The spectrum of allergic diseases

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

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

4. J Debruyn BW Lee H Van Bever HR Lee SI Lee Chen P Vichyanond KH Hseih JL Huang A Tam G Wong S Siregar M Bautista Pediatric Allergy in Asia (APAPARI) 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. NgaNN 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. 6 – 7 yrs-old 2001 4 - 6 yrs-old 2000 12 – 15 yr-old 2001 1 - 2 yrs-old 2002 -2003

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

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

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

13. Positive skin tests in 273 HEALTHY children at the age 6-7 years (Belgium - 1996). ALLERGEN n % - HDM 21 8 % - Cat dander 6 2 % - Birch pollen 1 0 % - Grass pollen 8 3 % - ANY 29 11 %

14. Allergy, one feature with many faces AIRWAYS SKIN

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. microgr/g dust 10 1 0.1 0.01 ovomucoid b-lactoglobulin The amount of ovomucoid and b-lactoglobulin in 11 house dust samples 0.073 microg/g dust = detection limit ovomucoid 0.016 microg/g dust = detection limit b-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 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 Parents Risk 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 Allergic (Th2) allergic profile (Th2 predominance) Birth Factors 1. constitution 2. bacterial load 3. allergen exposure Non-allergic (Th1)

30. ATOPY = inbalance Th1 Th3 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 / Allergic disease Orihara, Kanami et al., WAO 2008

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