1. The spectrum of allergic diseases Hugo Van Bever Department of Pediatrics National University Singapore APAPARI workshop – Hanoi, Vietnam – May 2008

3. 1.Clean - well organized - tropical 2.High prevalence of allergic diseases 3.A lot of HDMs (Blomia tropicalis) 4.Strange food allergies (bird nest, etc…) HDB flat skyline

4. KH Hseih JL Huang A Tam G Wong HR Lee SI Lee S SiregarP Vichyanond Chen Pediatric Allergy in Asia (APAPARI) J Debruyn BW Lee H Van Bever M Bautista Starting 1998 Morikawa

5. APAPARI – JACIN MEETING, JAKARTA – APRIL 2006

6. APAPARI - Education 1. Joint meetings with Allergy Societies - 2002: Japan (Tokyo) - 2003:Singapore (workshop) - 2004: Hong Kong (IPRAIC) - 2005: S-Korea (Seoul) - 2006: Indonesia (Jakarta) - 2007: Philippines (Manila) & WAO (Bangkok) - 2008: Singapore (SPS – Oct 2008) 2. Training courses on pediatric allergy - 2006: Jakarta (Indonesia) / Balikpapan (Borneo) - 2007: Phom Penh (Cambodia) / Jakarta / Ho Chi Minh (Vietnam) - 2008: Hanoi (Vietnam)

7. Vietnamese studies on paediatric allergy -ISAAC-based asthma and atopic symptoms among Hanoi school children. Nga NN et al. Pediatr Allergy Immunol 2003, 14, 272-9. -Obesity is associated with increased risk of allergy in Vietnamese adolescents. Irei V et al. Eur J Clin Nutr 2005, 59, 571-7. -Poor sanitation and helminth infection protect against skin sensitization in Vietnamese children: a cross-sectional study. Flohr C, et val. J Allergy Clin Immunol 2006, 118, 1305 – 11. -Prevalence of asthma and asthma-like symptoms in Dalat Highlands, Vietnam. Sing Med J 2007, 48, 294 – 303.

8. ISAAC-based asthma and atopic symptoms among Hanoi school children. Nga NN et al. Pediatr Allergy Immunol 2003, 14, 272-9. - Hanoi -cross-sectional study -5 -11 year-old -Response rate 66.4% - 969 responders

9. Cumulative prevalence of asthma, rhinitis and eczema in Singaporean children. 1 - 2 yrs-old 2002 -2003 4 - 6 yrs-old 2000 6 – 7 yrs-old 2001 12 – 15 yr-old 2001

10. Increase in prevalence of allergic diseases - asthma - rhinitis - eczema Induction of the expression of allergy changes in the environment HYGIENE HYPOTHESIS

11. Allergy = a feature and NOT a disease ! = … the ability to produce specific antibodies (IgE) to different substances of the environment (inhalant and food allergens)… IgE inflammation shock organs symptoms = swelling - narrowing

12. Allergic diseases … ALLERGY healthy asthma rhinitis conjunctivitis enteritis migraine urticaria eczema

13. Positive skin tests in 273 HEALTHY children at the age 6-7 years (Belgium - 1996). ALLERGENn % - HDM218 % - Cat dander 62 % - Birch pollen 10 % - Grass pollen 83 % - ANY 29 11 %

14. Allergy, one feature with many faces SKIN AIRWAYS

15. Allergic diseases … mild to … severe

16. “ The Allergic March “

17. Environmental substances = allergens (proteins…) 1. Inhalant allergens house dust mites, pollen pets, moulds 2. Food allergens egg, cow’s milk, soy, wheat ( < 3 yrs) peanuts, fish, shrimp, etc… (> 3 yrs)

18. Contact with food allergens  eating – drinking  touching  smelling  breast milk - prenatal

19. Food allergens in house dust. Witteman AM, van Leeuwen J, van der Zee J, Aalberse RC. Int Arch Allergy Immunol. 1995 Aug;107(4):566-8. ovomucoid  -lactoglobulin microgr/g dust 10 1 0.1 0.01 The amount of ovomucoid and  -lactoglobulin in 11 house dust samples 0.073 microg/g dust = detection limit ovomucoid 0.016 microg/g dust = detection limit  lactoglobulin

20. “ Kiss of death “  5% of adults with food allergy  Foods: peanuts, nuts, apple, pea, fish  Relationship: husband, boyfriend, etc. Hallett et al, NEJM 2002, 346, 1833

21. House Dust Mites Blomia tropicalis Dermatophagoides farinae

22. Asthma Rhinitis Eczema

23. House Dust Mites in Singapore High temp and humidity provides perfect environment for HDMs High counts (> 100 mites/g dust) of HDM are isolated in Singapore A wide variety of mite species is isolated other than Dermatophagoides. Blomia tropicalis is predominant.

24. Mite Species Present in Singaporean Mattresses Species% (n = 50) B. tropicalis94 D. pteronyssinus80 S.brasiliensis84 T. granarius44 D. farinae26 A. malaysiensis20 C. malaccensis24 M. intermedius12 Chew FT 1999 Clin Exp Allergy 29:201-206

25. Allergic diseases 1. GENETIC CONSTITUTION 2. ENVIRONMENT - Prenatal (pregnancy) - Postnatal (first months of life)

26. Genetic constitution ParentsRisk 1. both are negative 18 % 2. mother negative – father positive 40 % 3. mother positive – father negative 50 % 4. both positive 70 % 5. both strongly positive 90 %

28. Allergic diseases 1. GENETIC CONSTITUTION 2. ENVIRONMENT - Prenatal (pregnancy) - Postnatal (first months of life)

29. Direction of immune responses in early life Birth Non-allergic (Th1) Allergic (Th2) allergic profile (Th2 predominance) Factors 1. constitution 2. bacterial load 3. allergen exposure

30. ATOPY = inbalance Th3 Th1 Th2 regulatory T cells IL-10, TGF-b

31. T helper lymphocytes Modified from S. Romagnani CEA, 36, 1357–1366

32. Roles of T cells Orihara, Kanami et al., WAO 2008 / Allergic disease

33. Postnatal immune deviation from allergic (Th2) to non-allergic (Th1) POSITIVE 1. Increased bacterial load - family size, farming - day care attendance - probiotics (Lactobacillus sp.) prebiotics, etc. 2. Tolerance through high exposure to allergens (pets – other allergens) NEGATIVE 1.House dust mite – pollen (low doses) 2. RSV 3. Pollution (DEPs – cigarette) 4. Antibiotics - paracetamol

34. Diagnosis of allergy 1. History 2. Clinical examination 3. SPT = golden standard ! 4. Specific IgE 5. Other lab tests: ECP, cytokines, etc… 6. eNO 7. Allergen provocation test (nasal, bronchial, etc…)

35. Unproven diagnostic tests for allergy… - IgG  against everything you can dream - Electrodermal tests (“ Bioreasonance tests “) - Other “witchcraft” (“ Kinesiology ”)

36. APPLIED KINESIOLOGY

37. Skin prick testing = golden standard for diagnosing allergy in children & adults