Accidental allergic reactions to immediate-type food allergens in Japanese children: A single-center study.

BACKGROUND: Few studies have assessed the nature of accidental allergic reactions (AAR). We assessed the prevalence and risk factors for AAR in Japanese children. METHODS: This study included children with immediate-type hen's egg (HE), cow's milk (CM), wheat, or peanut allergy who developed allergic reactions within at least 2 years and were followed up regularly at a single national allergy center in Japan. From January to December 2020, low-dose reactivity was defined as allergic reactions to ≤250, ≤102, ≤53, or ≤ 133 mg of HE, CM, wheat, or peanut protein, respectively. The annualized AAR rate showed the number of reactions per patient per year (95% confidence interval). AAR risk factors were analyzed using multiple logistic regression. RESULTS: Of the 1096 participants, 609, 457, 138, and 90 had HE, CM, wheat, and peanut allergies, respectively. The median (interquartile range) age was 5.0 (2.3-8.6) years, 39% had completely eliminated allergenic food, and 24% had low-dose reactivity. The annualized AAR rate was 0.130 (0.109-0.153) in all sub-cohorts. Moderate and severe symptoms occurred in 50% and 0.7%, respectively, of children who experienced AAR. Multiple logistic regression revealed that low-dose reactivity was a significant risk factor for AAR in the overall and CM cohorts, respectively (p < .001 and p = .036). CONCLUSION: In this single-center study in Japan, the annualized AAR rate was relatively low during the COVID-19 pandemic; however, half of the participants with AAR had moderate to severe symptoms. Especially in the case of low-dose reactivity, children would require careful AAR risk management.

Atopic diseases-Diagnostics, mechanisms, and exposures.

Epidemiological data suggest that atopic diseases begin in early life and that most cases present clinically during early childhood. The diseases are highly prevalent and increase as communities adopt western lifestyles. Disentangling the pathophysiological mechanisms leading to disease debut is necessary to identify beneficial/harmful exposures so that successful prevention and treatment can be generated. The objective of this review is to explore the definition of atopy and mechanisms of atopic diseases, and to investigate the importance of environmental factors in early life, prior to disease development. First, the distribution of sIgE levels in children is investigated, as this is one of the main criteria for the definition of atopy. Thereafter, it is explored how studies of parental atopic status, sensitization patterns, and early debut and severity of atopic dermatitis have substantiated the theory of an early-life window of opportunity for intervention that precedes the development of atopic diseases in childhood. Then, it is examined whether early-life exposures such as breastfeeding, dogs, cats, and house dust mites in the home perinatally constitute important influencers in this crucial time of life. Finally, it is discussed how these findings could be validated in randomized controlled trials, which might prepare the ground for improved diagnostics and prevention strategies to mitigate the current atopic pandemic.

Evaluation of atopic diseases in patients with allergic contact dermatitis.

Background: There is controversy on whether allergic contact dermatitis (ACD) is associated with atopy. Research on eczema and the risk of ACD is mixed, and there is sparse literature on other atopic conditions. Objective: Our study examined the prevalence of several atopic conditions, including allergic rhinitis, eczema, asthma, and food allergies in patients with ACD, and compared these to patients without ACD. Methods: We retrospectively reviewed adult patients ages ≥ 18 years with ACD (n = 162) with positive patch testing results and documented any history of atopy, including childhood eczema, asthma, allergic rhinitis, and immunoglobulin E-mediated food allergy. The prevalence of atopic conditions was compared between our ACD cohort and controls without ACD (n = 163) from our electronic medical records system (age and gender matched). Results: Among our patients with ACD, 53 (33%) had allergic rhinitis, 22 (14%) had childhood eczema, 32 (20%) had asthma, and 8 (5%) had food allergies. We observed that the odds of atopy overall (n = 76) in the ACD group compared with the control group were increased (odds ratio [OR] 1.88; p = 0.007). Allergic rhinitis was the highest risk factor (n = 53) with an OR of 12.64 (p < 0.001). Childhood eczema (n = 22) was also increased in the ACD group (OR 2.4; p = 0.026). The odds of asthma and food allergy in the ACD group were also increased; however, the difference was not statistically significant from the control group (OR 1.76 [p = 0.071] and OR 2.76 [p = 0.139], respectively). Conclusion: Patients with ACD had increased odds of eczema, allergic rhinitis, and atopic conditions overall. Asthma and food allergies were not found to have a statistically significant correlation. Larger studies that delve into atopic risk factors in ACD would be important to confirm these findings.

Childhood atopic disorders in relation to placental changes-A systematic review and meta-analysis.

Fetal programming may arise from prenatal exposure and increase the risk of diseases later in life, potentially mediated by the placenta. The objective of this systematic review was to summarize and critically evaluate publications describing associations between human placental changes and risk of atopic disorders during childhood. The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. The inclusion criteria were original research articles or case reports written in English describing a human placental change in relation to disease occurring in offspring during childhood. The MEDLINE and EMBASE databases were searched for eligible studies. Risk of bias (RoB) was assessed using the ROBINS-I tool. The results were pooled both in a narrative way and by a meta-analysis. Nineteen studies were included (n = 12,997 participants). All studies had an overall serious RoB, and publication bias could not be completely ruled out. However, five studies showed that histological chorioamnionitis in preterm-born children was associated with asthma-related problems (pooled odds ratio = 3.25 (95% confidence interval = 2.22-4.75)). In term-born children, a large placenta (≥750 g) increased the risk of being prescribed anti-asthma medications during the first year of life. Placental histone acetylation, DNA methylation, and gene expression differences were found to be associated with different atopic disorders in term-born children. There is some evidence supporting the idea that the placenta can mediate an increased risk of atopic disorders in children. However, further studies are needed to validate the findings, properly control for confounders, and examine potential mechanisms.

Special Issue "Molecular and Cellular Advances in Atopic Diseases".

Atopic diseases, which currently affect around one billion people worldwide, are experiencing a rising prevalence [...].

Specific IgE and Basophil Activation Test by Microarray: A Promising Tool for Diagnosis of Platinum Compound Hypersensitivity Reactions.

Drug hypersensitivity reactions (DHRs) to platinum-based compounds (PCs) are on the rise, and their personalized and safe management is essential to enable first-line treatment for these cancer patients. This study aimed to evaluate the usefulness of the basophil activation test by flow cytometry (BAT-FC) and the newly developed sIgE-microarray and BAT-microarray in diagnosing IgE-mediated hypersensitivity reactions to PCs. A total of 24 patients with DHRs to PCs (20 oxaliplatin and four carboplatin) were evaluated: thirteen patients were diagnosed as allergic with positive skin tests (STs) or drug provocation tests (DPTs), six patients were diagnosed as non-allergic with negative STs and DPTs, and five patients were classified as suspected allergic because DPTs could not be performed. In addition, four carboplatin-tolerant patients were included as controls. The BAT-FC was positive in 2 of 13 allergic patients, with a sensitivity of 15.4% and specificity of 100%. However, the sIgE- and BAT-microarray were positive in 11 of 13 DHR patients, giving a sensitivity of over 84.6% and a specificity of 90%. Except for one patient, all samples from the non-allergic and control groups were negative for sIgE- and BAT-microarray. Our experience indicated that the sIgE- and BAT-microarray could be helpful in the endophenotyping of IgE-mediated hypersensitivity reactions to PCs and may provide an advance in decision making for drug provocation testing.

Environmental Interventions for Preventing Atopic Diseases.

PURPOSE OF REVIEW: In this review, we detail the exposome (consisting of environmental factors such as diet, microbial colonization, allergens, pollutants, and stressors), mechanistic and clinical research supporting its influence on atopic disease, and potentiation from climate change. We highlight contemporary environmental interventions and available evidence substantiating their roles in atopic disease prevention, from observational cohorts to randomized controlled trials, when available. RECENT FINDINGS: Early introduction to allergenic foods is an effective primary prevention strategy to reduce food allergy. Diverse dietary intake also appears to be a promising strategy for allergic disease prevention, but additional study is necessary. Air pollution and tobacco smoke are highly associated with allergic disease, among other medical comorbidities, paving the way for campaigns and legislation to reduce these exposures. There is no clear evidence that oral vitamin D supplementation, prebiotic or probiotic supplementation, daily emollient application, and antiviral prophylaxis are effective in preventing atopic disease, but these interventions require further study. While some environmental interventions have a well-defined role in the prevention of atopic disease, additional study of many remaining interventions is necessary to enhance our understanding of their role in disease prevention. Alignment of research findings from randomized controlled trials with public policy is essential to develop meaningful public health outcomes and prevent allergic disease on the population level.

Involvement of autologous myeloid dendritic cells in the evaluation of immediate hypersensitivity reactions to betalactams.

BACKGROUND: Amoxicillin (AX) and clavulanic acid (CLV) are the betalactam antibiotics (BLs) most used to treat bacterial infections, although they can trigger immediate hypersensitivity reactions (IDHRs). The maturation analysis of monocyte-derived dendritic cells (moDCs) and their capacity to induce proliferative response of lymphocytes are useful to test the sensitisation to a drug, although without optimal sensitivity. Nevertheless, this can be improved using directly isolated DCs such as myeloid DCs (mDCs). METHODS: mDCs and moDCs were obtained from 28 allergic patients (AP), 14 to AX, 14 to CLV and from 10 healthy controls (HC). The expression of CCR7, CD40, CD80, CD83, and CD86 was analysed after stimulation with both BLs. We measured the capacity of these pre-primed DCs to induce drug-specific activation of different lymphocyte subpopulations, CD3+, CD4+, CD8+, CD4+Th1, and CD4+Th2, by flow cytometry. RESULTS: Higher expression of CCR7, CD40, CD80, CD83, and CD86 was observed on mDCs compared to moDCs from AP after stimulating with the culprit BL. Similarly, mDCs induced higher proliferative response, mainly of CD4+Th2 cells, compared to moDCs, reaching up to 67% of positive results with AX, whereas of only 25% with CLV. CONCLUSIONS: mDCs from selective AP efficiently recognise the culprit drug which trigger the IDHR. mDCs also trigger proliferation of lymphocytes, mainly those with a Th2 cytokine pattern, although these responses depend on the nature of the drug, mimicking the patient's reaction.

Exercise-induced bronchoconstriction, allergy and sports in children.

Exercise-induced bronchoconstriction (EIB) is characterized by the narrowing of airways during or after physical activity, leading to symptoms such as wheezing, coughing, and shortness of breath. Distinguishing between EIB and exercise-induced asthma (EIA) is essential, given their divergent therapeutic and prognostic considerations. EIB has been increasingly recognized as a significant concern in pediatric athletes. Moreover, studies indicate a noteworthy prevalence of EIB in children with atopic predispositions, unveiling a potential link between allergic sensitivities and exercise-induced respiratory symptoms, underpinned by an inflammatory reaction caused by mechanical, environmental, and genetic factors. Holistic management of EIB in children necessitates a correct diagnosis and a combination of pharmacological and non-pharmacological interventions. This review delves into the latest evidence concerning EIB in the pediatric population, exploring its associations with atopy and sports, and emphasizing the appropriate diagnostic and therapeutic approaches by highlighting various clinical scenarios.

Association between helminth infection and allergic disorders among children in Batu, Ethiopia.

BACKGROUND: Helminths are potent immunomodulators and in their chronic infection state they may protect against allergy-related disease and atopy. However, they are also known for inducing allergic conditions. This study aimed to assess the association between helminths,  atopy and allergic conditions. METHODS: A total of 461 school children participated in this cross-sectional study. Data on allergic symptoms and a range of confounding variables was gathered from parents via an interviewer-led questionnaire. Skin sensitization to house dust mite and cockroaches was analyzed, and a stool sample was collected for helminth analysis. Serum total Immunoglobulin E using enzyme-linked immunosorbent assay and eosinophil count were also measured. RESULTS: Overall sensitivity to both allergens was 2.4%. Self-reported allergic outcomes in the last 12 months for the 461 participants had been : wheezing 3.7%, asthma 2.2%, eczema 13.2% and hay fever 6.9%. Overall, the prevalence of helminth infection was 11.9% (53/444). A borderline significant association was found between atopy and any allergy symptoms (odds ratio [OR]: 3.32, 95% confidence interval [95% CI: 0.99, 11.1], p = .052). There was no significant association between helminths and atopy (OR: 0.64 [95% CI: 0.29, 1.41], p = .268) and also between helminths and allergic symptoms (OR: 0.64 [95% CI: 0.29, 1.41], p = .268). Bivariate analysis showed keeping an animal in the house increases the risk of atopy while maternal and paternal history of allergy increases the risk of developing allergic symptoms in the children. CONCLUSION AND CLINICAL RELEVANCE: This study found a non-significant inverse association between helminths infection and atopy and allergic disorders, likely due to reduced statistical power, resulting in a lower prevalence of atopy and allergic conditions. A high powered longtitudinal study is necessary to explore the casuality and potential therapeutic benefits of helminths for allergic disorders.

Endoscopic and Radiologic Central Compartment Disease as Predictors of Perennial Inhalant Allergen Sensitization in Chronic Rhinosinusitis.

BACKGROUND: Central compartment atopic disease (CCAD) is a recently described variant of chronic rhinosinusitis (CRS) strongly associated with atopy. The association between central compartment disease (CCD) and inhalant allergy is not well established in South-East Asia, where perennial allergic rhinitis is common. OBJECTIVES: The primary objective was to evaluate endoscopic and radiologic CCD as predictors of perennial allergen sensitization in primary CRS. The secondary objective was to compare clinical characteristics of CCAD with other CRS subtypes (CRSwNP and CRSsNP). METHODS: A retrospective study of consecutive patients with primary CRS who underwent endoscopic sinus surgery at our institution was performed. Allergen sensitization was confirmed by skin or serum testing. Endoscopy records and computed tomography scans of paranasal sinuses were reviewed for CCD. The diagnostic accuracy of endoscopic and radiologic CCD in predicting atopy was calculated. RESULTS: There were 104 patients (43 CCAD, 30 CRSwNP and 31 CRSsNP). Endoscopic CCD was significantly associated with aeroallergen sensitization (odds ratio (OR) 3.99, 95% confidence interval (CI) 1.65-9.67, P = 0.002). Endoscopic CCD predicted atopy with 57% sensitivity, 72% specificity, 69% positive predictive value and positive likelihood ratio of 2.05. Radiologic CCD was not associated with aeroallergen sensitization (OR 0.728, 95%CI 0.292-1.82, P = 0.496). There were more CCAD patients who reported hyposmia (86% vs 42%, P < 0.001) and had anosmia on olfactory testing than CRSsNP (65% vs 14%, P = 0.015). The prevalence of atopy was significantly higher in CCAD than CRSwNP and CRSsNP (70% vs 37% and 42%, P = 0.015 and P = 0.05, respectively). Median serum total immunoglobulin E was higher in CCAD (283 IU/ml) and CRSwNP (127 IU/ml) than CRSsNP (27 IU/ml, P = 0.006 and P = 0.042, respectively). CONCLUSIONS: Endoscopic CCD was a better predictor of inhalant allergy than radiologic CCD in primary CRS, in a locale of perennial allergic rhinitis.

IgG from Dermatophagoides pteronyssinus (Der p)-atopic individuals modulates non-atopic thymic B cell phenotype (alfa-4/beta-7) and cytokine production (IFN-γ, IL-9, and IL-10) with direct membrane interaction.

Studies about thymic B cells are scarce in the literature, but it was suggested that they can exert modulatory and regulatory functions on the immune system. Thymic B cells can play some role in regulating the most frequent allergic background worldwide, the atopy induced by the mite Dermatophagoides pteronyssinus (Der p). Here, we aimed to evaluate if the polyclonal IgG repertoire produced by Der p-atopic individuals can influence the homing and cytokine profile of human thymic B derived from non-atopic children aged less than seven days. With this purpose, we produced polyclonal IgG formulations and cultivated human thymocytes in their presence. We also assessed IgG subclasses and the direct interaction of IgG with thymic B cell membranes. Our results could demonstrate that Der p-atopic IgG could not reduce the expression of α4ß7 homing molecule as observed in response to the other IgG formulations and could reduce the frequency of IFN-γ- and IL-9-producing thymic B cells compared to the mock condition. Der p-atopic IgG could also induce thymic IL-10-producing B cells compared to control conditions. The IgG derived from Der p-atopic individuals failed to diminish the population of IL-13-producing thymic B cells, unlike the reduction observed with other IgG formulations when compared to the mock condition. All IgG formulations had similar levels of IgG subclasses and directly interacted with thymic B cell membranes. Finally, we performed experiments using peripheral non-atopic B cells where IgG effects were not observed. In conclusion, our observation demonstrates that IgG induced in allergic individuals can modulate non-atopic thymic B cells, potentially generating thymic B cells prone to allergy development, which seems to not occur in mature B cells.

Does having siblings really protect against childhood atopic diseases? A total population and within-family analysis.

The association between having older siblings and decreased risk for atopic symptoms is well-established. This has been interpreted as evidence for the microbiota hypothesis, i.e. that increased early-childhood microbial exposure caused by siblings protects from immune hypersensitivities. However, possible confounders of the association have received little attention. We used register data on Finnish cohorts born in 1995-2004 (N = 559,077) to assess medication purchases for atopic diseases: antihistamines, eczema medication, asthma medication and Epinephrine. We modelled the probability of atopic medication purchases at ages 0-15 by birth order controlling for important observed confounders and all unobserved genetic and environmental characteristics shared by siblings in a within-family fixed effects model. We further studied medication purchases among first-borns according to the age difference with younger siblings to assess whether having younger siblings in early childhood is beneficial. Having older siblings was associated with a lower probability of atopic medication purchases. Compared to first-borns, the probability was 10-20% lower among second-borns, 20-40% lower among third-borns, and 30-70% lower among subsequent children, depending on medication type. Confounding accounted for up to 75% of these differences, particularly for asthma and eczema medication, but significant differences by birth order remained across all medication types. Among first-borns, a smaller age difference with younger siblings was related to a lower likelihood of atopic medication use. Our results, based on designs that account for unobserved confounding, show that exposure to siblings in early childhood, protects from atopic diseases, and thus strongly support the microbiota hypothesis.

Association Between Early Patient Characteristics and IgE-Mediated Allergy in the Perioperative Setting.

BACKGROUND: Early recognition of perioperative anaphylaxis, a life-threatening, usually IgE-mediated, immediate hypersensitivity, is essential, but bedside diagnosis is not always straightforward because clinical presentation may vary. OBJECTIVES: To describe early characteristics of perioperative immediate hypersensitivity, with special attention to cutaneous phenotypes, and identify risk factors for IgE-mediated allergy. METHODS: We retrospectively analyzed data from adults with suspected perioperative immediate hypersensitivity who were investigated in two academic medical centers. Multivariable logistic regression was conducted to evaluate associations among patient, clinical, and paraclinical characteristics and IgE-mediated allergy. RESULTS: Of 145 enrolled patients, 99 (68.3%) and 46 (31.7%) were respectively categorized in the IgE-mediated allergy and non-allergy groups. Cutaneous vasoconstriction phenotype (pallor, piloerection, thelerethism, and sweating with or without cyanosis) occurring within minutes (or even 1 minute) of drug exposure was strongly associated with IgE-mediated allergy (adjusted odds ratio [aOR] = 28.02; 95% CI, 4.41-305.18). IgE-mediated allergy was always life-threatening in this setting. Other early factors associated with allergy were low end-tidal carbon dioxide 25 mm Hg or less (aOR = 5.45; 95% CI, 2.39-26.45), low mean arterial pressure 60 mm Hg or less (aOR = 3.82; 95% CI, 1.28-17.31), and early cutaneous vasodilation (erythema, urticaria, and/or angioedema) (aOR = 2.78; 95% CI, 0.73-20.54). Late cutaneous vasodilation after restoration of hemodynamics corroborated the diagnosis of allergy (aOR = 23.67; 95% CI, 4.94-205.09). The best-fit model including three readily available variables (cutaneous phenotype involving the three modalities [reference lack of cutaneous signs], low mean arterial pressure, and low end-tidal carbon dioxide) had an area under the curve of 0.91. CONCLUSIONS: Cutaneous vasoconstriction phenotype is associated with the strongest risk of life-threatening allergy and thus may be regarded as pathognomonic of perioperative IgE-mediated anaphylaxis.

Untargeted metabolomic profiling in children identifies novel pathways in asthma and atopy.

BACKGROUND: Asthma and other atopic disorders can present with varying clinical phenotypes marked by differential metabolomic manifestations and enriched biological pathways. OBJECTIVE: We sought to identify these unique metabolomic profiles in atopy and asthma. METHODS: We analyzed baseline nonfasted plasma samples from a large multisite pediatric population of 470 children aged <13 years from 3 different sites in the United States and France. Atopy positivity (At+) was defined as skin prick test result of ≥3 mm and/or specific IgE ≥ 0.35 IU/mL and/or total IgE ≥ 173 IU/mL. Asthma positivity (As+) was based on physician diagnosis. The cohort was divided into 4 groups of varying combinations of asthma and atopy, and 6 pairwise analyses were conducted to best assess the differential metabolomic profiles between groups. RESULTS: Two hundred ten children were classified as At-As-, 42 as At+As-, 74 as At-As+, and 144 as At+As+. Untargeted global metabolomic profiles were generated through ultra-high-performance liquid chromatography-tandem mass spectroscopy. We applied 2 independent machine learning classifiers and short-listed 362 metabolites as discriminant features. Our analysis showed the most diverse metabolomic profile in the At+As+/At-As- comparison, followed by the At-As+/At-As- comparison, indicating that asthma is the most discriminant condition associated with metabolomic changes. At+As+ metabolomic profiles were characterized by higher levels of bile acids, sphingolipids, and phospholipids, and lower levels of polyamine, tryptophan, and gamma-glutamyl amino acids. CONCLUSION: The At+As+ phenotype displays a distinct metabolomic profile suggesting underlying mechanisms such as modulation of host-pathogen and gut microbiota interactions, epigenetic changes in T-cell differentiation, and lower antioxidant properties of the airway epithelium.