Are we any closer to understanding the rise in food allergy?

Transcription

1 ILSI SEAR A Asia Maternal & Infant Nutrition Australia, August 2014 ( Professor Katie Allen Are we any closer to understanding the rise in food allergy?

2 Hospital admissions for food-induced anaphylaxis are rising Poulos et al., J Allergy Clin Immunol 2007, 120(4):

3 Clinical growing burden of allergy Waiting lists >12 mth, also: Earlier onset/ more severe Food allergies less likely to resolve than previously Anticipate even greater burden of allergic disease in Asia Skripak, JACI 2007; 120:1172; Savage, JACI 2007; 120:1413

4 The HealthNuts Study

5 Largest single centre study of food allergy in the world The Healthnuts study - Melbourne yr old infants attending community clinics for routine checks Any child with a positive skin prick test referred for a food challenge at hospital to determine if there was a clinical reaction Osborne et al. JACI 2011; 127: (Australian data)

6 De-identified location of HealthNuts participants in Melbourne

7 More than 20% with food sensitisation Rate of food sensitisation (positive allergy tests): egg: 16% peanut: 9% cows milk: 6% TOTAL: >20% But not all children with allergic antibodies will have a reaction: so need to challenge to determine clinical reactivity Osborne et al. JACI 2011; 127: (Australian data)

8 Over 10% with challenge-proven food allergy Reactions on challenge: (hives, swelling, noisy breathing, choking, vomiting, pallor, floppiness) egg: 9% peanut: 3% other: 2% TOTAL: >10% Osborne et al. JACI 2011; 127: More than 1 in 10 of all 1 year olds have clinical food allergy

9 Why is the prevalence of food allergy so high? What are the potential risk factors for food allergy?

10 Factors examined for possible association with food allergy in HealthNuts Parents country of birth (Asian infants at increased risk) Koplin et al Allergy 2012 egg allergy Martin et al CEA eczema Family history of allergy Koplin et al IJERPH 2013 Prenatal Genetic factors FLG null mutation Tan et al JACI 2012 fetal epigenetic modification through maternal exposure Maternal diet during pregnancy (consumption of egg) Koplin et al JACI 2010 Caesarean section delivery Koplin et al Allergy 2012 Infant dietary factors Later introduction of allergenic foods Duration of breastfeeding Maternal consumption of egg during breastfeeding Age at first introduction of solids Blue = no association Green = possibly protective Red = possible risk factor All in Koplin et al JACI 2010 Perinatal Postnatal Vitamin D insufficiency Allen et al JACI 2013 Factors associated with the hygiene hypothesis Presence of siblings Early childcare attendance Cat exposure Dog exposure Use of antibiotics All in Koplin et al Allergy 2012 Direct infant exposure Modified from JJ Koplin and KJ Allen 2011

11 Current leading hypotheses for the rise in food allergy Infant feeding Hygiene hypothesis (microbial diversity) Vitamin D hypothesis Genetics and skin barrier function

12 Current leading hypotheses for the rise in food allergy Infant feeding

13 Infants introducing cooked egg 4-6 mth were 5 times less likely to get egg allergy than if introduced after 10 months Cooked egg given first 4-6 months 7-9 months months Baked egg given first 4-6 months 7-9 months months Unadjusted Adjusted * N % allergic OR OR P (95% CI) (95% CI) P ( ) 4.4 ( ) ( ) 5.4 ( ) ( ) 0.9 ( ) ( ) 1.0 ( ) Koplin et al JACI 2010

14 Current leading hypotheses for the rise in food allergy Hygiene hypothesis (microbial diversity)

15 Infants of parent s born overseas are much more likely to have food allergy especially those from Asia Prevalence of food allergy stratified by parent's country of birth 30% 20% 10% 0 Both Aust One Europe Both Europe One Asia Both Asia Any food allergy N=408 Egg allergy N=370 Peanut allergy N=370 Sesame allergy N=22 Milk allergy N=23 *Adjusted for family history of allergy, eczema, timing of egg introduction, pet ownership and number of siblings Koplin et al, manuscript under review

16 Infants with siblings and dogs at home are much less likely to develop food allergy Koplin et al Allergy 2012

17 Current leading hypotheses for the rise in food allergy Vitamin D hypothesis

18 Vitamin D Food Allergy Hypothesis Indirect Evidence

19 Regional EpiPen prescriptions in United States and Australia Mullins et al. Ann Allergy Asthma Immunol, 2009) Camargo et al. J Allergy Clin Immunol, 2007)

20 The Longitudinal Study of Australian Children (n=10,000) Osborne et al. J Allergy Clin Immunol, 2012

21 Vitamin D insufficiency is rising in Australia High rates in Australia 40% of Australian pregnant women develop low vit D» (Morley MJA 2009, Teale 2010) Australia (unlike the Northern Hemisphere) does not recommend routine Vitamin D infant supplementation has no vitamin D fortification of the food chain (with the exception of margarine). Anti skin cancer campaigns initiated in the 1970s have been highly successful (slip, slop, slap, wrap) in Australia

22 Vitamin D Food Allergy Hypothesis Direct Evidence

23 Australian born infants with Vitamin D insufficiency at 12 months are much more likely to have food allergy Allen et al JACI 2013

24 Current leading hypotheses for the rise in food allergy Genetics and skin barrier function

25 Lack Hypothesis for cause of Food Allergy Allergic sensitization results from exposure through the skin Tolerance occurs as a result of oral exposure to food (Gideon Lack 2008)

26 Prevalence of eczema at 12mth P Martin et al, CEA 2013

27 Earlier onset and more severe eczema more likely to develop food allergy 80% Eczema treatment Strong topical corticosteroid 60% Mild topical corticosteroid Moisturizers only 40% No moisturizers or steroids 20% 0% Birth-3 months 4-6 months 7-9 months months Age of diagnosis P Martin et al manuscri

28 FLG mutations were associated with both food sensitization (all with a positive skin prick test) food allergy (only those with a positive food challenge) even after adjustment for eczema Negative control (%) Food sensitization (%) Food allergy (%) AA 121 (96.0) 374 (87.4) 283 (88.2) Aa/aa 5 (4.0) 54 (12.6) 38 (11.8) Total OR (95% CI) ( ) 3.2 ( ) χ 2 p-value Adjusted OR ( ) 2.9 ( ) (95% CI)* Adjusted p-value *adjusted for eczema

29 Tan et al JAC Conclusion FLG mutations increase the risk of food sensitization but do not play a further role in progression of food sensitization to food allergy.

30 These results suggest a biologically plausible role for FLG in the development of food sensitization (the Lack Hypothesis). Additional as yet undetermined factors are required to direct the immune response towards food tolerance or allergy in early life.

31 POPULATION RESPONSES TO CHANGE IN ASCIA INFANT FEEDING GUIDELINES Dean Tey et al JACI 2014

32 Aims 1. Establish if updated national allergy guidelines in 2008 were associated with changes in infant feeding practice in population-based cohort of infants (Healthnuts) 2. Identify if socio-demographic factors influenced these responses.

33 New ASCIA guidelines (Sep 2008) Feed solids at age 4-6 mo Not necessary to delay egg & peanut No change to recommendation re PHF Sep 2007 H E A L T H N U T S Aug 2011 AIM 1 Participants recruited in 1 st half of study (Sep 2007 to Aug 2009) Participants recruited in 2 nd half of study (Sep 2009 to Aug 2011) AIM 2 EFFECT MODIFERS Maternal birth country Socio-economic status Family history of allergies

34 Solids introduction between 4-6 months 91.7% (95%CI [ ]) Egg introduction between 7-12 months 70.6% (95%CI [ ]) Peanut introduction >12 months 71.6% (95%CI [ ]) Tey D et al JACI 2014

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38 Trend analysis p=0.009

39 What factors affect consumer response to guidelines?

40 Conclusions on prevention Introduction of egg and other allergenic solids at 4-6 mth is safe and may even be protective Owning a dog and more siblings appears protective (the hygeine hypothesis ) Maintaining Vit D in the normal range may be critical in the first year of life Prevention of eczema through maintaining the skin barrier function ( don t soap the baby ) may be important Genes, family history and migration all appear to play a part

41 Conclusions What we recommend does impact the way that families feed infants Evidence-base is vital for guideline recommendations International and expert consistency desirable

42 Acknowledgements HealthNuts Investigators Chief Investigators: Katie Allen (PI) Melissa Wake, Shyamali Dharmage, Mimi Tang, Lyle Gurrin, Melanie Matheson, Associate Investigators: Anne-Louise Ponsonby, David Hill, Adrian Lowe Post-doctoral Fellow Jennifer Koplin, Nick Osborne PhD Students Pamela Martin, Thanh Dang, Tina Tan, Rachel Peters Research Nurses Leone Thiele, Lucy Miles, Deborah Anderson, Holly Shaw Research Fellow Marnie Robinson, Dean Tey

43 Thank you for your attention!

44 NHMRC Centre of Food and Allergy Research Symposium September 9 th 2014 Melbourne, Australia Melbourne Royal Children s Hospital