Food Allergy studies in New ZealandAssociate Professor Rohan Ameratunga

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• 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 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) Non Toxic

Immune Non Immune (Food Allergy) (Food Intolerance)

IgE Non-IgE Enzymatic Chemical Pharmacologic

Unknown Food Aversion(lactase) (histamine)(eg eczema) (eg celiac) (eg.salicylate)

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 6.0 U/ml 61% 92%Milk 15 U/ml 51% 98%Peanut 15.0 U/ml 73% 92%Fish 19.5 U/ml 40% 99%

Wheat > 100 U/ml PPV 60%Soy > 100 U/ml PPV < 50%

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

• 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 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 avoidance

• Anti-IgE

• Peanut desensitisation

• Others incl Chinese herbs

The prevalence of food allergy: A meta-analysisRona 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

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

• Isle of Wight study:

• Examined sensitisation allergy

• Significance (p=0.001) (p=0.2)

• 1989-1994 1.1% 0.5%

• 1994-1996 3.3% 1%

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 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 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• 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• Egg 8.6mo• Fish 6.6mo• Shellfish 12.2mo• Fish introduced at the same time or earlier as

eggs in 83% of children

The changing epidemiology of food allergyFood allergy studies in NZ

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?• 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 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 medical services

• No paediatric allergy specialist in south Island

• Epipens unfunded

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 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 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• 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 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 unaware/ denial of risk

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 AucklandInterviewer 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 AucklandFA 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 AucklandInterviewer 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 AucklandFA symptoms: hives

Pilot study of Plunket Clinics in AucklandFA symptoms: eczema

Pilot study of Plunket Clinics in AucklandEthnicities of participants

study 2006 census

• NZ European 62% (60.4%)• Maori 20.8% (14.3%)• Chinese 9.4% (3.7%)• Samoan 8.3% (3.3%)• Indian 11.5% (2.7%)• Cook Island 5.2% (1.5%)• Tongan 5.2% (1.3%)• Niuean 4%

Pilot study of Plunket Clinics in AucklandResults: 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 AucklandFA 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 AucklandFA 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 AucklandConsulted GP but not investigated 6/8

Age Symptoms Suspected food

4/14 eczema milk formula

7/12 vomiting wheat, milk

17/12 hives kiwifruit

4/12 vomit/aspirate milk formula

9/12 angioedema wheat, milk, egg

30/12 hives/vomiting strawberries, tomato

Pilot study of Plunket Clinics in AucklandResults: 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 AucklandResults: 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 > 2yrs 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 AucklandLimitations

• 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 AucklandConclusions 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 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 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/ESPGHAN 1999,ESPGHAN 2008

SP-EEACI 2004, 2008

High risk Parent or sibling with documented allergy

Biparental or parent plus sibling

Parent or sibling Parent or sibling

Pregnancy avoidance Lack of evidence Possibly peanut No special diet*

Breast Feed exclusively until

Evidence for 3-4 Mo (4-6 Mo tied to solids introduction*)

6 Mo 4-6Mo* At least 4Mo, prefer 6Mo*

Maternal lactation avoidance of allergens

Some evidence for reduced atopic dermatitis

Peanuts, tree nuts (consider egg, milk, fish & perhaps other foods)

No special diet*

*advice that is the same as for not high risk

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

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 infantResponses in FA questionnaire

• Validate FA questionnaire

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 Phases

Study 3 Breast feeding and FA prevention

Food Allergy Prevention…Food for Thought Food Allergy Symptoms

Date completed: Infant’s date of birth: Infant’s ID:

1 In the last month has your infant had adverse symptoms after eating food (including breast milk and formula)?

0=No symptoms 1=Symptoms 9=Unsure if symptoms caused by food

2 What symptom(s) did your infant or young child experience immediately (within 2 hours) after eating food?

Symptom 0=No symptom 1=Symptom

What was the food?

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 3 Breast feeding and FA prevention

3 In the last month has your child been diagnosed with a food allergy by a health

professional?

NO YES

4 Which health professional or professionals made this diagnosis? ►Please tick all that apply

Doctor

Nurse

Plunket nurse

Pharmacist

Naturopath

Dietitian

Ear, nose and throat specialist

Allergy specialist

Paediatrician (Child specialist)

Other (Please list):

5 When your child was diagnosed with a food allergy which test or tests were

done? ►Please tick all that apply

No tests

Skin test ►Please go to question A7

Blood test ►Please go to question A8 Other (Please list):

6 Please list the food(s) that gave a positive result for the skin test your infant or

young child had…

7 Please list the food(s) that gave a positive result for the blood test your infant or

young child had…

Study 3 Breast feeding and FA prevention

Food Allergy Prevention…Food for thought Diet History Questionnaire

Date completed: Infant’s date of birth: Infant’s ID: Not breast feeding: Breast feeding only: Breast & complementary feeding 1) In the last month Have you followed a special diet due to medical reasons?

No Yes Medical condition:

Are you excluding foods for a special reason due to personal choice?

No Yes

Vegetarian No Yes Eat fish No Yes Vegan No Yes Due to babies allergies/intolerances No Yes Due to own allergy/intolerance No Yes Due to lactation No Yes Other reasons No Yes Please list Have there been peanut (peanut products) in the house?

No Yes

2) In the last month have you taken any of the following supplements?

Multi-vitamin No Yes Multi-mineral No Yes Calcium No Yes Iron No Yes Other No Yes 3) In the last month on average how often have you consumed these foods?

Never Up to 1 – 3 per week

Up to 1 - 2 per month

Milk and milk products (e.g, custard, yoghurt, ice-cream, flavoured milk drink, chocolate, butter, margarines, cheese-pizza, cheese sauce, lasagne, cheesey biscuits)

Wheat (e.g bread, cereals, pasta, pizza, cakes, pies and pastry, muffins)

White fish Shellfish Oily fish Peanuts (peanut butter) 4) In the last month how many helpings/ portions of fruit and vegetables do you eat daily? < 5 portions = 5 portions 5) In the last month Have you identified any foods in your diet that affected baby after breastfeeding?

No Yes

Study 3 Breast feeding and FA prevention

If yes what foods and what effect did they have? Food Code Effect Code

6) In the last month Have you taken any medication? No Yes If yes what? Antibiotics No Yes Paracetamol No Yes Aspirin No Yes Other No Yes Please list 7) In the last month Has you baby had an infant formula? No Yes If yes which formula? Wyeth S-26 formula No Yes Karicare starter formula No Yes Nuture starter formula No Yes Wyeth S26 Gold formula No Yes Karicare Gold starter formula No Yes Nuture Plus Gold No Yes Infasoy No Yes Karicare Goat Starter formula No Yes Karicare AR infant formula No Yes Karicare De Lact formula No Yes Karicare HA infant formula No Yes Wyeth S26HA No Yes Wyeth S26 Progress No Yes Karicare Follow-on No Yes Nuture Follow-on No Yes Karicare Gold Follow-on formula No Yes Infasoy progress No Yes Karicare Soy follow-on No Yes Karicare Goat follow-on formula No Yes SMA (Wyeth) No Yes Karicare Soy formula (All ages) No Yes S26 AR No Yes Wyeth S26 lactose free No Yes No Yes Other No Yes 8) Why have you chosen this formula? Treatment of allergy or intolerance No Yes Prevention of allergy No Yes Other child was allergic to milk No Yes One that was given in hospital No Yes Advised to do so No Yes Own preference No Yes Other No Yes

Study 3 Breast feeding and FA preventionEligibility

• 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

• ASCIA

• Australian Laboratory Sciences

• William and Lois Manchester trust

Food Allergy Research Group

• Christine Crooks (LabPlus)• Maia Brewerton (Wellington Hospital)• Steve Buetow (UoA)• Penny Jorgensen (Allergy New Zealand)• Elizabeth Robinson (UoA)• Shannon Brothers (Starship)• Clare Wall (UoA)• Allen Liang Allergy Specialist • Rohan Ameratunga (LabPlus, Chair)

Paediatric food allergy/ eczema clinic JHU

Prof Robert Wood

Prof Hugh Sampson

Prof Ken Schurberth