1、变应性疾病-如影相随Gupta R,et al.BMJ.2003 Nov 15x;327(7424):1142-3Ninan TK,et al.BMJ.1992 Apr 4;304(6831):873-52历史变迁Larch M,et al.Nat Rev Immunol.2006;6(10):761-71Von Pirquet3是Specific Immunotherapy(SIT)还是Allergen Immunotherapy(AIT)?Caldern MA,et al.Allergy.2013;68(7):825-84AIT的机制是什么？Akdis CA,et al.World All
2、ergy Organ J.2015;8(17):1-12.Mechanisms of allergen-Mechanisms of allergen-specific immunotherapy and immune tolerance to allergens.specific immunotherapy and immune tolerance to allergens.Very early basophil tolerance:Very early basophil tolerance:Early decrease in mast cell and basophil activity f
3、or systemic anaphylaxisEarly decrease in mast cell and basophil activity for systemic anaphylaxisType I skin test reactivityType I skin test reactivityEarly increase in specific IgE followed by a late decrease in specific IgEEarly increase in specific IgE followed by a late decrease in specific IgEI
4、ncrease in specific IgG4 and in some studies IgA and IgG1Increase in specific IgG4 and in some studies IgA and IgG1Decreased numbers of tissue mast cells and eosinophils and release of Decreased numbers of tissue mast cells and eosinophils and release of their mediators in nasal mucosal biopsies of
5、allergic rhinitis patientstheir mediators in nasal mucosal biopsies of allergic rhinitis patientsDecreased skin late-phase response in parallel to decreased lymphocyte Decreased skin late-phase response in parallel to decreased lymphocyte and eosinophil infiltrationand eosinophil infiltrationInducti
6、on of Treg and Breg cells suppression of Th2-Th1 cellsInduction of Treg and Breg cells suppression of Th2-Th1 cells5AIT可能的推手-Treg和BregAkdis CA,et al.World Allergy Organ J.2015;8(17):1-12.Mechanisms of allergen-specific Mechanisms of allergen-specific immunotherapy and immunotherapy and immuneimmune
7、tolerance to allergens.tolerance to allergens.6PharmacotherapyAllergen avoidanceAllergen immunotherapyPatient education变应性疾病综合治疗方案变应性疾病综合治疗方案Bousquet J,et al.J Allergy Clin Immunol.1998;102(4 Pt 1):558-62 Allergen Allergen immunotherapy:therapeutic vaccines for allergic diseases.A WHO position paper
8、.immunotherapy:therapeutic vaccines for allergic diseases.A WHO position paper.7内容建议推荐强度环境因素那些明确因环境变应原致病的患者应避免接触已知变应原或进行环境控制（不养宠物、使用过滤系统、防螨罩或杀螨剂）可选Seidman MD,et al.Otolaryngol Head Neck Surg.2015;152(1 Suppl):S1-438GINA和NAEPP关于环境控制的建议 GINA 2014N Engl Med 2009;360:1862-99 AIT对蜂毒过敏反应、过敏性鼻炎/结膜炎，过敏性哮喘有效
9、 免疫治疗是唯一可以影响变应性疾病自然病程的治疗方法，它还可阻止变应性鼻炎发展为哮喘 成功的免疫治疗取决于标准化的、可持续生产的高质量变应原疫苗Bousquet J,et al.J Allergy Clin Immunol.1998;102(4 Pt 1):558-621020062011201211欧美AIT现状Burks AW,et al.J Allergy Clin Immunol.2013;131(5):1288-9612变应原配方 疗效：由于研究设计的多样性，使得比较困难 总结：只给患者接种引起症状的变应原Nelson HS et al.J Allergy Clin Immunol.
10、2009;123:763-76913脱敏途径-SCIT或SLIT欧洲：SLIT占AIT的45%，区域差别大（北欧限新EMA注册变应原，德国25%，南欧80%）美国：2014年4月FDA批准3种舌下片剂传统治疗：SCIT14对AIT疗效的共识-过敏性疾病修饰剂Committee for Medicinal Products for Human Use(CHMP)and Efficacy Working Party(EWP)预防变应性鼻炎并发哮喘 预防对新变应原过敏 停用后保持长期临床效果15真实世界AIT对预防鼻炎进展为哮喘的肯定作用 -6年回顾性研究Schmitt J,et al.J Alle
11、rgy Clin Immunol.2015 Dec;136(6):1511-6 RA患者进行AIT发生哮喘的危险显著低于非AIT SCIT的预防作用显著 天然提取物制备的变应原作用显著 3年和更久的治疗作用显著16对AIT现状的共识-适应症适应症：同时罹患哮喘和鼻炎 变应性鼻炎 药物不能控制症状 严重药物不良反应 不愿长期用药 17对AIT现状的共识-操作指南1.适应症2.禁忌症3.治疗后观察30mins4.妊娠期AIT5.-阻滞剂的使用6.人员培训7.医疗器械准备8.医疗文件准备18对AIT现状的共识-低估AIT的治疗价值尽管均认为AIT是唯一对哮喘和鼻炎起到修饰作用的治疗，目前仅5%患者接
12、受AIT 疗效证据不充分 支出-获益比不明确 从业医生水准和认知水平不一 普通人群对AIT常识少 患者害怕治疗方案或药品申请过程 入选病例的差异(level D)-GINA 2015Jutel M,et al.J Allergy Clin Immunol.2015;136(3):556-6819未来关注20研究标准化Canonica GW,et al.Allergy.2007;62(3):317-24Recommendations for standardization of clinical trials with Allergen Specific Immunotherapy for re
13、spiratory allergy.A statement of a World Allergy Organization(WAO)taskforce 1911年SCIT首次应用于临床，1960年发表首个双盲安慰剂对照（DBPC）疗效观察的临床研究，SLIT的DBPC在1986年。方法学缺陷：样本小 退出率高 组间疾病严重程度不匹配 变应原效价无法比较 单独症状评价或用药评分William Frankland(1912-)AIT 100年纪念21变应原标准化美国FDA生物检测研究中心CBER(center for biologics evaluation and research)标准化和非标
14、准化制剂欧洲欧洲药物局（EMA）统一审查认证变应原工业化生产，新产品进行注册22Jutel M,et al.J Allergy Clin Immunol.2015;136(3):556-68Cox L,et al.J Allergy Clin Immunol.2011;127(1 Suppl):S1-55Wheatley LM,et al.N Engl J Med.2015 Jan 29;372(5):456-63 单一变应原效果肯定It is not know whether multi-allergen therapy results in better outcomes than sin
15、gle-allergen therapy.Althrough some older studies suggest a benefit of multi-allergen immunotherapy,most trails showing the efficacy of immunotherapy involve a signle allergen.-Clinical practice.Allergic rhinitis-Allergen immunotherapy:a practice parameter third updateSummary Statement 72:There are
16、few studies that investigated the efficacy of multiallergen subcutaneous immunotherapy.These studies have produced conflicting results,with some demonstrating significant clinical improvement compared with placebo and others showing no benefit over optimal pharmacotherapy and environmental control m
17、easures.Thus it is important to treat the patients only with relevant allergens.(B)变应原种类：强调使用主要变应原23AIT的安全性SCIT:注射部位充血、肿胀、瘙痒（85%）全身反应：1次注射 致命过敏反应：1/100万次注射SLIT：口咽瘙痒、肿胀（75%）无致命过敏反应Wheatley LM,et al.Clinical practice.Allergic rhinitis.Clinical practice.Allergic rhinitis.N Engl J Med.2015;372(5):456-63
18、24减少SCIT风险Epstein TG.J Allergy Clin Immunol Pract.2014;2(2):161-7.哮喘未控制、重症哮喘是导致严重不良反应的主要原因哮喘未控制、重症哮喘是导致严重不良反应的主要原因 措施1 每次治疗前进行哮喘控制评估2 遵循标准操作规范3 花粉季调整剂量4 避免集群免疫治疗25分子诊断技术的应用Molecular-based allergy(MA)diagnostics鉴别多重过敏患者真正的致敏源 真正的变应原 vs 交联反应（泛变应原）减少食物过敏诊断的风险 稳定的变应原分子 vs 易变的变应原分子可能提高AIT的疗效 Canonica GW,
19、et al.World Allergy Organ J.2013 Oct 3;6(1):17.A WAO-ARIA-GALEN consensus document on molecular-based allergy diagnostics.26AIT在个体化治疗中的作用27AIT 现状综合评价-SWOTJutel M,et al.J Allergy Clin Immunol.2015;136(3):556-68Strengh Weakness Opportunity Threats28谢 谢！29人有了知识，就会具备各种分析能力，明辨是非的能力。所以我们要勤恳读书，广泛阅读，古人说“书中自有黄金屋。”通过阅读科技书籍，我们能丰富知识，培养逻辑思维能力；通过阅读文学作品，我们能提高文学鉴赏水平，培养文学情趣；通过阅读报刊，我们能增长见识，扩大自己的知识面。有许多书籍还能培养我们的道德情操，给我们巨大的精神力量，鼓舞我们前进。
