定病因诊断。,中国慢性咳嗽的病因分布（EB、CVA和CA为主要病因）与欧美国家（PNDs、CVA和GERC为主要病因）相比，存在较大差别There is a great difference between the causes to chronic cough in China(EB、CVA and CA are main reasons)and those in western countries(PNDs、CVA and GERC are main reasons),Lai K,et al.Chest.2013;143(3):613-620,UACS：上气道咳嗽综合征；EB：嗜酸粒细胞性支气管炎；AC：过敏性咳嗽；GERC：胃食管反流病,对中国五个地区8大城市9家综合医院763例成人慢性咳嗽患者（以咳嗽为惟一或主要症状，病程超过8周，胸部X线检查无明显异常）进行的多中心、前瞻性调查。What is carried out is the multi-center,prospective survey of the adult patients with chronic cough admitted to 9 general hospitals in 8 cities from 5 regions in China,慢性咳嗽病因构成：中国慢性咳嗽前瞻性、多中心调查（2013）The Etiology of Chronic Cough:the prospective,multi-center survey of chronic cough in China(2013),CVA为中国慢性咳嗽患者的首要病因CVA is the leading cause of patients with chronic cough in China,10,CVA疾病进展及相关因素The Disease Progression and Related Factors of CVA,Matsumoto H,et al.J Asthma.2006;43(2):131-5,日本的一项回顾性分析对42例成人CVA患者进行长达4年的随访。,单因素和多因素分析显示，早期使用ICS治疗可预防喘息发生，OR=0.12（95%CI:0.02-0.87,P=0.037）,早期使用ICS,Corrano MW,et al.(1979)33%随访18个月Branman S,et al.(1981)38%随访3-5.5年Fujimura M,et al.(2003)30%随访3.9年Matsumoto H,et al.(2006)31%随访4年,进展为典型哮喘,30%-40%的CVA患者最终进展为典型哮喘早期明确诊断并尽早治疗CVA，对预防这部分患者最终发展为典型哮喘具有重要临床意义。30%to 40%of CVA patients ultimately progress to typical asthmaEarly diagnosis and treatment on CVA has important clinical significance in preventing these patients progress to typical asthma eventually.,CVA疾病进展及相关因素The Disease Progression and Related Factors of CVA,Fujimura M,et al.Thorax.2003;58(1):14-8.,日本的一项研究回顾性，分析了55例CVA成人患者的预后。其中35人接受ICS长期治疗，20人未接受ICS治疗，在接受治疗前，对47例CVA患者进行乙酰甲胆碱激发试验。中位随访期3.7年。,若未接受ICS治疗，CVA患者有30%进展为典型哮喘，而接受ICS长期治疗的患者，进展为典型哮喘的比例则显著降低。,进展为典型哮喘的CVA患者PC20浓度显著低于未进展为典型哮喘者，即气道反应性显著更高。,主要内容 Content,CVA的流行病学 The Epidemiology of CVA,CVA的诊断进展 The Progress on Treatment of CVA,CVA的治疗现状 The Present Situation of Treatment on CVA,中国成人慢性咳嗽患者诊断现状The situation of diagnosis of chronic cough in Chinese adults,赖克方等.国际呼吸杂志 2011;31(9):645-647,为了解慢性咳嗽患者的诊疗状况，以首次到广州呼研所门诊就诊的慢性咳嗽患者（以咳嗽为惟一或主要症状，病程超过8周，胸部X线检查无明显异常）为对象，通过调查问卷方式，记录其病情及诊治情况。共调查558例成人慢性咳嗽患者。,80.82%,慢性咳嗽存在严重的误诊误治现象，临床医生对慢性咳嗽的病因分布认识不足。慢性咳嗽的病因诊断有待进一步加强。There do exist serious misdiagnosis and mistherapy on chronic cough because clinicians have inadequate awareness of the constituent of causes to chronic cough.Etiological diagnosis of chronic cough needs further improvement.,CVA的诊断标准The diagnostic criteria of CVA,中华医学会呼吸病学分会哮喘学组.中华结核和呼吸杂志2009;32(6):407-413,咳嗽的诊断与治疗指南2009,Chinese National Guidelines on Diagnosis and Management of Cough 2009Chronic cough,along with obvious irritating cough at nightPositive bronchial provocative test,or the day variation of peak expiratory flow 20,or positive bronchodilation testTreatment with bronchodilators is effective,15,中华医学会呼吸病学分会哮喘学组.中华结核和呼吸杂志2009;32(6):407-413赖克方等.中华结核和呼吸杂志2006;29(2):96-99,注：ACEI：血管紧张素转换酶抑制剂；UACS：上气道咳嗽综合征；PNDS：鼻后滴流综合征；CVA：咳嗽变异性哮喘；EB：嗜酸粒细胞性支气管炎；纤支镜：纤维支气管镜；SPT：过敏原皮试；IgE：免疫球蛋白E；GERC：胃食管反流性咳嗽；AC：变应性咳嗽。,根据患者病史选择相关检查，检查由简单到复杂，先常见病，后少见病，降低患者的诊断成本。由于CVA是慢性咳嗽首要病因，BHR是诊断CVA重要标准，也是与EB鉴别的主要标准，故将肺通气功能和激发试验列为首要检查项目。若患者经济条件或医院设备条件有限，可根据临床特征进行诊断性治疗，如有夜间咳嗽，高度怀疑CVA，可予以2受体激动剂诊断性治疗，根据治疗反应确认病因诊断。,咳嗽的诊断与治疗指南2009The Guidelines on Diagnosis and Management of Cough 2009:,中国咳嗽指南2009：慢性咳嗽病因诊断程序The Chinese National Guidelines on Diagnosis and Management of Cough 2009:etiological diagnostic procedure for chronic cough,Niimi A,et al.Curr Respir Med Rev.2011;7(1):47-54.,CVA与其他常见慢性咳嗽病因的鉴别诊断The differential diagnosis of pathogeny of CVA and other common chronic cough,17,Dicpinigaitis PV,et al.Chest 2006;129:75S-79S中华医学会呼吸病学分会哮喘学组.中华结核和呼吸杂志2009;32(6):407-413Niimi A,et al.Curr Respir Med Rev.2011;7(1):47-54,ACCP循证临床实践指南：慢性咳嗽诊断和治疗2006,BHR：支气管高反应性；UACS：上气道咳嗽综合征；PIC：呼吸道感染后咳嗽,ACCP慢性咳嗽指南2006：支气管激发试验阳性 CVAACCP Guidelines on Chronic Cough 2006:positive bronchial provocative test CVA,CVA以BHR和对支气管舒张剂治疗有反应性为特征。但BHR仅为构成CVA诊断的组成部分，而非等同于CVA诊断。有些CVA患者对2激动剂治疗有反应，但BHR可能尚未形成，单一依赖支气管激发试验诊断CVA有可能导致遗漏。而且，除了CVA患儿外，UACS以及PIC都存在有一过性的BHR。支气管舒张剂如2激动剂治疗后咳嗽缓解是诊断CVA的的必要条件。,仅有BHR并不等于可诊断为CVA，只有给予特异性哮喘治疗后咳嗽缓解，才可确诊CVA。但MIC试验的阴性预测值非常高，其结果阴性可将哮喘从慢性咳嗽的鉴别诊断中排除。BHR only is not equal to the diagnosis of CVA,which can be confirmed only by the remission of cough treated with specific asthma therapy The high negative predictive value of MIC test may exclude asthma from the differential diagnosis of chronic cough.,诊断性治疗：在CVA诊断中的关键地位Diagnostic treatment:the critical position in the diagnosis of CVA,Lai K,et al.Chest.2013;143(3):613-620中华医学会呼吸病学分会哮喘学组.中华结核和呼吸杂志2009;32(6):407-413,经相应治疗后症状缓解，病因诊断方能成立。The etiological diagnosis can be accepted only after remission of symptoms after relevant treatment.,基层医院条件有限，可能无法进行食管24小时PH监测、诱导痰细胞学检查，甚至有些无法进行肺通气功能和支气管激发试验，临床医生需要一种简易可行的诊断方法。ACCP慢性咳嗽指南2006指出，若不能进行支气管激发试验，应给予经验治疗。中国成人慢性咳嗽前瞻性、多中心调查（2013）显示，CVA是中国成人慢性咳嗽的首位病因。,Lai K,et al.Chest.2013;143(3):613-620Dicpinigaitis PV,et al.Chest 2006;129:75S-79S赖克方等.中华结核和呼吸杂志2006;29(2):96-99,若患者经济条件或医院设备条件有限，可根据临床特征进行诊断性治疗，优先使用2受体激动剂作为慢性咳嗽诊断性治疗的第一步，根据治疗反应确认病因诊断。If patients economic condition or equipment in hospital is limited,its better to perform diagnostic treatment based on clinical features.Prefer diagnostic treatment with 2 agonist to confirm etiological diagnosis based on response.,CVA诊断探讨：适合基层医疗机构的诊断方法The diagnosis and discussion of CVA:the diagnostic method suitable for primary medical organizations,20,Shimizu H,et al.Cough 2013;9:4-10,CVA诊断探讨：以2受体激动剂反应性对慢性咳嗽进行分类The diagnosis and discussion of CVA:classify chronic cough by the response to 2-agonist,21,Shimizu H,et al.Cough 2013;9:4-10,*BRC：2激动剂反应性咳嗽；BA：典型哮喘。NHBRC：无气道高反应性BRC。对2激动剂有反应，但PC2020mg/mL。,CVA诊断探讨：以2受体激动剂反应性对慢性咳嗽进行分类The diagnosis and discussion of CVA:classify chronic cough by the response to 2-agonist,NHBRC是一类新的慢性咳嗽类型，与CVA的区别在于支气管舒张剂治疗后PEFR无显著升高。NHBRC is a new type of chronic cough and its different from CVA because the PEFR has no significant increase after bronchodilators treatment.,22,Sato S,et al.Respir Med.2008;102(10):1452-9,CVA患者的FeNO水平显著高于EB和其他患者，可作为慢性咳嗽的诊断性标志物，尤其用于CVA与EB等的鉴别诊断。The FENO level of CVA patients is significantly higher than EB or other patients,which can be used as the diagnostic markers for chronic cough,particularly the differential diagnosis of CVA and EB.,分析FeNO（呼出气一氧化氮）是否适用于慢性咳嗽的鉴别诊断。共包括71例成人慢性咳嗽患者入选，对其进行FeNO、肺功能、支气管高反应性、IgE、诱导痰和外周血嗜酸粒细胞检测。,CVA诊断探讨：以FeNO作为CVA鉴别诊断标志物The diagnosis and discussion of CVA:FeNO is used as the markers for differential diagnosis of CVA,CVA诊断探讨：Eotaxin和小气道通气功能作为CVA早期诊断指标The diagnosis and discussion of CVA:Eotaxin and small airway ventilation function are used for the early diagnosis of CVA,武晓兰等.实用医学杂志2013;29(2):199-201,探讨CVA患者血清中嗜酸性粒细胞趋化因子（Eotaxin）水平的变化及其与肺功能的关系。,Eotaxin是参与CVA炎症反应的重要因子。肺功能小气道的改变对于早期诊断CVA具有一定意义。Eotaxin is an important factor that participates in inflammatory response to CVA.The change of small airway function has certain significance on the early diagnosis of CVA.,主要内容 Content,CVA的流行病学 The Epidemiology of CVA,CVA的诊断进展 The Progress on Treatment of CVA,CVA的治疗现状 The Present Situation of Treatment on CVA,CVA的治疗原则The principle of treatment on CVA,CVA治疗原则与支气管哮喘治疗相同。大多数患者吸入小剂量糖皮质激素联合支气管舒张剂（如2受体激动剂）即可，或用两者的复方制剂，如布地奈德/福莫特罗。必要时可短期口服小剂量糖皮质激素治疗。治疗时间不少于8周。有报道抗白三烯受体拮抗剂治疗CVA有效，但观察例数较少。,中华医学会呼吸病学分会哮喘学组.中华结核和呼吸杂志2009;32(6):407-413,咳嗽的诊断与治疗指南2009Guidelines on the Diagnosis and Treatment of Cough 2009,The principle of treatment on CVA is the same as the one on bronchial asthma.Inhalation of low doses of corticosteroids plus bronchodilators(such as 2 agonists)is enough for most patients,or compound of two medications,such as Budesonide/Fomoterol.If necessary,patients may take low dose of glucocorticoid for less than 8 weeks.There are reports that Leukotriene Receptor Antagonist(LTRA)may effectively treat CVA,but the number of cases is small.,26,中国成人慢性咳嗽患者治疗现状The present situation of treatment on chronic cough in Chinese adults,赖克方等.国际呼吸杂志 2011;31(9):645-647,90%以上的慢性咳嗽患者被反复使用抗生素或进行镇咳治疗，由此反映了误治的情况。在治疗效果上，大多数患者疗效不满意，说明治疗不得当。90%of patients with chronic cough have been treated with antibiotics and cough suppressants repeatedly,which reflects the situation of mistherapy.Most patients complain about the treatment outcome,which reflect inappropriate treatment.,为了解慢性咳嗽患者的诊疗状况，以首次到广州呼研所门诊就诊的慢性咳嗽患者为对象，通过调查问卷方式，记录其病情及诊治情况。共调查558例成人慢性咳嗽患者。,平均就诊次数：20.830次,ICS在CVA治疗中的重要作用The important role of ICS in the treatment of CVA,Niimi A,et al.Curr Respir Med Rev.2011;7(1):47-54.,ICS在CVA治疗中非常重要。不仅控制CVA的咳嗽症状，而且与预后相关，可预防疾病进展为喘息、气道重构和慢性气流阻塞。正如典型哮喘，嗜酸粒细胞性炎症和气道重构在CVA中同样存在，因此ICS是CVA的一线治疗，尤其对于那些存在持续咳嗽的患者。若ICS单药不足以控制，可添加其他药物如LABA。,ICS is very important in the treatment of CVA.It not only controls cough of CVA,but also is relevant to prognosis and may prevent the disease from progressing to wheezing,airway remodelling and chronic airflow limitation.Just like typical asthma,there also exist eosinophilic inflammation and airway remodelling in CVA,therefore ICS is the first-line treatment for CVA，particularly for patients with chronic cough.If ICS only cannot control the condition,it is fine to add other drugs,like LABA.,ICS在CVA治疗中的作用：降低气道高反应性The role of ICS in the treatment of CVA:reduce bronchial hyperresponsiveness,观察CVA患者接受长期ICS治疗期间，诱导痰中炎性介质水平和气道高反应性的改善情况。研究共包括35名CVA患者、26名典型哮喘患者和24名健康成人，均接受布地奈德400g/d治疗。,Liu M,et al.Mediators Inflamm.2012;2012:403868,PD20-FEV1：支气管激发试验中导致FEV1降低20%所需的激发物累计浓度。,CVA患者在接受布地奈德治疗后3个月AHR即显著降低，但对于大多数患者而言，为了完全消除气道炎症，仍需长期ICS治疗The AHR of patients with CVA significantly decreased after 3-month treatment with Budesonide;however,for the majority of patients,it is necessary to receive long-term ICS treatment so as to completely eliminate airway inflammation.,Liu M,et al.Mediators Inflamm.2012;2012:403868,观察CVA患者接受长期ICS治疗期间，诱导痰中炎性介质水平和气道高反应性的改善情况。研究共包括35名CVA患者、26名典型哮喘患者和24名健康成人，均接受布地奈德400g/d治疗。,ICS在CVA治疗中的作用：全面抑制气道炎症The role of ICS in the treatment of CVA:completely suppress inflammation,CVA患者在布地奈德治疗后气道炎症的改善比典型哮喘患者更显著。The improvement of airway inflammation after Budesonide treatment in CVA patients is more obvious than that in patients with typical asthma.,30,白三烯受体拮抗剂在CVA治疗中的作用：有限抗炎，对气道高反应性无作用The role of Leukotriene Receptor Antagonist(LTRA)in the treatment of CVA:limited anti-inflammation and no effect on airway highresponsiveness,为了分析LTRAs治疗CVA患者的作用机制，前瞻性观察23例未吸烟、未接受过抗炎治疗的成人CVA患者接受孟鲁司特（10mg/d）治疗4周的疗效。,*乙酰甲胆碱-呼吸阻力剂量-反应曲线斜率（SRs）：用于评估气道反应性的指标,Eos：嗜酸粒细胞；LTB4：白三烯B4；PGE2：前列腺素E2；TXB2：血栓素B2。,Takemura M,et al.Respiration.2012;83(4):308-15,孟鲁司特可改善咳嗽症状，降低痰嗜酸粒细胞计数和咳嗽敏感度，但对于肺功能、气道高反应性和痰炎性介质水平没有改善作用。Montelukast may improve cough,reduce the counts of sputum eosinophilia granulocyte and cough sensitivity;however,it has no effect on lung function,airway hyperresponsiveness or sputum inflammatory mediators.,总结 Summary,CVA是一种特殊类型的哮喘，咳嗽是其惟一或主要临床表现。CVA在中国成人慢性咳嗽患者中占32.6%，为首要病因。30%-40%的CVA患者最终进展为典型哮喘，早期使用ICS治疗可显著降低CVA患者疾病进展风险。目前中国慢性咳嗽的病因诊断有待进一步加强。根据慢性咳嗽病因诊断程序，肺通气功能和支气管激发试验为CVA的主要检查项目，但只有经相应治疗后症状缓解，病因诊断方能成立。若条件有限，可优先使用2受体激动剂作为诊断性治疗。目前慢性咳嗽患者存在误治现象。ICS是CVA的一线治疗药物，不仅控制CVA的咳嗽症状，而且与预后相关，可预防疾病进展为喘息、气道重构和慢性气流阻塞。若ICS单药不足以控制，可添加其他药物如LABA。白三烯受体拮抗剂在CVA治疗中抗炎作用有效，且对气道高反应性无作用。,CVA is a special type of asthma with cough as the only or main clinical manifestation.CVA is the leading cause to Chinese patients with chronic cough and accounts for 32.6%.30%to 40%of CVA patients ultimately progress to typical asthma.The early treatment with ICS may significantly reduce the risk The etiological diagnosis of chronic cough in China needs further improvement.According to the etiologic diagnostic procedure,pulmonary ventilation function test and provocation test are the main examinations for CVA.The etiological diagnosis can be accepted only after remission of symptoms after relevant treatment.When there is limited resources,its better to use 2 agonist in the diagnostic treatment.At present,there do exist mistherapy in patients with chronic cough.ICS is the first-line treatment for CVA.It not only controls cough of CVA,but also is relevant to prognosis and may prevent the disease from progressing to wheezing,airway remodelling and chronic airflow limitation.If ICS only cannot control the condition,it is fine to add other drugs,like LABA.Leukotriene Receptor Antagonist(LTRA)has an anti-inflammation effect in the treatment of CVA,but has no effect on airway highresponsiveness.,
