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A listening experiment was designed to test whether modern listeners perceive the same affective content in Baroque music as the composer intended to portray. Listeners rated three musical examples from Johann David Heinichen’s 1728 treatise Der General-Bass in der Composition for valence and arousal. Examples were chosen based on descriptions by the composer in which he outlined their intended affective content. Results showed a significant mismatch between original descriptions and listener ratings, indicating a change in the perceived affective content of the music. The historical variability of musical-emotional expression in general, with a focus on the role of structural emotion cues (particularly mode), is discussed, closing with suggestions for future research in the area of historical musical emotion

Cow's milk allergy (CMA) is one of the most common presentations of food allergy in early childhood. Management of CMA involves individualized avoidance of cow's milk and other mammalian milk and foods containing these. Optimal elimination of cow's milk avoidance includes: label reading; information about safe and nutritious substitute foods; appropriate choice of infant formula or a plant-based food; establishing tolerance to baked milk and monitoring nutritional intake and growth. Substitute formulas are divided into soy formula (not hydrolyzed), milk-based extensively hydrolyzed formulas, rice based extensive, and partially hydrolyzed formulas and amino acid-based formulas. The use of other mammalian milks is not recommended for the management of cow's milk allergy due to a high level of cross-reactivity and nutritional concerns. For toddlers who are eating well, children, and adults, a suitable plant-based beverage may be a suitable alternative to a specialized formula, following careful nutritional considerations. Families need to be instructed on finding suitable nutritious foods and how to prepare suitable meals at home. Individuals with CMA also need to know how to identify and treat acute severe reactions.

Background: Research on reported food-related triggers of atopic disease in South Asian adults is lacking despite the region’s large population and the global significance of allergic diseases. Objectives: The study aimed to identify prevalent local food items and assess allergic sensitization rates to potential trigger foods for atopic diseases via skin prick and specific IgE testing. Methods: The study began with a pilot survey of 100 subjects recruited from 4 hospitals in Hyderabad, India, focusing on foods perceived to relate to asthma, allergic rhinitis, atopic dermatitis, urticaria, and gastrointestinal allergic symptoms. A subsequent main study evaluated 2010 participants, 1754 of whom were diagnosed with an aforementioned atopic disease and who reported allergic symptoms related to any of 77 foods identified in the pilot study. Ultimately 1622 patients who consented to skin prick and specific IgE testing and who reported at least 1 food item triggering allergic diseases were included in the final analysis. Results: Among 1622 patients (average age, 42.6 ± 12.9 years; 55.5% male), asthma was the most commonly diagnosed atopic disease (26.4%), with itching and rash being frequently reported symptoms (22.7%). Notably, 94.9% of patients had total serum IgE > 144 kU/L. Chickpea, cabbage, eggplant, walnut, cumin, and betel leaf were the most commonly reported trigger foods. Conclusion: In this sample of South Indian adults diagnosed with allergic disease, reported food triggers were most commonly local dietary staples, while reported reactions to priority allergens like peanut and sesame were conspicuously absent. Observed concordance between patient-reported food triggers and sensitization to reported food triggers was low, highlighting the need for improved clinical evaluation of suspected triggers.

Background: Cow's milk allergy (CMA) is the most common food allergy in infants. The replacement with specialized formulas is an established clinical approach to ensure adequate growth and minimize the risk of severe allergic reactions when breastfeeding is not possible. Still, given the availability of multiple options, such as extensively hydrolyzed cow's milk protein formula (eHF-CM), amino acid formula (AAF), hydrolyzed rice formula (HRF) and soy formulas (SF), there is some uncertainty as to the most suitable choice with respect to health outcomes. Furthermore, the addition of probiotics to a formula has been proposed as a potential approach to maximize benefit. Objective: These evidence-based guidelines from the World Allergy Organization (WAO) intend to support patients, clinicians, and others in decisions about the use of milk specialized formulas, with and without probiotics, for individuals with CMA. Methods: WAO formed a multidisciplinary guideline panel balanced to include the views of all stakeholders and to minimize potential biases from competing interests. The McMaster University GRADE Centre supported the guideline-development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used, including GRADE Evidence-to-Decision frameworks, which were subject to review by stakeholders. Results: After reviewing the summarized evidence and thoroughly discussing the different management options, the WAO guideline panel suggests: a) using an extensively hydrolyzed (cow's milk) formula or a hydrolyzed rice formula as the first option for managing infants with immunoglobulin E (IgE) and non-IgE-mediated CMA who are not being breastfed. An amino-acid formula or a soy formula could be regarded as second and third options respectively; b) using either a formula without a probiotic or a casein-based extensively hydrolyzed formula containing Lacticaseibacillus rhamnosus GG (LGG) for infants with either IgE or non-IgE-mediated CMA.The issued recommendations are labeled as “conditional” following the GRADE approach due to the very low certainty about the health effects based on the available evidence. Conclusions: If breastfeeding is not available, clinicians, patients, and their family members might want to discuss all the potential desirable and undesirable consequences of each formula in infants with CMA, integrating them with the patients' and caregivers’ values and preferences, local availability, and cost, before deciding on a treatment option. We also suggest what research is needed to determine with greater certainty which formulas are likely to be the most beneficial, cost-effective, and equitable.

Cow’s milk allergy (CMA) is one of the most common and complex presentations of allergy in early childhood. CMA can present as IgE and non-IgE mediated forms of food allergy. Non-IgE mediated CMA includes food protein-induced enterocolitis syndrome (FPIES), eosinophilic gastrointestinal disorders (EGIDs), and food protein-induced proctocolitis (FPIAP). There are recent guidelines addressing CMA diagnosis, management, and treatment. Each of these guidelines have their own strengths and limitations. To best manage CMA, individualized avoidance advice should be given. Cow’s milk (CM) can be replaced in the diet by using hypoallergenic formulas or plant-based milk, depending on factors such as the child’s age and their current food intake. Oral and epicutaneous immunotherapy is used to increase tolerance in children with CMA but is not without risk, and the long-term outcome of sustained unresponsiveness is still unclear. The allergenicity of CM proteins are affected differently by different forms of heating, leading to the use of baked milk or milk ladders in the management of CMA, most likely the most promising option for future management and treatment of CMA. Future management of children with CMA will also include discussion around the immunomodulatory potential of the child’s dietary intake.

Abstract Background The 2014 estimates of prevalence of food allergy (FA) in Europe published by the European Academy of Allergy and Clinical Immunology included only the eight so‐called big foods (cow's milk/egg/wheat/soy/peanut/tree nuts/fish/shellfish). Those estimates have recently been updated. Complementing this, we sought to identify and estimate the prevalence of allergy to other foods that have been reported during the last decade. Methods Six databases were searched for studies published 2012–2021. Random‐effects meta‐analysis was performed to derive pooled prevalence of allergy to each food. Results Twenty‐seven studies were included, containing a total of 66 FAs. Among the most frequently reported FAs, the lifetime and point prevalence range of self‐reported kiwi allergy was 0.1%–1.0% and 0.2%–8.1%, respectively, while the food challenge (FC)‐verified kiwi allergy point prevalence range was 0.01%–0.10%. The point prevalence range for self‐reported peach allergy was 0.2%–3.2%, while the range for FC‐verified peach allergy was 0.02%–0.05%. The lifetime and point prevalence range for self‐reported tomato allergy was 0.01%–1.8% and 0.2%–2.1%, respectively. Conclusion Allergy to some foods traditionally not considered important are now emerging as relevant FAs. The focus on FA in Europe should not be limited to the so‐called eight big FA, but extended to other types of foods which need to be considered both for clinical purposes and population risk assessment.

Pediatric food allergy remains commonplace, despite the advancement in our understanding of risk factors and prevention modalities for the condition. Early allergen introduction, a dietary intervention, has been endorsed by professional societies globally as an effective primary preventive measure, yet awareness among medical professionals and parents is lacking. Alongside food allergen introduction, overall nutrition, such as diet diversity, also plays an important role in allergy prevention. To address both food allergen introduction and overall nutrition, dietitians play a pivotal role in the dissemination and education of current guidelines to caregivers. This review addresses the particular role of the dietitian in food allergy prevention consultations, providing up-to-date information on food allergies, their development and prevalence, risk factors, dietary factors and an overview of the current guidelines in the United States. This has not been addressed in any of the current food allergy or nutrition guidelines.

Cow's milk allergy is rare in exclusively breastfed infants. To support the continuation of breastfeeding an infant after diagnosis with a cow's milk allergy, it is critical to examine the evidence for and against any form of cow's milk elimination diet for lactating mothers. In this narrative review, we highlight the lack of high-quality evidence, hence subsequent controversy, regarding whether the minuscule quantities of cow's milk proteins detectable in human milk cause infant cow's milk allergy symptoms. Current clinical practice recommendations advise a 2–4 week trial of maternal cow's milk dietary elimination for: a) IgE-mediated cow's milk allergy only if the infant is symptomatic on breastfeeding alone; b) non-IgE-mediated associated symptoms only if the history and examination strongly suggest cow's milk allergy; and c) infants with moderate to severe eczema/atopic dermatitis, unresponsive to topical steroids and sensitized to cow's milk protein. There should be a clear plan for home reintroduction of cow's milk into the maternal diet for a period of 1 week to determine that the cow's milk elimination is responsible for resolution of symptoms, and then subsequent reoccurrence of infant symptoms upon maternal cow's milk reintroduction. The evidence base to support the use of maternal cow's milk avoidance for the treatment of a breastfed infant with cow's milk allergy is of limited strength due to a lack of high-quality, adequately powered, randomised controlled trials. It is important to consider the consequences of maternal cow's milk avoidance on reducing immune enhancing factors in breast milk, as well as the potential nutritional and quality of life impacts on the mother. Referral to a dietitian is advised for dietary education, along with calcium and vitamin D supplementation according to local recommendations, and a maternal substitute milk should be advised. However, for most breastfed infants with cow's milk allergy maternal cow's milk dietary elimination will not be required, and active support of the mother to continue breastfeeding is essential.

Abstract Background To date, little consideration has been given to access to allergy-related care, despite the fact that food allergy affects a considerable proportion of children. As such, the current study aimed to describe access to food allergy-related services in Canada and the United States (US). Methods Participants were recruited via social media from March-July 2021 and were asked to complete an online survey focused on food allergy-related medical care. Participants were Canadian and US residents who live with a child

The diagnosis of cow's milk allergy (CMA) in infants and young children remains a challenge because many of the presenting symptoms are similar to those experienced in other diagnoses. Both over- and under-diagnosis occur frequently. Misdiagnosis carries allergic and nutritional risks, including acute reactions, growth faltering, micronutrient deficiencies and a diminished quality of life for infants and caregivers. An inappropriate diagnosis may also add a financial burden on families and on the healthcare system.Elimination and reintroduction of cow's milk (CM) and its derivatives is essential for diagnosing CMA as well as inducing tolerance to CM. In non-IgE mediated CMA, the diagnostic elimination diet typically requires 2–4 weeks before reintroduction, while for IgE mediated allergy the time window may be shorter (1–2 weeks). An oral food challenge (OFC) under medical supervision remains the most reliable diagnostic method for IgE mediated and more severe types of non-IgE mediated CMA such as food protein induced enterocolitis syndrome (FPIES). Conversely, for other forms of non-IgE mediated CMA, reintroduction can be performed at home. The OFC cannot be replaced by the milk ladder after a diagnostic elimination diet. The duration of the therapeutic elimination diet, once a diagnosis was confirmed, can only be established through testing changes in sensitization status, OFCs or home reintroduction, which are directed by local protocols and services' availability. Prior non-evidence-based recommendations suggest that the first therapeutic elimination diet should last for at least 6 months or up to the age of 9–12 months, whichever is reached first. After a therapeutic elimination diet, a milk-ladder approach can be used for non-IgE mediated allergies to determine tolerance. Whilst some centers use the milk ladder also for IgE mediated allergies, there are concerns about the risk of having immediate-type reactions at home. Milk ladders have been adapted to local dietary habits, and typically start with small amounts of baked milk which then step up in the ladder to less heated and fermented foods, increasing the allergenicity.This publication aims to narratively review the risks associated with under- and over-diagnosis of CMA, therefore stressing the necessity of an appropriate diagnosis and management.

Background: Maternal diet during pregnancy may play a role in infant health outcomes via the maternal microbiota. We assessed the association of the maternal diet index for the Mediterranean area (MDI-med) with infant gut microbiota at 1 month of life. Methods: The MAMI study is a longitudinal birth cohort in the Mediterranean area. In this work, a cross-sectional study, including 120 mother–infant dyads with available maternal diet and infant microbiota at 1-month-old data, was undertaken. The MDI developed in the US (MDI-US) was adapted for the MAMI cohort (MDI-med). Stratification based on extreme values resulted (22 in the “lower” MDI-med group and 23 in the “upper” group from the mean). Relative microbial abundances and alpha (microbial richness and diversity indexes) and beta diversity (Bray–Curtis distance matrix) were compared between the groups. Results: Higher maternal daily vegetable intake and lower red meat intake were the characteristics of the “upper” MDI-med group. Significantly lower microbial diversity (Shannon and InvSimpson index (p = 0.01)), but no changes in richness (Chao1 index) nor in beta-diversity, using Bray–Curtis distance, were observed in the “upper” group, compared to the “lower” MDI-med group. A higher relative abundance of the Bifidobacterium genus (Actinomycetota phylum) was associated with maternal daily vegetable and yogurt intake. Conclusion: Reduced infant microbial diversity at 1 month of age was associated with “upper” MDI-med scores. Higher maternal intakes of vegetables and yogurt were associated with higher relative abundances of the Bifidobacterium genus in the infant gut. Further studies are needed to understand the link between pregnancy diet, infant microbiota, and health outcomes.

Background: While several scoring systems for the severity of anaphylactic reactions have been developed, there is a lack of consensus on definition and categorisation of severity of food allergy disease as a whole. Aim: To develop an international consensus on the severity of food allergy (DEfinition of Food Allergy Severity, DEFASE) scoring system, to be used globally. Methods: Phase 1: We conducted a mixed-method systematic review (SR) of 11 databases for published and unpublished literature on severity of food allergy management and set up a panel of international experts. Phase 2: Based on our findings in Phase 1, we drafted statements for a two-round modified electronic Delphi (e-Delphi) survey. A purposefully selected multidisciplinary international expert panel on food allergy (n = 60) was identified and sent a structured questionnaire, including a set of statements on different domains of food allergy severity related to symptoms, health-related quality of life, and economic impact. Participants were asked to score their agreement on each statement on a 5-point Likert scale ranging from “strongly agree” to “strongly disagree”. Median scores and percentage agreements were calculated. Consensus was defined a priori as being achieved if 70% or more of panel members rated a statement as “strongly agree” to “agree” after the second round. Based on feedback, 2 additional online voting rounds were conducted. Results: We received responses from 92% of Delphi panel members in round 1 and 85% in round 2. Consensus was achieved on the overall score and in all of the 5 specific key domains as essential components of the DEFASE score. Conclusions: The DEFASE score is the first comprehensive grading of food allergy severity that considers not only the severity of a single reaction, but the whole disease spectrum. An international consensus has been achieved regarding a scoring system for food allergy disease. It offers an evaluation grid, which may help to rate the severity of food allergy. Phase 3 will involve validating the scoring system in research settings, and implementing it in clinical practice.

Guidelines and recommendations for the diagnosis and management of cow’s milk allergy (CMA) in childhood are based on scientific review of the available evidence. While this approach is the most rigorous, guidelines may not fully address all scenarios encountered by clinicians. Many symptoms of CMA overlap with other common childhood illnesses and are subjectively reported by the caregivers of the infant, as is the interpretation of the dietary interventions. Additionally, many healthcare professionals and caregivers do not follow the recommendations to perform an oral food challenge or reintroduction of cow’s milk after a diagnostic elimination diet because (1) the infant is doing well and (2) the carer’s fear of symptoms relapsing with this procedure. As a result, CMA in infants may be either under-diagnosed leading to reduced quality of life for families or over-diagnosed, resulting in unnecessary long-term elimination diets and increasing the risk for nutritional deficiencies. This paper discusses some of these controversial topics, focusing on misdiagnosis and mismanagement in clinical practice. The lack of objective diagnostic criteria can hamper the diagnosis and management of CMA in daily practice.

Early life feeding practices may affect the long-term health of individuals, particularly in terms of the development of non-communicable diseases, such as metabolic and allergic diseases. Accumulating evidence suggests that the interplay of breastfeeding and/or formula feeding followed by the introduction of solids plays a role in the occurrence of non-communicable diseases both in the short and long term. International food allergy guidelines recommend that breastfeeding women do not need to avoid food allergens and do not recommend any infant formula for allergy prevention. Guidelines regarding solid food introduction for food allergy prevention recommend the introduction of well-cooked eggs and peanuts around 4–6 months of age, and not to delay the introduction of other food allergens. There is also an increasing trend to feed infants a plant-based or plant-forward diet and have access to infant formulas based on plant-based ingredients. The use of novel plant-based infant formulas raises a few questions reviewed in this paper: (1) Do fortified, plant-based infant formulas, compliant with US Food and Drug Administration (FDA) regulations and European Food Safety Authority (EFSA) (European) guidelines, support adequate infant growth? (2) Are plant-based infant formulas suitable for the management of cow’s milk allergy? (3) Does feeding with novel, plant-based infant formulas increase the risk of food allergies to the food allergens they contain? (4) Does feeding infants plant-based food allergens in early life increase the risk of allergic and severe allergic reactions? The review of the literature indicated that (1) plant-based formulas supplemented with amino acids and micronutrients to comply with FDA regulations and EFSA guidelines, evaluated in sufficiently powered growth studies, can support adequate growth in infants; (2) currently available plant-based infant formulas are suitable for the management of CMA; (3) an early introduction and continuous intake of food allergens are more likely to prevent food allergies than to increase their risk; and (4) an early introduction of food allergens in young infants is safe.

Background: Cow’s milk allergy (CMA) is one of the most common and complex food allergies affecting children worldwide and, with a few exceptions, presents in the first few months of life. Baked-milk-containing diets are well tolerated in the majority of milk-allergic children and allow dietary restrictions to be relaxed. In addition, the early introduction of tolerated forms of allergenic foods to an infant’s diet in small amounts may enhance the outgrowth of their milk allergy through oral tolerance induction. The methods of milk introduction vary widely across the globe. Methods: We convened an expert group to develop a comprehensive milk ladder based on the calculated milk protein content of Indian foods. To validate the milk ladder, the foods chosen for the ladder were analyzed and the ladder was re-evaluated based on the cooked milk protein content. Results: Combining expert consensus and validation of milk protein content, we created the world’s first milk ladder containing Indian foods. This is the first ladder that provides information on the timing and temperature of cooking, with validated milk protein content. Conclusions: This is the first milk ladder based on the unique features of Indian food habits built by the consensus of Indian experts along with international collaboration with laboratory quantification of milk protein in each step. We believe the “The Indian Milk Ladder” will be a very helpful tool for pediatricians helping manage CMA in children as well as their parents and caregivers, not only in India, but in countries world-wide where these foods are commonly consumed.

Background: Allergic diseases are increasing globally and are a significant public health challenge, especially in children. Cow's milk allergy (CMA) is one of the most common food allergies in early childhood. When CMA is diagnosed and exclusive breastfeeding is not possible, current guidelines recommend extensively hydrolyzed formulas (eHF) or amino acid-based formulas (AAF), depending on the diagnosis and severity of symptoms. Hydrolyzed rice formulas (HRF) are considered an alternative to eHF and AAF where available. Objectives & methods: We aimed to understand how HRF are being used and their position in the management of CMA, and to generate consensus on indications for use. Two virtual roundtables of international healthcare experts in pediatric food allergy focused on HRF were convened in May and October 2021. Experts provided multiple perspectives due to different specialties, locations, healthcare settings, and availability of HRF. Following discussion of international CMA guidelines and HRF use, identification of challenges along the diagnosis and treatment pathway, and translation of guidelines into clinical practice, an expert consensus on the use of HRF for CMA was developed. This involved repeated voting followed by statement amendment to reach 100% agreement. This publication summarizes insights from these meetings. Results: There was 100% agreement on all 8 statements: (1) While breastmilk is the best source of nutrition for infants with CMA, when breastfeeding is not possible, a hypoallergenic formula can be used; (2) Per definition, a HRF is cow's milk protein-free; (3) A minority of infants with immunoglobulin (Ig)E-mediated CMA react to eHF due to residual cow's milk protein; (4) More infants with non-IgE-mediated CMA than IgE-mediated CMA react to eHF likely due to residual cow's milk protein; (5) When a diagnostic elimination diet is indicated, HRF can be used; (6) A HRF can be recommended as a first-line option for CMA, where available, as outlined in the Diagnosis and Rationale for Action against Cow's Milk Allergy guidelines; (7) HRFs have proven hypoallergenicity and are suitable for the dietary management of CMA; (8) HRFs have been shown to support growth in infants with CMA, similar to other hypoallergenic formulas. Participants recommend healthcare professionals take these statements as guidance to use HRF in clinical practice. Based on efficacy and growth evidence, the experts found HRF a suitable option for the dietary management of CMA. Conclusion: HRF can be recommended as a first-line alternative to cow's milk-based eHF or AAF, where available, in the dietary management of CMA.

Abstract Owing to a collaborative approach to patient care, and a paucity of allergists in Canada, there is a need to develop a food allergy educational program for allied health care professionals in Canada. Such programs already exist in the United States and Britain. Herein, we describe the outcomes of recent conference proceedings to inform the educational needs for such a program. As part of the 76th Annual Meeting of the Canadian Society of Allergy and Clinical Immunology (CSACI), held virtually due to the COVID-19 pandemic, we hosted a virtual workshop on the need for a food allergy educator program for Canadian allied health professionals. This workshop was co-developed with the CSACI and an industry partner, and featured allergy specialist dietitians. Attendance was open to all conference delegates, and to allied health professionals. As part of the registration process, registrants posed diverse food allergy-related questions, ranging from how to use an epinephrine autoinjector, to daily management and, how to cure food allergy. A national food allergy educator program will empower both allergy and non-allergy specialist healthcare professionals to appropriately counsel patients. This virtually-delivered program will begin to close a gap in healthcare access resulting from the geographic size of Canada, as it will enhance allied healthcare providers’ confidence to provide evidence-based food allergy care appropriately for those with food allergy.

Background: Allergy to cow's milk is the most common food allergy in infants and it is usually outgrown by 5 years of age. In some individuals it persists beyond early childhood. Oral immunotherapy (OIT, oral desensitization, specific oral tolerance induction) has been proposed as a promising therapeutic strategy for persistent IgE-mediated cow's milk allergy. We previously published the systematic review of OIT for cow's milk allergy (CMA) in 2010 as part of the World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines. Objective: To systematically synthesize the currently available evidence about OIT for IgE-mediated CMA and to inform the updated 2022 WAO guidelines. Methods: We searched the electronic databases including PubMed, Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and the websites of selected allergy organizations. We included all studies irrespective of the language of the original publication. The last search was conducted in February 2021. We registered the protocol on Open Science Framework (10.17605/OSF.IO/AH2DT). Results: We identified 2147 unique records published between 2010 and 2021, including 13 randomized trials and 109 observational studies addressing cow's milk OIT. We found low-certainty evidence that OIT with unheated cow's milk, compared to elimination diet alone, increased the likelihood of being able to consume ≥150 ml of cow's milk in controlled settings (risk ratio (RR): 12.3, 95% CI: 5.9 to 26.0; risk difference (RD): 25 more per 100, 95% CI 11 to 56) as well as accidently ingest a small amount (≥5 ml) of cow's milk (RR: 8.7, 95% CI: 4.7 to 16.1; RD: 25 more per 100, 95% CI 12 to 50). However, 2–8 weeks after discontinuation of a successful OIT, tolerance of cow's milk persisted in only 36% (range: 20%–91%) of patients. OIT increased the frequency of anaphylaxis (rate ratio: 60.0, 95% CI 15 to 244; rate difference 5 more anaphylactic reactions per 1 person per year, 95% CI: 4 to 6; moderate evidence) and the frequency of epinephrine use (rate ratio: 35.2, 95% CI: 9 to 136.5; rate difference 268 more events per 100 person-years, 95% CI: 203 to 333; high certainty). OIT also increased the risk of gastrointestinal symptoms (RR 6.9, 95% CI 1.6–30.9; RD 28 more per 100, CI 3 to 100) and respiratory symptoms (RR 49.0, 95% CI 3.12–770.6; RD 77 more per 100, CI 62 to 92), compared with avoidance diet alone. Single-arm observational studies showed that on average 6.9% of OIT patients (95% CI: 3.8%–10%) developed eosinophilic esophagitis (very low certainty evidence). We found 1 trial and 2 small case series of OIT with baked milk. Conclusions: Moderate certainty evidence shows that OIT with unheated cow's milk in patients with IgE-mediated CMA is associated with an increased probability of being able to drink milk and, at the same time, an increased risk of serious adverse effects.

Background: The immunopathogenesis of cow's milk protein allergy (CMPA) is based on different mechanisms related to immune recognition of protein epitopes, which are affected by industrial processing. Purpose: The purpose of this WAO DRACMA paper is to: (i) give a comprehensive overview of milk protein allergens, (ii) to review their immunogenicity and allergenicity in the context of industrial processing, and (iii) to review the milk-related immune mechanisms triggering IgE-mediated immediate type hypersensitivity reactions, mixed reactions and non-IgE mediated hypersensitivities. Results: The main cow’s milk allergens – α-lactalbumin, β-lactoglobulin, serum albumin, caseins, bovine serum albumins, and others – may determine allergic reactions through a range of mechanisms. All marketed milk and milk products have undergone industrial processing that involves heating, filtration, and defatting. Milk processing results in structural changes of immunomodulatory proteins, leads to a loss of lipophilic compounds in the matrix, and hence to a higher allergenicity of industrially processed milk products. Thereby, the tolerogenic capacity of raw farm milk, associated with the whey proteins α-lactalbumin and β-lactoglobulin and their lipophilic ligands, is lost. Conclusion: The spectrum of immunopathogenic mechanisms underlying cow's milk allergy (CMA) is wide. Unprocessed, fresh cow's milk, like human breast milk, contains various tolerogenic factors that are impaired by industrial processing. Further studies focusing on the immunological consequences of milk processing are warranted to understand on a molecular basis to what extent processing procedures make single milk compounds into allergens.

Food allergy affects approximately 2–4% of children and adults. This guideline provides recommendations for managing food allergy from the Global Allergy and Asthma European Network (GA2LEN). A multidisciplinary international Task Force developed the guideline using the Appraisal of Guidelines for Research and Evaluation (AGREE) II framework and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We reviewed the latest available evidence as of April 2021 (161 studies) and created recommendations by balancing benefits, harms, feasibility, and patient and clinician experiences. We suggest that people diagnosed with food allergy avoid triggering allergens (low certainty evidence). We suggest that infants with cow's milk allergy who need a breastmilk alternative use either hypoallergenic extensively hydrolyzed cow's milk formula or an amino acid-based formula (moderate certainty). For selected children with peanut allergy, we recommend oral immunotherapy (high certainty), though epicutaneous immunotherapy might be considered depending on individual preferences and availability (moderate certainty). We suggest considering oral immunotherapy for children with persistent severe hen's egg or cow's milk allergy (moderate certainty). There are significant gaps in evidence about safety and effectiveness of the various strategies. Research is needed to determine the best approaches to education, how to predict the risk of severe reactions, whether immunotherapy is cost-effective and whether biological therapies are effective alone or combined with allergen immunotherapy.

Abstract Background Recent reports indicate that the prevalence of food allergy is increasing, but accurate estimates remain a challenge due to cross‐reactivity and limited use of precise diagnostic methods. Molecular allergy diagnostics, in which sensitization to individual molecular allergens is measured, is emerging as a promising tool for evaluation of sensitization profiles. In this systematic review, we summarized estimates of prevalence of sensitization to molecular food allergens in the general population in Europe. Methods Following a protocol prospectively registered with the International Prospective Register of Systematic Reviews (PROSPERO; reference CRD42021266657), we searched seven databases with no restrictions on publication date or language. Two reviewers independently screened the literature, extracted data, and appraised the risk of bias in the included studies. The findings were synthesized narratively. Results From 4776 de‐duplicated records, five studies, with low to moderate overall risk of bias, were included. Forty‐six molecular allergens from 18 foods were investigated. Overall, the prevalence of sensitization was low, particularly for major allergens, and non‐existent for 10 molecular allergens (0% [95% CI 0–0.8]). The highest prevalence was seen for PR‐10 proteins, such as Cor a 1.04 (13.6% [95% CI 10.9–16.9]). Conclusions Available data, primarily from North‐western Europe, indicate that sensitization to molecular food allergens is overall low. The highest estimates were found for cross‐reactive PR‐10 proteins. There were not enough studies to discern regional differences or perform meta‐analysis, highlighting the need for more population‐representative studies in order to elucidate patterns of sensitization to molecular food allergens in Europe.

Background: The prevalence of cow's milk allergy (CMA) is approximately 2–4.5% in infants and less than 0.5% in adults. Most children outgrow cow's milk allergy in early childhood, particularly that to the baked milk products. Immunotherapy with unheated cow's milk has been used as a treatment option for those who have not yet outgrown CMA, but the benefits must be balanced with the adverse effects. Objective: These evidence-based guidelines from the World Allergy Organization (WAO) intend to support patients, clinicians, and others in decisions about the use of oral and epicutaneous immunotherapy for the treatment of IgE-mediated CMA. Methods: WAO formed a multidisciplinary guideline panel balanced to include the views of all stakeholders and to minimize potential biases from competing interests. The McMaster University GRADE Centre supported the guideline-development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used, including GRADE Evidence-to-Decision frameworks, which were subject to public comment. Results: After a careful review of the summarized evidence and thorough discussions the WAO guideline panel suggests: a) using oral immunotherapy with unheated cow's milk in those individuals with confirmed IgE-mediated CMA who value the ability to consume controlled quantities of milk more than avoiding the large adverse effects of therapy, b) not using oral immunotherapy with unheated cow's milk in those who value avoiding large adverse effects of therapy more than the ability to consume controlled quantities of milk, c) using omalizumab in those starting oral immunotherapy with unheated cow's milk, d) not using oral immunotherapy with baked cow's milk in those who do not tolerate both unheated and baked milk, and e) not using epicutaneous immunotherapy outside of a research setting. The recommendations are labeled “conditional” due to the low certainty about the health effects based on the available evidence. Conclusions: Clinicians, patients, and their family members might want to discuss all the potential desirable and undesirable effects of oral immunotherapy for IgE-mediated CMA and integrate them with the patients' values and preferences before deciding on a treatment option. More robust research is needed to determine with greater certainty which interventions are likely to be the most beneficial with the least harms, and to develop safer, low-cost, and equitable treatments.

Background: Since the publication of The World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines in 2010, a number of other guidelines, expert opinions, and position papers relating to the management of cow's milk allergy (CMA) have been published. We aimed to systematically review the quality of the guidelines on CMA diagnosis and management in children and/or adults published between 2010 and 2020. Methods: The MEDLINE, EMBASE, ISI Web of Science, World Health Organization Global Index Medicus, and Turning Research into Practice databases as well as website guideline repositories were searched from January 2010 until May 2020. Any clinical practice recommendations and/or guidelines focusing on the diagnosis and management of CMA in children and/or adults developed or endorsed by professional scientific societies or organizations were included. The guidelines were evaluated using the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool, a 23-item tool organized within 6 domains and 2 global rating items. Results: We included 12 guidelines; 8 were developed by national and 4 by international organizations. The quality scores for each domain varied: of all domains, the clarity of presentation domain had the highest median score (92%; Q1-Q3 81–100%), whereas rigor of development had the lowest median score (30%; Q1-Q3 15–67%). The median scores (Q1-Q3) for individual domains were as follows: scope and purpose 82% (70–99%), stakeholder involvement 63% (21–79%), rigor of development 30% (15–67%), clarity of presentation 92% (81–100%), applicability 68% (57–75%), and editorial independence 75% (69–100%). The median overall score was 70% (58–89%). Only 1 guideline (from the National Institute for Health and Care Excellence [NICE]) achieved top ratings (100%) in five domains and the overall score. Three guidelines (from the NICE, the British Society for Allergy & Clinical Immunology [BSACI] and WAO) achieved the highest ratings (100%) in at least 3 domains and the overall score. Conclusion: The majority of identified guidelines were of good or very good quality. However, the weakest point was the rigor of development domain, mostly due to unclear description of strengths and limitations of the body of evidence and the procedure for updating the guidelines.

Since the World Allergy Organization (WAO) Diagnosis and Rationale against Cow's Milk Allergy (DRACMA) Guidelines were published 10 years ago, new evidence has accumulated about the diagnosis, therapy, and specific immunotherapy for cow's milk allergy (CMA). For this reason, WAO has felt the need to update the guidelines.We introduce here this update. The new DRACMA guidelines aim to comprehensively address the guidance on diagnosis and therapy of both IgE non-IgE-mediated forms of cow's milk allergy in children and adults. They will be divided into 18 chapters, each of which will be dedicated to an aspect. The focus will be on the meta-analyzes and recommendations that will be expressed for the 3 most relevant clinical aspects: (a) the diagnostic identification of the condition; (b) the choice of the replacement formula in case of CMA in infancy when the mother is not able to breastfeed, and (c) the use of specific immunotherapy for cow's milk protein allergy.

The process of gradually reintroducing food allergens into an individual’s diet is referred to as a food allergen “ladder”, and the most recent edition of the original Milk Allergy in Primary (MAP) Care Guidelines, as well as the International Milk Allergy in Primary Care (IMAP), includes a shortened, improved, and international version with specific recipes, indicating the exact milk protein content, as well as the duration of heating and the temperature for each step of the ladder. Food allergen ladders are being used increasingly in clinical practice. The aim of this study was to develop a Mediterranean milk ladder based on the principles of the Mediterranean eating pattern. The protein content delivered in a portion of the final food product in each step of the ladder in the Mediterranean version corresponds to that provided in the IMAP ladder. Different recipes for the various steps were provided to increase acceptability and variety. Quantification of the total milk protein, casein content, and beta-lactoglobulin by Enzyme-linked immunosorbent assay (ELISA) could detect the gradual increase in concentrations, but the accuracy of the method was affected by the presence of the other ingredients in the mixtures. When developing the Mediterranean milk ladder, a key consideration was to reduce the amount of sugar by using limited amounts of brown sugar and substituting sugar with fresh fruit juice or honey for children aged older than one year. The proposed Mediterranean milk ladder includes principles of (a) healthy eating based on the Mediterranean diet and (b) the acceptability of foods across different age groups.

Abstract Introduction Eosinophilic oesophagitis (EoE) is an immune‐mediated, chronic disease characterized by eosinophilic inflammation and esophageal dysfunction. Specific food allergens including cow's milk protein, are partially causative to disease progression, and dietary management forms three main options; the elemental diet (ED), the empirical elimination diet (EED), and the targeted elimination diet (TED). The dietary choice should be individualized, however, the European Society for Pediatric Gastroenterology, Hepatology and Nutrition guidelines recommend an ED for pediatric EoE with multiple food allergies, failure to thrive, unresponsive disease or unable to follow a highly restricted diet. The aim of this narrative review was to explore the effectiveness of the ED (using amino acid formula [AAF]), in the management of pediatric EoE. Methods Literature searches were performed to identify eligible studies that described outcomes including eosinophil count, clinical symptoms, growth, and medications. Results Overall, 10 eligible studies were found, with n = 462 patients assigned to receive AAF from a total of n = 748 (average age 6.7 years), for a duration of 4 to 8 weeks. The use of AAF reduced eosinophil levels and demonstrated remission (defined as ≤10 eosinophils per high power field) in 75%‐100% of children with improvements, if not resolution, in clinical symptoms. AAF was more clinically effective than the use of the EED or TED, where remission rates were 75%‐81% and 40%‐69%, respectively. Few studies collected growth outcomes, however where documented these were positive for those on AAF. The long‐term impacts of each diet were not thoroughly explored. Conclusions The use of AAF is a clinically effective management option for pediatric EoE, and further research is required to guide long‐term management.

There is a wide time gap between the publication of evidence and the application of new knowledge into routine clinical practice. The consequence is sub-optimal outcomes, particularly concerning for long-term relapsing/remitting conditions such as allergic diseases. In response, there has been a proliferation of published guidelines which systematically review evidence for the gold-standard management of most allergic disorders. However, this has not necessarily been followed by improved outcomes, partly due to a lack of coordination across the patient pathway. This has become known as the ''second translational gap''. A proposed solution is the development and implementation of integrated care pathways (ICPs) to optimize patient outcomes, with the notion that evidence-based medicine requires evidence-based implementation. ICP implementation is shown to improve short-term outcomes for acute conditions and routine surgery, including reduced length of hospital stay, improved documentation and improved patient safety. However, this improvement is not reflected in patient experience or patient-centered functional outcomes. The implementation of life-long, cost-effective interventions within comprehensive pathways requires a deep appreciation for complexity within allergy care.We promote an evidence-based methodology for the implementation of ICPs for allergic disorders in which all stakeholders in allergy care are positioned equally and encouraged to contribute, particularly patients and their caregivers. This evidence-based process commences with scoping the unmet needs, followed by stakeholder mapping. All stakeholders are invited to meetings to develop a common vision and mission through the generation of action/effect diagrams which helps build concordance across the agencies. Dividing the interventions into achievable steps and reviewing with plan/do/study/act cycles will gradually modify the pathway to achieve the best outcomes. While the management guidelines provide the core knowledge, the key component of implementation involves education, training, and support of all healthcare professionals (HCPs), patients and their caregivers.The pathways should define the level of competence required for each clinical task. It may be useful to leave the setting of care delivery or the specific HCP involved undefined to account for variable patterns of health service delivery as well as local socioeconomic, ethnic, environmental, and political imperatives. In all cases, where competence is exceeded, it is necessary to refer to the next stage in the pathway. The success and sustainability of ICPs would ideally be judged by patient experience, health outcomes, and health economics. We provide examples of successful programs, most notably from Finland, but recommend that further research is required in diverse settings to optimize outcomes worldwide.

The increasing prevalence of allergic diseases has placed a significant burden on global healthcare and society as whole. This has necessitated a rapid development of “allergy” as a specialist area. However, as allergy is so common and, for most, relatively easy to diagnose and control, all clinicians need to have basic knowledge and competence to manage mild disease and recognize when referral is required. The allergology specialty has not yet been recognized in many countries and even where allergy is fully recognized as a specialty, the approach to training in allergy differs significantly.In the light of recent developments in allergy diagnosis and management, there is an urgent need to harmonize core competences for physicians, as well as the standardization of core principles for medical education and post-graduate training in allergy. All physicians and allied health professionals must appreciate the multidisciplinary team (MDT) approach to allergy, which is key to achieving the highest standards in holistic care. Due to worldwide variation in resources and personnel, some MDT roles will need to be absorbed by the treating physician or other healthcare professionals. We draw particular attention to the role of psychological input for all allergy patients, dietetic input in the case of food allergy and patient education to support all patients in the supported self-management of their condition on a daily basis. A strong appreciation of these multidisciplinary aspects will help physicians provide quality patient-centered care.We consider that harmonization of allergy components within undergraduate curricula is crucial to ensure all physicians develop the appropriate allergy-related knowledge and skills, particularly in light of inconsistencies seen in the primary care management of allergy. This review from the World Allergy Organization (WAO) Education and Training Committee also outlines allergy-related competences required of physicians working with allergic patients and provides recommendations to promote harmonization of allergy training and practice worldwide.

Abstract The Milk Allergy in Primary (MAP) Care guideline was first published in 2013 in this journal. MAP aimed to provide simple and accessible algorithms for UK clinicians in primary care, detailing all the steps between initial presentation, through diagnosis, management and tolerance development. Despite its UK focus, it soon became clear that MAP was being accessed internationally and thus an updated International Milk Allergy in Primary Care (iMAP) guideline was published in 2017. Both guidelines used existing international consensus guidelines to develop accessible algorithms accompanied by patient information leaflets. In 2018, the guidelines were criticised for 3 distinct reasons: promoting the overdiagnosis of cow’s milk allergy (CMA), negatively impacting breastfeeding and the possibility of industry influence on the guidelines. The authors address these criticisms using available evidence and, in the context of this and in consultation with patient groups, members of the General Practice Infant Feeding Network and other infant feeding healthcare leads, have collaboratively produced updated algorithms and an information leaflet to support breastfeeding. We believe iMAP is now closer to its original aim of facilitating early and accurate diagnosis of CMA, whilst minimising, as far as possible, any concerns around overdiagnosis or a risk to breastfeeding rates. We continue to welcome open and constructive engagement about how best to achieve these aims to provide evidence-based, practical guidelines for the primary care practitioner.

Background: Studying the developmental precursors of allergy may help explain the mechanisms (or etiology) of allergic disease. We studied childhood respiratory and allergic diseases in a pre-birth cohort from the United States. Objective: We assessed the associations between maternal history of asthma and the development of respiratory and allergic diseases in offspring. We also assessed associations with maternal history of allergic rhinitis. Methods: Maternal history of asthma and allergic rhinitis was self-reported during early pregnancy. Offspring respiratory and allergy information was obtained from electronic medical records. Adjusted Cox proportional hazard models assessed the associations between maternal history of asthma and development of respiratory and allergic diseases in the offspring up to 8 years. A similar approach was used for maternal history of allergic rhinitis. Results: Children born to women with a history of asthma had a 77% greater risk of developing asthma, a 45% greater risk of atopic dermatitis/eczema, and a 65% greater risk of wheeze (all p

Nutrients in foods are not eaten in isolation and food intake interacts in a complex manner, affecting health and disease outcomes. For this reason, focusing on the whole “pattern” of dietary intake instead of the single nutrients or groups of nutrients when studying diseases outcomes is increasingly appealing and growing. Diet diversity refers to the variety of foods being eaten, and the terms, diversity or variety, are often used interchangeably. When the overall diet is characterized by healthy foods, diet diversity will reflect a diversity/variety of healthy foods eaten over a period of time. The introduction of solid foods in the 1st year of life is considered a measure of increased diet diversity. Consuming a diverse range of foods and food allergens in the first year of life may increase intake of important nutrients and positively affect the gut microbiome structure and function. Intake of omega-3 fatty acids and fibers/prebiotics may be particularly important but more information is required about dose and which individuals are most likely to benefit. Increased diet diversity in the first year of life is also associated with reduced food allergy outcomes. In addition to diet diversity, diet indices are considered measures of overall diet quality and can be used as a simple assessment of dietary intake. The focus of this paper is to review and critically address the current knowledge of the association between diet diversity and diet indices and allergy outcomes. Based on the current evidence, we recommend the introduction of solid foods, including common allergenic solids, during the 1st year of life, according to the infant's neuro-developmental abilities and familial or cultural habits. For infants with severe AD and/or FA, medical assessment may be advisable before introducing common food allergens into the diet. Limited evidence exist about the role of diet indices in pregnancy and allergic disease in the offspring, and the most promising results indicate a reduction in childhood wheeze and/or asthma intake.

Background: Although oral food challenge (OFC) is an important clinical procedure for diagnosing food allergy, there is a paucity of literature on the outcome of the procedure and specifically the patients on whom the procedure is performed from the aspects of their age, sex, race/ethnicity, health insurance status, and serum specific IgE to the food tested. Objective: We aimed to review results of OFC and determine the impact of patient age, sex, race/ethnicity, insurance status, private or public, and food specific serum IgE on the outcome of OFC. Methods: A retrospective chart review was performed of patients undergoing OFCs at a children's hospital outpatient allergy clinic over a two-year period. The outcome of OFC was allergic or non-allergic based on determination and documentation by the treating physician. A logistic regression model was built to determine the association between the OFC outcomes, age, and symptoms at the time of OFC. A Chi-square analysis was performed to check for any significant relationship between the OFC outcome and age when stratified by insurance status. Results: Five hundred and eight children underwent 641 OFCs. Twenty nine percent of OFCs had an allergic outcome with the most commonly challenged foods being peanuts, eggs, and milk. Patient age and gender, when stratified by insurance status, did not have a significant effect on OFC outcomes. Serum IgE to peanuts and egg was significantly different between allergic OFC and non-allergic outcome. Vomiting and urticaria/angioedema correlated with an allergic OFC outcome. Conclusion: OFCs confirm the food allergy diagnosis in about one-third of patients tested, and they should continue to be used when possible for an accurate diagnosis. Age, sex, and insurance status do not have a significant association with the outcome of OFC and cannot be added as predictive factors.

Enthusiasm exists for the potential of diet to impact the immune system, prevent disease and its therapeutic potential. Herein, we describe the challenge to nutrition scientists in defining this relationship through case studies of diets and nutrients in the context of allergic and autoimmune diseases. Moderate-quality evidence exists from both human intervention and observational studies to suggest that diet and individual nutrients can influence systemic markers of immune function and inflammation; numerous challenges exist for demonstrating the impact of defined diets and nutrient interventions on clearly influencing immune-mediated-clinical disease endpoints. A growing body of evidence suggests that further consideration of dietary patterns, immune system and gut microbiome composition and function, and subsequent epigenetic modifications are needed to improve our understanding of diet−immune system interactions.

Background Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy.Objectives Prompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy groups, the National Institute of Allergy and Infectious Diseases facilitated development of addendum guidelines to specifically address the prevention of peanut allergy.Results The addendum provides 3 separate guidelines for infants at various risk levels for the development of peanut allergy and is intended for use by a wide variety of health care providers. Topics addressed include the definition of risk categories, appropriate use of testing (specific IgE measurement, skin prick tests, and oral food challenges), and the timing and approaches for introduction of peanut-containing foods in the health care provider’s office or at home. The addendum guidelines provide the background, rationale, and strength of evidence for each recommendation.Conclusions Guidelines have been developed for early introduction of peanut-containing foods into the diets of infants at various risk levels for peanut allergy. Keywords: Food, Peanut, Allergy, Prevention, Guidelines

The prevalence of food allergy appears to be steadily increasing in infants and young children. One of the major challenges of modern clinical nutrition is the implementation of individualized nutritional recommendations. The management of food allergy (FA) has seen major changes in recent years. While strict allergen avoidance is still the key treatment principle, it is increasingly clear that the avoidance diet should be tailored according to the patient FA phenotype. Furthermore, new insights into the gut microbiome and immune system explain the rising interest in tolerance induction and immunomodulation by microbiota-targeted dietary intervention. This review article focuses on the nutritional management of IgE mediated food allergy, mainly focusing on different aspects of the avoidance diet. A personalized approach to managing the food allergic individual is becoming more feasible as we are learning more about diagnostic modalities and allergic phenotypes. However, some unmet needs should be addressed to fully attain this goal.

The timing of introduction of solid food on the subsequent development of food allergy is under debate and the role of concurrent breastfeeding is unclear. The aim of the present study was to investigate the role of solid food introduction whilst concurrently breastfeeding on food allergy outcome, with a specific focus on cows’ milk allergy. Prospectively collected infant feeding data from a birth cohort were analysed. Participants with histories suggestive of food allergy underwent diagnostic food challenges. Children with food allergy were matched to control participants for age and sex. Mann–Whitney U tests, χ2, Fisher exact tests and logistic regression calculations were undertaken. A total of thirty-nine food-allergic children and seventy-eight matched controls were identified, including twenty-two cows’ milk-allergic children and forty-four matched controls. The control group introduced solid food earlier than the food-allergic group (P

Abstract In the original version of this article [1], published on 23 August 2017, an incorrect version of Additional file 4 has been used. The corrected version of Additional file 4 is given in this correction.

The prevalence of food allergy in childhood appears to be increasing in both developed and transitional countries. The aim of this paper is to review and summarise key findings in the prevention and management of food allergy, focusing on the role of dietary components and nutritional habits in the development and optimal functioning of the immune system. Essential fatty acids, zinc and vitamin D are likely to enhance the anti-inflammatory and antioxidative barrier and promote immunologic tolerance. Additionally, nutritional components such as pre- and probiotics represent a novel research approach in the attempt to induce a tolerogenic immune environment. For all these reasons, the traditional avoidance diet has been, in recent years, completely reconsidered. New findings on the protective effect of an increased diversity of food introduced in the first year of life on allergic diseases are consistent with the hypothesis that exposure to a variety of food antigens during early life might play a role in the development of immune tolerance. Accordingly, therapeutic (and even preventive) interventions should be planned on an individual basis.