过敏性鼻炎对哮喘的影响

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,过敏性鼻炎对哮喘控制的影响,流行病学,发病机制,治疗,内 容,GINA Global burden of asthma 2009,哮喘的发病率,2.1%,过敏性鼻炎的发病率,全球过敏性鼻炎的发病率为,10%-42%,亚洲的发病率为,1%-20%,在中国,13-14,岁的儿童中，,10.4%,患有过敏性鼻炎，并且每年增加,0.33%,ARIA 2008,哮喘和过敏性鼻炎常同时存在,约有,80%,的哮喘患者合并过敏性鼻炎,约有,20%,的过敏性鼻炎患者合并有哮喘,单一哮喘,单一过敏性鼻炎,过敏性鼻炎,+,哮喘,Bousquet J et al. J Allergy Clin Immunol 2001;108(Suppl 5):S147-S334.,过敏性鼻炎,哮喘和过敏性鼻炎流行病学模式相似,在,463,，,801,个,13-14,岁的儿童中进行遗传过敏症世界范围的发病率研究。超过,12,个月的儿童自述症状的问卷调查,.,Adapted from t,he International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee.,Lancet,1998;351:1225-1232,.,英国,澳大利亚,加拿大,巴西,美国,南非,德国,法国,阿根廷,阿尔及利亚,中国,俄国,0,5,10,15,20,25,30,35,40,%,发病率,英国,澳大利亚,加拿大,巴西,美国,南非,德国,法国,阿根廷,阿尔及利亚,中国,俄国,0,5,10,15,20,25,30,35,40,%,发病率,哮喘,不同地区哮喘合并过敏性鼻炎流调结果,Erkka Valovirta, Ruby Pawankar. Survey on the impact of comorbid allergic rhinitis in patients with asthma.,BMC Pulmonary Medicine,2006, 6(Suppl 1):S3,Fanny WS Ko, Mary SM Ip, CM Chu et al. Prevalence of allergic rhinitis and its associated morbidity in adults with asthma: a multicentre study. Hong Kong Med J 2010;16:354-61.,过敏性鼻炎是哮喘的一个危险因素,过敏性鼻炎增加哮喘的危险约,3,倍,此研究是一项为期,23,年的对,738,名大学新生（,69%,为男性）的长期随访，结果表明，在平均年龄为,40,岁时，患过敏性鼻炎的人群中发生哮喘的比例约为无过敏性鼻炎人群的,3,倍。,Adapted from Settipane RJ et al,Allergy Proc,1994;15:21-25.,12,10,8,6,4,2,0,出现哮喘,的患者,%,10.5,基线时有过敏性鼻炎,(n=162),3.6,基线时无过敏性鼻炎,(n=528),p0.002,过敏性鼻炎增加哮喘发作的风险,25,20,15,10,5,0,哮喘发作,患者, %,21.3,哮喘合并变应性鼻炎患者,(n=893),17.1,哮喘患者,(n=597),P,=0.046,Bousquet J et al.,Clin Exp Allergy 2005;35:723727.,过敏性鼻炎使哮喘患者的住院治疗风险增高,50%,0.8,0.7,0.6,0.5,0.4,0.3,0.2,0.1,0,每年住院,患者, %,0.76,哮喘合并变应性鼻炎患者,(n=4,611),0.45,哮喘患者,(n=22,692),P,0.006,Price D et al. Clin Exp Allergy 2005;35:282287.,哮喘与过敏性鼻炎的流行病学特点,哮喘和过敏性鼻炎的发病率及发病人数逐年增加,哮喘和过敏性鼻炎的流行病学模式相似,哮喘和过敏性鼻炎常合并发生,过敏性鼻炎是哮喘的一个危险因素，可增加哮喘发作及住院治疗的风险,流行病学,发病机制,治疗,内 容,过敏性鼻炎和哮喘的病理生理特点,过敏性鼻炎和哮喘有相同的多种病理生理学特点,相同的诱因,暴露在过敏原下的相似的炎症连锁反应,相似的早发相和晚发相应答模式,相同的炎症细胞浸润（嗜酸性细胞）,各种潜在的相关途径包括炎症介质的全身传送,研究证实上下气道的炎症存在相互影响，过敏性鼻炎可能通过一系列机制引起哮喘的发生或加重,Adapted from National Institutes of Health,Global Initiative for Asthma: Global Strategy for Asthma Management and Prevention: A Pocket Guide for Physicians and Nurses.,Publication No. 95-3659B. Bethesda, MD: National Institutes of Health, 1998; Workshop Expert Panel,Management of Allergic Rhinitis and its Impact on Asthma (ARIA) Pocket Guide. A Pocket Guide for Physicians and Nurses.,2001; Kay AB,N Engl J Med,2001;344:30-37; Varner AE, Lemanske RF Jr. In:,Asthma and Rhinitis,. 2nd ed. Oxford, UK: Blackwell Science, 2000:1172-1185; Togias A,J Allergy Clin Immunol,2000;105(6 pt 2):S599-S604; Togias A,Allergy,1999;54(suppl 57):94-105.,过敏性鼻炎和哮喘存在共同的过敏原、炎症细胞与介质,Adapted from Casale TB et al,Clin Rev Allergy Immunol,2001;21:2749; Kay AB,N Engl J Med,2001;344:3037.,Adapted from National Institutes of Health Global Initiative for Asthma: Global Strategy for Asthma Management and Prevention: A Pocket Guide for Physicians and Nurses. Publication No. 95-3659B. Bethesda, MD: National Institutes of Health, 1998; Workshop Expert Panel Management of Allergic Rhinitis and its Impact on Asthma (ARIA) Pocket Guide. A Pocket Guide for Physicians and Nurses, 2001.,早发相,晚发相,T cells,过敏原,细胞因子,炎症介质,半胱氨酰白三烯,前列腺素,血小板活化因子,Eosinophils,膜,-,IgE,Mastcell,炎症介质,半胱氨酰白三烯,前列腺素,血小板活化因子,过敏性鼻炎和哮喘有相似的早发相和晚发相应答,Adapted from Varner AE, Lemanske RF Jr. In:,Asthma and Rhinitis.,2nd ed. Oxford: Blackwell Science, 2000:1172-1185; Togias A,J Allergy Clin Immunol,2000;105(6 pt 2):S599-S604.,哮喘,过敏性鼻炎,症状评分,刺激后时间（小时）,1,过敏原刺激,34,812,24,早发相,晚发相,FEV1,（变化率,%,）,时间（小时）,1,10,24,0,2,3,4,5,6,7,8,9,0,50,100,过敏性鼻炎和哮喘在免疫病理上相似,Eos=,嗜酸性粒细胞,; neut=,中性粒细胞,; MC=,肥大细胞,; Ly=,淋巴细胞,; MP=,巨噬细胞,Adapted from Bousquet J et al,J Allergy Clin Immunol,2001;108(suppl 5):S148S149,.,嗜酸性粒细胞浸润,过敏性鼻炎,哮喘,鼻粘膜层,支气管粘膜层,变应原激发鼻粘膜增加支气管高反应性,PC,20,*,与基线水平相比,本随机交叉实验探讨了过敏性鼻炎合并哮喘的患者过敏性鼻炎和下气道功能紊乱的关系。,PC=post-challenge,*,越低的,PC,20,值表明越高的反应性,Adapted from Corren J et al,J Allergy Clin Immunol,1992;89:611618.,基线,3,2,0,PC,20,均值的几何图形,(,乙酰胆碱,mg/ml),安慰剂,(n=5),变应原,(n=5),0.5 hour,激发后,4.5 hours,激发后,p=0.011,p=0.0009,本研究评估单纯过敏性鼻炎患者支气管激发后在上下气道的炎症反应,T,0,=,变应原刺激前,;,T,24,=,变应原刺激,24,小时后,a,p0.05;,b,p0.01;,c,p=0.001;,d,p=0.002,Adapted from Braunstahl G-J et al,Am J Respir Crit Care Med,2000;161:20512057.,T,0,100,80,60,40,20,0,嗜酸性粒细胞,(number cells/,mm,2,),Control patients (n=8),Allergic patients (n=8),T,24,T,24,T,0,1600,1200,800,400,0,未激发,左肺,变应原激发,右中肺叶,b,鼻组织,(,粘膜固有层,),支气管组织,(,上皮下层,),a,c,a,d,变应原激发支气管增加鼻和支气管组织的炎症反应标志物（嗜酸粒细胞）,过敏性鼻炎对哮喘影响的可能机制,J Allergy Clin Immunol, 2003 Jun;111(6):1171-83; quiz 1184.,炎性分泌物的吸入从上呼吸道到下呼吸道,鼻粘膜受损降低了其对吸入气体的调节作用（加湿、加温、过滤颗粒）,鼻部炎性介质吸收入血，到达肺部，诱发支气管炎症反应,因“鼻肺反射”，鼻粘膜刺激可引起支气管收缩,流行病学,发病机制,治疗,内 容,过敏性鼻炎与哮喘的综合治疗,避免接触过敏原,应尽可能做到,药物治疗,安全,有效,易行,免疫治疗,有效,专科医生的处方,可能改变自然病程,患者教育,常规要求,费用,Allergic Rhinitis and its Impact on Asthma (ARIA) 2008. Allergy 2008;63(Suppl 86),Upper airway treatment options,上气道治疗方法,Lower airway treatment options,下气道治疗方法,Nasal steroids,鼻用激素,Inhaled steroids,吸入激素,Antihistamines,抗组胺药,Upper and lower airway treatment options,上下气道均覆盖的药物,Leukotriene receptor antagonists,白三烯受体拮抗剂,Anti-IgE,Immunotherapy,免疫治疗,上下气道炎症同治,哮喘合并过敏性鼻炎的患者,LTRA,与,ICS,联用控制哮喘的疗效优于双倍剂量,ICS,0,4,8,12,P,=0.028,周,孟鲁司特,+,布地奈德,(n=216),a,双倍剂量布地奈德,(n=184),b,均值,标准误,清晨PEF自基线的改变值（l/min）,50,40,30,20,10,0,a,孟鲁司特,10mg,，一日一次,+,布地奈德,400 g,一日两次,;,b,布地奈德,800 g,一日两次,.,COMPACT,研究的首要终点为清晨,PEF.,Price DB, et al. Allergy. 2006;61:737742.,a,患者应用,鼻用激素,、抗组胺药或其他鼻炎治疗药物,Price DB et al. Allergy 2006;61:737742.,0,4,8,12,P,=0.017,周,孟鲁司特,10 mg +,布地奈德,800,g (n=33),a,布地奈德,1600,g,(n=23),a,60,40,20,0,20,清晨,PEF,自基线的改变（,L/min,）,哮喘合并过敏性鼻炎的患者,LTRA,与,ICS,联用控制哮喘的疗效,优于双倍剂量,ICS,LTRA,联合,ICS/ICS+LABA,可显著提高哮喘控制,a,的比例,n=312.,a,符合加拿大哮喘共识指南（,CAC,）的诊断标准,Keith PK et al.,Can Respir J,. 2009;16(suppl A):17A24A.,达到哮喘控制的患者比例,%,孟鲁司特,+ ICS(n=151),孟鲁司特,+ ICS/LABA,(n=146),0,100,75,50,25,73.5,78.1,哮喘控制,:,治疗,8,周后与基线比较显著提高,(,P,0.001),LTRA,联合,ICS/ICS+LABA,可显著降低,ACQ,评分,a,P,=0.003 vs,基线,;,b,P,0.001 vs,基线,;,c,P,=0.053 vs,基线,.,Keith PK et al.,Can Respir J,.,2009;16(suppl A):17A24A,.,孟鲁司特,+ ICS,孟鲁司特,+ ICS/LABA,ACQ,评分平均值,0.5,3.5,2.5,0.5,Baseline,Week 8,1.0,1.5,Low Dose (n=89),Moderate Dose (n=50),High Dose (n=15),2.0,0,Mean (SD) ACQ Score,Low Dose (n=93),Moderate Dose (n=51),High Dose (n=9),3.0,0.5,3.5,2.5,0.5,1.0,1.5,2.0,0,3.0,Baseline,Week 8,a,b,b,c,b,b,LTRA,联合,ICS/ICS+LABA,可显著改善哮喘和并过敏性鼻炎患者的鼻部症状,a,a,A Mini RQLQ,评分改善,0.7,则认为有显著的临床意义,;,b,P,0.001 vs,基线,;,c,P,=0.003 vs,基线,;,d,P,=0.128 vs,基线,Keith PK et al.,Can Respir J,. 2009;16(suppl A):17A24A.,MiniRQLQ,评分的平均改变值,低剂量,ICS,中剂量,ICS,高剂量,ICS,孟鲁司特,+ ICS,孟鲁司特,+ ICS/LABA,2.0,0,0.5,1.0,1.5,1.5,b,1.33,b,1.57,c,1.5,b,1.46,b,0.98,d,所有患者,MiniRQLQ,评分较基线改善有显著性差异,(,P,0.001).,低剂量,ICS,中剂量,ICS,高剂量,ICS,谢谢！,