,哮喘变应原免疫治疗现状与思考,上海交通大学医学院苏州九龙医院 倪殿涛,过敏性疾病作为一个全球性问题,WAO White Book on Allergy 2011-2012,A steady increase in the prevalence of allergic diseases globally has occurred with about 30-40% of the world population now being affected by one or more allergic conditions,Types of allergies,Allergen,Any substance often a protein that induces an allergy Common allergens,过敏原种类很多 “除了水、 葡萄糖和盐之外 都可以成为过敏原”,Common cold or allergy,Asthma,Derived from the Greek root Originally did not define a disease, but was employed to describe respiratory symptoms of a variety of pulmonary conditions By the beginning of the 20th century, asthma was seen to be a unique illness characterized by spasmodic afflictions of the bronchial tubes. Today, asthma is seen as a chronic inflammatory disease which is not yet fully understood in its pathophysiology Therapy is still on the path to becoming optimal.,Bergmann KC.Asthma.Chem Immunol Allergy. 2014;100:69-80.,盲人摸象,2014 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 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 remodeling. Asthma with obesity: some obese patients with asthma have prominent respiratory symptoms and little eosinophilic airway inflammation.,GINA Guidelines for Asthma 2014,Terminology of allergic phenomena,idiosyncrasy - antipathy - Hypersensitivity -Anaphylaxis -allergy A.F. Coca and R.A. Cooke introduced the term atopy：hypersensitiveness occurred spontaneously atopy 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 intrinsic variants of the same disease,Chem Immunol Allergy. 2014;100:46-52.,Coombs and Gells Classification of Hypersensitivity,Does “intrinsic“ asthma exist?,Ten to forty percent of asthmatics are “intrinsic“ Analysis of bronchial mucosal 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 nonatopic,Humbert M.Does “intrinsic“ asthma exist?Rev Mal Respir. 2000 Feb;17(1 Pt 2):245-54,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 duration,Allergy. 2002 Jul;57(7):607-13.,Asthma phenotypes: nonallergic (intrinsic) asthma.,The definition ：subjects with asthma and with whom allergic sensitization cannot be demonstrated negative skin prick test or in vitro specific-IgE test to a panel of seasonal and perennial allergens Nonallergic 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 therapy,Peters SP. Asthma phenotypes: nonallergic (intrinsic) asthma. J Allergy Clin Immunol Pract. 2014 Nov-Dec;2(6):650-2,Novel diagnostic approaches and biological therapeutics for intrinsic asthma.,Controversies have emerged in relation to this concept Not finding specific allergen sensitization in an asthmatic patient neither excludes an allergic component nor the essential role that immunoglobulin E may play in asthma The atopic status is one among many other questions Omalizumab, the only monoclonal anti-immunoglobulin E antibody commercialized for asthma, should be tried in 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. 2014 Jul 8;7:365-71.,哪些哮喘患者需要行AIT？,过敏的概念 总tIgE,Senti et al Allergy 2011;66(6):798,1911 Noon 1th SCIT 1950s 1th SCIT Control Study; 1980s 1th DBPC SLIT; 2000s 1th sublingual Tablet 2011s Innovating for patient benefit,100 yeas of antigen specific immunotherpy,Allergen specific immunotherapy,Self-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 reactions Since even IgE dependent allergic reactions are carried out through activation of mast cells and basophils, and all allergens mentioned above can activate these cells we hypothesize that allergic reactions are mast cell and basophil mediated inflammatory process as it is the activated mast cells