Is there a Food Allergy Epidemic in Asia?

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1 Session 1: Understanding Food Allergies 2011 Prevalence of Food Allergies in Southeast Asia Food Allergy: A hot topic BW Lee, Dept Paediatrics National University of Singapore 2nd wave of the allergy epidemic? Food Allergy Studies reporting Food Allergy Prevalence in preschool children < 5 years J Allergy Clin Immunol 2007 Is there a Food Allergy Epidemic in Asia? Published data only available from 16/89 countries (those without data not shown) OFC proven food allergy Symptoms and sensitisation Parental reporting Prescott SL et al WAOJ 2013

2 Summary of Prevalence of Food Allergies in Singapore Peanut Allergy Around the World 3 % Prevalence UK 1 (Peanut/tree nut) USA Canada Australia Singapore Philippines China 0 Thailand Lee AJ and Shek LP Singapore Med J 2014 Shek et al, J Allergy Clin Immunol, 2010 Hourihane et al, J Allergy Clin Immunol 2007 Gusto Cohort, Singapore (unpublished) Sicherer et al, J Allergy Clin Immunol 2010 Chen et al, Pediatric Allergy Immunol 2011 Kagan et al, J Allergy Clin Immunol 2003 Tang et al, J Allergy Clin Immunol 2012 Osborne et al, J Allergy Clin Immunol 2011 Lao-Araya Ped Int 2012 Peanut Allergy and Country of Birth Data From Singapore 1999 Born in the West Caucasian 5.5 p<0.05 Odds ratio (Compared vs Asia born Asians) Asian 3.8 No peanut anaphylaxis cases Asian = Chinese, Malay, Indian, Filipino Western countries = Australia, New Zealand, United Kingdom, North America and Western Europe Shek et al J Allergy Clin Immunol 2010 Goh DL et al Allergy 1999

3 Singapore (KKH) Paediatric Food Anaphylaxis Jan 2005 to Dec 2009 Common Food Allergies in Asia Peanut Food Anaphylaxis (n=73) Median age 6.2 years Seafood 8% 1% 4% 15% 19% 12% Bird's Nest Egg Cow milk Fruits (banana, jackfruit, mango) Fish Shellfish Allergy 4% Treenuts 4% 12% 5% 5% 11% 13 Peanut anaphylaxis over 5 years 12 Chinese (1 born in Canada), 1 Caucasian Honey Wheat Others (HDM contaminated flour, Preservatives/colouring) Unknown Liew WK et al. AP Allergy 2013

4 % Shellfish Allergy Population-based Surveys 5.2 Shellfish Most Common Cause of Anaphylaxis in Asia Thailand Adults and Children Singapore Adults Hongkong Adults Taiwan Adults and Children 0 USA (6-17yr) Singapore/Philippines (14-16yr) Sicherer S, J Allergy Clin Immunol 2004 Shek LP, J Allergy Clin Immunol 2010 Jirapongsaranuruk O et al Ann Allergy Immunol 2007 Thong B et al Sing Med J 2005 Smit DV et al J Emerg Med 2005 Hsin Y et al Asian Pac J Allergy Immunol 2011 Food Challenge Provocation Dose Thai, children 1g to 63g, cooked prawn Jirapongsananuruk et al Clin Exp Allergy 2008 Order: Decapods Singapore, Adolescents and Adults: 2g to 80g, cooked prawn Gerez et al, unpublished Canada, Adult (1 patient): 14g, freeze dried, capsule Bernstein et al J Allergy Clin Immunol 1982; 70:205 10

5 Fig 1. % of students with symptom Distribution of symptoms during the most severe reaction (n=674) to shellfish Hives Swollen eyes & lips Vomiting & Diarrhoea Abdominal pain Runny nose Itchy throat Throat tightness & Wheezing Coughing Feeling faint or dizzy & Loss of consciousness Redness of skin Challenge + - Shek et al, J Allergy Clin Immunol, /39 shellfish allergy cases specific IgE to shrimp (-) shrimp tropomyosin (Pen a 1, Pen m1, Pen I 1, Lit v 1) (-) dust mite tropomyosin (Der p 10, Blo t 10) (+) Mild Crustacean Seafood Allergy Tropomyosin A pan-allergen Inhalant-food syndrome Dust mites as the sensitizing allergen Crustacean shellfish as the cross reactive allergen Thayalasingham M et al, Clin Exp Allergy 2015

6 Conclusions from reciprocal IgE inhibition Studies: It s Not Always Just Food Allergy Mites are the primary sensitizer in humid-climate 15 year Old Girl Has asthma and allergic rhinitis Ingested home-made tempura prawns fried coated with Japanese flour Developed urticaria, throat discomfort, severe wheezing 20 min later Treated at emergency dept for anaphylaxis - SaO 2 77%

7 Gross Appearance of Flour Areas of light brown discolouration

8 Prebiotic (Carbohydrate) Triggered Anaphylaxis Anaphylaxis to Cow s milk formula Anaphylaxis to cow s milk formula containing short-chain galacto-oligosaccharide (GOS) Report of 5 Cases SKIN PRICK TEST SPT to CMF negative Chiang et al J Allergy Clin Immunol 2012 A: COW S MILK FORMULA (numerical refer to diameters weal) Patient Positive Histamine 7 x 5 10 x 7 5 x 5 6 x 6 9x7 Negative Control Cow s Milk CMF1 with prebiotics scgos + lcfos 7 x 6 3 x 3 1 x 1 4 x 4 6x5 CMF1 without prebiotics CMF2 with prebiotic scgos 7 x 6 5 x 3 5 x 5 6 x 6 14x10 Std Vivinal GOS (7.2mg/ml) 3 x 3 7 x x 5 3 x 3 SPT to CMF without PREBIOTICS negative SPT to CMF containing GOS positive scgos = short chain Galacto-oligosaccharides lcfos = long chain Fructo-oliogosaccharides Chiang et al J Allergy Clin Immunol 2012 CD203c (MFI) CD63 (%) Basophil Activation Tests a-ige E CMF1 w/o prebiotics IcFOS S Cow s milk formula Galacto-oligosaccharide CMF1 CMF2 Std GOS Actual GOS concentration in the samples (mg/ml) Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 whole blood whole blood Chiang et al J Allergy Clin Immunol 2012

9 GOS GRAS dossier 2007 Structure of GOS GOS is produced by enzymatic transgalactosylation of lactose by β-galactosidase Variable chains of galactose with one molecule of glucose Fractions of GOS mixture High-Performance Anion-Exchange Chromatography with Pulsed Amperometric Detection (HPAEC-PAD) Dose-dependent effect of scgos fractions on activation of in vitro sensitized control basophils Inhibition of scgos-induced basophil degranulation by the phosphatidylinositol 3-kinase inhibitor wortmannin DP=degrees of polymerization (Gal)6-Glu (Gal)5-Glu (Gal)4-Glu (Gal)3-Glu (Gal)2-Glu Gal-Glu Glu or Gal scgos activation of basophils requires the PI-3-kinase pathway. This is consistent with IgE-mediated activation. Chiang et al J Allergy Clin Immunol 2012

10 Milk product with GOS introduced in Sept million cartons sold a day in Vietnam 15/16 cases aged 2-15 years old consumed milk with GOS 12/15 within 3 to 20 mins of milk consumption. 3/15 with acute respiratory problems

11 Hoya Antigen Asthma in Japan What is the Primary Sensitizer? Sea squirt antigen H or Hoya antigen It is a hexosamine rich glycoprotein Causes occupational asthma in oyster shucklers Alpha-Galactose IgE Epitopes (mammalian CCD) Cabohydrate Allergen Epitopes - cross-reactive carbohydrate determinants (CCD) of N-linked glycans Aalberse RC, J Allergy Clin Immunol 1981; 68: Cetuximab: N-linked oligosaccharides contains the a- gal epitopes Immediate onset anaphylaxis Mammalian meat - Pork and Beef: gal-a-1,3-gal-b- 1,4-GlcNAc Delayed anaphylaxis reaction (3-6 hours) Clinically insignificant Low titre anti-glycan IgE antibodies High affinity blocking IgG antibodies False positive specific IgE tests Commins and Platts Mills J Allergy Clin Immunol 2015

12 Examples of plant and insect N-glycans Conclusions Plant (pollen, vegetables, fruits and natural rubber latex) It does not appear that Asia is facing a food allergy epidemic Better oral tolerance? Insect (Bee venom) Pattern of food allergy is different and may be related to environmental allergens Inhalant/environmental and food allergens Curr Opin Allergy Clin Immunol Aug;13(4):360-4

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