Download Free Medical New Approaches to Cows Milk Allergy During Infancy PowerPoint Presentation

New Approaches to Cows Milk Allergy During Infancy PowerPoint Presentation

DOWNLOAD MEDICAL POWERPOINT PRESENTATION

About This Presentation

Description : Check out this medical PowerPoint presentation titled "New Approaches to Cow’s Milk Allergy during Infancy” by Craig Jensen, MD.

This medical PowerPoint presentation talks about cows milk allergy, a common condition that can occur during infancy. It is an immune response to one or more proteins found in cows milk. The allergy can cause a range of symptoms, from mild to severe, and can affect different parts of the body, including the skin, gastrointestinal system, and respiratory system.

Tags : Cow’s Milk Allergy during Infancy, Food allergies, food intolerances, healthy eating

Published on : Apr 24, 2023 | Views : 850 | Downloads : 1

Shareable Url :

Embed Code :

Comment

Transcript

Slide 1-

New Approaches to Cow’s Milk Allergy during Infancy: Clinical Benefits of an Extensively Hydrolyzed Casein Formula with Lactobacillus rhamnosus GG Craig Jensen, M.D. Section of Gastroenterology, Hepatology and Nutrition Department of Pediatrics Baylor College of Medicine Houston, Texas
Slide 2-

Disclosures: Consultant/Speaker: Mead Johnson Nutrition
Slide 3-

Objectives Distinguish IgE and non-IgE mediated aspects of cow’s milk allergy (CMA) Recognize the importance of acquisition of tolerance in the context of CMA Review the clinical effects of extensively hydrolyzed casein-based formula with Lactobacillus rhamnosus GG (LGG) in infants with CMA
Slide 4-

A Case Vital Stats Girl 3 months old Length 50th percentile Weight 40th percentile
Slide 5-

Vital Stats Boy 4 months old Length 30th percentile Weight 3rd percentile Another Case t.
Slide 6-

Cow’s Milk Allergy (CMA): Key Concepts
Slide 7-

Cow’s Milk USDA Dairy Products: Per capita consumption, United States. http://www.ers.usda.gov/data-products/dairy-data.aspx #.U+QWEPtRbTo
Slide 8-

Classification of Adverse Reactions to Food Adverse Reaction to Food Enzymatic Pharmacologic Other Nontoxic Toxic Non-Immune–Mediated Reaction1,2 (Food Intolerance) Due to lack of particular enzyme Due to components of the trigger food Immediate food allergy Oral allergy syndrome Food protein enteropathies Eosinophilic gastroenteropathies IgE-mediated Non-IgE mediated (eg, T cell–mediated) Immune-Mediated Reaction1-3 (Food Allergy) Neurologic IgE=immunoglobulin E. 1. Burks AW, et al. Pediatrics. 2011;128(5):955-965. 2. Burks AW, et al. J Allergy Clin Immunol. 2012;129(4):906-920. 3. Spergel JM. Allergy Asthma Clin Immunol. 2006;2(2):78-85.
Slide 9-

Diagnostic Approach to the Evaluation of Food Allergy 1. Sampson HA. J Allergy Clin Immunol. 1999;103(6):981-989. 2. Sampson HA et al. J Allergy Clin Immunol. 2014;134(5):1016-1025.e40. Reprinted from J Allergy Clin Immunol. 1999; 103(6):981-989. Food allergy. Part 2: Diagnosis and management. Sampson HA et al. ©1999, with permission from Elsevier. Detailed History and Physical Examination IgE-mediated PST or ImmunoCAP® Done Elimination Diet Food Challenge or Done Done Non-IgE−mediated Challenge or Endoscopy Food Challenge Specific Allergen Elimination Diet Done + + + + - - + + - - IgE=immunoglobulin E; PST=percutaneous skin testing. ImmunoCAP ® is a laboratory test from Quest Diagnostics performed to rule in or rule out atopy in patients with allergy-like symptoms.
Slide 10-

Family History and Physical Examination During Early Diagnosis Key observations helpful upfront1: Learn about personal and family history of allergic disease Identify and create a list of suspected foods Document the precise description of reactions Key symptoms to watch for during a physical examination1,2: Cutaneous: Flushing, hives, angioedema, and eczema Gastrointestinal: Oropharyngeal pruritus and edema, abdominal cramping, nausea, vomiting, and diarrhea Pulmonary: Rhinorrhea, laryngeal edema, wheezing, coughing and shortness of breath Cardiovascular: Hypotension, tachycardia, and arrhythmias Behavioral: Irritability (preceding or in combination with other symptoms) 1. Sampson HA. J Allergy Clin Immunol. 1999;103(6):981-989. 2. Burks AW, et al. Pediatrics. 2011;128(5):955-965.
Slide 11-

Important Gastrointestinal Manifestations Associated With Non-IgE–mediated Food Allergy Eosinophilic esophagitis, Gastroenteritis1,2: Postprandial vomiting, anorexia, abdominal distention, steatorrhea, failure to thrive, weight loss, food impaction, and gastric outlet obstruction A subset with food-induced IgE-mediated reactions Dietary protein enteropathy2: Diarrhea, failure to thrive, abdominal distention, and malabsorption Less frequent anemia, edema, and hypoproteinemia Dietary protein enterocolitis2: Vomiting and diarrhea Dietary protein proctocolitis2: Gross blood in stool + other symptoms Celiac disease1: Diarrhea, steatorrhea, malabsorption, abdominal distention, flatulence, + nausea and vomiting, failure to thrive, oral ulcers Associated skin disease: dermatitis herpetiformis Spergel JM. Allergy Asthma Clin Immunol. 2006;2(2):78-85. Burks AW, et al. J Allergy Clin Immunol. 2012;129(4):906-920.
Slide 12-

Description of Allergic Reactions: Timing and Reproducibility Are of the Essence Key items to note during an early diagnosis1,2: Timing of onset in relation to food ingestion Symptoms, their severity and duration of reaction Treatment of reaction Reproducibility of reaction after ingestion of suspected food Most recent reaction 1. Sampson HA. J Allergy Clin Immunol . 1999;103(6):981-989. 2. Sampson HA et al. J Allergy Clin Immunol. 2014;134(5):1016-1025.e40.
Slide 13-

Impact of Food Allergies Direct medical costs to the US health care systemof $4.3 billion annually for childhood food allergies1 Include clinician visits, emergency department visits, and hospitalization Costs borne by the family of $20.5 billion annually for childhood food allergies1 Include lost labor productivity, out-of-pocket, and opportunity costs (caregiver needing to leave or change job) Quality of life decreased in UK, North American, European, and Asian studies2-5 Risk of compromised nutrition Long-term impact on feeding behaviors Risk of fatal reaction6 1. Gupta R, et al. JAMA Pediatr. 2013;167(11):1026-1031. 2. Avery NJ, et al. Pediatr Allergy Immunol. 2003;14(5):378-382. 3. Leung TF, et al. Clin Exp Allergy. 2009;539(6):890-896. 4. Flokstra-de Blok B, et al. Allergy. 2010;65(2):238-244. 5. Primeau MN, et al. Clin Exp Allergy. 2000;30(8):1135-1143. 6. Bock SA, et al. J Allergy Clin Immunol. 2001;107(1):191-193.
Slide 14-

Quick onset1-3 Anaphylaxis, etc1-3 Well-defined mechanism1 Easier to diagnose1 Validated tests1-3,a Delayed onset1-3 Eczema, reflux, etc2 Mechanism unclear2 Harder to diagnose2 No validated tests1,2 IgE-Mediated Versus Non-IgE–Mediated Reactions IgE Non-IgE aNot in infants. Burks AW, et al. J Allergy Clin Immunol. 2012;129(4):906-920. Burks AW, et al. Pediatrics. 2011;128(5):955-965. Wang J, Sampson HA. J Clin Invest. 2011;121(3):827-835.
Slide 15-

Features of IgE-Mediated Allergy1-3 Burks AW, et al. J Allergy Clin Immunol. 2012;129(4):906-920. Burks AW, et al. Pediatrics. 2011;128(5):955-965. Sicherer SH, et al. Pediatrics. 2012;129(1):193-197. Quick onset Reproducible Specific symptoms Specific foods Positive tests
Slide 16-

Some Non-IgE–Mediated Reactions Eosinophilic gastroenteropathies Food protein–induced proctocolitis Food protein–induced enteropathy Food protein–induced enterocolitis Eczema Reflux,colic Constipation Burks AW, et al. J Allergy Clin Immunol. 2012;129(4):906-920. Burks AW, et al. Pediatrics. 2011;128(5):955-965.
Slide 17-

What Is Primary Prevention and Why Does It Matter? Primary allergy prevention refers to inhibiting the development of clinical disease before it occurs1 Prevalence of food allergy (and other allergic diseases) has increased within the past 2 decades2,3 Peanut allergy: US: Prevalence of PA in children <18 y.o. increased from 0.4% in 1997 to 0.8% in 2002 and 1.4% in 20082 UK: Prevalence of PA in children increased from 0.6% to 1.8% over the last2 decades3 Tree nut allergy: US: Prevalence of tree nut allergy in children increased from 0.2% in 1997 to 1.1% in 20082 Food allergy is now considered a public health concern, as the condition is associated with significant morbidity and occasional mortality4 PA=peanut allergy. 1. Fleischer DM et al. J Allergy Clin Immunol Pract. 2013;1(1):29-36. 2. Sicherer SH et al. J Allergy Clin Immunol 2010;125(6):1322-1326. 3. Hourihane JO et al. J Allergy Clin Immunol 2007;119:1197-1202. 4. Sicherer SH et al. J Allergy Clin Immunol 2014;133(2):291-307.
Slide 18-

Increasing Linear Trend for Food and Skin Allergic Conditions Among Children in the United States (1997–2011) Among children aged less than 17 years, the prevalence of food allergies increased from 3.4% in 1997–1999 to 5.1% in 2009–2011 The corresponding prevalence of skin allergies increased from 7.4% in 1997–1999 to 12.5% in 2009–2011 Percentage of Children Aged Less Than 17 Years With a Reported Allergic Condition in the Past 12 months: United States, 1997–2011. 3-year period Jackson KD et al. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics National Health Interview Survey, NCHS Data Brief 2013;(121):1-8. *Significant increasing linear trend for food and skin allergy from 1997–1999 to 2009–2011. Data source : CDC/NCHS, Health Data interactive, National Health Interview Survey. 20 15 10 5 0 1997-1999 2000-2002 2003-2005 2006-2008 Percent Food allergy* Skin allergy* Respiratory allergy 2009-2011
Slide 19-

What Factors May Help Explain an Increase in Food Allergy Prevalence? Changes in Diet1,2 Vitamin D: An association between low Vitamin D levels and increased risk of FA has been suggested1 Antioxidants: Some data with asthma but none yet with FA1 Obesity: Obesity is associated with an inflammatory state; mostly studied in asthma1 Dietary Fat: Despite the earlier results, recent meta-analysis found no clear evidence to support the use of Omega 3 and Omega 6 fatty acids for the primary prevention of atopic allergic disease development or sensitization2 Hygiene Hypothesis3 Lack of exposure to infectious agents and gut flora increases susceptibility to allergic diseases; limited data for FA, except for mild effect of cesarean delivery FA=food allergy. 1. Sicherer SH et al. J Allergy Clin Immunol. 2014;133(2):291-307. 2. Anandan C et al. Allergy. 2009;64(6):840-848. 3. Kim H et al. Korean J Pediatr. 2013;56(9):369-376.
Slide 20-

Food Allergy Management Current management of food allergy includes Chapman JA, et al. Ann Allergy Asthma Immunol. 2006;96(suppl):S1-S68.
Slide 21-

Acquisition of IgE-Mediated Tolerance Takes Longer Than Previously Thought The average age of tolerance was thought tobe 3 years, based on very small studies In this retrospective chart review of more than 800 children by Skripak et al, the median age of outgrowing IgE-mediated milk allergy was ~10 years Skripak JM, et al. J Allergy Clin Immunol. 2007;120(5):1172-1177. Retrospective Chart Review:Resolution of CMA n=807 15 30 45 60 75 90 <4 years <8 years < 12 years <16 years 21 36 58 81 Allergic to CMP (%) 0 CMP=cow’s milk protein
Slide 22-

Acquisition of Tolerance in Non-IgE–Mediated CMPA FPIES Non-IgE−mediated reaction to food Acute gastrointestinal presentation; symptoms include vomitingand diarrhea The most common triggers are cow's milk and soy Large, prospective, population-based study onCMP-induced FPIES 13,019 infants with probable adverse reactions to CMP 44 patients (0.34%) fit FPIES criteria 50% of FPIES patients tolerated milk by age 1 year 75% of FPIES patients tolerated milk by age 18 months 90% of FPIES patients tolerated milk by age 3 years No other robust studies on natural history of tolerance development in non-IgE–mediated milk allergy FPIES=food protein–induced enterocolitis syndrome. Katz Y, et al. J Allergy Clin Immunol. 2011;127:647-653.
Slide 23-

Can Tolerance to CMP Be Predicted? In the previously mentioned study on the resolution ofIgE-mediated milk allergy by Skripak et al, patients with persistent CMPA had higher IgE levels in the first 2 yearsof life1 The higher the peak IgE level, the lower the chanceof tolerance Presence of asthma and allergic rhinitis predicted delayed development of tolerance Results were similar for egg allergy2,3 1. Skripak JM, et al. J Allergy Clin Immunol. 2007;120(5):1172-1177. 2. Savage JH, et al. J Allergy Clin Immunol. 2007;120(6):1413-1417. 3. Benhamou AH, et al. Pediatr Allergy Immunol. 2008;19(2):173-179.
Slide 24-

Early Exposure to Cow’s Milk Protein Is Protective Against IgE-mediated CMA A prospective study of 13,019 infants by telephone (95.8%) or questionnaire (4.2%) in Israel Infants with probable adverse reactions to milk were examined, skin prick-tested, and orally challenged 0.5% (66) of the infants were diagnosed with IgE-mediated CMA 0.05% of infants started on CMP formula ≤14 days versus 1.75% started on the formula between ages 105-194 days had IgE-mediated CMA (P < .001) The odds ratio was 19.3 (95% CI, 6.0-62.1) for the development of IgE-mediated CMA among infants with late exposure to CMP (15-194 days vs <14 d) (P < .001). CMA=cow’s milk allergy; CMP=cow’s milk protein. Katz Y et al. J Allergy Clin Immunol. 2010;126(1):77-82. Overall Study Conclusion: “Supplementation at birth with CMP should be recommended to promote its tolerance. The data should not be interpreted as discouraging breastfeeding.”
Slide 25-

The Long-term Effect of Nutritional Intervention With Hydrolysate Infant Formulas on Allergy in High-risk Children—The German Infant Nutrition Intervention (GINI) Study GINI was a study of 2,252 infants at high risk for atopy, enrolled at birth and followed through 10 years Infants randomized at birth to receive 1 of 4 formulas: an intact cow’s milk formula or 1 of 3 hydrolyzed formulas: pHF-W, eHF-W, eHF-C Strict intervention period as substitute for breast milk was 4 months to avoid modification of formula effect by solid foods Follow-up at 10 years with ISAAC questionnaire and invitation to study center for examination and blood sampling eHF-C=extensively hydrolyzed casein formula; eHF-W=extensively hydrolyzed whey formula; ISAAC=International Study of Asthma and Allergies in Childhood; pHF-W=partially hydrolyzed whey formula. von Berg A et al. J Allergy Clin Immunol. 2013;131(6):1565-1573.
Slide 26-

The GINI Study—10 Year Analysis 2 key takeaway points from the GINI study: Feeding with the pHF-W and eHF-C formulas in the first 4 months has a positive effect on cumulative incidence of atopic eczema/dermatitis in high-risk children, lasting until 10 years However, feeding cow’s milk protein hydrolysate formulas compared with cow’s milk formula has neither a positive effect on asthma and allergic rhinitis nor such an effecton allergic sensitization Physician diagnosed eczema [adj. %] Adjusted cumulative incidence of parent-reported physician-diagnosed eczema 45 40 35 30 25 20 15 10 9 8 7 6 0 1 2 3 4 5 6 7 8 9 10 Age [years] pHF-W eHF-C eHF-W CMF CMF=standard cow’s milk formula; eHF-C=extensively hydrolyzed casein formula; eHF-W=extensively hydrolyzed whey formula; pHF-W=partially hydrolyzed whey formula. Reprinted from J Allergy Clin Immunol. 2013;131(6):1565-1573. Von Berg A et al. Allergies in high-risk schoolchildren after early intervention with cow’s milk protein hydrolysates: 10-year results from the German Infant Nutritional Intervention (GINI) study. ©2013, with permission from Elsevier. Overall Study Conclusion: These results support the use of cow’s milk protein hydrolysate infant formula in high-risk infants to reduce the risk for atopic eczema but not for respiratory allergies
Slide 27-

Symptoms of Cow’s Milk Protein Allergy Can Mimic GERD in Infants Recent American Academy of Pediatrics (AAP) guidelines (2013) for the management of gastroesophageal reflux recognize that cow’s milk protein allergy may have a clinical presentation that mimics GERD in infants AAP treatment algorithm (2013) for recurrent regurgitation and weight loss Lightdale JR, et al. Pediatrics. 2013;131(5):e1684-e1695. Algorithm used with permission of American Academy of Pediatrics. Accordingly, AAP recommends the following dietary modifications as afirst-line approach to reflux management: Exclusion of cow’s milk and eggsfrom the diet of mothers whobreast-feed their infants Protein hydrolysate formulain formula-fed infants Thickened feeding
Slide 28-

Key Points Milk allergy can be IgE mediated or non-IgE mediated Children usually develop tolerance to milk by late childhood 1 The age of tolerance development is hard to predict, although the results of initial allergy tests may have some predictive value for IgE-mediated allergy 2 3
Slide 29-

PROBIOTICS …
Slide 30-

What Are Probiotics? Lactobacillus sp1,2 L acidophilus, L brevis,L delbrueckii, L fermentum,L gasseri, L johnsonii, L paracasei,L plantarum, L reuteri, L rhamnosus GG (LGG), L salivarius Bifidobacterium sp1,2 B bifidum, B breve, B infantis,B longum, B adolescentis, B lactis (Bb12) Other microbes2 Escherichia coli Nissle 1917, Saccharomyces cerevisiae, Enterococcus sp FAO /WHO. Health and nutritional properties of probiotics in food including powder milk with live lactic acid bacteria. Oct 2001. http://www.who.int/foodsafety/publications/fs_management/probiotics/en/ 2. Holzapfel WH, et al. Am J Clin Nutr. 2001;73(suppl):365S-373S.
Slide 31-

Application of Probiotics for Human Health Diarrhea (associated with antibiotics, rotavirus, or Clostridium difficile) Prevention of atopic disease Prevention of allergic diseases CMP allergy Vaginal infection Necrotizing enterocolitis Irritable bowel syndrome Colic Bowel transit Helicobacter pylori infection Lactose intolerance Inflammatory bowel disease Prevention of systemic infections Colon cancer Sanders ME, et al. Gut. 2013;62(5):787-796.
Slide 32-

Probiotics Affect Allergies in Multiple Ways Degradation/structural modification of enteral antigens1 Normalization of the properties of aberrant indigenous microbiota and gut barrier functions2 Regulation of the secretion of inflammatory mediators and promotion of immune system development1 Prevention of food allergy through promotion of endogenous barrier mechanisms and alleviation of intestinal inflammation2 Stimulation of immune response and reduction of serum IgE levels3 Reduction of T helper 2 (Th2) cytokine response2 Isolauri E, et al. Gastroenterol Clin North Am. 2012;41(4):747-762. Butel MJ. Med Mal Infect. 2014;44(1):1-8. Kim HJ, et al. Korean J Pediatr. 2013;56(9):369-376.
Slide 33-

Probiotics in Sensitization and Allergic Diseases
Slide 34-

Probiotics in Atopic Disease
Slide 35-

Probiotics in Atopic Disease (cont’d)
Slide 36-

Why Can Probiotics’ Effects Differ?
Slide 37-

Probiotics’ Properties Are Strain Dependent PCR=polymerase chain reaction. Holzapfel WH, et al. Am J Clin Nutr. 2001;73(suppl):365S-373S.
Slide 38-

Probiotic Isolates of Different Origins Can Have Different Effects Study conducted with LGG from 14 different sources and manufacturing processes All L rhamnosus isolates showed similar tolerance to acid All isolates were able to bind to human colonic mucus However, the ability to inhibit the adhesion of pathogens to colonic mucus differed among the L rhamnosus isolates Grześkowiak Ł, et al. Br J Nutr. 2011;105(6):887-894.
Slide 39-

Inhibition of Adhesion of Pathogenic Bacteriato Colonic Mucus by Different LGG Isolates Grześkowiak Ł,et al. Br J Nutr. 2011;105(6):887-894. Probiotic strain OL NL ML LL KL JL IL HL FL EL DL CL BL AL -300 -250 -200 -150 -100 -50 0 ** * * * OL NL ML LL KL JL IL HL FL EL DL CL BL AL -250 -200 -150 -100 -50 0 50 * * -40 -30 -20 -10 10 20 0 -200 -150 -100 -50 0 * *If P<0.05. **If 0.05 ≤P<0.10.
Slide 40-

Key Points There is a large amount of data on the preventive and therapeutic effects of probiotics in allergies and atopic diseases, with varying results Results can be affected by several factors, including the type of probiotic, source of probiotic, target group, and probiotic combinations 1 Results from meta-analyses and systematic reviews that combine results of studies with different designs, target groups, and ages should be interpreted with caution 2 3
Slide 41-

Lactobacillus rhamnosus GG (LGG, ATCC 53103) Isolated from a healthy human source World's most researched probiotic bacterium Multiple scientifically demonstrated beneficial effects Lower incidence and shorter duration of diarrhea1 Lower incidence of respiratory infections2,3 Increased IgA antibody production after rotavirus infection4 Enhanced level of rotavirus vaccine-specific antibodies5 Decreased risk of atopic eczema in high-risk children6 1. Szajewska H, et al. Aliment Pharmacol Ther. 2007;25:871-881. 2. Hojsak I, et al. Clin Nutr. 2010;29:312-316. 3. Luoto R, et al. J Allergy Clin Immunol. 2014;133(2):405-413. 4. Majamaa H, et al. J Pediatr Gastroenterol Nutr. 1995;20(3):333-338. 5. Isolauri E, et al. Vaccine. 1995;13(3):310-312. 6. Kalliomaki M, et al. Lancet. 2001;357(9262):1076-1079.
Slide 42-

The Role of LGG in Allergy Reported to reduce severity of atopic dermatitis when administered to breastfeeding mothers of infants with atopic eczema/dermatitis due to cow’s milk allergy1 May be effective in preventing atopic eczema in high-risk infants when administered postnatally for 6 months and to pregnant mothers2 May balance the generation of cytokines (ie, IL-4, IL-5, IL-10, IFN-γ, TGF-β, and TNF-α), which can contribute to down-regulation of inflammatory processes3-5 IL=interleukin; IFN-γ=interferon gamma; TGF-β=transforming growth factor beta; TNF-α=tumor necrosis factor alpha. 1. Majamaa H, et al. J Allergy Clin Immunol.1997;99(2):179-185. 2. Kalliomaki, et al. Lancet. 2001;357(9262):1076-1079. 3. Pohjavuori E, et al. J Allergy Clin Immunol. 2004;114(1):131-136. 4. Ghadimi D, et al. Immunobiology. 2008;213(8):677-692. 5. Donato KA, et al. Microbiology. 2010;156(pt 11):3288-3297.
Slide 43-

Mechanisms of CMA and LGG APC Th0 Th2 Th2 Th2 Treg IL-10TGF-ß LGG Activated macrophages TNF-α IgE-Mediated Allergy Non-IgE–Mediated Allergy APC=antigen-presenting cell. Berni Canani R, et al. Pharmaceuticals. 2012;5:655-664. Th1 Th1 Th1 IL-4 B cell IgE IFN-γ Milk antigens Mast cell/ basophildegranulation Histamine TNF-α LGG Mast cell/ basophildegranulation NON-IgE–MEDIATED ALLERGY IgE-MEDIATED ALLERGY
Slide 44-

Mechanisms of Action for the Protective Effects of LGG Interaction with other microbes in the gastrointestinal tract In vitro studies have demonstrated that LGG produces a variety of antimicrobial compounds that inhibit the growth of potential pathogens, including E coli, Salmonella typhi, and Staphylococcus aureus1,2 LGG reduces the adhesion of potentially pathogenic bacteria to the epithelial mucus cell and in vitro3,4 Direct influence on barrier function LGG supports the integrity of the gut epithelium via several mechanisms in vitro, including modulation of mucus production and strengthening of the epithelial tight junctions5,6 Animal models suggest LGG may help normalize gut permeability7 1. Carey C, et al. J Microbiol Methods. 2008;73:125-132. 2. Lu R, et al. J Pediatr Gastroenterol Nutr. 2009;49:23-30. 3. Collado MC, et al. Lett Appl Microbiol. 2007;45(4):454-460.4. Lee YK, et al. Appl Environ Microbiol. 2000;66(9):3692-3697. 5. Donato KA, et al. Microbiology. 2010;156(pt 11):3288-3297. 6. Mattar AF, et al. Pediatr Surg Int. 2002;18:586-590.7. Isolauri E, et al. Pediatr Res. 1993;33(6):548-553.
Slide 45-

Mechanisms of Action for the Protective Effects of LGG (cont’d) Gene expression Gene expression studies show that probiotic administration of LGG alters the expression of over 400 genes in the duodenal mucosa in patients with esophagitis Genes affected are those involved in immune response and inflammation, cell growth and differentiation, signaling, and adhesion1 Modulation of the immune system In children with acute diarrhea, administration of LGG enhances the number of antibody-secreting cells2 LGG administration is also associated with reduced levels of markers of inflammation in healthy adults3 1. Di Caro S, et al. Dig Liver Dis. 2005;37:320-329. 2. Kaila M, et al. Pediatr Res. 1992;32(2):141-144. 3. Kekkonen RA, et al. World J Gastroenterol. 2008;14(13):2029-2036.
Slide 46-

LGG Promotes Gut Barrier Function The gut barrier includes a single layer of epithelial cellsheld together by tight junctions Johnson-Henry KC, et al. Infec Immun. 2008;76:1340-1348. Reproduced with permission of American Society for Microbiology. E coli O157:H7 LGG followed by E coli O157:H7 20 m 20 m When these junctions are disrupted, integrity of the gut barrier is compromised
Slide 47-

The Role of LGG in Allergy Management Modified from Özdemir. Clin Exp Immunol. 2010;160(3):295-304.
Slide 48-

Mixed Outcomes of LGG Administration No effect against mild to moderate atopic dermatitis in infancy when LGG(5 109 CFU twice daily for 12 weeks) was mixed with water and given by spoon1 No clinical effect on atopic dermatitis or asthma-related events, and only mild effects on allergic sensitization, when LGG (1010 CFU in capsules, 2 per day for 6 months) was reconstituted with 5 mL of water and given by spoon2 Effective in preventing early atopic disease in children at high risk when LGG (1 1010 CFU for 6 months postnatally) capsules were consumed by mothers and/or mixed with water for infants3 Effective in preventing development of eczema during the first7 years4 when LGG (1 1010 CFU) capsules were consumed by mothers and/or mixed with water and given by spoon to infants for 6 months postnatally3 Follow-up of the cohort showed reduced risk of developing eczema during the first 7 years4 CFU=colony-forming units. 1. Grüber C, et al. Allergy . 2007;62(11):1270-1276. 2. Rose MA, et al. Clin Exp Allergy. 2010;40(9):1398-1405. 3. Kalliomaki M, et al. Lancet. 2001:357(9262):1076-1079.4. Kalliomaki M, et al. J Allergy Clin Immunol. 2007;119(4):1019-1021.
Slide 49-

LGG provides significant improvements in gut and skin symptoms and gut barrier function, and significantly accelerates acquisition of tolerance to cow’s milk protein The efficacy of LGG in CMA has been shown in many clinical studies CMA and LGG: Clinical Study Overview
Slide 50-

Lactobacillus rhamnosus GG (LGG) and Extensively Hydrolyzed Casein Formula
Slide 51-

Extensively Hydrolyzed Protein (EHP) Formula + LGG®* Interrupts CMA Cycle at Each Stage *LGG is a registered trademark of Valio, LTD. CMP=cow’s milk protein; LGG=Lactobacillus rhamnosus GG. 1. Majamaa H et al. J Allergy Clin Immunol. 1997;99:179-185. 2. Isolauri E et al. J Clin Gastroenterol. 2008;42(suppl 2):S91-S96. 3. Baldassarre ME et al. J Pediatr. 2010;156:397-401. 4. Petschow B et al. J Clin Gastroenterol. 2005;39:786-790. 5. Isolauri E et al. Gastroenterology. 1993;105:1643-1650. 6. Isolauri E. Am J Clin Nutr. 2001;73(suppl):1142S-1146S. `
Slide 52-

LGG®* Improves Recovery in Infants With CMA Colitis: Overview Objective: To determine whether extensively hydrolyzed casein formula (EHCF) plus LGG improves hematochezia and fecal calprotectin (FC) in infants vs EHCF alone Subjects: Infants aged 0-12 months fed casein-based routine formula or breast milk with presumptive diagnosis of cow’s milk allergic colitis† (CMAC) and age-, sex-, feeding practice–matched healthy infants Methods: Prospective, randomized, double-blind, placebo-controlled trial (formula-fed infants) *LGG is a registered trademark of Valio, LTD. † CMAC was suspected in infants with: (1) presence of macroscopic or occult blood in stool; (2) with or without mucus; and (3) with or without diarrhea or increased number of stools, or loose stools in the absence of any systemic symptoms. Baldassarre ME et al. J Pediatr. 2010;156:397-401.
Slide 53-

LGG Improves Recovery in Infants With CMAC: Fecal Calprotectin Results FC is elevated in infants with hematochezia and CMAC Use of EHCF + LGG resulted in a reduction of FC compared with EHCF alone *Interaction: 4-week diet effect for type of milk F=12.45; P<0.0001. Adapted from Baldassarre ME et al. J Pediatr. 2010;156:397-401. With permission of Mosby, Inc. Mean Fecal Calprotectin (µg/g) 400 Enrollment Group A EHCF + LGG (n=12)† EHCF - LGG (n=14) Breastfed (n=4)* 4 Weeks After Group B Formula-fed (n=18) Breastfed (n=14) * * 300 200 100 0
Slide 54-

* LGG is a registered trademark of Valio, LTD. † χ2 =11.85; P=0.027. OBS=occult blood stool. Baldassarre ME, et al. J Pediatr. 2010;156:397-401. With permission of Mosby, Inc. LGG* Improves Recovery After 4 Weeks in Infants With CMAC: Occult Blood Stool Results EHCF + LGG resulted in significant improvement of hematochezia compared with EHCF alone EHCF EHCF + LGG
Slide 55-

LGG and Acquisition of Tolerance to Cow’s Milk Protein 80 infants with suspectedCMA were randomized toreceive Nutramigen® (control)or Nutramigen + LGG CMA was confirmed by oral challenge in 55 patients (study population) Patients were rechallenged at6 and 12 months At both time points, significantly more infants built tolerance in the LGG group vs controls Berni Canani R, et al. J Allergy Clin Immunol. 2012;129(2):580-582. Impact of Formula Selectionon Tolerance Building Infants building tolerance (%) At 6 months Cumulative at 12 months 90 Nutramigen Nutramigen + LGG 10 20 30 40 50 60 70 80 21 59 54 81 P=0.004a P=0.027a aData on file.
Slide 56-

LGG and Acquisition of Tolerance:By CMA Mechanism Analyzed by CMA mechanism subgroups IgE-mediated CMA Non-IgE–mediated CMA Number of patients building tolerance increased in both groups at 6 and 12 months vs controls Statistically significant in non-IgE–mediated group at 6 months and in both groups at 12 months Berni Canani R, et al. J Allergy Clin Immunol. 2012;129(2):580-582. 565.6 Tolerance by CMA Mechanism Subgroup Patients building tolerance (%) IgE-mediated CMA 6 mo 12 mo 6 mo 12 mo Non-IgE–mediated CMA 100 Nutramigen® Nutramigen + LGG 0 10 20 30 40 50 60 70 80 90 *P <0.05. * * * 8.3 56 37.5 89
Slide 57-

LGG and Acquisition of Tolerance in Multiple Management Approaches 260 infants with CMA were subdivided into 5 groups EHCF, Nutramigen®, n=52; Nutriben® hydrolyzed n=3; EHCF + LGG, Nutramigen® + LGG n=71; Hydrolyzed rice formula (RHF), Risolac® n=46; Soy formula, Isomil® n=23; Sinelac®, n=18; Nutrilon® Soya, n=14 Amino acid–based formula, Neocate®, n=16; Nutramigen AA® n=9; and Sineall® n=8 EHCF=extensively hydrolyzed casein formula. Berni Canani R, et al. J Pediatr. 2013;163(3):771-777. Impact of Formula Selection on Tolerance Building Children building tolerance (%) EHCF RHF SF AAF EHCF + LGG 43.6 78.9 32.6 18.2 23.6 100 0 20 40 60 80 P<0.05 A food challenge wasperformed after 12 months to assess tolerance EHCF + LGG helps build tolerance in children with CMA
Slide 58-

Tolerance by CMA Mechanism Subgroup Children buildingtolerance (%) IgE-mediated CMA Non-IgE–mediated CMA 100 0 10 20 30 40 50 60 70 80 90 * LGG and Acquisition of Tolerance in Multiple Management Approaches: by CMA Mechanism Analyzed by CMAmechanism subgroup IgE-mediated CMA Non-IgE–mediated CMA Number of patients building tolerance increased in both subgroups at 12 months with EHCF + LGG (Nutramigen® + LGG) vs other formulas In subgroup analysis, oral tolerance was higher with EHCF + LGG (Nutramigen + LGG) vs EHCF (Nutramigen) Oral tolerance was influenced by CMA mechanisms (non-IgE and IgE) *P <0.05 vs EHCF (and other groups). Berni Canani R, et al. J Pediatr. 2013;163(3):771-777. * EHCF EHCF + LGG RHF SF AAF EHCF EHCF + LGG RHF SF AAF
Slide 59-

Reduced Incidence of Allergic Manifestations In a 3-year RCT, extensively hydrolyzed casein-based formula with Lactobacillus rhamnosus GG reduced future manifestations of allergy (atopic dermatitis, urticaria, rhinoconjunctivitis, asthma) in children with IgE-mediated CMA by ~50% (vs extensively hydrolyzed casein-based formula without Lactobacillus rhamnosus GG)
Slide 60-

Summary – Key Points Extensively hydrolyzed casein-based formula with Lactobacillus rhamnosus GG (LGG) achieves faster resolution of CMA-associated proctocolitis compared to the same formula without LGGExtensively hydrolyzed casein formula with Lactobacillus rhamnosus GG (LGG) enhances acquisition of tolerance to cow’s milk protein compared to the same formula without LGG as well as other types of formula (hydrolyzed rice formula, soy formula, and amino acid–based formula) without LGGExtensively hydrolyzed casein based formula with Lactobacillus rhamnosus GG reduced future manifestations of allergy (atopic dermatitis, urticaria, rhinoconjunctivitis, asthma) in children with IgE-mediated CMA by ~50%