Allergy prevention through nutrition intervention Abdulwahab Telmesani FRCPC, FAAP Associate prof of Pediatrics College of Medicine and Medical science Umm Al-Qura University

غراء فرعاء مصقول عوارضهـا تمشى الهوينا كما يمشى الوجى الوحل _________ يكاد يقتلها لـــــولا تشددهــــــــا اذ تقوم الى جـــــــاراتهــا الكســـــــــل ألأعشى ( صناجة العرب ) غراء فرعاء مصقول عوارضهـا تمشى الهوينا كما يمشى الوجى الوحل _________ يكاد يقتلها لـــــولا تشددهــــــــا اذ تقوم الى جـــــــاراتهــا الكســـــــــل ألأعشى ( صناجة العرب )

اْْن المتانة فى الأجسم يصحبها متانة العقل والتفكير والحــــــلم ________ ________ ماذا يسرك من جرداء ناحلة كأنها ريشة تزهو على عـــــــلم ________ ________ ما المرأة الحق الا من اذا درجت يكاد يهتز وجه الأرض للقدم شاعر معاصر شاعر معاصر

EVE PBUH Had no formulas Had no formulas Had no infants cereals Had no infants cereals No blenders No blenders

Recent trends in infant nutrition NO For Early infant feeding For Early infant feeding Aggett PJ et al a commentary by the ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol Nutr. 2001

Incidence of allergies increases Incidence of allergy over the last 20 years S H Downs et al Arch Dis Child 2001;84:20 – 23.

Food Allergy

Small Gut & Allergy Main Target Organ Main Target Organ Main Port of Entry Main Port of Entry

Food Allergy Level of Contact G.I % G.I % Skin % Skin % Respiratory % Respiratory %

Gut is a major lymphoid organ Network of Macrophages Network of Macrophages Mast Cells Mast Cells Ig producing Cells Ig producing Cells T- cells T- cells

Immune response Antigen exposure (e.g.bacteria,pollen,protein) Mucosal barrier (e.g.skin,gut) Immunologic processing Protection Tolerance Allergy

Pathogenesis Type I allergy: Type I allergy: Degranulation of mast cells Degranulation of mast cells Type III allergy: Type III allergy: Immune-complex mediated Spread from G.I to distant organs e.g. skin, kidney etc. Immune-complex mediated Spread from G.I to distant organs e.g. skin, kidney etc. Type IV: Type IV: T-cells + Antigens = Production of cytokines T-cells + Antigens = Production of cytokines (IL-4, interferon-γ, TNF- α etc.), Esinophilic (IL-4, interferon-γ, TNF- α etc.), Esinophilic gastroenteritis gastroenteritis

T Cell Balance Th1 ________ Th0 _________ Th2 Th1 ________ Th0 _________ Th2

Hygiene hypothesis Infections stimulate Th 1 response Infections stimulate Th 1 response Th1 cytokines inhibit Th 2 function Th1 cytokines inhibit Th 2 function lack of microbial exposure due to improved hygiene is responsible for the observed increase in allergies lack of microbial exposure due to improved hygiene is responsible for the observed increase in allergies

T Cell Balance Th1 ________ Th0 _________ Th2 Th1 ________ Th0 _________ Th2

T Cell Imbalance Th1 ___ Th0 _______ Th2 Th1 ___ Th0 _______ Th2

REVIEW Distinct differences between CMP-specific T cell reactivity in the blood of infants with or with out CMA, especially expressed by the release of Th2 cytokines Distinct differences between CMP-specific T cell reactivity in the blood of infants with or with out CMA, especially expressed by the release of Th2 cytokines R. P. Schade et al R. P. Schade et al clin. Exp. Allergy 2003 clin. Exp. Allergy 2003

POSPECTIVE COHORT STUDY We conclude that in infants at atopic risk, exclusive breast-feeding for at least 4 months is effective in reducing atopic dermatitis We conclude that in infants at atopic risk, exclusive breast-feeding for at least 4 months is effective in reducing atopic dermatitis Schoetzau et al Schoetzau et al Pediatr Allergy Immunol 2002 Pediatr Allergy Immunol 2002

How about when breastfeeding is not possible ?

AN EXTENSIVE REVIEW BY AN EXPERT GROUP In infants, breast-feeding with avoidance of solid food and cow’s milk for at least 4-6 months is the most effective preventive regimen. In the absence of breast milk, formula with documented reduced allergenicity for at least 4-6 months should be used In infants, breast-feeding with avoidance of solid food and cow’s milk for at least 4-6 months is the most effective preventive regimen. In the absence of breast milk, formula with documented reduced allergenicity for at least 4-6 months should be used Section on Pediatrics, Section on Pediatrics, European Academy of Allergology and European Academy of Allergology and Immunology Immunology Muraro et al Muraro et al Pediatr. Allergy Immunol 2004 Pediatr. Allergy Immunol 2004

Frequency of Atopic Symptoms in Infants With a Family Risk of Allergy Y. VANDENPLAS et al. J Pediatr 1995

Predisposition to food allergy Family history (atopy, asthma etc.) Family history (atopy, asthma etc.) Immune deficiency (IgA) Immune deficiency (IgA) Gut barrier defect Gut barrier defect Early antigen exposure Early antigen exposure Antigen provocation Antigen provocation

G.I Manifestations Vomiting Vomiting Diarrhea Diarrhea Malabsorption Malabsorption Esinophilic gastroenteritis Esinophilic gastroenteritis Allergic colitis Allergic colitis FTT FTT

Skin Manifestations Atopic Dermatitis Atopic Dermatitis -12% Prevalence in School children -12% Prevalence in School children -80% Have high IgE and positive skin test to -80% Have high IgE and positive skin test to food antigens food antigens

Respiratory Manifestations Allergic Rhinitis Allergic Rhinitis Asthma Asthma

Diagnosis Elimination and Challenge Elimination and Challenge Skin testing Skin testing G.I. Biopsy G.I. Biopsy

Therapy

Food allergy is a a diagnosis frequently entertained, occasionally evaluated and rarely established Food allergy is a a diagnosis frequently entertained, occasionally evaluated and rarely established Franz Ingelfiger Franz Ingelfiger

Therapy Elimination Diet Elimination Diet Medical e.g. Ketotifen, SCG, Stroids etc. Medical e.g. Ketotifen, SCG, Stroids etc.

Brake

Therapy Elimination Diet Elimination Diet Medical e.g. Ketotifen, SCG, Stroids etc. Medical e.g. Ketotifen, SCG, Stroids etc.

Prevention

Prevention Identify infants at risk Identify infants at risk Exclusive BREST MILK for 4-6/12 Exclusive BREST MILK for 4-6/12 Hydrolyzed (partial, extensive) formula as an alternative to B.M when truly not possible Hydrolyzed (partial, extensive) formula as an alternative to B.M when truly not possible Delay solid food after 6 months Delay solid food after 6 months Avoid Cows milk and Eggs in the first year Avoid Cows milk and Eggs in the first year

Prevention cont. Remove house hold allergens Remove house hold allergens -Smoking -Smoking -Pets -Pets -Mite/Molds -Mite/Molds Avoid early day care centers Avoid early day care centers -decreases respiratory infections -decreases respiratory infections

Cow’s milk protein avoidance and development of childhood wheeze in children with family history of atopy Ram FSF, Ducharme FM, Scarlett J Background: In infants with a family history of atopy, food allergen avoidance has been advocated as means of preventing the development of atopic disease. When breast-feeding is not possible or supplemental feeding is needed, alternative choices include soy based and hydrolysed cows milk formulas. Background: In infants with a family history of atopy, food allergen avoidance has been advocated as means of preventing the development of atopic disease. When breast-feeding is not possible or supplemental feeding is needed, alternative choices include soy based and hydrolysed cows milk formulas. (Cochrane Review) (Cochrane Review)

Authors' conclusions: Breast-milk should remain the feed of choice for all babies. In infants with at least one first degree relative with atopy, hydrolysed formula for a minimum of four months combined with dietary restrictions and environment measures may reduce the risk of developing asthma or wheeze in the first year of life. There is insufficient evidence to suggest that soya-based milk formula has any benefit. (Cochrane Review) (Cochrane Review)

Probiotic (For Life)

Probiotic Lactobacillus Bacteria Lactobacillus Bacteria Bifidobacteria spp Bifidobacteria spp

Porbiotic or no probiotic ?

Porbiotic Recent current research and publications are more pro probiotic Recent current research and publications are more pro probiotic

Probiotics & Allergy management Eczema severity (SCORAD score) Isolauri E et al. Probiotics in management of atopic eczema..Clin Exp Allergy 2000;30:

Intestinal flora and allergy Colonisation frequency Björksten B, Sepp E, Julge K,. Allergy development and the intestinal microflora during the first Year of life. J Allergy Clin Immunol 2001

Porbiotic Benefits Four weeks of LGG improved the intestinal inflammation in infants with atopy and CMA Four weeks of LGG improved the intestinal inflammation in infants with atopy and CMA In vitro LGG and Bb modified the cytokines In vitro LGG and Bb modified the cytokines In mice Probiotic prevented the Th2 dominance caused by antibiotics in mice In mice Probiotic prevented the Th2 dominance caused by antibiotics in mice Probiotic help in decreasing the rate of sensitization of infants during their weaning period Probiotic help in decreasing the rate of sensitization of infants during their weaning period LcS suppressed IgE and IgI in a food allergy model LcS suppressed IgE and IgI in a food allergy model

OBSERVATIONAL BIRTH COHORT STUDY Parental eczema is the major risk factor for eczema. But in this study, each month of breastfeeding also increased the risk Parental eczema is the major risk factor for eczema. But in this study, each month of breastfeeding also increased the risk R.L. Bergmann et al R.L. Bergmann et al Clin Exp All 2002 Clin Exp All 2002

Grabbing the bull by the horn for allergy prevention Editorial It may be more appropiate in an allergen modification strategy to expose the fetus and infants to high doses in some form of immunotherapy It may be more appropiate in an allergen modification strategy to expose the fetus and infants to high doses in some form of immunotherapy J. O. Warner J. O. Warner Editor in chief Editor in chief Pediar Allergy Immunol 2004 Pediar Allergy Immunol 2004

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