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

2. 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)

3. 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.

4. 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

5. 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

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

7. 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

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

9. 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 %

10. 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)

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

12. 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

13. “ 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

14. 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.

15. 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

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

17. 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 %

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

19. 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

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

21. 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

22. 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…)

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

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