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Non‐steroidal anti‐inflammatory drugs (NSAIDs) are available as over‐the‐counter drugs, and they are commonly used in children for their antipyretic, analgesic, and anti‐inflammatory effects. NSAIDs are among the most frequently reported drugs associated with hypersensitivity reactions and even with anaphylaxis. A complete evaluation of the patients based on reported clinical manifestations, timing of the reaction, the presence of underlying disease, and reactions to other NSAIDs allows clinicians to stratify children with a history of reaction to NSAIDs. Although NSAID‐induced hypersensitivity reactions have mainly been investigated in adults, recent studies have aimed to explore their epidemiology in the pediatric population. This review will cover the current understanding of clinical manifestations, the risk factors, and the different phenotypes of NSAID‐induced hypersensitivity reactions with a comprehensive overview of the epidemiologic data from past to present and the practical approach to the management of NSAID hypersensitivity in children and adolescents. [ABSTRACT FROM AUTHOR]

Background High serum basal tryptase ( sBT) levels have been identified as a risk factor for both venom- and food-induced severe allergic reactions. The aim of this study was to compare sBT levels in children with different severity of actual drug hypersensitivity reactions ( DHRs) with those of age- and sex-matched controls without any history of DHRs. Method Patients between 0 and 18 years of age with a history of immediate-type DHRs manifested in 0-6 h after the culprit drug intake were included. Following ENDA (European Network for Drug Allergy) inquiries, patients were evaluated with skin and/or provocation tests to define the actual drug-hypersensitive patients. Serum BT levels were determined for both patients and controls. Results Of 345 children, 106 patients (30.7%) [(58.5% male), median age (interquartile range) 8.0 years (4.2-12.2)] were diagnosed as drug hypersensitive. Ninety-eight controls were also included. The sBT levels of drug-hypersensitive patients with and without anaphylaxis and the control group were similar [2.6 (2.0-3.6) μg/l vs. 2.8 (1.6-4.3) μg/l vs. 2.6 (1.8-3.6) μg/l, respectively, (p > 0.05)]. The sBT levels of the patients with sole cutaneous symptoms 2.8 (1.6-4.3) μg/l, mild anaphylaxis 3.0 (1.9-4.9) μg/l, and moderate-to-severe anaphylaxis 2.6 (2.0-3.6) μg/l were also comparable (p > 0.05). The onset of DHRs [those occurring in 1 h (n = 87) or in 1-6 h (n = 19) after the drug intake], positive results with skin tests with the culprit drug, or the classification of the patients according to different age groups [(0-2 years), (2-6 years), (6-12 years), (12-18 years)] did not correlate with sBT levels. Conclusion The sBT levels in children with actual drug hypersensitivity would not be a risk factor for severe systemic reactions on the contrary to children with allergic reactions to food or insect venom. [ABSTRACT FROM AUTHOR]

Background Although right middle lobe (RML)-atelectasis of the lungs is a common complication of asthma, the relevant data is limited. The aim of this study is to define the characteristics of RML atelectasis in asthma during childhood. Methods Children with asthma who had recently developed RML atelectasis were included; anti-inflammatory medications, clarithromycin, and inhaled salbutamol were prescribed, chest-physiotherapy (starting on the sixth day) was applied. Patients were reevaluated on the sixth, fourteenth, thirtieth, and ninetieth days, chest X-rays were taken if the atelectasis had not resolved at the time of the previous visit. Results Twenty-seven patients (6.8 (4.8–8.3) years, 48.1% male) with RML atelectasis were included. Symptoms started 15 (7–30) days before admission. The thickness of the atelectasis was 11.8 ± 5.8 mm; FEV 1 % was 75.9 ± 14.2 and Childhood Asthma Control Test scores were 11.8 ± 5.6 at the time of admission. The atelectasis had been resolved by the sixth (n = 3), fourteenth (n = 9), thirtieth (n = 10), and ninetieth days (n = 3). The treatment response of the patients whose atelectasis resolved in fourteen days was better on the sixth-day (atelectasis thickness: 4.7 ± 1.7 vs. 11.9 ± 7.3 mm, p = 0.021) compared to those whose atelectasis resolved later. Nearly half (54.5%) of the patients whose atelectasis had resolved by fourteen days were using controller medications at the time of admission. However, only two patients (13.3%) were on controller treatment in the latter group (p = 0.032). Regression analysis didn't reveal any prognostic factors for the early resolution of atelectasis. Conclusions Early diagnosis and treatment of RML atelectasis prevents complications. Patients who had early resolution of atelectasis had already been on anti-inflammatory medications, and responded better to aggressive treatment within the first week. [ABSTRACT FROM AUTHOR]

The possible risk of adverse effects due to regular use of inhaled corticosteroids (ICS) is a real concern. Our aim was to describe the factors that have an impact on hypothalamic-pituitary-adrenal axis suppression (HPA-AS) in children and adolescents taking ICS regularly. The HPA axis status of patients who were on moderate-to-high-dose ICS [>176 and >264 μg/day fluticasone propionate-hydrofluoroalkane (FP-HFA) for patients 0-11 and ≥12 years, respectively] was investigated. Various types of ICS were converted to FP-HFA equivalent according to National Asthma Education and Prevention Program (NAEPP) guidelines. Participants with a baseline (8 a.m.) serum cortisol <15 μg/dL underwent a low-dose ACTH stimulation test (LDAT) to diagnose HPA-AS. Among 91 patients, 60 (75.9 %) participants underwent LDAT, and seven (7.7, 95 % CI 3.5-15.3 %) were diagnosed with HPA-AS. Ciclesonide was more frequently used by the participants with HPA-AS compared to patients with a normal HPA axis (42.9 vs. 4.8 %, p = 0.009). Use of ICS at moderate-to-high doses for at least 7 months distinguished participants with HPA-AS from those with a normal HPA axis. Among the duration, type, and dose of ICS, solely the use of ICS with a body mass index (BMI)-adjusted daily dose of ≥22 μg FP was found to increase the risk for HPA-AS (odds ratio (OR) 7.22, 95 % confidence interval (CI) 1.23-42.26, p = 0.028). The receiver operating characteristics (ROC) curve analysis revealed a cutoff value of 291 μg/day FP (area under the curve (AUC) = 0.840, p = 0.003) for predicting HPA-AS Conclusion: The prevalence of HPA-AS was found to be 7.7 % in children taking not only high-dose ICS but also moderate-dose ICS. Dose alone was found to be an actual risk factor for HPA-AS. [ABSTRACT FROM AUTHOR]

Background: Although non-steroidal anti-inflammatory drug hypersensitivity (NSAID-H) has been widely studied in adults, there is still a lack of data regarding the features and phenotypes of NSAID-H in children. Our aim was to define risk factors and different phenotypes according to clinical patterns. Methods: Patients with a history of reaction to any NSAIDs referred between January 2012 and October 2014 were included. After completing a European Network for Drug Allergy (ENDA) questionnaire, initial skin and/or oral provocation tests (OPTs) were performed for the offending drug. Additional OPTs were done with aspirin in case of NSAID-H to determine cross-reactivity. NSAID-hypersensitive patients were defined as being either a selective responder (SR) or cross-intolerant (CI) and further categorized according to either the ENDA/GA2LEN classification or an alternative scheme by Caimmi et al. [Int Arch Allergy Immunol 2012;159:306-312]. Results: Among 121 patients [58.7% male, average age 7.8 years (4.7-10.8)] with 161 NSAID-related reactions, 110 patients with 148 reactions were assessed. NSAID-H was diagnosed in 30 (27%) patients with 37 (25%) reactions. Multivariate regression analysis revealed that an immediate-type reaction and respiratory symptoms during the reaction increased the risk of a reproducible NSAID-related reaction (OR 3.508, 95% CI 1.42-8.7, p = 0.007; OR 3.951, 95% CI 1.33-11.77, p = 0.014, respectively). Additional OPTs revealed 13 SRs and 14 CIs. A family history of allergic disease was more frequent in CIs compared to SRs (57.1 vs. 15.4%, p = 0.031). Reactions belonging to CIs were more frequently characterized by angioedema compared to those of SRs (81.3 vs. 46.2%, p = 0.019). SRs and CIs were further classified as single NSAID-induced urticaria/angioedema and/or anaphylaxis (n = 13), NSAID-induced urticaria/angioedema (n = 7), NSAID-exacerbated cutaneous disease (n = 2) and NSAID-exacerbated respiratory disease (n = 1). Four CIs could not be categorized according to either classification system. One SR could not be categorized according to ENDA/GA2LEN. Conclusion: During childhood, NSAID-H exhibits different phenotypes and the majority of them can be categorized with current classification systems; however, classifications based on adult data may not exactly fit NSAID-H in paediatric patients. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article discusses several conferences and meetings of European Academy of Allergy and Clinical Immunology (EAACI). Topics discussed include The Allergy School organized by The Pediatrics Section that was held in Sicily, Taormina from March 5-7, 2015, the Food Allergy and Anaphylaxis Meeting 2014 (FAAM 2014) held in Dublin, Ireland, and the Pediatric Allergy and Asthma Meeting (PAAM) to be held in Berlin, Germany from October 15-17, 2015.

Background Nonsteroidal anti-inflammatory drug ( NSAID) exacerbated cutaneous disease is defined as the exacerbation of wheals and/or angioedema in patients with a history of chronic spontaneous urticaria ( CSU). The objective of this study was to define 'aspirin-hypersensitive' children and adolescents in a clearly defined group of patients with CSU and to describe their clinical features. Methods Eighty-one children with a history of CSU were enrolled over a 3-year period. The daily or almost daily (>4 days a week) presence of urticaria was defined as 'chronic persistent urticaria' ( CPU), while the presence of urticaria for 2-4 days a week was defined as 'chronic recurrent urticaria' ( CRU). Single-blind, placebo-controlled provocation tests ( SBPCPTs) with aspirin were performed for children with CSU. Results Patients with CRU had a longer duration of cutaneous symptoms [1.6 (0.5-4) vs 0.6 (0.3-1.5) years], and stress was less frequently experienced as an eliciting factor in patients with CRU compared with the patients with CPU ( P < 0.016, P = 0.024, respectively). SBPCPTs with aspirin revealed that 14 of 58 patients (24%) with CPU and one of 10 patients with CRU (10%) were aspirin hypersensitive. Aspirin hypersensitivity rate was 26.5% in patients <12 years of age. All of the 15 aspirin-hypersensitive patients (aged between 6.6 and 17.4 years), except for three, experienced an unequivocal angioedema of the lips as a positive reaction in SBPCPT. Conclusions Nearly a quarter of children and adolescents with CSU were hypersensitive to aspirin. For children with chronic urticaria, determination of NSAID hypersensitivity in a well-controlled clinical setting will help to avoid severe drug hypersensitivity reactions. [ABSTRACT FROM AUTHOR]

Allergen immunotherapy (AIT) has been used for 100 years and until now different immunoregulatory pathways have been shown to take place in its mechanisms of action. It is characterized by administration of the causative allergen and is shown to be clinically efficient even after discontinuation of therapy particularly in allergic respiratory diseases, bee venom allergy, and food allergy. Generation of antigen/allergen-specific peripheral tolerance is the key mechanism during immunotherapy. It is mediated by development of T and B regulatory cells, IgG4 isotype allergen-specific antibodies and the involvement of multiple suppressor factors, which lead to decreased tissue inflammation, early and late phase responses. Describing novel regulatory mechanisms in the process of immune tolerance induction will help to identify treatment modalities not only for allergic disorders, but also for autoimmune diseases, organ transplantation, chronic infections, and cancer. [ABSTRACT FROM AUTHOR]

The recognition of constipation as a possible non‐Immunoglobulin E (IgE)‐mediated allergic condition is challenging because functional constipation (unrelated to food allergies) is a common health problem with a reported worldwide prevalence rate of up to 32.2% in children. However, many studies in children report challenge proven cow's milk allergy and constipation as a primary symptom and have found that between 28% and 78% of children improve on a cow's milk elimination diet. Due to the paucity of data and a focus on IgE‐mediated allergy, not all food allergy guidelines list constipation as a symptom of food allergy. Yet, it is included in all cow's milk allergy guidelines available in English language. The Exploring Non‐IgE‐Mediated Allergy (ENIGMA) Task Force (TF) of the European Academy for Allergy and Clinical Immunology (EAACI) considers in this paper constipation in the context of failure of standard treatment and discuss the role of food allergens as culprit in constipation in children. This position paper used the Delphi approach in reaching consensus on both diagnosis and management, as currently published data are insufficient to support a systematic review. [ABSTRACT FROM AUTHOR]

Aim: Patients experiencing persistent complaints of moderate-severe allergic rhinoconjunctivitis despite symptomatic treatment are considered candidates for Allergen Specific Immunotherapy (ASIT). The present study aims to assess the effectiveness and safety of ASIT using Gramineae pollen in children afflicted by allergic rhinoconjunctivitis. Materials and Methods: The study involved participants between 5 and 18 years of age who had allergic rhinoconjunctivitis. These participants were divided into two distinct groups. The initial group underwent ASIT, while the other constituted the control group that refrained from it. The control group comprised participants with akin ages and equivalent disease durations. Visual analog scores (VAS), daily symptom scores (dSS), daily medication scores (dMS), and combined symptom and medication scores (CSMS) were assessed at three specific time junctures: Baseline, post the initial year of ASIT, and after the second year of ASIT. Results: The study encompassed 188 children who had been diagnosed with allergic rhinoconjunctivitis. Among these, 94 patients had undergone immunotherapy. Of the total cases, 105 (55.9%) were male, with a median age of 14 years (range: 7-18 years). Among the patients who had received ASIT, there were statistically significant reductions in VAS, dSS, dMS, and CSMS after one and two years of therapy when compared to the baseline values (p<0.001). Upon comparing the group receiving ASIT with the control group after a two-year follow-up, notable reductions were observed in VAS, dSS, dMS, and CSMS (p<0.001). Five patients (5.3%) experienced systemic reactions. Conclusion: The current study demonstrated that ASIT with Gramineae pollen is clinically effective in patients with Graminae pollen-induced allergic rhinoconjunctivitis. [ABSTRACT FROM AUTHOR]

A letter to the editor in response to the article "Egg yolk: An unusual trigger of food protein-induced enterocolitis syndrome," that was published in a previous issue of the journal is presented.

Two letters to the editor are presented in response to the article "Dupilumab in Persistent Asthma With Elevated Eosinophil Levels" by S. Wenzel and colleagues in the June 27, 2013 issue.

Gastro‐oesophageal reflux (GOR) and food allergy (FA) are common conditions, especially during the first 12 months of life. When GOR leads to troublesome symptoms, that affect the daily functioning of the infant and family, it is referred to as GOR disease (GORD). The role of food allergens as a cause of GORD remains controversial. This European Academy of Allergy and Clinical Immunology (EAACI) position paper aims to review the evidence for FA‐associated GORD in young children and translate this into clinical practice that guides healthcare professionals through the diagnosis of suspected FA‐associated GORD and medical and dietary management. The task force (TF) on non‐IgE mediated allergy consists of EAACI experts in paediatric gastroenterology, allergy, dietetics and psychology from Europe, United Kingdom, United States, Turkey and Brazil. Six clinical questions were formulated, amended and approved by the TF to guide this publication. A systematic literature search using PubMed, Cochrane and EMBASE databases (until June 2021) using predefined inclusion criteria based on the 6 questions was used. The TF also gained access to the database from the European Society of Paediatric Gastroenterology and Hepatology working group, who published guidelines on GORD and ensured that all publications used within that position paper were included. For each of the 6 questions, practice points were formulated, followed by a modified Delphi method consisting of anonymous web‐based voting that was repeated with modified practice points where required, until at least 80% consensus for each practice point was achieved. This TF position paper shares the process, the discussion and consensus on all practice points on FA‐associated GORD. [ABSTRACT FROM AUTHOR]

Her family history was significant for atopic diseases as her father has atopic dermatitis and seborrheic dermatitis and multiple paternal relatives has atopic dermatitis, allergic rhinitis and allergic asthma. Skin biopsy samples from the patient, the father and an unrelated control (taken from healthy skin region of an actinic keratosis patient) were investigated with respect to the expression of I RORC i , I FOXP3 i , I IL i - I 22 i , I AREG i , I IL4 i , I IL5 i , I IL13 i , I CSF2 i genes by real-time qPCR (Figure 2D). For this patient, due to increased baseline STAT5B activity, treatment with JAK inhibitors10 will likely be a good option in future follow-up. A novel gain-of-function mutation in STAT5B is associated with treatment-resistant severe atopic dermatitis. [Extracted from the article]

Objective. It is difficult to determine if preschool children with recurrent wheezing are suffering from asthma or will suffer from asthma in the future. The aim of this study was to investigate the prognosis and risk factors of recurrent wheezing in children, beginning in the first 3 years of life. Method. Children who were referred because of recurrent wheezing episodes during the first 3 years of life were evaluated for the presence of asthma over a 4-year period. A child without any symptoms within the last 12 months was considered to be in remission. Results. The study included 529 (male/female: 2.17) children with a median (inter-quartile) age of 0.6 years (0.3-1.0) at symptom onset. The median follow-up and symptom durations were 2.93 years (1.74-4.76) and 4.30 years (2.91-5.97), respectively. Remission/recovery was achieved in 1.7%, 8.0%, and 14.4% of the children within 12, 24, and 36 months, respectively. A negative 'stringent asthma predictive index' (API) significantly shortened the time to recovery of wheezing compared to the positive API ( p = .036). Maternal smoking during pregnancy (OR = 4.35; 95% CI = 1.29-14.63); p = .018) and the number of emergency room admissions within the first 3 years of life (OR = 1.10; 95% CI = 1.01-1.19); p = .031) were found to be independent risk factors for the persistence of wheezing symptoms. Conclusion. Most of the children who were referred with frequent wheezing remain symptomatic 3 years after the initial wheezing episodes. A negative API is related to a shorter wheezing duration. Maternal smoking during pregnancy and the severity of the wheezing episodes appeared to be significant risk factors for the persistence of wheezing symptoms. [ABSTRACT FROM AUTHOR]

Background: Urticaria can be the only sign of a food allergy or can be seen together with other signs and symptoms of a food allergy. Objective: To determine the demographic, etiologic, and clinical features of food-induced acute urticaria in childhood. Methods: Patients suspected of food-induced acute urticaria were included in this prospective cross-sectional multicenter study. Results: Two hundred twenty-nine urticaria cases were included in this study. Seventeen patients who did not meet the inclusion criteria of the study were excluded. Of the 212 included cases, 179 (84.4%) were diagnosed with definitive food-induced acute urticaria. The most common foods causing acute urticaria were cow's milk, hen's eggs, and nuts in 56.4, 35.2, and 19% of cases, respectively. The positive predictive value of a history of milk-induced acute urticaria together with a milk-specific IgE >5 kU/L for cow's milk-induced acute urticaria was 92% (95% CI: 81–96%). A history of cow's milk-induced and/or hen's egg-induced acute urticaria was consistent with a definitive diagnosis of food-induced urticaria (Chen's kappa: 0.664 and 0.627 for milk and eggs, respectively). Urticaria activity scores were higher in patients with food-induced acute urticaria (p = 0.002). Conclusion: Cow's milk, hen's eggs, and nuts were the most common allergens in the etiology of childhood food-induced acute urticaria. Although the urticaria activity score provides guidance for diagnosis, an oral food challenge is often essential for the definitive diagnosis of a patient with a history of food-induced acute urticaria. [ABSTRACT FROM AUTHOR]

Background: Oral food challenges (OFCs) assist in the diagnosis of food allergies and are essential to determine whether an allergy has been outgrown. During the OFC, a medical procedure e introduces foods suspected to be allergenic orally in increasing doses. Mild skin reactions such as urticaria or rarely serious life-threatening reactions such as anaphylaxis may develop.Objective: In this study, we aimed to retrospectively evaluate the clinical and laboratory characteristics of patients who experienced anaphylaxis during open OFCs in a tertiary care children's hospital.Methods: Patients who underwent OFCs to confirm the presence of a food allergy or to assess tolerance status at the University of Health Sciences, Ankara, Dr. Sami Ulus Maternity and Children Training and Research Hospital, Pediatric Allergy and Immunology Outpatient Clinic between 1 January 2013 and 1 February 2016, were included in the study. Patients' data were obtained retrospectively from electronic medical records and challenge chart reviews.Results: A total of 623 OFCs were performed during the period studied. Nine patients (1.4%) between 13 and 67 months of age (mean age: 38.3 months) developed anaphylaxis during their OFC.Conclusion: OFCs should be performed in a hospital or outpatient office under medical supervision that is adequate for anaphylaxis intervention by an allergy specialist. Close observation of objective and subjective symptoms is essential during the challenge because there are no laboratory tests that can predict an anaphylactic diagnosis or the severity of the reaction. [ABSTRACT FROM AUTHOR]

Background: Asthma‐like symptoms in preschool children, such as wheezing and dyspnea, are common time‐ and resource‐consuming diagnostic and management challenges. Quality of wheezing and asthma recommendations varies. The purpose of this study, carried out by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force for Preschool Wheeze, was to systematically review and assess the quality of guidelines for diagnosis and treatment of preschool wheezing and/or asthma. Methods: The Cochrane Library, MEDLINE, and EMBASE were searched until June 2018. The methodological rigor, quality, and transparency of relevant guidelines were assessed with the use of the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool. Results: We identified 26 guidelines. The quality scores for each domain varied. Of all domains, clarity and presentation had the highest mean score, whereas applicability and stakeholder involvement had the lowest. The scores (median) for individual domains were as follows: score and purpose 86%; stakeholder involvement 49%; rigor of development 54%; clarity of presentation 85%; applicability 51%; and editorial independence 63%. Conclusion: Although several guidelines on asthma management in children are available, however, their quality varies. Additionally, there is a considerable gap in reliable recommendations on the management and treatment of non‐asthmatic preschool wheeze. [ABSTRACT FROM AUTHOR]

Allergen immunotherapy is a cornerstone in the treatment of allergic children. The clinical efficiency relies on a well‐defined immunologic mechanism promoting regulatory T cells and downplaying the immune response induced by allergens. Clinical indications have been well documented for respiratory allergy in the presence of rhinitis and/or allergic asthma, to pollens and dust mites. Patients who have had an anaphylactic reaction to hymenoptera venom are also good candidates for allergen immunotherapy. Administration of allergen is currently mostly either by subcutaneous injections or by sublingual administration. Both methods have been extensively studied and have pros and cons. Specifically in children, the choice of the method of administration according to the patient's profile is important. Although allergen immunotherapy is widely used, there is a need for improvement. More particularly, biomarkers for prediction of the success of the treatments are needed. The strength and efficiency of the immune response may also be boosted by the use of better adjuvants. Finally, novel formulations might be more efficient and might improve the patient's adherence to the treatment. This user's guide reviews current knowledge and aims to provide clinical guidance to healthcare professionals taking care of children undergoing allergen immunotherapy. [ABSTRACT FROM AUTHOR]

Preschool wheezing diagnosis and management-Survey of physicians' and caregivers' perspective The most frequent response (50.7%) points out response to treatment, while allergy tests were also very popular, having been chosen by 34.1%. This is the first survey exploring physicians' views on preschool wheeze, showing that wheezing itself and its association with future asthma remain a substantial challenge for most physicians. Furthermore, this study does not include a completely random sample of physicians, due to methodology used (email and social network), so only physicians familiar with the technology were able to participate. [Extracted from the article]

Background: The consumption of lentil is common in the Mediterranean area and is one of the causes of IgE‐mediated food allergy in many countries. Len c 1 is a well‐defined allergen of lentil and approximately 80% of the patients with lentil allergy recognize the purified Len c 1 protein. We sought to identify IgE and IgG4 sequential epitopes of Len c 1 in patients with red and/or green lentil allergy. We also aimed to determine IgE and IgG4 binding differences between those patients who had outgrown or remained reactive to lentil. Methods: Children with IgE‐mediated lentil allergy were included in the study. We applied a microarray immunoassay to determine the characterization of positive IgE and IgG4 binding to Len c 1 epitopes in the patients' sera. Results: The peptides specifically recognized by IgE and IgG4 antibodies were mainly detected between peptides 107 and 135 of Len c 1. The signal intensities of positive epitopes were significantly greater in reactive patients than tolerant ones (P =.008 for IgE and P =.002 for IgG4). Moreover, IgE and IgG4 antibodies bound largely the same sequential epitopes in patients who remained reactive or outgrew their allergy. Conclusion: IgG4‐binding epitopes in lentil allergy were identified and IgE and IgG4 binding to epitopes in both red and green lentils was compared. Our data regarding signal intensity differences between reactive and outgrown patients and overlap binding of IgE and IgG4 antibodies may be important for the development of more accurate diagnostic tests and understanding of natural tolerance development. [ABSTRACT FROM AUTHOR]

It is well‐established that food proteins, such as egg, soya, cow's milk and wheat, are detectable in breastmilk for many hours or days after ingestion. Exposure to these proteins is important to the process of developing tolerance but can also sometimes elicit IgE‐mediated and non–IgE‐mediated allergic symptoms in breastfed infants. Non–IgE‐mediated allergy, outside of food protein‐induced allergic proctocolitis and eosinophilic oesophagitis, is not well understood, leading to variations in the diagnosis and management thereof. A primary objective of the European Academy for Allergy and Clinical Immunology is to support breastfeeding in all infants, including those with food allergies. A Task Force was established, to explore the clinical spectrum of non–IgE‐mediated allergies, and part of its objectives was to establish diagnosis and management of non–IgE‐mediated allergies in breastfed infants. Eight questions were formulated using the Patient, Intervention, Comparison, Outcome (PICO) system and Scottish Intercollegiate Guideline Network (SIGN) criteria for data inclusion, and consensus was achieved on practice points through the Delphi method. This publication aims to provide a comprehensive overview on this topic with practice points for healthcare professionals. [ABSTRACT FROM AUTHOR]

Allergen immunotherapy (AIT) has been in use for the treatment of allergic disease for more than 100 years. Asthma treatment relies mainly on corticosteroids and other controllers recommended to achieve and maintain asthma control, prevent exacerbations, and improve quality of life. AIT is underused in asthma, both in children and in adults. Notably, patients with allergic asthma not adequately controlled on pharmacotherapy (including biologics) represent an unmet health need. The European Academy of Allergy and Clinical Immunology has developed a clinical practice guideline providing evidence‐based recommendations for the use of house dust mites (HDM) AIT as add‐on treatment for HDM‐driven allergic asthma. This guideline was developed by a multi‐disciplinary working group using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. HDM AIT was separately evaluated by route of administration and children and adults: subcutaneous (SCIT) and sublingual AIT (SLIT), drops, and tablets. Recommendations were formulated for each. The important prerequisites for successful treatment with HDM AIT are (a) selection of patients most likely to respond to AIT and (b) use of allergen extracts and desensitization protocols of proven efficacy. To date, only AIT with HDM SLIT‐tablet has demonstrated a robust effect in adults for critical end points (exacerbations, asthma control, and safety). Thus, it is recommended as an add‐on to regular asthma therapy for adults with controlled or partially controlled HDM‐driven allergic asthma (conditional recommendation, moderate‐quality evidence). HDM SCIT is recommended for adults and children, and SLIT drops are recommended for children with controlled HDM‐driven allergic asthma as the add‐on to regular asthma therapy to decrease symptoms and medication needs (conditional recommendation, low‐quality evidence). [ABSTRACT FROM AUTHOR]

Background: The majority of children with cow's milk allergy (CMA) tolerate baked milk. However, reactivity to fermented milk products such as yogurt/cheese has not been previously evaluated. We sought to determine whether children with CMA could tolerate yogurt/cheese and whether a patient's IgE and IgG4‐binding pattern to milk protein epitopes could distinguish clinical reactivity. Methods: Four groups of reactivity were identified by Oral food challenge: baked milk reactive, fermented milk reactive, whole milk reactive, and outgrown. sIgE and sIgG4 binding to milk protein epitopes were assessed with a novel Luminex‐based peptide assay (LPA). Using machine learning techniques, a model was developed to predict different degrees of CMA. Results: The baked milk reactive patients demonstrated the highest degree of IgE epitope binding, which was followed sequentially by fermented milk reactive, whole milk reactive, and outgrown. Data were randomly divided into two groups with 75% of the data utilized for model development (n = 68) and 25% for testing (n = 21). All 68 children used for training were correctly classified with models using IgE and IgG4 epitopes. The average cross‐validation accuracy was much higher for models using IgE plus IgG4 epitopes by LPA (84.8%), twice the performance of the serum component proteins assayed by UniCAP (41.9%). The performance of the model on "unseen data" was tested using the 21 withheld patients, and the accuracy of IgE was 86% (AUC = 0.89) while of IgE+IgG4 model was 81% (AUC = 0.94). Conclusion: Using a novel high‐throughput LPA, we were able to distinguish the diversity of IgE/IgG4 binding to epitopes in the varying CMA phenotypes. LPA is a promising tool to predict correctly different degrees of CMA. The new food challenge sequence and Luminex‐based peptide assay to identify the clinical phenotypes of reactivity to baked, fermented, and whole cow's milk. [ABSTRACT FROM AUTHOR]

Background: There is clinical uncertainty about the effectiveness and safety of allergen immunotherapy (AIT) for the treatment of allergic asthma. Objectives: To undertake a systematic overview of the effectiveness, cost-effectiveness and safety of AIT for the treatment of allergic asthma. Methods: We searched nine electronic databases from inception to October 31, 2015. Systematic reviews were independently screened by two reviewers against pre-defined eligibility criteria and critically appraised using the Critical Appraisal Skills Programme quality assessment tool for systematic reviews. Data were descriptively and thematically synthesized. Results: We identified nine eligible systematic reviews; these focused on delivery of AIT through the following routes: subcutaneous (SCIT; n = 3); sublingual (SLIT; n = 4); and both SCIT and SLIT (n = 2). This evidence found that AIT delivered by SCIT and SLIT can improve medication and symptom scores and measures of bronchial hyper-reactivity. The impact on measures of lung function or asthma control was however less clear. We found no systematic review level evidence on the cost-effectiveness of SCIT or SLIT. SLIT had a favorable safety profile when compared to SCIT, particularly in relation to the risk of systemic reactions. Conclusions: AIT has the potential to achieve reductions in symptom and medication scores, but there is no clear or consistent evidence that measures of lung function can be improved. Bearing in mind the limitations of synthesizing evidence from systematic reviews and the fact that these reviews include mainly dated studies, a systematic review of current primary studies is now needed to update this evidence base, estimate the effectiveness of AIT on asthma outcomes and to investigate the relative effectiveness, cost-effectiveness and safety of SCIT and SLIT. [ABSTRACT FROM AUTHOR]

Background: Parasites have been proposed to be an underlying cause of chronic spontaneous urticaria (CSU) in childhood, but a clear causal relationship between them has not been established. This study aimed to investigate the prevalence of parasitic infection-related CSU (PIRCSU) in children and to determine the factors associated with PIRCSU. Method: Data from 211 children with CSU were analyzed. Information on stool examination, antiparasitic medications received, and response to treatment was recorded. The disappearance of urticaria for more than 6 months is defined as remission, and remission of urticaria after antiparasitic treatment is defined as PIRCSU. Results: Parasites were detected in 21 (10%) patients. Blastocystis hominis was the most common parasite. After antiparasitic medication, all samples became normal; urticaria continued in 5, was reduced in 6, and disappeared in 10 patients. The latter 10 patients were considered as cases of PIRCSU (4.7%). The erythrocyte sedimentation rate was significantly higher in patients with PIRCSU than in those without [8.5 mm/h (3.5-14.5) vs. 2 (0-7), p = 0.011]. Gastrointestinal complaints were significantly more frequent in patients with PIRCSU than in those without. The occurrence of abdominal pain was a significant risk factor that increased the probability of PIRCSU [OR = 6.60, 95% CI = 1.35-32.23, p = 0.020]. Conclusion: Parasites may cause CSU even in nontropical countries, and remission may only be possible with the treatment of the parasitic infection. The occurrence of abdominal pain points to parasitic infection in patients with CSU. Therefore, we suggest that parasites should be investigated routinely, especially if the patient has gastrointestinal symptoms of CSU in childhood. [ABSTRACT FROM AUTHOR]

Background: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for Allergic Asthma. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT in the management of allergic asthma. Methods: We will undertake a systematic review, which will involve searching international biomedical databases for published, in progress and unpublished evidence. Studies will be independently screened against pre-defined eligibility criteria and critically appraised using established instruments. Data will be descriptively and, if possible and appropriate, quantitatively synthesised. Discussion: The findings from this review will be used to inform the development of recommendations for EAACI's Guidelines on AIT. [ABSTRACT FROM AUTHOR]

Background: Venom immunotherapy (VIT) has its effect by modulating various mediators resulting in immune tolerance. The aim of this study was to measure changes in plasma osteopontin (OPN) and serum basal tryptase (sBT) levels over the course of 1 year of VIT in children with venom allergy. Methods: Children who suffered from a large local reaction (LLR) or a systemic reaction (SR) after insect stings were included along with control subjects. Measurements were performed before the initiation of VIT and 6 and 12 months after it had been started. Results: A total of 58 children (24 with SR, 18 with LLR and 16 control subjects) with a median age of 9.5 years (range 6.7-12.8) were enrolled. The plasma OPN levels of patients with LLR [median 1,477 ng/ml, interquartile range (IQR) 1,123-1,772] were significantly higher than patients with SR (882 ng/ml, 579-1,086; p < 0.001) and healthy control subjects (1,015 ng/ml, 815-1,203; p = 0.002). A significant increase in plasma OPN levels in children was determined after the 1-year VIT. The sBT levels of children with SR (4.1 ng/ml, 3.6-5.8) were significantly higher than children with LLR (3.1 ng/ml, 2.5-4.0) and control subjects (3.0 ng/ml, 2.9-3.8; p = 0.001). There was no significant change in the sBT levels of the patients after the 1-year VIT. Conclusions: The results of our study showed higher baseline levels of OPN in children with LLR compared to control subjects and children with SR. In children with SR, OPN levels were increased after the 1-year VIT. Our results may suggest a possible association between OPN and successful VIT in children. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Test for Respiratory and Asthma Control in Kids (TRACK) questionnaire is the first to measure both the risk and impairment domains of the current guidelines in preschool children. We aimed to measure the reliability, validity and responsiveness of the Turkish version of the TRACK. Methods: A total of 268 children (69.8% boys) were included in the study. Caregivers responded to three individual TRACK questionnaires, at each clinical visit (baseline, 1st month, and 3rd month). At each visit, physicians determined the control level and the treatment strategy based on the GINA guideline recommendations. Results: The internal consistency reliability of the Turkish version of the TRACK questionnaire was found to be 0.74, 0.74, and 0.76 at each of the three visits, respectively (reliability statistics, Cronbach's alpha). There was a significant difference between the mean TRACK scores of the patients in different asthma control status categories ( p < 0.001). The test-retest reliability in stable patients was 0.90. The optimal cut-off scores according to the Youden index were 80 and 60 points for uncontrolled and very poorly controlled children, respectively. Conclusion: The Turkish version of the TRACK is an accurate and reliable tool for evaluating asthma control status among preschool Turkish children. Its widespread use may help physicians correctly assess control levels among children and may improve the quality of life for both patients and their caregivers. [ABSTRACT FROM AUTHOR]

Background: Studies comparing skin prick test (SPT) devices have revealed varying results in performance and there is little known about their use on children. Methods: We performed 2 complementary studies to test the sensitivity, reproducibility and acceptability of commercially available SPT devices (Stallerpoint, Antony, France) using different application techniques. In the first part, histamine/saline was put on as a drop by use of a vial (V), and in the second part it was transferred from a well with the aid of the test device (W). The techniques were as follows: apply vertical pressure (Stallerpoint-VP or Stallerpoint-WP), apply vertical pressure with 90° clockwise rotation (Stallerpoint-VC or Stallerpoint-WC) and apply vertical pressure with 90° clockwise and counter-clockwise rotations (Stallerpoint-VCC or Stallerpoint-WCC). For comparison, ALK Lancet was used with a technique of 'drop and apply vertical pressure'. Results: In the first part, sensitivities of the Stallerpoint-VC (96.6%), Stallerpoint-VCC (95.5%) and ALK Lancet (93.2%) techniques were superior (p < 0.001) to the other Stallerpoint-VP and Stallerpoint-WP techniques (76.1 and 46.6%). Intrapatient coefficient of variation (CV) values were 15.0, 18.9, 15.4, 22.4 and 48.5%, respectively. Interpatient CV ranged between 22.8 and 55.1%. In the second part, the Stallerpoint-WC (98.8%), WCC (97.5%) and ALK Lancet (98.8%) techniques yielded high sensitivities, whereas the sensitivity of Stallerpoint-WP (28.7%) was very low. There were false-positive reactions in the Stallerpoint-VCC and WCC techniques. Conclusion: In children, the SPT technique was found to be as important as the testing device. Stallerpoint-VC and WC techniques are reliable, tolerable and comparable with the ALK Lancet technique. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background Legumes, and particularly lentils, are frequently consumed in Mediterranean, Middle Eastern, and some Asian countries. The aim of this study was to document the demographic features of children with lentil allergy and to determine the role of specific Ig E (s Ig E) in predicting the risk of clinical reactivity and disease persistence. Methods Thirty children were enrolled. The diagnosis of lentil allergy was based on convincing history of symptoms or anaphylaxis after the ingestion of lentils, with positive skin tests and/or s Ig E to lentils. To determine the diagnosis and prognosis of lentil allergy, 24 children were evaluated with food challenges. Results The median age at the onset of symptoms was 1.5 yr (0.9-2.3) (inter-quartile range). The most frequent symptoms were immediate cutaneous (97%) and respiratory (30%) reactions, whereas eight patients (27%) reported anaphylactic reactions. The median level of lentil s Ig E at the time of diagnosis was 3 kU/l (1.2-9.6). Of the 24 challenges, 12 were positive. Fifteen patients (50%) outgrew the lentil allergy by the age of 3.5 (2.5-11) years. Children with an initial lentil s Ig E < 4.9 kU/l had a significantly higher likelihood (68.4% vs. 18.2%) of outgrowing the lentil allergy than children with an initial lentil s Ig E ≥ 4.9 k/l (p = 0.008). Conclusions Our results suggest that s Ig E levels may be important for predicting clinical reactivity and persistence of lentil allergy. [ABSTRACT FROM AUTHOR]

First, regarding the definitions of bronchiolitis and wheeze, Manti et al state that bronchiolitis and wheezing are profoundly different clinical entities without overlap and therefore require different diagnostic and therapeutic approaches. 4 Lehtinen P, Ruohola A, Vanto T, Vuorinen T, Ruuskanen O, Jartti T. Prednisolone reduces recurrent wheezing after a first wheezing episode associated with rhinovirus infection or eczema. [Extracted from the article]