小气道病变在哮喘中的地位ppt课件.ppt

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,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,小气道病变在哮喘中的地位,内容,哮喘的小气道病变,慢性炎症,气道重塑,气道阻力增高,哮喘小气道病变和哮喘临床的关系,患者的临床表型和小气道病变,小气道病变和哮喘控制不佳相关,小气道的定义,*Hogg JC et al,N Engl J Med 2004;350:2645-53,*Sturton et al,2008;Hogg JC et al,2008;Kraft M,2007;Tulic MK et al,2003,小气道的定义*,:,直径,2mm,包括细支气管和终末支气管,难以到达和进行研究,在哮喘和,COPD,发病机制中越来越被重视*,小气道和大气道的不同,小气道炎症,哮喘患者小气道炎症,:,炎症细胞在哮喘中起到了核心的作用,.,Th2,细胞,和嗜酸粒细胞均在小气道中有明显的浸润,重要的炎性介质,IL-5,在小气道表达,Tulic 123:348S355S,Barnes PJ,Nature Reviews Immunology 2008;8:183-192,Tulic 123:348S355S,小气道的慢性炎症,哮喘患者小气道,T,细胞和嗜酸粒细胞显著增高,哮喘患者小气道的,IL-5,的表达增高,MBP:,总嗜酸粒细胞,主要碱性蛋白,EG2:,活化嗜酸粒细胞,Pi:,气道内周长,哮喘患者小气道活化嗜酸粒细胞高于大气道,600,500,400,300,200,100,0,2,2,2,2,p0.05,气道直径,(mm),Positive cells/mm,2,T cells(CD3),Eosinophils(MBP),Eosinophils activated EG2),Mast cells(tryptase),Hamid et al JACI 1997,Kraft,et al.,AJRCCM 1996,无夜间哮喘,夜间哮喘,0,10,20,30,40,近端气道,远端肺组织,下午,04,:00,嗜酸粒细胞,(10,3,/mm,3,),0,10,20,30,40,凌晨,04:00,夜间发作哮喘患者小气道嗜酸粒细胞浸润显著增高,近端气道,远端肺组织,嗜酸粒细胞,(10,3,/mm,3,),N.Carroll,et al.The distribution of eosinophils and lymphocytes in the large and small airways of asthmatics.,Eur Respir J 1997,10:292300,哮喘患者小气道基底膜中可见多种炎症细胞,膜性细支气管,:,基底膜周长（,Pbm,）,6 mm,采用光学显微镜计数，结果提示，小气道基底膜（,Pbm 6mm,）可见淋巴细胞、嗜酸性淋巴细胞等多种炎性细胞。,无论致死性还是非致死性哮喘患者,小气道内壁均增厚,Carroll N,et al.Am Rev Respir Dis.1993;147:405-410.,Nihlberg,K et al.Thorax 2010,collagen,Distal tissue,Asthma,Controls,10,8,6,4,2,0,%Collagen area of total tissue,*,轻度哮喘患者存在小气道重塑,Bergeron C et al,J Allergy Clin Immunol 2005;116:983-9,与大气道相同,哮喘患者小气道出现,III,型胶原沉积和,-,平滑肌肌动蛋白增加,外周气道,中央气道,致死性哮喘患者小气道平滑肌层增厚,杯状细胞化生,正常对照者小气道,致死性哮喘患者小气道,M:,粘液栓,gcm:goblet cell,Metaplasia,杯状细胞化生,asm:airway smooth muscle,气道平滑肌层,Thais Mauad et al,Am J Respir Crit Care Med Vol 170.pp 857862,2004,*p=0.013 vs.,健康人,Wagner EM,et al.Am Rev Respir Dis 1990,平均外周气道阻力,(cm H,2,O/mL/min),健康人,轻度哮喘患者,*,0.069,n=15,0,0.009,0.069,0.02,0.04,0.06,0.08,0,轻度哮喘患者小气道阻力增加,哮喘患者外周气道的阻力比正常人显著增高,Wagner EM,et al.Am Rev Respir Dis.1990;141:584-586.,6,个正常人和,9,个哮喘患者,气道阻力和气体容量用,Constant-Volume,体描箱测定,Pressure(P,B,)-Flow(V)relationships,有症状,(,夜间憋醒,),哮喘患者小气道阻力高于没有症状的哮喘患者,10,个有夜间憋醒的哮喘患者,4,个无夜间憋醒的哮喘患者及,4,个正常对照者,下午,4:00,和凌晨,4:00,通过支气管镜测量外周气道阻力,(Rp),*,P=0.0003,凌晨,4:00(,各组间,),+P=0.0001,下午,4:00(,各组间,),Rp(cmH,2,O/ml/min),*,*,*,+,+,+,Kraft M,et al,Am J Respir Crit Care Med Vol 163.pp 15511556,2001,内容,哮喘的小气道病变,慢性炎症,气道重塑,气道阻力增高,哮喘小气道病变和哮喘临床的关系,Anderson et al,Ann Allergy Asthma Immunol 2012,Measurements with IOS,Step 2=64.6%,Step 3=63.5%,Step 4=69.9%,p=ns,p=0.006,p=0.006,小气道阻塞存在于不同程度哮喘患者,中重度哮喘患者小气道阻力增加明显,*p0.01 vs normal subjects,Tulic 72:10161023,有夜间症状的哮喘患者外周气道的炎症显著高于没有夜间症状的哮喘患者,Lehtimaki L et al.,Eur Respir J 2002;20:841845,有夜间症状的哮喘患者,(n=19),无夜间症状的哮喘患者,(n=21),健康对照,(n=40),ppb:parts per billion,p=0.453,p=0.032,p=0.012,150,100,50,0,FEV,1,TLC,FRC,RV,dN,2,CV/,VC,CC/,TLC,RV/,TLC,预计的百分数,（,%,）,难治性,哮喘,稳定的哮喘,p=0.02,p=0.03,远端,气道,病变增高,哮喘反复急性发作,风险,Hohannes C.C.M,et al.Recurrent Exacerbations in Severe Asthma Are Associated with Enhanced Airway Closure During Stable Episodes.Am J Respir Crit Care Med.2000,161:1902-1906.,研究结果提示，与对照组相比较，重症哮喘并在,1,年内有,2,次以上哮喘急性发作组的患者，,CV/VC,、,CC/TLC,明显增高，具有统计学差异，,P,值分别为,0.02,、,0.03.,Bourdin A et al,Allergy 2006,小气道病变和哮喘急性发作次数相关,dN2:slope of phase III of the SBNT,小气道病变和哮喘患者的生活质量相关,Boudin A et al.Allergy 2006;61:8589,更差,dN2:slope of phase III of the SBNT,Thompson B et al JACI 2013,Sacin(L,-1,),Scond(L,-1,),100,0,200,300,400,500,600,700,800,900,1000,100,200,300,400,500,0,%predicted,%predicted,exa,stable,exa,stable,小气道病变和哮喘控制状况相关,Scond:index of conductive ventilation heterogeneity,Sacin:,index of,acinar(distal airway),ventilation heterogeneity,小气道病变对哮喘患者临床结局的不良影响,小气道病变,加重气管高反应性,疾病的慢性症状期,降低生活质量,急性严重哮喘（致死性哮喘）,导致肺功能丧失,加速气道重塑,增加哮喘治疗难度,Tadeusz Plusa.Small airways and new therapeutic perspectives in asthma and COPD.,Int.Rev.Allergol.Clin.Immunol.2011;17:5-9,