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Hugh A Sampson - One of the best experts on this subject based on the ideXlab platform.
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mechanistic correlates of clinical responses to omalizumab in the setting of oral immunotherapy for Milk Allergy
The Journal of Allergy and Clinical Immunology, 2017Co-Authors: Pamela A Frischmeyerguerrerio, Kari C. Nadeau, Robert A. Wood, Madhan Masilamani, Erica Brittain, Jennifer S Kim, Kirsi M Jarvinen, Alexander Grishin, Robert Lindblad, Hugh A SampsonAbstract:Background In our recent clinical trial, the addition of omalizumab to oral immunotherapy (OIT) for Milk Allergy improved safety, but no significant clinical benefit was detected. Objective We sought to investigate mechanisms by which omalizumab modulates immunity in the context of OIT and to identify baseline biomarkers that predict subgroups of patients most likely to benefit from omalizumab. Methods Blood was obtained at baseline and multiple time points during a placebo-controlled trial of OIT for Milk Allergy in which subjects were randomized to receive omalizumab or placebo. Immunologic outcomes included measurement of basophil CD63 expression and histamine release and casein-specific CD4 + regulatory T-cell proliferation. Biomarkers were analyzed in relationship to measurements of safety and efficacy. Results Milk-induced basophil CD63 expression was transiently reduced in whole blood samples from both omalizumab- and placebo-treated subjects. However, IgE-dependent histamine release increased in washed cell preparations from omalizumab- but not placebo-treated subjects. No increase in regulatory T-cell frequency was evident in either group. Subjects with lower rates of adverse reactions, regardless of arm, experienced better clinical outcomes. Pre-OIT basophil reactivity positively associated with occurrence of symptoms during OIT, whereas the baseline Milk IgE/total IgE ratio correlated with the likelihood of achieving sustained unresponsiveness. A combination of baseline basophil and serologic biomarkers defined a subset of patients in which adjunctive therapy with omalizumab was associated with attainment of sustained unresponsiveness and a reduction in adverse reactions. Conclusions Combining omalizumab therapy with Milk OIT led to distinct alterations in basophil reactivity but not T-cell responses. Baseline biomarkers can identify subjects most likely to benefit from adjunctive therapy with omalizumab.
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early life gut microbiome composition and Milk Allergy resolution
The Journal of Allergy and Clinical Immunology, 2016Co-Authors: Supinda Bunyavanich, Alexander Grishin, Hugh A Sampson, Nan Shen, Robert J Wood, Wesley Burks, Peter Dawson, Stacie M Jones, Donald Y M Leung, Scott H SichererAbstract:Background Gut microbiota may play a role in the natural history of cow's Milk Allergy. Objective We sought to examine the association between early-life gut microbiota and the resolution of cow's Milk Allergy. Methods We studied 226 children with Milk Allergy who were enrolled at infancy in the Consortium of Food Allergy observational study of food Allergy. Fecal samples were collected at age 3 to 16 months, and the children were followed longitudinally with clinical evaluation, Milk-specific IgE levels, and Milk skin prick test performed at enrollment, 6 months, 12 months, and yearly thereafter up until age 8 years. Gut microbiome was profiled by 16s rRNA sequencing and microbiome analyses performed using Quantitative Insights into Microbial Ecology (QIIME), Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt), and Statistical Analysis of Metagenomic Profiles (STAMP). Results Milk Allergy resolved by age 8 years in 128 (56.6%) of the 226 children. Gut microbiome composition at age 3 to 6 months was associated with Milk Allergy resolution by age 8 years (PERMANOVA P = .047), with enrichment of Clostridia and Firmicutes in the infant gut microbiome of subjects whose Milk Allergy resolved. Metagenome functional prediction supported decreased fatty acid metabolism in the gut microbiome of subjects whose Milk Allergy resolved (η 2 = 0.43; ANOVA P = .034). Conclusions Early infancy is a window during which gut microbiota may shape food Allergy outcomes in childhood. Bacterial taxa within Clostridia and Firmicutes could be studied as probiotic candidates for Milk Allergy therapy.
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dietary baked Milk accelerates the resolution of cow s Milk Allergy in children
The Journal of Allergy and Clinical Immunology, 2011Co-Authors: Jennifer S Kim, Scott H Sicherer, Anna Nowakwegrzyn, Sally Noone, Erin Moshier, Hugh A SampsonAbstract:Background The majority (approximately 75%) of children with cow's Milk Allergy tolerate extensively heated (baked) Milk products. Long-term effects of inclusion of dietary baked Milk have not been reported. Objective We report on the outcomes of children who incorporated baked Milk products into their diets. Methods Children evaluated for tolerance to baked Milk (muffin) underwent sequential food challenges to baked cheese (pizza) followed by unheated Milk. Immunologic parameters were measured at challenge visits. The comparison group was matched to active subjects (by using age, sex, and baseline Milk-specific IgE levels) to evaluate the natural history of development of tolerance. Results Over a median of 37 months (range, 8-75 months), 88 children underwent challenges at varying intervals (range, 6-54 months). Among 65 subjects initially tolerant to baked Milk, 39 (60%) now tolerate unheated Milk, 18 (28%) tolerate baked Milk/baked cheese, and 8 (12%) chose to avoid Milk strictly. Among the baked Milk–reactive subgroup (n = 23), 2 (9%) tolerate unheated Milk, and 3 (13%) tolerate baked Milk/baked cheese, whereas the majority (78%) avoid Milk strictly. Subjects who were initially tolerant to baked Milk were 28 times more likely to become unheated Milk tolerant compared with baked Milk–reactive subjects ( P P 4 levels in the baked Milk–tolerant group increased significantly ( P Conclusions Tolerance of baked Milk is a marker of transient IgE-mediated cow's Milk Allergy, whereas reactivity to baked Milk portends a more persistent phenotype. The addition of baked Milk to the diet of children tolerating such foods appears to accelerate the development of unheated Milk tolerance compared with strict avoidance.
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correlation of ige igg4 Milk epitopes and affinity of Milk specific ige antibodies with different phenotypes of clinical Milk Allergy
The Journal of Allergy and Clinical Immunology, 2010Co-Authors: Julie Wang, Anna Nowakwegrzyn, Wayne G Shreffler, Jing Lin, Ludmilla Bardina, Marina Goldis, Hugh A SampsonAbstract:Background Results from large-scale epitope mapping with a peptide microarray have been shown to correlate with clinical features of Milk Allergy. Objectives We sought to assess IgE and IgG4 epitope diversity and IgE affinity in different clinical phenotypes of Milk Allergy and identify informative epitopes that might be predictive of clinical outcomes of Milk Allergy. Methods Forty-one subjects were recruited from a larger study on the effects of ingesting heat-denatured Milk proteins in subjects with Milk Allergy. Using food challenges, subjects were characterized as being clinically reactive to all forms of Milk (n = 17), being tolerant to heated Milk (HM) products (n = 16), or having outgrown their Milk Allergy (n = 8). Eleven healthy volunteers without Milk Allergy served as control subjects. A peptide microarray was performed by using the previously published protocol. Results Subjects with Milk Allergy had increased epitope diversity compared with those who outgrew their Allergy. HM-tolerant subjects had IgE-binding patterns similar to those who had outgrown their Allergy, but IgG4-binding patterns that were more similar to those of the allergic group. Binding to higher numbers of IgE peptides was associated with more severe allergic reactions during challenge. There was no association between IgG4 peptides and clinical features of Milk Allergy. Using a competitive peptide microarray assay, allergic patients demonstrated a combination of high- and low-affinity IgE binding, whereas HM-tolerant subjects and those who had outgrown their Milk Allergy had primarily low-affinity binding. Conclusions Greater IgE epitope diversity and higher affinity, as determined by using the peptide microarray, were associated with clinical phenotypes and severity of Milk Allergy.
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allergen specific basophil suppression associated with clinical tolerance in patients with Milk Allergy
The Journal of Allergy and Clinical Immunology, 2009Co-Authors: Niya Wanich, Hugh A Sampson, Anna Nowakwegrzyn, Wayne G ShrefflerAbstract:Background Children with Milk Allergy who tolerate heat-denatured Milk (HM) have less severe reactions and outgrow the condition earlier than those who react to HM, which might be related to differences in IgE-dependent effector cell function. Objective We sought to apply a novel assay to test the hypothesis that HM-tolerant children have suppressed IgE-mediated basophil responses. Methods Allergic, HM-tolerant, outgrown, or control subjects were defined based on oral food challenges. Whole blood cells were stimulated in vitro with a range of Milk allergen doses in the presence or absence of autologous serum or with dilutions of autologous serum. Activated basophils were identified by means of flow cytometry as CD63 bright CD123 + CD203c + HLA-DR − CD41a − . Results HM-tolerant subjects' basophils were significantly less responsive to Milk allergen stimulation at all doses than were basophils from HM-reactive (allergic) individuals. In the absence of autologous serum, HM-tolerant subjects' basophils were significantly more reactive at low allergen concentrations. To a lesser extent, autologous serum also inhibited IL-3– and anti-IgE–induced, but not N-formyl-methionyl-leucyl-phenylalanine–induced, responses. The allergen-specific responsiveness of HM-tolerant subjects' basophils increased with dilution of autologous serum with normal pooled serum. Conclusion Children with Milk Allergy with a favorable prognosis have evidence of extrinsically suppressed allergen-specific effector cell reactivity.
Alessandro Fiocchi - One of the best experts on this subject based on the ideXlab platform.
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the potential for pre pro and synbiotics in the management of infants at risk of cow s Milk Allergy or with cow s Milk Allergy an exploration of the rationale available evidence and remaining questions
World Allergy Organization Journal, 2019Co-Authors: Andrew J Bird, Alessandro Fiocchi, Rosan Meyer, Jan Knol, Seppo Salminen, Gong Sitang, Hania Szajewska, Nikolaos G PapadopoulosAbstract:Cow's Milk Allergy is one of the most commonly reported childhood food allergies, with increasing incidence, persistence and severity in many countries across the world. The World Allergy Organization Special Committee on Food Allergy has identified cow's Milk Allergy as an area in need of a rationale-based approach in order to make progress against what it considered an onerous problem, with worldwide public health impact. There is growing interest in the potential role of the gut microbiota in the early programming and development of immune responses and Allergy. This discussion paper considers the rationale and available evidence for modulation of the gut microbiota and for the use of synbiotics in the management of infants at risk of, or living with cow's Milk Allergy and summarizes remaining research questions that need to be answered for the development of evidence-based recommendations.
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the global impact of the dracma guidelines cow s Milk Allergy clinical practice
World Allergy Organization Journal, 2018Co-Authors: Alessandro Fiocchi, Christophe Dupont, Holger J. Schünemann, Roberto Berni Canani, Sami L Bahna, Ignacio J Ansotegui, Amal Assaad, Martin Bozzola, Lamia Dahdah, Motohiro EbisawaAbstract:The 2010 Diagnosis and Rationale for Action against Cow’s Milk Allergy (DRACMA) guidelines are the only Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines for cow’s Milk Allergy (CMA). They indicate oral food challenge (OFC) as the reference test for diagnosis, and suggest the choice of specific alternative formula in different clinical conditions. Their recommendations are flexible, both in diagnosis and in treatment. Using the Scopus citation records, we evaluated the influence of the DRACMA guidelines on Milk Allergy literature. We also reviewed their impact on successive food Allergy and CMA guidelines at national and international level. We describe some economic consequences of their application. DRACMA are the most cited CMA guidelines, and the second cited guidelines on food Allergy. Many subsequent guidelines took stock of DRACMA’s metanalyses adapting recommendations to the local context. Some of these chose not to consider OFC as an absolute requirement for the diagnosis of CMA. Studies on their implementation show that in this case, the treatment costs may increase and there is a risk of overdiagnosis. Interestingly, we observed a reduction in the cost of alternative formulas following the publication of the DRACMA guidelines. DRACMA reconciled international differences in the diagnosis and management of CMA. They promoted a cultural debate, improved clinician’s knowledge of CMA, improved the quality of diagnosis and care, reduced inappropriate practices, fostered the efficient use of resources, empowered patients, and influenced some public policies. The accruing evidence on diagnosis and treatment of CMA necessitates their update in the near future.
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anaphylactic shock with methylprednisolone sodium succinate in a child with short bowel syndrome and cow s Milk Allergy
Italian Journal of Pediatrics, 2017Co-Authors: Federica Porcaro, Alessandro Fiocchi, Maria Giovanna Paglietti, Antonella Diamanti, Francesca Petreschi, Alessandra Schiavino, Valentina Negro, Valentina Pecora, Renato CutreraAbstract:Medications with methyl-prednisolone sodium succinate containing lactose, which potentially contains traces of cow’s Milk proteins (CMP), could cause allergic reactions or compromise treatment of acute allergic reactions in sensitized patients. We describe the unusual case of a one-year-old child affected by short bowel syndrome and history of severe cow’s Milk Allergy (CMA) and anaphylactic reaction due to intravenous administration of methyl-prednisolone sodium succinate (Solu-Medrol 40 mg, Pfizer). He was admitted to our hospital for severe respiratory failure and was initially treated with methyl-prednisolone (Urbason 40 mg, Sanofi Aventis), then with methyl-prednisolone sodium succinate (Solu-Medrol 40 mg, Pfizer). After the intravenous administration of second steroid, immediate anaphylaxis was recorded and treatment was stopped. Antihistamine and epinephrine were required and symptom resolution occurred. Children who are highly sensitive to Milk may have severe allergic reactions also after exposure to CMP through a different administration route than the oral one. Patients who have food allergies need to pay particular attention to the prescription of drugs and their formulation.
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Anaphylactic shock with methylprednisolone sodium succinate in a child with short bowel syndrome and cow’s Milk Allergy
'Springer Science and Business Media LLC', 2017Co-Authors: Federica Porcaro, Alessandro Fiocchi, Maria Giovanna Paglietti, Antonella Diamanti, Francesca Petreschi, Alessandra Schiavino, Valentina Negro, Valentina Pecora, Renato CutreraAbstract:Abstract Background Medications with methyl-prednisolone sodium succinate containing lactose, which potentially contains traces of cow’s Milk proteins (CMP), could cause allergic reactions or compromise treatment of acute allergic reactions in sensitized patients. Case presentation We describe the unusual case of a one-year-old child affected by short bowel syndrome and history of severe cow’s Milk Allergy (CMA) and anaphylactic reaction due to intravenous administration of methyl-prednisolone sodium succinate (Solu-Medrol 40 mg, Pfizer). He was admitted to our hospital for severe respiratory failure and was initially treated with methyl-prednisolone (Urbason 40 mg, Sanofi Aventis), then with methyl-prednisolone sodium succinate (Solu-Medrol 40 mg, Pfizer). After the intravenous administration of second steroid, immediate anaphylaxis was recorded and treatment was stopped. Antihistamine and epinephrine were required and symptom resolution occurred. Conclusion Children who are highly sensitive to Milk may have severe allergic reactions also after exposure to CMP through a different administration route than the oral one. Patients who have food allergies need to pay particular attention to the prescription of drugs and their formulation
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cow s Milk Allergy towards an update of dracma guidelines
World Allergy Organization Journal, 2016Co-Authors: Alessandro Fiocchi, Christophe Dupont, Lamia Dahda, Cristina Campoy, Vincenzo Fierro, Antonio NietoAbstract:In 2010, the diagnosis and treatment of IgE-mediated CMA were systematized in a GRADE guideline. After 6 years, the state of the knowledge in diagnosis and treatment of CMA has largely evolved. We summarize here the main advances, and exemplify indicating some specific points: studies aimed at better knowledge of the effects of breastfeeding and the production of new special formulae intended for the treatment of CMA. The literature (PubMed/MEDLINE) was searched using the following algorithms: (1) [Milk Allergy] AND diagnosis; (2) [Milk Allergy] AND [formul*] OR [breast*], setting the search engine [6-years] time and [human] limits. The authors drew on their collective clinical experience to restrict retrieved studies to those of relevance to a pediatric Allergy practice. Several clinical studies did address the possibility to diagnose CMA using new tools in vitro and in vivo, or to diagnose it without any evaluation of sensitization. Some studies also addressed the clinical role of formulae based on Milk hydrolysates, soy, or rice hydrolysates in the treatment of CMA. Many studies have elucidated the effects of selective nutrients in breastfed infants on their immunologic and neurologic characteristics. Evidence-based diagnostic criteria should be identified for non-IgE-mediated CMA. Debate is ongoing about the best substitute for infants with CMA. In particular, Hydrolyzed Rice Formulae have been widely assessed in the last six years. In the substitute choice, clinicians should be aware of recent studies that can modify the interpretation of the current recommendations. New systematic reviews and metanalyses are needed to confirm or modify the current DRACMA recommendations.
Scott H Sicherer - One of the best experts on this subject based on the ideXlab platform.
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epidemiology of cow s Milk Allergy
Nutrients, 2019Co-Authors: Julie D. Flom, Scott H SichererAbstract:Immunoglobulin E (IgE)-mediated cow’s Milk Allergy (CMA) is one of the most common food allergies in infants and young children. CMA can result in anaphylactic reactions, and has long term implications on growth and nutrition. There are several studies in diverse populations assessing the epidemiology of CMA. However, assessment is complicated by the presence of other immune-mediated reactions to cow’s Milk. These include non-IgE and mixed (IgE and non-IgE) reactions and common non-immune mediated reactions, such as lactose intolerance. Estimates of prevalence and population-level patterns are further complicated by the natural history of CMA (given its relatively high rate of resolution) and variation in phenotype (with a large proportion of patients able to tolerate baked cow’s Milk). Prevalence, natural history, demographic patterns, and long-term outcomes of CMA have been explored in several disparate populations over the past 30 to 40 years, with differences seen based on the method of outcome assessment, study population, time period, and geographic region. The primary aim of this review is to describe the epidemiology of CMA. The review also briefly discusses topics related to prevalence studies and specific implications of CMA, including severity, natural course, nutritional impact, and risk factors.
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Epidemiology of Cow’s Milk Allergy
MDPI AG, 2019Co-Authors: Julie D. Flom, Scott H SichererAbstract:Immunoglobulin E (IgE)-mediated cow’s Milk Allergy (CMA) is one of the most common food allergies in infants and young children. CMA can result in anaphylactic reactions, and has long term implications on growth and nutrition. There are several studies in diverse populations assessing the epidemiology of CMA. However, assessment is complicated by the presence of other immune-mediated reactions to cow’s Milk. These include non-IgE and mixed (IgE and non-IgE) reactions and common non-immune mediated reactions, such as lactose intolerance. Estimates of prevalence and population-level patterns are further complicated by the natural history of CMA (given its relatively high rate of resolution) and variation in phenotype (with a large proportion of patients able to tolerate baked cow’s Milk). Prevalence, natural history, demographic patterns, and long-term outcomes of CMA have been explored in several disparate populations over the past 30 to 40 years, with differences seen based on the method of outcome assessment, study population, time period, and geographic region. The primary aim of this review is to describe the epidemiology of CMA. The review also briefly discusses topics related to prevalence studies and specific implications of CMA, including severity, natural course, nutritional impact, and risk factors
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early life gut microbiome composition and Milk Allergy resolution
The Journal of Allergy and Clinical Immunology, 2016Co-Authors: Supinda Bunyavanich, Alexander Grishin, Hugh A Sampson, Nan Shen, Robert J Wood, Wesley Burks, Peter Dawson, Stacie M Jones, Donald Y M Leung, Scott H SichererAbstract:Background Gut microbiota may play a role in the natural history of cow's Milk Allergy. Objective We sought to examine the association between early-life gut microbiota and the resolution of cow's Milk Allergy. Methods We studied 226 children with Milk Allergy who were enrolled at infancy in the Consortium of Food Allergy observational study of food Allergy. Fecal samples were collected at age 3 to 16 months, and the children were followed longitudinally with clinical evaluation, Milk-specific IgE levels, and Milk skin prick test performed at enrollment, 6 months, 12 months, and yearly thereafter up until age 8 years. Gut microbiome was profiled by 16s rRNA sequencing and microbiome analyses performed using Quantitative Insights into Microbial Ecology (QIIME), Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt), and Statistical Analysis of Metagenomic Profiles (STAMP). Results Milk Allergy resolved by age 8 years in 128 (56.6%) of the 226 children. Gut microbiome composition at age 3 to 6 months was associated with Milk Allergy resolution by age 8 years (PERMANOVA P = .047), with enrichment of Clostridia and Firmicutes in the infant gut microbiome of subjects whose Milk Allergy resolved. Metagenome functional prediction supported decreased fatty acid metabolism in the gut microbiome of subjects whose Milk Allergy resolved (η 2 = 0.43; ANOVA P = .034). Conclusions Early infancy is a window during which gut microbiota may shape food Allergy outcomes in childhood. Bacterial taxa within Clostridia and Firmicutes could be studied as probiotic candidates for Milk Allergy therapy.
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dietary baked Milk accelerates the resolution of cow s Milk Allergy in children
The Journal of Allergy and Clinical Immunology, 2011Co-Authors: Jennifer S Kim, Scott H Sicherer, Anna Nowakwegrzyn, Sally Noone, Erin Moshier, Hugh A SampsonAbstract:Background The majority (approximately 75%) of children with cow's Milk Allergy tolerate extensively heated (baked) Milk products. Long-term effects of inclusion of dietary baked Milk have not been reported. Objective We report on the outcomes of children who incorporated baked Milk products into their diets. Methods Children evaluated for tolerance to baked Milk (muffin) underwent sequential food challenges to baked cheese (pizza) followed by unheated Milk. Immunologic parameters were measured at challenge visits. The comparison group was matched to active subjects (by using age, sex, and baseline Milk-specific IgE levels) to evaluate the natural history of development of tolerance. Results Over a median of 37 months (range, 8-75 months), 88 children underwent challenges at varying intervals (range, 6-54 months). Among 65 subjects initially tolerant to baked Milk, 39 (60%) now tolerate unheated Milk, 18 (28%) tolerate baked Milk/baked cheese, and 8 (12%) chose to avoid Milk strictly. Among the baked Milk–reactive subgroup (n = 23), 2 (9%) tolerate unheated Milk, and 3 (13%) tolerate baked Milk/baked cheese, whereas the majority (78%) avoid Milk strictly. Subjects who were initially tolerant to baked Milk were 28 times more likely to become unheated Milk tolerant compared with baked Milk–reactive subjects ( P P 4 levels in the baked Milk–tolerant group increased significantly ( P Conclusions Tolerance of baked Milk is a marker of transient IgE-mediated cow's Milk Allergy, whereas reactivity to baked Milk portends a more persistent phenotype. The addition of baked Milk to the diet of children tolerating such foods appears to accelerate the development of unheated Milk tolerance compared with strict avoidance.
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tolerance to extensively heated Milk in children with cow s Milk Allergy
The Journal of Allergy and Clinical Immunology, 2008Co-Authors: Anna Nowakwegrzyn, Scott H Sicherer, K A Bloom, Wayne G Shreffler, Sally Noone, Niya Wanich, Hugh A SampsonAbstract:Background Cow's Milk Allergy is the most common childhood food Allergy. Previously we noted that children who outgrew their Milk Allergy had Milk-specific IgE antibodies primarily directed against conformational epitopes; those with persistent Milk Allergy also had IgE antibodies directed against specific sequential epitopes. Objective Because high temperature largely destroys conformational epitopes, we hypothesized that some children with Milk Allergy would tolerate extensively heated (baked) Milk products. Methods Children with Milk Allergy were challenged with heated Milk products; heated Milk–tolerant subjects were subsequently challenged with unheated Milk. Heated Milk–tolerant, unheated Milk–reactive subjects ingested heated Milk products for 3 months and were then re-evaluated. Immune responses were assessed in all subjects; growth and intestinal permeability were followed in heated Milk–tolerant subjects. Results One hundred children (mean age, 7.5 years; range, 2.1-17.3 years) underwent heated Milk challenges. Sixty-eight subjects tolerated extensively heated Milk only, 23 reacted to heated Milk, and 9 tolerated both heated and unheated Milk. Heated Milk–reactive subjects had significantly larger skin prick test wheals and higher Milk-specific and casein-specific IgE levels than other groups. At 3 months, subjects ingesting heated Milk products had significantly smaller skin prick test wheals and higher casein-IgG 4 compared with baseline; other immunologic parameters, growth, and intestinal permeability were not significantly different. Heated Milk–reactive subjects had more severe symptoms during heated Milk challenge than heated Milk–tolerant subjects experienced during their unheated Milk challenge. Conclusion The majority (75%) of children with Milk Allergy tolerate heated Milk.
Erkki Savilahti - One of the best experts on this subject based on the ideXlab platform.
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specific antibodies in oral immunotherapy for cow s Milk Allergy kinetics and prediction of clinical outcome
International Archives of Allergy and Immunology, 2014Co-Authors: E Savilahti, Erkki Savilahti, Mikael Kuitunen, Mika J MakelaAbstract:Background: Methods for predicting the clinical outcome of specific oral immunotherapy (OIT) would improve the safety of the therapy. Methods: We investigated 40 children aged 6-17 years with IgE-mediated cow's Milk Allergy (CMA) who either successfully completed OIT (n = 32) or discontinued the therapy due to adverse reactions (n = 8). From sera drawn before and after OIT, we analyzed specific IgA, IgG, IgG1 and IgG4 to cow's Milk (CM), casein, β-lactoglobulin and ovalbumin (with enzyme-linked immunosorbent assay) and IgE to CM and hen's egg white [with enzymatic fluoroimmunoassay (Phadia ThermoFisher Scientific CAP system)]. As a reference, we also analyzed serum samples from 8- to 9-year-old children who either had no history of CMA (n = 76) or who had spontaneously recovered from IgE-mediated CMA (n = 56). Results: Levels of specific IgA, IgG, IgG1 and IgG4 to CM and casein, and CM-specific IgE prior to OIT were higher in children who discontinued the therapy than in those who achieved desensitization (p Conclusions: High specific IgE, IgA and IgG-class antibodies to CM proteins appear to predict failure to achieve desensitization in CM OIT. Specific IgA and IgG-class antibodies to CM increase and CM IgE decreases during desensitization.
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development of natural tolerance and induced desensitization in cow s Milk Allergy
Pediatric Allergy and Immunology, 2013Co-Authors: E Savilahti, Erkki SavilahtiAbstract:Cow's Milk Allergy (CMA) affects 2-3% of infants. It resolves in the great majority spontaneously during childhood. CMA encompasses a spectrum of clinical and immunologic characteristics. Non-IgE-mediated Allergy typically resolves earlier than IgE-mediated Allergy. The most documented prognostic characteristic is that intense-specific IgE response predicts persistence of CMA. Low serum levels of cow's Milk (CM)-specific IgG4 are also associated with persistent CMA. Natural development of tolerance involves an immunologic shift where Th2 responses diminish, and Th1 as well as T regulatory cell responses strengthen. Accordingly, specific IgE levels decrease and specific IgG4, possibly also IgA, levels increase in serum. Specific oral immunotherapy (OIT) with CM induces desensitization in most cases where spontaneous recovery has not yet occurred. Data on long-term tolerance induction are still scarce. According to current research data, the immunologic changes induced by OIT resemble those seen during natural development of tolerance.
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specific antibodies to cow s Milk proteins in infants effect of early feeding and diagnosis of cow s Milk Allergy
European Journal of Nutrition, 2010Co-Authors: E Savilahti, Kristiina M. Saarinen, Erkki SavilahtiAbstract:Purpose To investigate whether specific IgA, IgG, IgG1 and IgG4 responses to cow’s Milk proteins differ between infants with cow’s Milk Allergy and infants with cow’s Milk related symptoms (control subjects), and whether early feeding affects these responses as well as specific IgE.
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clinical course and prognosis of cow s Milk Allergy are dependent on Milk specific ige status
The Journal of Allergy and Clinical Immunology, 2005Co-Authors: Kristiina M. Saarinen, Mika J Makela, Anna S Pelkonen, Erkki SavilahtiAbstract:Background Large, prospective population-based studies on clinical course, development of tolerance, and risk for other atopy in children with cow's Milk Allergy (CMA) are lacking. Objective We investigated the development of tolerance and the risk for asthma, rhinoconjunctivitis, atopic dermatitis, and sensitization in children with CMA followed to school age. Methods We followed 118 children with CMA until recovery and repeatedly measured their sensitization to cow's Milk (CM). At age 8.6 years, 94 allergic subjects and 80 control subjects from the same cohort were studied for atopic diseases and sensitization. In addition, the parents of 12 allergic subjects and 26 control children returned a questionnaire on atopy, respectively. Results IgE-mediated CMA was detected in 86 (73%) children; at age 8.6 years, 13 (15%) had persistent CMA. All children with IgE-negative CMA were tolerant by age 5.0 years ( P P ≤ .01), rhinoconjunctivitis (66% vs 21%, P ≤ .001), atopic eczema (81% vs 26%, P ≤ .001), and sensitization to any allergen (88% vs 39%, P ≤ .001) than control subjects. CMA and family history of atopy were independent risk factors for atopic diseases, and CMA was also a risk factor for sensitization to inhalant allergens. Conclusion IgE-mediated CMA often persists to school age and is a risk factor for other atopy; non–IgE-mediated CMA, by contrast, is a benign infantile condition.
Roberto Berni Canani - One of the best experts on this subject based on the ideXlab platform.
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Tolerability of a new amino acid-based formula for children with IgE-mediated cow’s Milk Allergy
'Springer Science and Business Media LLC', 2021Co-Authors: Rita Nocerino, Carmen Di Scala, Laura Carucci, Serena Coppola, Anna Luzzetti, Luana Voto, Veronica Giglio, Linda Cosenza, Anna Maria Iannicelli, Roberto Berni CananiAbstract:Abstract Background Amino acid-based formula (AAF) is a relevant dietary strategy for paediatric patients affected by cow’s Milk Allergy (CMA). The present study was designed to evaluate the hypoallergenicity of a new AAF in children with immunoglobulin (Ig)E-mediated CMA. Methods According to the criteria provided by the American Academy of Pediatrics Subcommittee on Nutrition and Allergic Diseases, we designed a prospective trial in CMA children (aged 1–36 months) aimed to demonstrate the hypoallergenicity of the new AAF in 90% of subjects with 95% confidence during the double-blind, placebo-controlled challenge (DBPCFC). A skin prick test (SPT) with the new AAF was also performed. Results Twenty-nine children [all Caucasian, 55.2% male, mean age (±SD) 16.9 ± 5.7 months] were enrolled. The SPT and the DBPCFC with the new AAF were negative in all study subjects. Conclusions The study results support the hypoallergenicity of the new AAF. This formula could be considered an additional dietary option for non-breastfed children affected by CMA. Trial registration The trial was registered in the ClinicalTrials.gov Protocol Registration System (ID number: NCT03909113 )
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the global impact of the dracma guidelines cow s Milk Allergy clinical practice
World Allergy Organization Journal, 2018Co-Authors: Alessandro Fiocchi, Christophe Dupont, Holger J. Schünemann, Roberto Berni Canani, Sami L Bahna, Ignacio J Ansotegui, Amal Assaad, Martin Bozzola, Lamia Dahdah, Motohiro EbisawaAbstract:The 2010 Diagnosis and Rationale for Action against Cow’s Milk Allergy (DRACMA) guidelines are the only Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines for cow’s Milk Allergy (CMA). They indicate oral food challenge (OFC) as the reference test for diagnosis, and suggest the choice of specific alternative formula in different clinical conditions. Their recommendations are flexible, both in diagnosis and in treatment. Using the Scopus citation records, we evaluated the influence of the DRACMA guidelines on Milk Allergy literature. We also reviewed their impact on successive food Allergy and CMA guidelines at national and international level. We describe some economic consequences of their application. DRACMA are the most cited CMA guidelines, and the second cited guidelines on food Allergy. Many subsequent guidelines took stock of DRACMA’s metanalyses adapting recommendations to the local context. Some of these chose not to consider OFC as an absolute requirement for the diagnosis of CMA. Studies on their implementation show that in this case, the treatment costs may increase and there is a risk of overdiagnosis. Interestingly, we observed a reduction in the cost of alternative formulas following the publication of the DRACMA guidelines. DRACMA reconciled international differences in the diagnosis and management of CMA. They promoted a cultural debate, improved clinician’s knowledge of CMA, improved the quality of diagnosis and care, reduced inappropriate practices, fostered the efficient use of resources, empowered patients, and influenced some public policies. The accruing evidence on diagnosis and treatment of CMA necessitates their update in the near future.
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amino acid based formula in cow s Milk Allergy long term effects on body growth and protein metabolism
Journal of Pediatric Gastroenterology and Nutrition, 2017Co-Authors: Roberto Berni Canani, Rita Nocerino, T Frediani, S Lucarelli, Carmen Di Scala, Elena Varin, Ludovica Leone, Antonella Muraro, Carlo AgostoniAbstract:ABSTRACTObjectives:The long-term effects of amino acid–based formula (AAF) in the treatment of cow's Milk Allergy (CMA) are largely unexplored. The present study comparatively evaluates body growth and protein metabolism in CMA children treated with AAF or with extensively hydrolyzed whey formula (e
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gut microbiota as potential therapeutic target for the treatment of cow s Milk Allergy
Nutrients, 2013Co-Authors: Roberto Berni Canani, Margherita Di CostanzoAbstract:Cow’s Milk Allergy (CMA) continues to be a growing health concern for infants living in Western countries. The long-term prognosis for the majority of affected infants is good, with about 80% naturally acquiring tolerance by the age of four years. However, recent studies suggest that the natural history of CMA is changing, with an increasing persistence until later ages. The pathogenesis of CMA, as well as oral tolerance, is complex and not completely known, although numerous studies implicate gut-associated immunity and enteric microflora, and it has been suggested that an altered composition of intestinal microflora results in an unbalanced local and systemic immune response to food allergens. In addition, there are qualitative and quantitative differences in the composition of gut microbiota between patients affected by CMA and healthy infants. These findings prompt the concept that specific beneficial bacteria from the human intestinal microflora, designated probiotics, could restore intestinal homeostasis and prevent or alleviate Allergy, at least in part by interacting with the intestinal immune cells. The aim of this paper is to review what is currently known about the use of probiotics as dietary supplements in CMA.