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Statistics Archives - LACK

What is allergy?

Definition of allergy

  • A misguided reaction to foreign substances by the immune system, the body system of defense against pathogens
  • The allergic reaction is misguided in that these foreign substances are usually harmless
  • The substances that trigger allergy are called allergen
  • Examples include pollens, dust mite, moulds, animal dander and certain foods.
  • People prone to allergies are said to be allergic or atopic

Mechanism of allergic reaction

  • Prevalence of allergic disease
  • Food allergy: Classification
  • Clinical presentation of food allergy
  • Diagnosis of food allergy
  • Treatment of food allergy
  • Asthma
  • Allergic rhinitis
  • Eczema
  • Prevalence of allergic disease
  • Food allergy: Classification
  • Clinical presentation of food allergy
  • Diagnosis of food allergy
  • Treatment of food allergy
  • Asthma
  • Allergic rhinitis
  • Eczema

Allergy epidemic

  • Most common long-term condition in UK children
  • 39% children diagnosed with allergic disease
  • 12.5 million GP visits per year
  • Annual cost to the NHS exceeds £1 billion

Food allergy rates in young children

How common is allergic rhinitis?

Allergic reaction in a child

Clinical presentation

  • Most food-induced allergic reactions occur on first known oral exposure
  • Especially in the case of eggs and peanuts
  • Most likely in children with a history of severe, early onset eczema

Clues to food allergy in eczema

  • Atopic family history
  • Early onset of eczema
  • Severity of eczema
  • Resistant to treatment
  • Gastrointestinal symptoms
  • Faltering growth

Medical history in a workup for food allergy

Medical history in a workup for food allergy

Secondary care referral

IgE mediated symptoms

  • Anaphylaxis
  • IgE mediated food allergy and concurrent asthma
  • Possible multiple food allergies
  • Strong clinical suspicion despite negative tests

Non IgE mediated symptoms

  • Faltering growth and gastrointestinal symptoms
  • Symptoms do not respond to single elimination diet
  • Significant eczema where multiple food allergies are suspected
  • Persistent parental suspicion of food allergy despite lack of supporting history

In vivo tests

In vitro tests

Food challenge test

Management Principles

  • Allergen avoidance
  • Recognition & treatment of reactions
    Parental and child education
    Medication
    Management in school
    Follow up
  • Asthma control

Allergen avoidance

  • Can’t be overemphasized
  • Most severe reactions occur in known food allergy, where food accidentally eaten in commercially prepared food
  • Most reactions occur at home but 20% in school
  • Paediatric dietician is central

Food labelling

  • 2004 EU regulations to draw attention to presence of 14 allergens
  • Foreign foods
  • Cross contamination
  • Restaurants/takeaways

EU 2004 labelling

  1. Cereals containing gluten (i.e. wheat, rye, barley, oats, spelt, kamut)
  2. Crustaceans
  3. Eggs
  4. Fish
  5. Peanuts
  6. Soybeans
  7. Milk (including lactose)
  8. Nuts
  9. Celery
  10. Mustard
  11. Sesame seeds
  12. Sulphur dioxide and sulphites (> 10 mg/kg)
  13. Lupin
  14. Molluscs

Recognition and treatment

  • Educate all family members and carers (including school staff)
  • Written treatment plan
  • Stress early treatment
  • Carry medications all the times
  • Medicalert
  • Planning eg overseas travel

The management of anaphylaxis in childhood: position paper of the European academy of allergology and clinical immunology

Cross-Reactivity between Common Food Allergens

Natural History of Food Allergy

Asthma Control

  • Approximately 50% of children with food allergy will wheeze
  • Active asthma is the major risk factor for severe allergic reactions
  • Almost every recorded child death from food allergy also had poorly controlled asthma

Allergic asthma

  • Allergic asthma is the most common form of asthma
  • Many of the symptoms of allergic and non-allergic asthma are the same
  • However, allergic asthma is triggered by inhaling allergens

Allergen exposure and asthma

Allergen avoidance

  • HDM reduction measures to prevent asthma – NO
  • HDM reduction measures in HDM sensitized individual for symptom relief:
  • Asthma – NO
  • Perennial allergic rhinitis – YES (extensive only)
  • Pet dander control for allergic asthma
  • No trials on pet allergen reduction or rehousing – ?

Asthma Management

Asthma in the UK

  • UK rates of wheeze 2-3 times higher than rates in Europe, but mortality is 5-10 times higher
  • Emergency admission rate for asthmatic children 26-642/100,000 (25-fold variation) in 2012

NRAD – 195 deaths 2012-2013

  • Excessive prescription of reliever medication
  • Inadequate prescription of preventer medication
  • Inappropriate prescribing of LABAs
  • 23% had personalised asthma action plan (PAAP)
  • Use of PAAP reduces risk of hospital admission 4-fold

NRAD – 18 deaths in children

  • Majority of children dies before reaching hospital
  • 8 out of 10 (80%) aged <10 years
  • 13 out of 18 (72%) aged 10 – 19 years
  • 43% were managed only in primary care
  • 78% aged 10-19 years died between March-Sept
  • 39% had known allergic comorbidities

NRAD Recommendations

  • PAAP in all children
  • Details of asthma triggers
  • Current asthma treatment
  • What to do in exacerbation and how to seek help
  • Review at least annually
  • Inhaler technique training
  • Compliance with preventer treatment
  • Minimise exposure to allergens and smoke
  • 12 reliever prescription should trigger urgent review
  • How, why and when they should use asthma medication

Allergic rhinitis and asthma

  • Asthma is increased in allergic rhinitis
  • 19–38% AR vs. 3–5% general population
  • Allergic rhinitis almost always present in asthma
  • 78% asthmatics vs 20% general population
  • AR increases asthma severity risk
  • 3-fold risk of frequent wheezing attacks
  • 10-fold risk of frequent GP visits for asthma

Allergic rhinitis

Common causes of Allergic Rhinitis

  • Grass pollen
  • April-September
  • Tree pollen
  • February-May
  • Perennial allergens
  • House dust mite
  • Animals

ARIA Classification of allergic rhinitis

Treatment of allergic rhinitis

Eczema

Emollients: 500g/week

Take home messages

  • Think of food allergy in child with early onset severe eczema
  • Differences between IgE and non IgE mediated food allergy
  • Stress early use of adrenaline autoinjector if breathing difficulties or lethargic
  • Children with food allergy need optimum treatment of their asthma

Take home messages

  • Look for allergic rhinitis in children with asthma
  • All children with asthma should have a personalised asthma action plan
  • Most effective treatment for allergic rhinitis is intranasal steroid spray (used correctly)
  • In children with eczema use 500g emollient/week

 

Statistics Archives - LACK

Food Allergy – A multisystem disorder

I wish to declare the following conflicts of interest:

  • Research funding: NIHR, FARE, NPB, ITN (NIH), Thermo Scientific, Stallergenes, Meridien foods
  • Conference fees: BSACI, MEDA, Danone, Mead-Johnson, ALK

EGID and allergic diseases

Overlap in clinical presentation

Allergy in EoE vs. UK population

Allergic March including EGID

Atopic eczema

Emollients: 500g/week

Topical steroids

Allergic rhinitis

Treatment of allergic rhinitis

Seasonal variability of EoE

  • Most commonly diagnosed in spring in paediatric patients
  • 5% patients had seasonal variation confirmed by biopsy

  • Other studies in adults and adolescents no seasonality
  • Frederickson NW et al. Un Europ Gastroenterol 2014;2(2):69-76
  • EoE induced by aeroallergen exposure (grass and HDM)

Immunotherapy and EoE

  • Two studies have shown EoE resolution/ improvement after HDM immunotherapy
  • Induction of EoE following pollen immunotherapy
  • Systematic review: Egg, milk, peanut OIT induced EoE in 2.7%

Role of allergy testing for EoE

  • 53 children with confirmed EoE on biopsy
  • 80% children had either inhalant or food sensitization
  • Most common specific IgE raised to cow’s milk
  • Allergy testing not related to symptoms/endoscopy findings

EoE histological remission rate

Progression to IgE mediated allergy

EoE consensus recommendations

  • ‘SPT, sIgE and APT can help identify foods that are associated with EoE but these tests are not sufficient alone to make the diagnosis of food allergy-driven EoE.’
  • ‘Medically supervised food reintroduction might be necessary for patients with positive SPT or sIgE because of loss of tolerance during food avoidance might results in significant reactions on reintroduction’

Summary

  • High rates of concurrent allergic rhinitis, eczema, asthma and IgE mediated food allergy in EGID
  • Allergy-testing directed elimination diet less useful than empirical elimination diets
  • Consider risk of IgE mediated allergy after prolonged avoidance
  • Joint working of Allergists & Gastroenterologists

Characteristics of EGID patients and family

Topical steroid potency

Aetiology

Eosinophils and TH2 cytokines

  • Atopic eczema
  • Nasal lavage allergic rhinitis
  • BAL asthma
  • EoE biopsy

Mechanism of sensitization

IgE mediated allergy:

  • Epicutaneous ovalbumin exposure leads to increased eosinophils in BAL and hyperresponsiveness to metacholine

Eosinphilic eosophagitis:

  • Epicutaneous followed by intranasal challenge to ovalbumin / Aspergillus leads to EoE

Epicutaneous + intranasal allergen challenge EoE

ARIA Classification of allergic rhinitis

Topical steroids

Food vs. aeroallergen sensitivity in EoE

 

 

 

Statistics Archives - LACK

Allergic Asthma

OVERVIEW

 

    • Prevalence
    • Pre-school wheeze
    • Asthma
    • Allergen exposure and asthma
    • The Allergic March

http://www.londonallergy.com/wp-admin/post.php?post=878&action=edit#

  • Asthma Management

Pre-school wheeze

Transient early wheeze

Risk factors

  • Reduced pulmonary function in infancy
  • Prematurity
  • Male gender
  • Exposure to siblings and day care
  • Prenatal and post-natal smoking exposure
  • Resolves around the age of 3 yrs

Non-atopic viral wheeze

  • Principally due to recurrent viral infections
  • Non-atopic wheezers have normal lung function in early life but intermittent airways obstruction secondary to viral infections
  • Origin of wheezing in these children is not clear

Persistent atopic wheeze

  • First episode usually after infancy
  • Discrete attacks with symptom-free intervals
  • Symptoms worse at night
  • Family history of asthma or atopy
  • Elevated serum IgE and blood eosinophilia
  • Bronchodilator and corticosteroid responders
  • Normal lung function in infancy
  • Develop asthma in later childhood

Asthma

Allergic asthma

  • Allergic asthma is the most common form of asthma
  • Many of the symptoms of allergic and non-allergic asthma are the same
  • However, allergic asthma is triggered by inhaling allergens

How much asthma is atopic?

Allergen exposure and asthma

Allergen exposure and asthma

  • Indoor allergen exposure, allergen specific sensitization and asthma
  • Bell-shaped curve relationship
  • Environment * environment interactions
  • Endotoxin and HDM
  • Gene * environment interactions
  • CD14 (LPS receptor) and endotoxin

Allergen avoidance

  • HDM reduction measures to prevent asthma – NO
  • HDM reduction measures in HDM sensitized individuals for symptom relief:
  • Asthma – NO
  • Perennial allergic rhinitis – YES (extensive only)
  • Pet dander control for allergic asthma
  • No trials on pet allergen reduction or rehousing – ?

The Allergic March

Sensitization and allergic disease

Sensitization and allergic disease

Number of food allergies and asthma

Severity of food allergy and asthma

Food allergy causes respiratory symptoms

 

Allergic rhinitis and asthma

  • 19–38% AR vs. 3–5% general population
  • Allergic rhinitis almost always present in asthma
  • 78% asthmatics vs 20% general population
  • AR increases asthma severity risk
  • 3-fold risk of frequent wheezing attacks
  • 10-fold risk of frequent GP visits for asthma

Immunotherapy for AR in children

Asthma Management

Asthma in the UK

  • UK rates of wheeze 2-3 times higher than rates in Europe, but mortality is 5-10 times higher
  • Emergency admission rate for asthmatic children 26-642/100,000 (25-fold variation) in 2012

NRAD – 195 deaths 2012-2013

  • Excessive prescription of reliever medication
  • Inadequate prescription of preventer medication
  • Inappropriate prescribing of LABAs
  • 23% had personalised asthma action plan (PAAP)
  • Use of PAAP reduces risk of hospital admission 4-fold

NRAD – 18 deaths in children

  • Majority of children dies before reaching hospital
  • 8 out of 10 (80%) aged <10 years
  • 13 out of 18 (72%) aged 10 – 19 years
  • 43% were managed only in primary care
  • 78% aged 10-19 years died between March-Sept
  • 39% had known allergic comorbidities

NRAD Recommendations

  • PAAP in all children
  • Details of asthma triggers
  • Current asthma treatment
  • What to do in exacerbation and how to seek help
  • Review at least annually
  • Inhaler technique training
  • Compliance with preventer treatment
  • Minimise exposure to allergens and smoke
  • 12 reliever prescription should trigger urgent review
  • How, why and when they should use asthma medication

New BTS guidelines – 2014

Summary

  • Atopic wheeze and allergic asthma
  • Allergens induce asthma but ? causation
  • Asthma comorbities
  • Treat asthma to prevent fatal food induced anaphylaxis
  • Treat AR to reduce asthma exacerbations
  • Personalised asthma action plan reduces asthma hospitalisations 4-fold

Timing of allergic march

 

 

Statistics Archives - LACK

The Allergic March

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Overview

Increase in allergic conditions

  • The allergic march
  • Relationship between atopic conditions:
  • Eczema and food allergy
  • Food allergy and asthma
  • Allergic rhinitis and asthma

Allergy epidemic

Allergic conditions (eczema, food allergy, asthma, allergic rhinitis) affect 52% of UK children

Commonest long-term childhood condition in the UK

12.5 million GP visits per year

Increasing prevalence eczema 6-7yrs

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Gupta et al. Increasing hospital admissions for systemic allergic disorders in England: analysis of national admissions data. BMJ 2003;327:1142

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Asthma

Most common long-term condition to affect UK children (1 million). Phase 3 ISAAC 2000-2003 age 13-14 years

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Decreasing prevalence asthma 13-14yrs

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Asher MI, Montefort S, Bjorksten B, Lai CK, et al. Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases 1 and 3 repeat multicountry cross-sectional surveys. Lancet 2006; 368(9537):733–743.

The Allergic March

Allergic conditions often co-exist

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Atopy and allergic disease

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What is the relationship?

Eczema and food allergy:

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Food allergies in children with eczema

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Clues to food allergy in eczema

  • Atopic family history
  • Early onset of eczema
  • Severity of eczema
  • Resistant to treatment
  • Gastrointestinal symptoms
  • Faltering growth

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Evidence for cutaneous sensitisation

  • Severe eczema is associated with food allergy
  • The skin barrier is impaired in children with eczema
  • Topical exposure to peanut oil is associated with peanut allergy
  • High exposure to environmental peanut is associated with peanut allergy

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Evidence for cutaneous sensitisation

  • Severe eczema is associated with food allergy
  • The skin barrier is impaired in children with eczema
  • Topical exposure to peanut oil is associated with peanut allergy
  • High exposure to environmental peanut is associated with peanut allergy

screen-shot-2016-11-30-at-10-49-05

The brick wall analogy of the stratum corneum of the epidermal barrier. In healthy skin the corneodesmosomes (iron rods) are intact throughout the stratum corneum. At the surface, the corneodesmosomes start to break down as part of the normal desquamation process, analogous to iron rods rusting (A). In an individual genetically predisposed to AD, premature breakdown of the corneodesmosomes leads to enhanced desquamation, analogous to having rusty iron rods all the way down through the brick wall (B). If the iron rods are already weakened, an environmental agent, such as soap, can corrode them much more easily. The brick wall starts falling apart (C) and allows the penetration of allergens (D).

Evidence for cutaneous sensitisation

  • Severe eczema is associated with food allergy
  • The skin barrier is impaired in children with eczema
  • Topical exposure to peanut oil is associated with peanut allergy
  • High exposure to environmental peanut is associated with peanut allergy

Arachis oil containing creams

90% of peanut allergic children with eczema were exposed to creams containing Arachis (peanut) oil in the first 6 months of life

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Evidence for cutaneous sensitisation

  • Severe eczema is associated with food allergy
  • The skin barrier is impaired in children with eczema
  • Topical exposure to peanut oil is associated with peanut allergy
  • High exposure to environmental peanut is associated with peanut allergy

Household peanut consumption a risk factor for peanut allergy

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Environmental exposure to food?

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Eczema modifies effect of environmental peanut exposure on peanut allergy 

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Eczema and Food allergy – Conclusions

  • 33-81% of children with moderate – severe eczema have immediate food allergies
  • Think about food allergy driving eczema in severe, early onset eczema
  • Children with inflamed, porous skin may become allergic to foods through the skin
  • Importance of using emollient to maintain the skin barrier in eczema

Food allergy and asthma

screen-shot-2016-11-30-at-10-50-16

Food allergy causes respiratory symptoms

  • 50% of food allergic children have allergic reactions involving respiratory symptoms
  • Ingested and aerosolised foods can induce allergic reactions
  • Fish, egg and cow’s milk are known to aerosolise

53. Synek M. Anto JM. Beasley R. Frew AJ. Holloway L. Lampe FC. Lloreta JL. Sunyer J. Thornton A. Holgate ST. Immunopathology of fatal soybean dust-induced asthma. European Respiratory Journal 1996; 9:54-7.

More food allergies = more asthma

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More severe food allergy = more asthma

 

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Fatal / near-fatal anaphylactic food reactions are associated with asthma 

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Patients with food allergies  and asthma should always have immediate access to inhaled beta-agonist and self-injectable adrenaline

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Food allergy and Asthma – Conclusions

  • 4 – 8 % of asthmatic patients have food allergy
  • About 50% of food allergic patients have asthma
  • Food allergy, especially multiple food allergies is associated with an increased risk of asthma
  • Severe asthmatics have 3.3 times increased risk of anaphylaxis vs. non asthmatics

Allergic rhinitis and asthma

screen-shot-2016-11-30-at-10-54-19

Allergic rhinitis and asthma

  • Asthma is increased in allergic rhinitis
    19–38% allergic rhinitis vs. 3–5% general population
  • Allergic rhinitis almost always present in asthma
    78% asthmatics vs 20% general population
  • Allergic rhinitis increases asthma severity risk
    3-fold risk of frequent wheezing attacks
    10-fold risk of frequent GP visits for asthma

Risk of developing asthma

screen-shot-2016-11-30-at-10-54-27

Allergic rhinitis treatment improves asthma control

  • Treatment of allergic rhinitis
    lower risk of asthma-related A&E visits
    lower risk of asthma-related hospitalisation
  • 47% did not have an asthma-related event
  • Hospitalisation reduced by 61%

Immunotherapy for AR prevents asthma

screen-shot-2016-11-30-at-10-54-36

Allergic rhinitis & Asthma – Conclusions

  • 80% of asthmatic patients have allergic rhinitis
  • Patients with allergic rhinitis have an increased risk of developing asthma
  • Especially patients with house dust mite allergy
  • United airway approach
  • Allergic rhinitis increases risk of asthma severity
  • Treating allergic rhinitis improved asthma control

Look for all allergic conditions

  • Active and early treatment of eczema to repair the skin
  • Think about food allergy in early onset severe eczema
  • Patients with food allergies and asthma
  • Need to ensure that asthma is well controlled
  • Should always have immediate access to an inhaled beta-agonist and self-injectable adrenaline
  • Treatment of allergic rhinitis improves asthma control
  • Immunotherapy in allergic rhinitis may prevent asthma

screen-shot-2016-11-30-at-10-54-48

Acknowledgements

  • Gideon Lack
  • George Du Toit
  • Adam Fox
  • Kerry Richards
  • Asha Sudra
  • Alexandra Santos
  • Victor Turcanu
  • Alick Stephens
  • Martin Penagos
  • Suzana Radulovic
  • Monica Basting
  • Adnan Custovic
  • Angela Simpson
  • Nicolaos Nicolaou
  • Irwin McLean
  • Sara Brown
  • Hugh Sampson
  • Andy Liu
  • Scott Sicherer
  • Marshall Plaut
  • Peter Sayre
  • Action Medical Research
  • National Peanut Board
  • Immune Tolerance Network
  • Food Allergy Research & Education
  • Biomedical Research Centre

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Learning Early About Peanut Allergy

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Talk about:

  • These data are out of date – NS survey / audit
  • Evolution of immune system development during first year of life
  • Immune tolerance – low dose Treg vs high dose thymic effects
  • Manifestations of GI food allergy change with age
  • Rates of waning of allergy differ with different food allergens

screen-shot-2016-11-30-at-10-56-26

Cutaneous Route

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Hygiene hypothesis

Breast-feeding
Conflicting evidence (protective vs. risk)
Reverse causality
Unable to do RCT (Belarus study had no effect)

Breastfeeding has been associated repeatedly with a protective effect against both eczema (72) and asthma in early life (73). However, recent studies, including one from our
group, have linked both breastfeeding and prolonged breastfeeding with increased eczema (74) and asthma risks (75,76). Methodological issues may explain the discrepancies between studies that assess the association between breastfeeding and allergic diseases (77). Ethically it is not possible to randomize mother-baby pairs to breastfeeding. A recent study overcame this by randomizing maternity hospitals in Belarus with historically lowrates of breastfeeding to either a breastfeeding promotion arm or no intervention (78). Despite increased breastfeeding in the intervention groups, there was no significant difference in the rate of asthma, allergic rhinitis, or eczema between the groups. In summary, the role of breastfeeding as a risk factor for both eczema and asthma is far from clear.

The premise of the hygiene hypothesis is that exposure to microbial factors in infancy induces the immune system to switch from the dominant Th2 response present at birth to a dominant Th1 response associated with normal immune function (79). If that switch is not made and the Th2 response remains dominant, the immune system is primed for allergic diseases

 

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Statistics Archives - LACK

Alimentation for primary and secondary prevention of food allergy

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Primary and secondary prevention of atopy through alimentation (feeding /diet / food)
Feeding pattern and timing of food introduction

Overview

  • Maternal diet
  • Breast-feeding
  • Complementary foods during infancy
  • Allergenic foods during infancy
  • Dietary nutrient intake during pregnancy and infancy

Maternal diet 

  • No evidence that avoidance of cow’s milk or egg during pregnancy reduces allergic disease
  • Inconclusive data for peanut ingestion during pregnancy
  • No evidence for maternal avoidance of allergenic foods during lactation

The development and prediction of atopy in high-risk children: Follow-up at age seven years in a prospective randomized study of combined maternal and infant food allergen avoidance

  • 1981 – 1984 study
  • Prophylaxis group
    Last trimester – avoid milk, egg and peanuts
    Breast feeding – avoid milk, egg and peanuts
  • Solids – 6 mo
    CM – 12 mo
    Egg – 24 mo
    Peanuts – 36 mo

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Breast-feeding

  • Exclusive breastfeeding for 3-4 months reduces:
  • Infantile eczema in high-risk infants
    Gdalevich M et al. Breastfeeding and the onset of AD in childhood: a systematic review and meta-analysis of prospective studies J. Am Acad Dermatol 2001; 45:520-7
  • Wheezing under 4 years
    Kull I et al. JACI 2004;114:755-60, Giwercman C et al. JACI 2010; 125:806-71, Elliott L et al. JACI 2008;122:49-54
  • Cow’s milk allergy until 18 months (not food allergy in general)
    Muraro A. et al. PAI 2004; 15:291-307, Kramer MS et al. Cochrane review 2002
  • Allergic rhinitis (borderline significance)

Early complementary foods

Introduction before 17 weeks increases risk of:

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Late complementary foods

  • Introduction > 4-6 months
  • Not protective for AD, asthma, AR
    Zutavern A et al. Timing of solid food introduction
    in relation to eczema, AR, food and inhalant
    sensitization: a prospective birth cohort.
    Pediatrics 2006;117:401-11
  • Later food sensitization
    Nwaru BI et al. Age at introduction of solid foods
    during the first year and allergic sensitization at
    age 5 years. Pediatrics 2010;125:50-59
  • Joseph CLM et al. Early complementary
    feeding and risk of food sensitization
    in a birth cohort. JACI 2011;127:1203-10

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Diversity of complementary foods

  • Low food diversity at 6 months (<4 foods) associated with food and inhalant sensitization age 5 years
  • Stronger effect in children with AD or parental atopy

Complementary foods and breastfeeding

  • Concomitant breastfeeding with cow’s milk protein associated with reduction in food allergy (DBPCFC)
  • Breastmilk contains:
  • Allergenic proteins (oral exposure)
    Immunologic factors (TGF-β, IL-12 (Th1), soluble CD14)
    Prebiotics

Allergenic foods during infancy

  • Observational studies
  • Timing of introduction of egg, fish, wheat, cow’s milk
  • Although adjusted still possibility of bias
  • Prospective randomised controlled studies
  • Primary prevention
  • Secondary prevention

Introduction of cooked egg at 4-6 months is associated with reduction in egg allergy

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Wheat introduction by 6 months is associated with a lower rate of wheat allergy

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Early cow’s milk introduction associated with reduced incidence of cow’s milk protein allergy

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Early consumption of peanuts in infancy is associated with a low prevalence of peanut allergy 

Methods

5171 Jewish school children in UK and 5615 Jewish school children in Israel were compared for food allergies and atopy.

Questionnaire based assessment of peanut allergy validated by challenges.

Infant weaning for peanut and other foods was determined in infants using a validated FFQ.

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Early consumption of peanuts in infancy is associated with a low prevalence of peanut allergy

 

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Peanut allergy as a function of household peanut consumption and whether child ate peanut by 12 months 

High Household Peanut Consumption in subgroup of High-Risk Controls

If sensitisation occurs through environmental exposure in atopic individuals, one would not expect to find children in the high-risk control group (EA but not PA) with substantial environmental exposure to peanut. Surprisingly, although the median environmental peanut exposure in this group was very low, 11% had a household consumption of over 20g/week and in 1.9% it was over 50g/week.
One possible explanation is that these children had milder eczema, and peanut was unable to penetrate the skin barrier. However, there was no difference in eczema severity or age of onset between this sub-group (>20g/week) and the other high-risk controls.
Another explanation is that early introduction of peanut into the diet may have tolerised these infants, protecting them from PA, despite high environmental exposure. Figure 4 illustrates how the strong relationship between PA (in high-risk children) and environmental exposure breaks down in the subgroup of children who themselves ate peanuts by 12 months. It is noteworthy that 5 of the 15 EA children who ate peanuts by 1 year had environmental exposure of over 20g/week. 29%(2/7) of children who ate peanuts by 1 year and whose environmental exposure was over 20g/week were peanut allergic compared to 82%(60/73) of those who did not eat peanuts by 1 year(p=0.0012).

 

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German Infant Nutritional Intervention

  • Multicentre randomised controlled trial
  • Efficacy of 3 infant formulas vs. CMF in infancy
  • 2252 high risk infants received 1 of 4 formulas for first 4 months if mothers unable to breast-feed
  • Main outcomes were patient reported, physician diagnosed allergic disease

Largest study of its kind – Multicentre RCT to assess efficacy of 3 infant formulas vs CM in infancy. Recruited 1995-1998 in 2 regions of germany 2252 high risk infants randomised to receive 1 of 4 formulas for first 4/12 as a BM substitute – high risk defined as a first degree relative with allergy. Formulas were cow’s milk formula, partial whey hydrosylate (no longer available in UK), casein based eHF (nutramigen), whey based eHF (nutramigen) Only had it if they needed a BM substitute so some didn’t use their formula as they stuck to BM. Also some deviated from the prescribed formula  so again will have per protocol and ITT analyses. Main outcomes were patient reported, physician diagnosed allergic disease

Reported at 1yr, 3yr & 6yr

Headline showed persistent effect on AD thru all 3 ages but no effect on asthma

German Infant Nutrition Study

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Study shows us the change from age 7-10yrs.
Graph shows point prevalence of eczema and whilst the results look impressive there actually wasn’t really an additional effect of decreased eczema during the 7-10yr period – the overall 10 yr difference- which still stands – is driven by the effect in earlier life. Only exception is EHF-C in the per protocol group where there is an additional effect.

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Cochrane systematic review

  • No evidence to support feeding with hydrolysed formula compared to exclusive breast feeding
  • High risk infants unable to breastfeed, hydrolysed formula vs. cow’s milk formula reduces infant and childhood allergy and infant cow’s milk allergy
  • Further RCTs comparing partially hydrolysed whey, or extensively hydrolysed casein to cow’s milk formulas

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Dietary nutrient intake

  • Fruit and vegetables
  • Mediterranean diet
  • Vitamin A, D and E and zinc
  • Omega 3 and 6

Maternal recommendations

Maternal diet during pregnancy and lactation

  • No recommendation to avoid any allergenic foods
  • Diet rich in fruit and vegetables / Mediterranean diet
  • Studies ongoing regarding Vitamin D supplementation

Breastfeeding

  • Exclusive breast-feeding for 4 months
  • Continued breast-feeding during introduction of complementary foods
  • If unable to breastfeed consider hydrolysed formula

Weaning recommendations

  • Do not commence weaning before 17 weeks
  • Commence weaning between 17 weeks to 26 weeks
  • Introduce >4 weaning foods by 26 weeks
  • One new food every 3 days
  • Diet rich in fruits and vegetables

Allergenic foods

Introduce all allergenic foods from 6 months

  • Introduce cow’s milk whilst breastfeeding (4-6 months)
  • Introduce wheat and egg around 6 months
  • Introduce fish by 9 months
  • Introduce peanut between 6-12 months
  • If child has moderate eczema or family history of peanut allergy may consider testing prior to introduction

Acknowledgements

  • Gideon Lack
  • Adam Fox
  • Sophie Flammarion
  • Kerry Makinson
  • Martin Penagos
  • Allergy Team GSTT

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Oral Route

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Endoscopic and biopsy findings in patients with and without celiac disease. (A) High-definition endoscopic photo of normal small intestine. The villi are clearly visible with no evidence of atrophy or scalloping of the folds. (B) Biopsy specimen of normal small intestine (hematoxylin-eosin; original magnification, × 100). (C) PillCam image of small intestine in a patient with celiac disease, showing scalloping of the mucosal folds (arrows) characteristic of a malabsorption pattern. There is also evidence of villous atrophy compared with normal. (D) Biopsy specimen of small intestine in a patient with celiac disease (hematoxylin-eosin; original magnification, × 100). Note the loss of villous architecture.

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Cohort analysis for egg allergy

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Cohort analysis for cow’s milk allergy

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Actual vs target enrolment
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Identifying infants at high risk of peanut allergy: LEAP screening study

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Primary Endpoint

  • The proportion of participants with peanut allergy at 60 months of age.
  • Peanut allergy is defined by the Double Blind Placebo Controlled Food Challenge

Secondary Endpoints

  • The proportion of participants with allergic sensitisation to food allergens (30 and 60 months)
  • The proportion of participants with allergic rhinoconjunctivitis and asthma (30 and 60 months)
  • The proportion of participants with food allergy at 60 months
  • Incidence of adverse events, laboratory anomalies, and nutritional evaluations
  • Results of cellular and humoral immune response to peanut and other specific allergens

Can you avoid…

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Food antigen exposure is a necessary but not a sufficient condition for oral tolerance

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In high-risk infants [….] the following recommendations seem reasonable at this time:

Breastfeeding mothers should continue breastfeeding for the first year of life or longer. During this time, for infants at risk, hypoallergenic formulas can be used to supplement breastfeeding.

Mothers should eliminate peanuts and tree nuts (eg, almonds, walnuts, etc) and consider eliminating eggs, cow’s milk, fish, and perhaps other foods from their diets while nursing. Solid foods should not be introduced into the diet of high-risk infants until 6 months of age, with dairy products delayed until 1 year, eggs until 2 years, and peanuts, nuts, and fish until 3 years of age.

b) No maternal dietary restrictions during pregnancy are necessary with the possible exception of excluding peanuts;

 

AMERICAN ACADEMY OF PEDIATRICS
Committee on Nutrition 2008

Section on Allergy and Immunology

Although solid foods should not be introduced before 4 to 6 months of age, there is no current convincing evidence that delaying their introduction beyond this period has a significant protective effect on the development of atopic disease regardless of whether infants are fed cow milk protein formula or human milk. This includes delaying the introduction of foods that are considered to be highly allergic, such as fish, eggs, and foods containing peanut protein.

6. For infants after 4 to 6 months of age, there are insufficient data to support a protective effect of any dietary intervention for the development of atopic disease.

 

Avoidance Studies

Avoidance studies have failed to reduce the rate of food allergies. This is because:

  • They were not sufficiently rigorous
  • The concept of avoidance is wrong

 

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