Food Allergy studies in New Zealand Associate Professor

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Food Allergy studies in New Zealand Associate Professor Rohan Ameratunga

Food Allergy studies in New Zealand Associate Professor Rohan Ameratunga

Outline of talk • Case history: management of food allergy • Food allergens incl

Outline of talk • Case history: management of food allergy • Food allergens incl cross-reactions • Epidemiology of food allergy • Is food allergy increasing? • Consequences of lack of FA data in NZ • Food allergy studies in NZ

Case history (type 1 reaction) • Emma aged 18 months • Chronic eczema •

Case history (type 1 reaction) • Emma aged 18 months • Chronic eczema • Ate peanut butter • Within 5 minutes developed hives, • angioedema and breathing difficulty Treated appropriately-recovery

Case history (type 1 reaction) • Diagnostic procedures • Management plan- reduce risk of

Case history (type 1 reaction) • Diagnostic procedures • Management plan- reduce risk of recurrence • Is there any specific treatment? • What is her long-term prognosis? • How common is this problem? • Is this problem increasing? • What medical services are available in NZ? • Can this problem be prevented?

Adverse Reactions to Food Toxic (eg. Ciguatera) Immune (Food Allergy) Ig. E Non Toxic

Adverse Reactions to Food Toxic (eg. Ciguatera) Immune (Food Allergy) Ig. E Non Toxic Non Immune (Food Intolerance) Non-Ig. E Enzymatic Chemical Pharmacologic (eg eczema) (eg celiac) Unknown (lactase) (eg. salicylate) (histamine) Food Aversion

Diagnostic procedures • Short term elimination diets • Trial of Neocate (with above) •

Diagnostic procedures • Short term elimination diets • Trial of Neocate (with above) • Food challenges • Skin testing • RAST testing • Food patch testing • Novel methods incl peptide microarrays

RAST testing Food cut-off sensitivity specificity Egg Milk Peanut Fish 6. 0 U/ml 15.

RAST testing Food cut-off sensitivity specificity Egg Milk Peanut Fish 6. 0 U/ml 15. 0 U/ml 19. 5 U/ml 61% 51% 73% 40% 92% 98% 92% 99% Wheat > Soy > 100 U/ml PPV 60% < 50%

Food allergen avoidance/ Long-term elimination diets • Accurate diagnosis is critical • Paediatric dietician

Food allergen avoidance/ Long-term elimination diets • Accurate diagnosis is critical • Paediatric dietician assessment essential • Reading food labels • Manufactured Food Database • Allergy New Zealand incl e-mail alerts

Food allergy management plan • Education re foods and avoidance-dietician • Written action plan

Food allergy management plan • Education re foods and avoidance-dietician • Written action plan • MEDIC-ALERT emblem-velcro • ACC form • Public Health nurses to visit school/daycare • Anaphylaxis video (Allergy NZ) • Follow up RAST testing 6 -12 monthly • Food challenge if RAST becomes negative

Food allergens • When food allergy is confirmed, it usually proves • • to

Food allergens • When food allergy is confirmed, it usually proves • • to be restricted to 1 or 2 foods Young children: milk, egg, peanut, tree nuts, soy, and wheat account for about 90% of cases Adolescents and adults: peanut, fish, shellfish, and tree nuts account for about 85% Cultural variation eg rice in Japan, increasing sesame allergy in NZ and Australia Newly recognized allergens incl Anisakis, Lupin

Treatment of food allergy • Avoidance, avoidance • Anti-Ig. E • Peanut desensitisation •

Treatment of food allergy • Avoidance, avoidance • Anti-Ig. E • Peanut desensitisation • Others incl Chinese herbs

The prevalence of food allergy: A meta-analysis Rona et al JACI Sep 2007 •

The prevalence of food allergy: A meta-analysis Rona et al JACI Sep 2007 • Papers selected from the literature • Categorised according to methodology • Cochrane methodology • Stringent criteria for inclusion • Divided according to age group • Unselected population papers, not enriched populations such as clinic patients

Symptoms, testing and food challenges

Symptoms, testing and food challenges

Is peanut allergy increasing? Grundy et al 2002 JACI 110(5) 784 -789 • Isle

Is peanut allergy increasing? Grundy et al 2002 JACI 110(5) 784 -789 • Isle of Wight study: • Examined sensitisation • Significance (p=0. 001) • 1989 -1994 1. 1% • 1994 -1996 3. 3% allergy (p=0. 2) 0. 5% 1%

Is food allergy increasing? • Increase in hospital admissions for • anaphylaxis in Australia

Is food allergy increasing? • Increase in hospital admissions for • anaphylaxis in Australia Consistent methodologies needed, therefore, Uncertain…

The changing face of food hypersensitivity in an Asian community Chiang et al Clin

The changing face of food hypersensitivity in an Asian community Chiang et al Clin Exp Allergy 2007 • Very little data on food allergy in Asia • Different diets • Ethnic makeup Chinese, Indian, Malays, • • • Eurasian Melting pot: Rapidly changing lifestyle Increasing westernisation of diet Previous data indicates Chinese have major issues with fish and shellfish

The changing face of food hypersensitivity in an Asian community • Study centre Kerdang

The changing face of food hypersensitivity in an Asian community • Study centre Kerdang Kerbau children's • • Hospital outpatient centre Methods prospective data on children referred with suspected food allergy Spt data collected 2003 -2006 Inclusion compatible history and + spt Other allergies documented eczema and allergic rhinitis, asthma

The changing face of food hypersensitivity in an Asian community • Spt positive results

The changing face of food hypersensitivity in an Asian community • Spt positive results • Egg 40% • Shellfish 39% • Peanuts 27% • Fish 13% • Cow’s milk 12% • Sesame 9% • Wheat 6% • Soy 3%

The changing face of food hypersensitivity in an Asian community • Food introduction •

The changing face of food hypersensitivity in an Asian community • Food introduction • Egg 8. 6 mo • Fish 6. 6 mo • Shellfish 12. 2 mo • Fish introduced at the same time or earlier as eggs in 83% of children

The changing epidemiology of food allergy Food allergy studies in NZ

The changing epidemiology of food allergy Food allergy studies in NZ

Lack of food allergy data in New Zealand • Currently no data • May

Lack of food allergy data in New Zealand • Currently no data • May be similar to overseas? ? • However ethnic makeup different • Ethnic makeup rapidly changing • Role of genetics • Feeding practices may be different • Available foods are different eg shellfish

Food allergy studies: unanswered questions • • What is the burden of food allergy?

Food allergy studies: unanswered questions • • What is the burden of food allergy? What services are utilised by patients What are the gaps in services What is the response of Gov’t agencies? Are there any unusual food allergies in NZ? What is the natural history of food allergy? Can food allergy be prevented?

Agencies involved in food allergy • • • Ministry of health ARPHS DHBNZ Ministry

Agencies involved in food allergy • • • Ministry of health ARPHS DHBNZ Ministry of Education PHARMAC MEDSAFE ACC Ministry of Trade and Industry FSANZ NZFSA IGA

Lack of food allergy Research in New Zealand • Lack of data is hindering

Lack of food allergy Research in New Zealand • Lack of data is hindering medical services • No paediatric allergy specialist in south • Island Epipens unfunded

Lack of food allergy Research in New Zealand • Ad hoc approach in schools

Lack of food allergy Research in New Zealand • Ad hoc approach in schools • Issues with preschools

Lack of food allergy Research in New Zealand • Risk management issues for food

Lack of food allergy Research in New Zealand • Risk management issues for food industry • • • and hospitality industry Important for food export industry Public not aware of the problem Impact on quality of life not appreciated

Is there an ideal method to determine food allergy prevalence? • Large scale unselected

Is there an ideal method to determine food allergy prevalence? • Large scale unselected cohort • Regular clinical review and testing • DBPCFC for patients with Sx or +ve tests • But. . .

Is there an ideal method? • Time dependent data • Risk of food challenges

Is there an ideal method? • Time dependent data • Risk of food challenges • Expense of studies • No data on adults • Change in demographics • Change in feeding practices • Changes in available foods • Therefore likely to be different in others parts of NZ

Difficulties with food allergy Epidemiology • Symptoms vary according to age • Symptoms not

Difficulties with food allergy Epidemiology • Symptoms vary according to age • Symptoms not confined to one organ system • Delayed reactions • Patients may not be aware a food is • • triggering symptoms Survey instruments are not well established The need for lab tests Need for food challenges- expense and risks Studies are therefore expensive

Difficulties with FA studies in NZ • Funding agencies- low priority • Food industry

Difficulties with FA studies in NZ • Funding agencies- low priority • Food industry unaware/ denial of risk

Advantages of working with Plunket clinics • • • Up to 90% of New

Advantages of working with Plunket clinics • • • Up to 90% of New Zealand’s infants/young children are monitored through Plunket clinics Conducting our studies through Plunket is likely to give us a relatively unbiased sample for community studies of FA in NZ This work may increase the awareness of immune-mediated FA symptoms and encourage patients to seek medical help.

Study 1: Pilot study of Plunket Clinics in Auckland Interviewer assisted food allergy questionnaire

Study 1: Pilot study of Plunket Clinics in Auckland Interviewer assisted food allergy questionnaire • Clinics Manurewa, Tuakau, Sylvia Park • Participation rate 62% (68/102) • Total number of interviews 68 • Total number of children 96

Pilot study of Plunket Clinics in Auckland FA symptoms-associated with foods • Hives •

Pilot study of Plunket Clinics in Auckland FA symptoms-associated with foods • Hives • Swelling in the skin • Itchy skin • Eczema (skin inflammation) • Stomach upset (nausea, vomiting, pain) • Mouth and or throat swelling • Eye and nose problems (hay-fever) • Throat tightness • Breathing difficulties (not wheeze) • Wheeze (asthma) • Life threatening reaction (anaphylaxis) • Other symptom (please list)

Study 1: Pilot study of Plunket Clinics in Auckland Interviewer assisted food allergy questionnaire

Study 1: Pilot study of Plunket Clinics in Auckland Interviewer assisted food allergy questionnaire • Which health professional made Dx? • Type of testing undertaken • Treatments given • Demographic questions including ethnicity, education level etc

Pilot study of Plunket Clinics in Auckland FA symptoms: hives

Pilot study of Plunket Clinics in Auckland FA symptoms: hives

Pilot study of Plunket Clinics in Auckland FA symptoms: eczema

Pilot study of Plunket Clinics in Auckland FA symptoms: eczema

Pilot study of Plunket Clinics in Auckland Ethnicities of participants • NZ European •

Pilot study of Plunket Clinics in Auckland Ethnicities of participants • NZ European • Maori • Chinese • Samoan • Indian • Cook Island • Tongan • Niuean study 2006 census 62% 20. 8% 9. 4% 8. 3% 11. 5% 5. 2% 4% (60. 4%) (14. 3%) (3. 7%) (3. 3%) (2. 7%) (1. 5%) (1. 3%)

Pilot study of Plunket Clinics in Auckland Results: FA symptoms • FA symptoms 11/96

Pilot study of Plunket Clinics in Auckland Results: FA symptoms • FA symptoms 11/96 • Males: females 4: 7 • Diagnosed by allergy specialist 3/11 • Consulted GP 8/11 • FA suspected by GP (no testing) 2/8 • Consulted GP: FA not considered 6/8 • Ethnicities: NZE, Maori, Indian, Chinese, Niuean

Pilot study of Plunket Clinics in Auckland FA symptoms: Allergy specialist • 39/12 male

Pilot study of Plunket Clinics in Auckland FA symptoms: Allergy specialist • 39/12 male infant: hives with baby cereal: • peanuts, milk allergy 36/12 female twins: hives with formula: milk, egg peanut, soy

Pilot study of Plunket Clinics in Auckland FA suspected by GP- not tested •

Pilot study of Plunket Clinics in Auckland FA suspected by GP- not tested • FA symptoms - not investigated 8/11 • FA suspected by GP 2/8 • 14/12 Hives with strawberry yoghurt • 60/12 Worsening eczema after cow’s milk • Advised “too young” to do skin tests • Neither tested

Pilot study of Plunket Clinics in Auckland Consulted GP but not investigated 6/8 Age

Pilot study of Plunket Clinics in Auckland Consulted GP but not investigated 6/8 Age 4/14 7/12 17/12 4/12 9/12 30/12 Symptoms eczema vomiting hives vomit/aspirate angioedema hives/vomiting Suspected food milk formula wheat, milk kiwifruit milk formula wheat, milk, egg strawberries, tomato

Pilot study of Plunket Clinics in Auckland Results: Eczema • Eczema 29/96 (30%) •

Pilot study of Plunket Clinics in Auckland Results: Eczema • Eczema 29/96 (30%) • Treated by GP 17/96 (18%) • NZ Health survey 14% with eczema • Some mothers (4/29) changed own diet • while breast feeding- eczema improved. Nutritional risks of ad hoc diets

Pilot study of Plunket Clinics in Auckland Results: FA and family history of allergies

Pilot study of Plunket Clinics in Auckland Results: FA and family history of allergies FA Sx No FA Sx • FH allergies 55% 16% • No FH allergies 45% 84%

Disadvantages of working with Plunket clinics • • Parents of children > 2 yrs

Disadvantages of working with Plunket clinics • • Parents of children > 2 yrs stop attending Plunket clinics May not attend frequently with second child Ethnic issues Language, transport Other providers eg Tamariki ora

Pilot study of Plunket Clinics in Auckland Limitations • Limitations of using Plunket •

Pilot study of Plunket Clinics in Auckland Limitations • Limitations of using Plunket • No testing was undertaken • No food challenges were undertaken • Small sample size • Geographic variation • Questionnaire needs to be validated

Pilot study of Plunket Clinics in Auckland Conclusions from preliminary findings • FA probably

Pilot study of Plunket Clinics in Auckland Conclusions from preliminary findings • FA probably at least as common in NZ • Eczema is a major issue • Under recognised • Under investigated • Under treated • Affects all ethnicities • Lactating mothers are running significant health risks with ad hoc diets

Study 2 Larger cross-sectional study of FA • Larger study of FA symptoms in

Study 2 Larger cross-sectional study of FA • Larger study of FA symptoms in Auckland • Practical issues • Interview room ? Mobile office • Languages • Cost of testing • Food challenges • Funding • Value? ? ?

Study 3 Breast feeding and FA prevention • Currently no data on the role

Study 3 Breast feeding and FA prevention • Currently no data on the role of elimination • • diets and breast feeding Mothers are given conflicting advice on early vs delayed introduction of allergenic foods Nutritional risks in ad hoc diets

Dietary prevention recommendations (Sicherer and Burks, 2008) AAP 2008 Clinical Report AAP 2000 ESPACI/ESPGH

Dietary prevention recommendations (Sicherer and Burks, 2008) AAP 2008 Clinical Report AAP 2000 ESPACI/ESPGH AN 1999, ESPGHAN 2008 SP-EEACI 2004, 2008 High risk Parent or sibling with documented allergy Biparental or parent plus sibling Parent or sibling Pregnancy avoidance Lack of evidence Possibly peanut Breast Feed exclusively until Evidence for 3 -4 Mo (4 -6 Mo tied to solids introduction*) 6 Mo Maternal lactation avoidance of allergens Some evidence for reduced atopic dermatitis Peanuts, tree nuts (consider egg, milk, fish & perhaps other foods) *advice that is the same as for not high risk No special diet* 4 -6 Mo* At least 4 Mo, prefer 6 Mo* No special diet*

Study 3 Breast feeding and FA prevention Aim: To determine whether dietary exposure (the

Study 3 Breast feeding and FA prevention Aim: To determine whether dietary exposure (the mother’s dietary intake while breastfeeding, formula feeding and the introduction of solids) influences allergen sensitisation in infants at high risk of FA up to one year

Study Phases Phase 1 • Pretest food frequency questionnaire (FFQ) with mothers of high

Study Phases Phase 1 • Pretest food frequency questionnaire (FFQ) with mothers of high risk FA children • Pretest FFQ with FA dietitians • Seek feedback on proposed methodology Phase 2 • • Validate FFQ (frequency of maternal intake of allergen containing foods) by: Compare dietary intake with food sensitivity in infant Responses in FA questionnaire Validate FA questionnaire

Study Phases Phase 3 • • • Pilot study over 1 year Ability to

Study Phases Phase 3 • • • Pilot study over 1 year Ability to recruit subjects Advice given Testing compliance Power calculations Phase 4 • Main study over 5 years.

Study 3 Breast feeding and FA prevention

Study 3 Breast feeding and FA prevention

Study 3 Breast feeding and FA prevention

Study 3 Breast feeding and FA prevention

Study 3 Breast feeding and FA prevention

Study 3 Breast feeding and FA prevention

Study 3 Breast feeding and FA prevention

Study 3 Breast feeding and FA prevention

Study 3 Breast feeding and FA prevention Eligibility • Have an older child with

Study 3 Breast feeding and FA prevention Eligibility • Have an older child with proven FA • Pregnant- 34/40+ • Regular FA questionnaire • Regular dietary assessment • RAST testing cord blood and 5 and 12 • months Prelude to a longer cohort study

Funding: unrestricted grants • Nutricia • ADHB Charitable trust • Allergy New Zealand •

Funding: unrestricted grants • Nutricia • ADHB Charitable trust • Allergy New Zealand • ASCIA • Australian Laboratory Sciences • William and Lois Manchester trust

Food Allergy Research Group • Christine Crooks (Lab. Plus) • Maia Brewerton (Wellington Hospital)

Food Allergy Research Group • Christine Crooks (Lab. Plus) • Maia Brewerton (Wellington Hospital) • Steve Buetow (Uo. A) • Penny Jorgensen (Allergy New Zealand) • Elizabeth Robinson (Uo. A) • Shannon Brothers (Starship) • Clare Wall (Uo. A) • Allen Liang Allergy Specialist • Rohan Ameratunga (Lab. Plus, Chair)

Paediatric food allergy/ eczema clinic JHU Prof Robert Wood Prof Hugh Sampson Prof Ken

Paediatric food allergy/ eczema clinic JHU Prof Robert Wood Prof Hugh Sampson Prof Ken Schurberth