哮喘變應(yīng)原免疫治療現(xiàn)狀與思考 某 某 九龍醫(yī)院倪殿濤課件

1、哮喘變應(yīng)原免疫治療現(xiàn)狀與思考蘇州九龍醫(yī)院倪殿濤哮喘變應(yīng)原免疫治療現(xiàn)狀與思考蘇州九龍醫(yī)院倪殿濤哮喘變應(yīng)原免疫治療現(xiàn)狀與思考蘇州九龍醫(yī)院倪殿濤Types of allergies2021/4/272哮喘變應(yīng)原免疫治療現(xiàn)狀與思考蘇州九龍醫(yī)院倪殿濤哮喘變應(yīng)原免疫Types of allergies2021/4/272Types of allergies2021/4/272AllergenAnysubstanceoftenaproteinthatinducesanallergyCommon allergens過敏原種類很多“除了水、葡萄糖和鹽之外都可以成為過敏原”2021/4/273AllergenAn

2、ysubstance過敏原種類很多2Common cold or allergy 2021/4/274Common cold or allergy 2021/4/AsthmaDerived from the Greek root Originally did not define a disease, but was employed to describe respiratory symptoms of a variety of pulmonary conditionsBy the beginning of the 20th century,asthmawas seen to be a un

3、ique illness characterized by spasmodic afflictions of the bronchial tubes.Today,asthmais seen as a chronic inflammatory disease which is not yet fully understood in its pathophysiologyTherapy is still on the path to becoming optimal.Bergmann KC.Asthma.Chem Immunol Allergy. 2014;100:69-80.2021/4/275

4、AsthmaDerived from the Greek r盲人摸象2021/4/276盲人摸象2021/4/2762014 GINA哮喘表型Allergic asthma: usually respond well to inhaled corticosteroid(ICS) treatment Non-allergic asthma: often respond less well to ICS.Late-allergic asthma: some adults, particularly women, patient with asthma for the first time in a

5、 dult life. These patients tend to be non-allergic, and often require higher doses of ICS or are relatively refractory to corticosteroid treatment Asthma with fixed airflow limitation: some patients with long-standing asthma develop fixed airflow limitation that is thought to be due to airway wall r

6、emodeling.Asthma with obesity: some obese patients with asthma have prominent respiratory symptoms and little eosinophilic airway inflammation.GINA Guidelines for Asthma 20142021/4/2772014 GINA哮喘表型Allergic asthma: Terminology of allergic phenomenaidiosyncrasy - antipathy - Hypersensitivity -Anaphyla

7、xis -allergyA.F. Coca and R.A. Cooke introduced the term atopy：hypersensitiveness occurred spontaneouslyatopy gained a new sense, since IgE is a characteristic - Clinically similar diseases such as asthma, rhinoconjunctivitis or eczema can be found in the absence of IgE, and are then called intrinsi

8、c variants of the same diseaseChem Immunol Allergy. 2014;100:46-52. 2021/4/278Terminology of allergic phenomCoombs and Gells Classification of Hypersensitivity2021/4/279Coombs and Gells ClassificatiDoes intrinsic asthma exist?Ten to forty percent of asthmatics are intrinsicAnalysis of bronchial muco

9、sal expression of pro-eosinophilic and pro-atopic markers IL-3, -4, -5, -13, GM-CSF, RANTES, MCP-3, IgE and high affinity IgE receptor (Fc epsilon RI) There were more similarities than differences in immunopathology between atopic and nonatopicHumbert M.Does intrinsic asthma exist?Rev Mal Respir.200

10、0 Feb;17(1 Pt 2):245-54.2021/4/2710Does intrinsic asthma exist?Allergic vs nonallergic asthma: what makes the difference?Nonallergic：Greater age, female sex, sinusal polyposis, and FEV1 below 80% of the predicted value Allergic：history of hay fever, seasonal exacerbation of asthma, and asthma durati

11、on Allergy. 2002 Jul;57(7):607-13.2021/4/2711Allergic vs nonallergic asthmaAsthma phenotypes: nonallergic (intrinsic) asthma.The definition ：subjects with asthma and with whom allergic sensitization cannot be demonstratednegative skin prick test or in vitro specific-IgE test to a panel of seasonal a

12、nd perennial allergensNonallergic asthma occurs in 10% to 33% of individuals with asthma and has a later onset than allergic asthma, with a female predominance.Nonallergic asthma appears to be more severe than allergic asthma in many cases and may be less responsive to standard therapyPeters SP. Ast

13、hma phenotypes: nonallergic (intrinsic) asthma.J Allergy Clin Immunol Pract.2014 Nov-Dec;2(6):650-2.2021/4/2712Asthma phenotypes: nonallergicNovel diagnostic approaches and biological therapeutics for intrinsic asthma.Controversies have emerged in relation to this conceptNot finding specific allerge

14、n sensitization in an asthmatic patient neither excludes an allergic component nor the essential role that immunoglobulin E may play in asthmaThe atopic status is one among many other questionsOmalizumab, the only monoclonal anti-immunoglobulin E antibody commercialized for asthma, should be tried i

15、n patients with uncontrolled severe asthma independent of their atopic status Vennera Mdel C1,Picado C1.Novel diagnostic approaches and biological therapeutics for intrinsic asthma.Int J Gen Med.2014Jul 8;7:365-71.2021/4/2713Novel diagnostic approaches an哪些哮喘患者需要行AIT？過敏的概念總tIgE2021/4/2714哪些哮喘患者需要行AI

16、T？過敏的概念2021/4/2714Senti et al Allergy 2011;66(6):798 1911 Noon 1th SCIT1950s 1th SCIT Control Study;1980s 1th DBPC SLIT;2000s 1th sublingual Tablet2011s Innovating for patient benefit100 yeas of antigen specific immunotherpy 2021/4/2715Senti et al Allergy 2011;66(Allergen specific immunotherapy2021/

17、4/2716Allergen specific immunotherapSelf-amplification mechanisms of mast cell activation: a new look in allergy.The current definition of allergy, a group of IgE mediated diseases appears difficult to cover all allergic reactionsSince even IgE dependent allergic reactions are carried out through ac

18、tivation of mast cells and basophils, and all allergens mentioned above can activate these cellswe hypothesize that allergic reactions are mast cell and basophil mediated inflammatory process as it is the activated mast cells and basophils that initiate the pathological process of the immediate alle

19、rgic reactionswhereas IgE only serves as one of the activators of these cells.He S, Zhang H, Zeng X, Yang P.Curr Mol Med. 2012 Dec;12(10):1329-39.2021/4/2717Self-amplification mechanisms 2021/4/27182021/4/2718過敏性疾病實驗室診斷的理想程序皮試、斑貼試驗 （陽性）過敏原、半抗原或小分子物質(zhì)嗜堿性粒細胞/肥大細胞激發(fā)試驗 （陽性）（陰性基本排除急性過敏） 特異性IgE 、IgG 檢測 （陰性

20、） （陽性） （陽性） 類過敏反應(yīng) IgE依賴性 IgG依賴性 （目前定義為過敏）（目前定義為食物不耐受） 避免接觸類過敏原 （IgG陽性） 脫敏療法的適應(yīng)癥 低敏食物、食物脫敏？2021/4/2719過敏性疾病實驗室診斷的理想程序皮試、斑貼試驗2021/4/2AIT適應(yīng)癥-中國專家共識2021/4/2720AIT適應(yīng)癥-中國專家共識2021/4/2720AIT禁忌癥-中國專家共識2021/4/2721AIT禁忌癥-中國專家共識2021/4/2721哮喘患者AIT現(xiàn)狀2021/4/2722哮喘患者AIT現(xiàn)狀2021/4/27222021/4/27232021/4/2723結(jié) 論2021/4/2

21、724結(jié) 論2021/4/27242021/4/27252021/4/2725Sublingual immunotherapyIncluded 5,131 patients from 63 studies were analyzed that sublingual immunotherapyimproves symptoms of asthma reduces the use of asthma medications improves the quality of lifeLin et al.Sublingual immunotherapy for the treatment of alle

22、rgic rhinoconjunctivitis and asthma: a systematic review. JAMA 2013;309:1278-882021/4/2726Sublingual immunotherapyInclud2021/4/27272021/4/27272021/4/27282021/4/2728AIT的安全性2021/4/2729AIT的安全性2021/4/2729哮喘AIT困惑與思考2021/4/2730哮喘AIT困惑與思考2021/4/2730過敏原識別過敏原的特異性診斷查找過敏原是與其他學(xué)科的基本區(qū)別2021/4/2731過敏原識別過敏原的特異性診斷202

23、1/4/2731IgE介導(dǎo)變態(tài)反應(yīng)的診斷Allergic rhinitis and its impact on asthma Allergy, 2008,s1-153.2021/4/2732IgE介導(dǎo)變態(tài)反應(yīng)的診斷Allergic rhinitis 體內(nèi)試驗-皮膚試驗皮內(nèi)試驗 I型速發(fā)性變態(tài)反應(yīng)點刺試驗 I型速發(fā)性變態(tài)反應(yīng)斑貼試驗 IV型遲發(fā)型變態(tài)反應(yīng)2021/4/2733體內(nèi)試驗-皮膚試驗皮內(nèi)試驗 I型速發(fā)性變態(tài)反應(yīng)2021/4常用過敏原點刺液種類螨屬：戶塵螨、粉塵螨、熱螨、倉儲螨寵物毛發(fā)皮屑：貓毛、狗毛樹木花粉：榿木、榛屬、楊屬、榆科、柳屬、懸鈴木雜草花粉：蒿草、豚草、葎草、雞足草、酥油草

24、、毒麥、梯牧草、牧場草作物花粉：向日葵、玉米真菌：鏈格孢、毛殼菌、芽枝霉、鐮刀菌、青霉、擴展青霉、點青霉蟑螂：德國小蠊、美洲大蠊2021/4/2734常用過敏原點刺液種類螨屬：戶塵螨、粉塵螨、熱螨、倉儲螨202體外試驗-sIgE檢測嚴重皮炎不能作皮試者皮試假陽性的劃痕癥患者皮膚反應(yīng)差的老年人及3歲以下兒童用藥的影響嚴重過敏狀態(tài)發(fā)作者對作皮試時產(chǎn)生的不適恐懼者對過敏嚴重度評估擬行特異性免疫治療者2021/4/2735體外試驗-sIgE檢測嚴重皮炎不能作皮試者2021/4/27我國過敏原體外診斷種類RAST-放射過敏原吸附試驗FEIA-固相熒光酶免疫技術(shù)（CAP）免疫印跡技術(shù)（AS）ELISA-酶

25、聯(lián)免疫吸附試驗免疫捕獲法（酶聯(lián)免疫吸附試驗中之一種）過敏原芯片：固相液相免疫化學(xué)發(fā)光法過敏原誘發(fā)組胺釋放試驗：期望能解決IgE不能解決的問題2021/4/2736我國過敏原體外診斷種類RAST-放射過敏原吸附試驗2021/五種免疫球蛋白的血漿濃度（mg/dL）IgG 1200 （40000）IgM 150 （5000）IgA 300 （10000）IgD 3 （100）IgE 0.03 （1）血中IgE含量甚微，僅為血中IgG的四萬分之一 特異性IgE含量則更甚微2021/4/2737五種免疫球蛋白的血漿濃度（mg/dL）IgG 1200一般的免疫學(xué)方法測不到sIgE放射過敏原吸附試驗(RAS

26、T)熒光免疫標(biāo)記分析法ELISA（酶聯(lián)免疫吸附測定）蛋白芯片檢測熒光酶免法（ImmunoCAP Sweden）是檢測的金標(biāo)準(zhǔn)2021/4/2738一般的免疫學(xué)方法測不到sIgE放射過敏原吸附試驗(RAST)總IgE的意義總IgE沒有正常值，只定上限端值，兒童50KU/L 成人60KU/L新生兒的總IgE很低，隨年齡增長升高，10-15歲達頂峰，以后又逐步下降，男性高于女性理想的情況下，總IgE應(yīng)該是0或極低2021/4/2739總IgE的意義總IgE沒有正常值，只定上限端值，兒童50KU對總IgE的認識總IgE=【各種特異性IgE】【其它因素】影響總IgE水平其它因素 年齡 性別 種族 寄生蟲感染 最重要，在農(nóng)村寄生蟲高發(fā)區(qū)總IgE的水平可能很高