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This article is an editorial comment on a systematic review and narrative synthesis of the management options for tree nut allergy. The review found that sublingual immunotherapy (SLIT) showed promising results in increasing the eliciting dose and had a good safety profile. Single-allergen oral immunotherapy (OIT) showed varying success rates and had more serious safety concerns. Multi-allergen OIT, with the addition of omalizumab, desensitized a high percentage of patients to tree nuts. Monotherapy with omalizumab and other biologics also showed positive results. The review emphasizes the need for further research, standardization of protocols, and long-term comparative studies to optimize treatment approaches for individuals with tree nut allergy. [Extracted from the article]

While both the incidence and general awareness of food allergies is increasing, the variety and clinical availability of therapeutics remain limited. Therefore, investigations into the potential factors contributing to the development of food allergy (FA) and the mechanisms of natural tolerance or induced desensitization are required. In addition, a detailed understanding of the pathophysiology of food allergies is needed to generate compelling, enduring, and safe treatment options. New findings regarding the contribution of barrier function, the effect of emollient interventions, mechanisms of allergen recognition, and the contributions of specific immune cell subsets through rodent models and human clinical studies provide novel insights. With the first approved treatment for peanut allergy, the clinical management of FA is evolving toward less intensive, alternative approaches involving fixed doses, lower maintenance dose targets, coadministration of biologicals, adjuvants, and tolerance‐inducing formulations. The ultimate goal is to improve immunotherapy and develop precision‐based medicine via risk phenotyping allowing optimal treatment for each food‐allergic patient. [ABSTRACT FROM AUTHOR]

Patients were included if they had symptoms commensurate with COVID-19 disease and tested positive for COVID-19 (Table 2). Patients with immunodeficiency,[3] primary (PID) or secondary (SID), are considered to be more susceptible than the general population to developing severe COVID-19 diseases, with some studies reporting high rates of hospital ICU admission and mortality especially in patients with Type 1 interferon defects.[4] However, severe COVID-19 risk assessment in this patient population, especially in children, remains inconclusive. Keywords: coronavirus; COVID-19; inborn errors of immunity; infection; pediatric; primary immunodeficiency; SARS-CoV-2 EN coronavirus COVID-19 inborn errors of immunity infection pediatric primary immunodeficiency SARS-CoV-2 1 6 6 03/30/23 20230301 NES 230301 To the Editor, In March 2020, coronavirus disease-2019 (COVID-19) caused by the novel coronavirus SARS-CoV-2 was declared a global pandemic, with an estimated more than half a billion infected individuals and more than six million fatalities. [Extracted from the article]

Background: Food allergy affects up to 10% of the pediatric population. Despite ongoing efforts, treatment options remain limited. Novel models of food allergy are needed to study response patterns downstream of IgE‐crosslinking and evaluate drugs modifying acute events. Here, we report a novel human ex vivo model that displays acute, allergen‐specific, IgE‐mediated smooth muscle contractions using precision cut intestinal slices (PCIS). Methods: PCIS were generated using gut tissue samples from children who underwent clinically indicated surgery. Viability and metabolic activity were assessed from 0 to 24 h. Distribution of relevant cell subsets was confirmed using single nucleus RNA sequencing. PCIS were passively sensitized using plasma from peanut allergic donors or peanut‐sensitized non‐allergic donors, and exposed to various stimuli including serotonin, histamine, FcɛRI‐crosslinker, and food allergens. Smooth muscle contractions and mediator release functioned as readouts. A novel program designed to measure contractions was developed to quantify responses. The ability to demonstrate the impact of antihistamines and immunomodulation from peanut oral immunotherapy (OIT) was assessed. Results: PCIS viability was maintained for 24 h. Cellular distribution confirmed the presence of key cell subsets including mast cells. The video analysis tool reliably quantified responses to different stimulatory conditions. Smooth muscle contractions were allergen‐specific and reflected the clinical phenotype of the plasma donor. Tryptase measurement confirmed IgE‐dependent mast cell‐derived mediator release. Antihistamines suppressed histamine‐induced contraction and plasma from successful peanut OIT suppressed peanut‐specific PCIS contraction. Conclusion: PCIS represent a novel human tissue‐based model to study acute, IgE‐mediated food allergy and pharmaceutical impacts on allergic responses in the gut. [ABSTRACT FROM AUTHOR]

Platelet‐activating factor (PAF) is a phospholipid‐derived mediator with an established role in multiple inflammatory states. PAF is synthesized and secreted by multiple cell types and is then rapidly hydrolyzed and degraded to an inactive metabolite, lyso‐PAF, by the enzyme PAF acetylhydrolase. In addition to its role in platelet aggregation and activation, PAF contributes to allergic and nonallergic inflammatory diseases such as anaphylaxis, sepsis, cardiovascular disease, neurological disease, and malignancy as demonstrated in multiple animal models and, increasingly, in human disease states. Recent research has demonstrated the importance of the PAF pathway in multiple conditions including the prediction of severe pediatric anaphylaxis, effects on blood–brain barrier permeability, effects on reproduction, ocular diseases, and further understanding of its role in cardiovascular risk. Investigation of PAF as both a biomarker and a therapeutic target continues because of the need for directed management of inflammation. Collectively, studies have shown that therapies focused on the PAF pathway have the potential to provide targeted and effective treatments for multiple inflammatory conditions. [ABSTRACT FROM AUTHOR]

Background: There is limited ability to predict the severity of allergic reactions in children. Data derived predominantly from adults have implicated the platelet‐activating factor pathway as a potential contributor to severe anaphylaxis. In this study, we sought to prospectively assess involvement of key components of the platelet‐activating factor pathway in pediatric patients with anaphylaxis. Methods: Forty‐six pediatric patients (<18 years) presenting with acute anaphylaxis were assessed. Anaphylaxis severity was graded and serum anaphylaxis markers were measured acutely and in 36 children who returned for follow‐up >4 weeks after their acute presentation. These markers were compared with pediatric laboratory reference sera. Results: Severe anaphylaxis was experienced by 12/46 (26%) and mild‐moderate anaphylaxis in 34/46 (74%) children. Platelet‐activating factor acetylhydrolase (PAF‐AH) activity was inversely associated with severe anaphylaxis: 9/12 children with severe anaphylaxis had reduced PAF‐AH activity as compared with 14/34 with mild‐moderate anaphylaxis (p <.05). Furthermore, 3/3 children who required intensive care had markedly reduced mean PAF‐AH (nmol/ml/min) (13.73, 95%CI: 7.42–20.03) versus 20/23 who required ward/emergency department care (17.81, 95%CI: 16.80–18.83; p <.05). In children with anaphylaxis, PAF‐AH during acute anaphylaxis was unchanged relative to the child's basal levels (mean, 17.26, 95%CI: 16.10–18.42 vs 17.50, 95%CI: 16.21–18.78, p =.63) and was lower than healthy pediatric controls (mean 19.21; 95%CI:18.21–20.21; p <.05). Conclusion: Decreased serum PAF‐AH activity is a biomarker of severe anaphylaxis. Levels of this enzyme do not change from basal levels during acute anaphylaxis. Our results show that PAF‐AH is a biomarker of anaphylaxis severity in children. This key regulatory enzyme may modulate susceptibility to severe anaphylaxis. [ABSTRACT FROM AUTHOR]

After adjustment, milk OIT, history of asthma, pre-OIT epinephrine use, skin prick wheal size, and single highest tolerated dose prior to OIT remained significantly associated with treatment failure. Oral immunotherapy (OIT) is a treatment for IgE-mediated food allergy. [Extracted from the article]

Background: Safe and effective vaccines provide the first hope for mitigating the devastating health and economic impacts resulting from coronavirus disease 2019 (COVID-19) and related public health orders. Recent case reports of reactions to COVID-19 vaccines have raised questions about their safety for use in individuals with allergies and those who are immunocompromised. In this document, we aim to address these concerns and provide guidance for allergists/immunologists. Methods: Scoping review of the literature regarding COVID-19 vaccination, adverse or allergic reactions, and immunocompromise from PubMed over the term of December 2020 to present date. We filtered our search with the terms "human" and "English" and limited the search to the relevant subject age range with the term "adult." Reports resulting from these searches and relevant references cited in those reports were reviewed and cited on the basis of their relevance. Results: Assessment by an allergist is warranted in any individual with a suspected allergy to a COVID-19 vaccine or any of its components. Assessment by an allergist is NOT required for individuals with a history of unrelated allergies, including to allergies to foods, drugs, insect venom or environmental allergens. COVID-19 vaccines should be offered to immunocompromised patients if the benefit is deemed to outweigh any potential risks of vaccination. Interpretation: This review provides the first Canadian guidance regarding assessment of an adolescent and adult with a suspected allergy to one of the COVID-19 vaccines currently available, or any of their known allergenic components, and for patients who are immunocompromised who require vaccination for COVID-19. As information is updated this guidance will be updated accordingly. [ABSTRACT FROM AUTHOR]

Background: Multiplex tests allow for measurement of allergen‐specific IgE responses to multiple extracts and molecular allergens and have several advantages for large cohort studies. Due to significant methodological differences, test systems are difficult to integrate in meta‐analyses/systematic reviews since there is a lack of datasets with direct comparison. We aimed to create models for statistical integration of allergen‐specific IgE to peanut/tree nut allergens from three IgE test platforms. Methods: Plasma from Canadian and Austrian children/adolescents with peanut/tree nut sensitization and a cohort of sensitized, high‐risk, pre‐school asthmatics (total n = 166) were measured with three R&D multiplex IgE test platforms: Allergy Explorer version 1 (ALEX) (Macro Array Dx), MeDALL‐chip (Mechanisms of Development of Allergy) (Thermo Fisher), and EUROLINE (EUROIMMUN). Skin prick test (n = 51) and ImmunoCAP (Thermo Fisher) (n = 62) results for extracts were available in a subset. Regression models (Multivariate Adaptive Regression Splines, local polynomial regression) were applied if >30% of samples were positive to the allergen. Intra‐test correlations between PR‐10 and nsLTP allergens were assessed. Results: Using two regression methods, we demonstrated the ability to model allergen‐specific relationships with acceptable measures of fit (r2 = 94%‐56%) for peanut and tree nut sIgE testing at the extract and molecular‐level, in order from highest to lowest: Ara h 2, Ara h 6, Jug r 1, Ana o 3, Ara h 1, Jug r 2, and Cor a 9. Conclusion: Our models support the notion that quantitative conversion is possible between sIgE multiplex platforms for extracts and molecular allergens and may provide options to aggregate data for future meta‐analysis. [ABSTRACT FROM AUTHOR]

In contrast to other environmental allergens, the association with atopic dermatitis was present for Fel d 1, which may suggest that the skin is an important route of sensitization for this allergen. GLO:1X5/01dec19:all13927-fig-0002.jpg PHOTO (COLOR): Hierarchical clustering performed on patient sensitization profiles and allergen components indicating clusters by allergen source and biochemical family (sensitized: N = 37; nonsensitized: N = 18). In conclusion, we provide data describing a potentially high-risk preschool asthma cohort in Canada using a comprehensive approach capturing sensitization to allergens of paramount importance. By applying both allergen extracts and components, we identified that peanut and animal allergens from cat and dog were major allergen sources in this North American cohort of preschool asthmatics. [Extracted from the article]

BACKGROUND AND OBJECTIVES: International efforts have been focused on identifying children at low risk of clinically important traumatic brain injury in whom computed tomography (CT) neuroimaging can be avoided. We sought to determine if CT use for pediatric head trauma has decreased among US emergency departments (EDs). METHODS: This was a cross-sectional analysis of the National Hospital Ambulatory Care Medical Survey database of nationally representative ED visits from 2007 to 2015. We included children <18 years of age evaluated in the ED for head injury. Survey weighting procedures were used to estimate the annual proportion of children who underwent CT neuroimaging and to perform multivariable logistic regression. RESULTS: There were an estimated 14.3 million pediatric head trauma visits during the 9-year study period. Overall, 32% (95% confidence interval [CI]: 29%--35%) of children underwent CT neuroimaging with no significant annual linear trend (P trend = .50). Multivariate analysis similarly revealed no difference by year (adjusted odds ratio [aOR]: 1.02; 95% CI: 0.97--1.07) after adjustment for patient- and ED-level covariates. CT use was associated with age ≥2 years (aOR: 1.51; 95% CI: 1.13--2.01), white race (aOR: 1.43; 95% CI: 1.10--1.86), highest triage acuity (aOR: 8.24 [95% CI: 4.00--16.95]; P < .001), and presentation to a nonteaching (aOR: 1.47; 95% CI: 1.05--2.06) or nonpediatric (aOR: 1.53; 95% CI: 1.05--2.23) hospital. CONCLUSIONS: CT neuroimaging did not decrease from 2007 to 2015. Findings suggest an important need for quality improvement initiatives to decrease CT use among children with head injuries. [ABSTRACT FROM AUTHOR]

The role of class IA phosphoinositide 3 kinases (PI3Ks) in immune function and regulation continues to expand with the identification of greater numbers of genetic variants. This case report is the second reported case of a homozygous premature stop codon within the PIK3R1 gene leading to autosomal recessive agammaglobulinemia. The proband, born to consanguineous parents, presented at 10 months of age with a history of oropharyngeal petechiae and bleeding from the mouth, gums, and tear ducts. Initial investigations revealed thrombocytopenia, neutropenia and the absence of B cells. Further genetic testing via a custom next-generation sequencing panel confirmed the presence of a homozygous mutation in PIK3R1, c.901 C>T, a premature stop codon at amino acid position 301. Given their many roles in immune regulation, recessive mutations in the PlK3R1 gene should be considered in infants presenting with hypogammaglobulinemia or agammaglobulinemia, particularly in the setting of parental consanguinity. [ABSTRACT FROM AUTHOR]

The article focuses on the best way to implement early introduction (EI) of foods to infants at high risk of food allergy (FA). Topics include high‐risk infants, as defined in the model, have a 16 percent risk of allergic reaction with EI to peanut at home; mentions to achieve high rates of compliance with EI, tools and programs aimed at medical professionals and parents need to continue to be developed; and also mentions cost should always be considered in light of the associated benefit.

Background Methods Results Conclusions Peanut allergy is among the most severe and common food allergies. The diagnosis has a significant impact on the quality of life for patients and their families. An effective management approach depends on accurate, safe, and easily implementable diagnostic methods. We previously developed a cell‐based assay using Hoxb8 mast cells (Hoxb8 MCs) aimed at improving clinical allergy diagnosis. In this study, we assessed its diagnostic performance by measuring blinded sera from a prospectively enrolled and pre‐validated peanut allergy cohort.Hoxb8 MCs were passively sensitized with sera from peanut‐allergic and peanut tolerant children and adolescents (n = 112). Degranulation of Hoxb8 MCs was quantified upon stimulation with dose‐titrated peanut extract by means of flow cytometry, using CD107a as activation marker. The results from the Hoxb8 mast cell activation test (Hoxb8 MAT) were compared to established diagnostic assays such as the skin prick test (SPT), specific IgE (sIgE) levels, and the basophil activation test (BAT). Additionally, serum samples from BAT nonresponders were assessed with the Hoxb8 MAT.Hoxb8 MAT displayed a robust dose‐dependent activation to peanut extract, with a cutoff value of ≤5.2% CD107a positive cells. The diagnostic accuracy was highest at allergen concentrations ≥100 ng/mL, with an area under the receiver operating characteristic curve (AUROC) of 0.97, 93% sensitivity, and 96% specificity, outperforming traditional SPT and sIgE tests. When compared to BAT, Hoxb8 MAT exhibited comparable diagnostic efficacy. Moreover, sera from BAT nonresponders were accurately classified into allergics and nonallergics by the Hoxb8 MAT.The Hoxb8 MAT demonstrated a very good diagnostic precision in patients prospectively assessed for peanut allergy comparable to the fresh whole blood‐based BAT. Additionally, it demonstrated its value for accurate classification of BAT nonresponders into allergic and nonallergic individuals. Further investigations into its utility in the routine clinical setting are warranted. [ABSTRACT FROM AUTHOR]