Introduction on Allergy and Allergic Diseases

Transcription

1 Introduction on Allergy and Allergic Diseases APAPARI Workshop Cambodia, September 12, 2015 Jiu Yao Wang, MD, DPhil Distinguished Professor of Pediatrics Director, Allergy and Clinical Immunology Research (ACIR) Center National Cheng Kung University Tainan, TAIWAN Allergic disease: A major global public health issue Asthma Allergic rhinitis Allergic dermatitis (eczema) Allergic conjunctivitis Allergic entrocolitis Food allergy Anaphylaxis Angioedma and urticara Eosinophlic disorder 1

2 Asthma prevalence in children Country Peru New Zealand Australia Uruguay Kuwait Canada USA Kenya Chile Japan Paraguay Hong Kong Singapore Philippines Malta France Pakistan Spain Morocco Argentina Thailand South Africa Portugal Malaysia Austria Sweden Germany Italy Finland Lebanon South Korea Poland Iran India China Estonia Taiwan Indonesia Uzbekistan Latvia Russia Albania Asthma is the most common disease among children 1,2 Children living in poverty: 2 Suffer the largest burden of childhood asthma morbidity Are more likely to receive inadequate therapy Prevalence of asthma symptoms (%) 3 1. Bibi HS et al. Respir Med 2006; 100: Halterman JS et al. Ambulatory Paed 2003; 3: ISAAC Steering Committee. Lancet 1998; 351: Asthma and Allergy: Diseases of the West? Global burden of asthma (WHO 2004) 2

3 Pediatric Allergy in Asia (APAPARI) Starting 1998 Chen HR Lee SI Lee Morikawa P Vichyanond KH Hseih JL Huang A Tam G Wong J Debruyn BW Lee H Van Bever S Siregar M Bautista Taipei Bangkok Yogyakarta Seoul 3

4 ISAAC based asthma and atopic symptoms among Hanoi school children Nga NN et al. Pediatr Allergy Immunol 2003, 14, Hanoi cross sectional study 5 11 year old Response rate 66.4% 969 responders The prevalence of allergic diseases in Taipei Primary school Junior High Allergic diseases Wheezing ever 16.1% 19.8% 10.6% Wheezing within one year 9.6% 10.1% 5.2% 14.3% 7.0% AR symptoms ever 36.5% 47.8% 35.1% 53.1% AR within one year 30.8% 43.5% 28.8% 43.6% Eczema ever Eczema within one year 5.2% 10.7% 3.5% 6.8% 2.9% 1.4% 7.4% 4.1% 4

5 Asthma prevalence Guo YL, 1999 Tainan adolescent >11% 9 Burden of Asthma in Children ~6.3 million 18 years of age ~3.5 million physician visits* ~ emergency department visits* ~ Hospitalizations* ~14 million missed school days annually *Includes 1999 or 2000 annual estimates for children <15 years of age. American Lung Association. 2003; Mannino et al. MMWR. 2002;51:1-13. ~1/3 of pediatric asthma deaths in those classified with mild asthma 5

6 The Allergy March Allergy: One disease with many faces 6

7 Genes and Hereditary Environmental Changes Atopy 1. Time of exposure 2. Duration Immunological Development 南瀛過敏氣喘兒保健協會 7

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9 Nature Rev Immunol, 2010 Dec prospective birth cohort study of 263,620 children born in 1998 and 9,910 children born in 2003, separately, from Taiwan national health insurance registry database (NHIRD). To determine the temporal relationship between acetaminophen and/or antibiotic exposure and the development of allergic diseases. International Journal of Epidemiology 2013;42:

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13 Airway Inflammation and Remodeling Ⅵ allergen histamine LT PAF TxA2 allergen MBP ECP EPO TGF-b SP NKA CGRP Ach mast cell IL-4 TNF macrophage Th0 neutrnophil eosinophil PAF LTC4 PGD2 platelet collagen Ⅲ, V fibronectin Th2 vascular permeability edema eosinophil macrophage TGF-b IL-1 PDGF TNF-a fibroblast IL-5 GM-CSF vascular endothelial cell ICAM VCAM Passge of eosinophil through the intracellular space inside of the vessel airway wall remodeling fibroblast activation epithelial fibrogenesis hypertrophy and hyperplasia of smooth muscle and mucous gland Interaction of Mite Allergens and Lung Epithelial Cells Dectin TLR2/4 MD2 CD14 Der p1 cysteine protease Der p3 and p9 serine proteases PAR-2 DC-SIGN CCL20 TSLP IL-25 IL-33 MR Type 2 innate helper cells NF- B activation CD161 CRTH2 GM-CSF, RANTES protein, and eotaxin Phosphoinositide hydrolysis Cytosolic Ca2+ mobilization Airway hyperresponsiveness and inflammation 13

14 Allergy skin prick testing Skin prick test / positive result Inhalant Allergens in 196 Asthmatic Children in Tainan Area 100 Cat dander Dog dander Feather mix 80 Cockroach HD(Der.f) HD(Der. f) Alteraria Penicillium Cladosporium Aspergillus Pigweed Mix Bermuda Grass Mulberry Mix Eucalyptus cotton wood Pine Mix Grass Mix Ragweed Mix 0 (%) House Dusts Fungus Pollens (ref: Wang JY. J Formosan Med Assoc 1992;91) 14

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16 Steps involved in the development of allergic diseases. A switch to the production of allergenspecific IgE detectable in serum leads to the sensitization of a patient, reflecting its atopic status. However, not all sensitized individuals suffer from allergic symptoms highlighting the limitation of in vitro allergy diagnoses. Allergen challenge tests are needed to confirm the clinical relevance of an allergy suspected from the clinical history and from the presence of allergen specific IgE in serum. 1. History 2. Clinical examination 3. SPT = golden standard! Diagnosis of allergy 4. Specific IgE in sera 5. Other lab tests: ECP, cytokines, etc 6. FeNO 7. Allergen provocation test (nasal, bronchial, etc ) 16

17 成大過敏與臨床免疫研究中心 17