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Abstract Background Fractional exhaled nitric oxide (FeNO) is used for the diagnosis and monitoring of asthma, although its utility to guide treatment and its correlation with other tools is still under discussion. We study the possibility to withdraw inhaled corticosteroid treatment in atopic patients with mild asthma based on the FeNO level, as well as to study its correlation with other clinical control tools. Methods Prospective and randomized study including atopic patients aged 18 to 65 with mild asthma, stable, on low-dose inhaled corticosteroid (ICS) treatment, who had their treatment withdrawn based on a FeNO level of 40 ppb. Patients were randomized into two groups: control group (treatment with ICS was withdrawn regardless of FeNO level) and experimental group (according to the FeNO levels, patients were assigned to one of two groups: FeNO > 40 ppb on treatment with budesonide 200 mcg every 12 h and SABA on demand; FeNO ≤ 40 ppb only with SABA on demand). Follow-up was conducted for one year, during which medical assessment was performed with FeNO measurements, asthma control test (ACT), lung function tests (FEV1, FEV1/FVC, PEF, and RV/TLC), and recording of the number of exacerbations. Results Ninety-two patients were included, with a mean age of 39.92 years (SD 13.99); 46 patients were assigned to the control group, and 46 patients to the experimental group. The number of exacerbations was similar between the groups (p = 0.301), while the time to the first exacerbation was significantly shorter in the control group (30.86 vs. 99.00 days), p 0.05). Both FeNO and ACT showed significant changes in the groups in which ICS was withdrawn (p

Eosinophilic ascites (EA) is a rare and enigmatic disorder characterized by elevated eosinophil counts in peritoneal fluid, commonly associated with eosinophilic gastroenteritis (EGE), hypereosinophilic syndrome (HES), and parasitic infections. Here, we present two cases of EA diagnosed and managed in our gastroenterology department. Case 1: A 45-year-old male presented with diffuse abdominal pain and distension. Imaging revealed septate abdominal ascites, prompting exploratory laparoscopy. Ascitic fluid analysis showed eosinophil predominance, leading to an EA diagnosis. The patient was treated with oral Albendazole, resulting in a favorable outcome. Case 2: A 52-year-old female complained of abdominal pain with alternating diarrhea and constipation. Imaging unveiled moderate ascites, pyloro-duodenal inflammation, and wall thickening. Eosinophilic leukocytosis prompted empirical treatment, yielding a positive response. In conclusion, diagnosing EA involves a combination of histological and laboratory methodologies. Corticosteroids emerge as the primary therapeutic avenue, with the imperative of eradicating parasitic infections before initiation. This study underscores the critical role of education in mitigating the risk of parasitic infections.

Elena Gavrilita,1,2 Simona Ioana Silion,1,2 Miruna Lorelei Bitca,1 Alin Laurentiu Tatu1– 3 1Dermatology Department, “Sf. Cuvioasa Parascheva” Clinical Hospital of Infectious Diseases, Galați, Romania; 2Multidisciplinary Integrated Center of Dermatological Interface Research MIC-DIR, “Dunărea de Jos” University, Galați, Romania; 3Clinical Medical Department, Faculty of Medicine and Pharmacy, “Dunărea de Jos” University, Galați, RomaniaCorrespondence: Elena Gavrilita, Tel +40746680485, Email dr.elenagavrilita@gmail.comAbstract: Atopic dermatitis (AD) is a frequent inflammatory condition that usually begins during early childhood, but it increasingly starts to debut, even in the elderly. Based on immunoglobulin E (IgE) levels and clinical features, two subsets of this disease have been recognized: intrinsic and extrinsic. When speaking about AD, most specialists think about filaggrin (FLG) mutations resulting in epidermal barrier defects, which is the case in most atopic patients, but some have a normal barrier, as seen by imaging, and still have specific clinical lesions along with metal allergies. Specific molecules (IL-10, IFN-γ, and HBD-3) have been shown to greatly impact the interactions between internal and external factors in this peculiar form of AD. A less-known protein, suprabasin, has been highlighted as a promising explanation for nickel anomalies in intrinsic AD.Keywords: atopy, OCT, RCM, HBD-3, IFN-γ, suprabasin

Abstract Background Alopecia areata (AA), a prevalent form of autoimmune hair loss, has a not well-defined relationship with atopic and allergic disorders, including eczema, hay fever, and asthma. Objectives This study aims to elucidate the genetic relationship between atopy, allergies, and alopecia areata (AA) using Mendelian randomization. We hypothesize that atopic and allergic conditions contribute to the genetic predisposition of AA. Methods We analyzed extensive genetic data from Genome-wide Association Studies (GWAS) involving over one million individuals. This analysis focused on assessing the genetic correlation between AA and various allergic conditions, including hay fever, eczema, asthma, and allergies to pollen, dust, and cats. The inverse variance weighted method served as our primary analytical tool, complemented by sensitivity analyses to verify the robustness of our results. Results Our findings reveal a significant genetic correlation between atopy/allergies and an increased risk of AA. Notably, strong associations were observed for hay fever, eczema, asthma, and specific allergies (pollen, dust, and cats). The sensitivity analyses corroborated these associations, reinforcing the reliability of our primary results. Conclusions This study provides compelling genetic evidence of an association between atopic and allergic conditions and the development of AA. These findings suggest that individuals with such conditions may benefit from enhanced surveillance for early signs of AA.

Abstract 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.

Abstract Background According to the Th1/Th2 paradigm, the expansion of Th1-type clones in individuals with type 1 diabetes results in reduced Th2-type clones, preventing the development of atopic diseases and vice versa. However, there is no consensus regarding the direct or inverse relationship between autoimmune and atopic diseases. Objective The aim of this scoping review was to examine the knowledge gap about the possibility of coexistence of asthma and type 1 diabetes and determine the prevalence of this association. Methods A scoping review was conducted, following the proposal of the Joanna Briggs Institute. The Population, Concept, and Context strategy was used to formulate the guiding question. The proposed question was: “What is the prevalence of asthma in people with T1DM?” After excluding duplicate articles, analyzing titles and abstracts, and excluding articles that did not answer the guiding question, 17 articles remained and were included in this review. Results Most of the articles selected conformed to the Th1/Th2 hypothesis, as the prevalence of asthma was lower in individuals with T1DM. However, similar or higher prevalence of asthma was found between cases and controls in few articles. Conclusion The prevalence of asthma in people with T1DM ranged from 1.7% to 23.1%. Maybe the mechanisms that characterizes the Th1/Th2 paradigm aren’t as simple as just the interaction of certain cytokines, since Th1-mediated autoimmune diseases and Th2- mediated atopy can coexist.

Among the diseases of small pets, skin diseases are one of the leading ones. Atopic dermatitis is a common skin condition in small pets, which, according to veterinarians’ estimates, affects 10-15% of dogs and 7-18% of cats. Depending on the allergens involved, clinical signs can be seasonal or non-seasonal, and the disease usually requires lifelong treatment. The purpose of this study was to investigate the therapeutic efficacy of treating atopy in dogs and cats with the use of triamcinolone-based veterinary medications (oral suspension). Standard clinical, haematological, biochemical, and immunological methods were used in the study. The increased content of total immunoglobulin E (Ig E) in the blood of experimental animals before treatment (Group I – 3.4 times, and Group II – 3.9 times compared to the control) indicates the presence of an allergic response in the body. It was found that the tested veterinary medications do not substantially affect the haematological parameters of dogs and cats when administered orally, and in therapeutic doses do not have a toxic effect on the functional state of the liver and kidneys. It was proved that on Day 4 of use of oral suspension No. 1 and No. 2 based on triamcinolone (1%) acetonide and a complex of B vitamins in a therapeutic dosage, an improvement in the general clinical condition of animals was recorded. On Day 8 of treatment, dogs and cats in experimental Groups I and II showed improvement in skin condition: a reduction in the lesion area, absence of redness, scratching, and exfoliation. The general clinical condition of the skin of the experimental animals stayed unchanged from Day 8 to Day 12. The developed oral suspensions have a pronounced anti-allergic effect and improve the skin condition of small pets (dogs and cats) with atopic dermatitis

ABSTRACTBackground The adoption of avoidance diets by adult-onset asthmatics has not previously been studied. We hypothesized that avoidance diets would associate with adult-onset asthma, allergy, and aspirin-exacerbated respiratory disease (AERD).Methods A total of 1247 subjects with adult-onset asthma (age range: 31–91) from the Finnish national registry, and age- and sex-matched controls (n = 1970) participated in a questionnaire study in 1997. We estimated the association between asthma/allergy/AERD and avoidance diets, adjusting for potential confounding factors and validated the results in two retrospective cohorts of 5080 rhinitis/rhinosinusitis patients and 167 AERD patients from 2019 to 2020.Results The presence of asthma positively associated with adoption of any avoidance diet (adjusted OR [CI95%] 1.24 [1.02–1.51], p = 0.029) as did allergic disease and self-reported AERD within the asthmatic group (1.79 [1.29–2.48], p = 0.001 and 1.69 [1.15–2.49], p = 0.007, respectively). Asthmatics and allergic asthmatics were more likely to report avoidance of fish, fruits and vegetables, and spices (p ≤ 0.03) compared to controls and non-allergic asthmatics. The adjusted OR for multiple diets among AERD patients was 2.57 [1.34–4.95] p = 0.005. In the validation, 26.2% of the allergic asthmatics and 10.8% of AERD patients had documented avoidance diets.Conclusions Our study shows a positive association between avoidance diets and adult-onset asthma, and with allergic disease or AERD within asthmatic patients. Although we lack information on the reason patients chose to observe a specific diet, our results reinforce the importance of asking patients about their diet and if needed, giving dietary advice for adult asthma patients to help them avoid the adoption of unnecessarily restrictive diets.

AbstractBackground A growing body of research supports the important role of the TH2 axis in alopecia areata (AA). Dupilumab is a humanized monoclonal antibody against IL-4Rα that downregulates TH2 response. Although efficacy has been shown in clinical trials, real-world data on the use of dupilumab in AA patients is limited.Objectives To report on a case series of 10 patients with AA who were treated with dupilumab and provide real-world evidence regarding its efficacy in treating severe AA.Methods In this retrospective single-center study, all AA patients treated with dupilumab treatment were included between May 2022 and October 2023. Clinical outcome measures (Severity of Alopecia Tool, SALT) and adverse events (AEs) were analyzed. In addition, a literature review was conducted to summarize the efficacy of AA with dupilumab and the characteristics of patients previously reported in the literature.Results We identified 10 patients with AA who were or are being treated with dupilumab, with a median (range) treatment duration of 8 (3-15) months. Of these, four patients have high serum immunoglobulin E (IgE) levels (≥200IU/ml). The mean (IQR) pretreatment SALT score was 79% (52-100). Seven of 10 patients achieved at least 50% re-growth. Of those who improved, the mean (IQR) percentage change in SALT score at 3 months and the end of follow-up was 57% (29%-89%) and 95% (68-100), respectively. Notably, seven patients (70%) had white hair regrowth, with the white hair slowly decreasing over time and the proportion of pigmented black hair increasing. Dupilumab was well tolerated by all patients. No adverse events were reported.Conclusions Overall, our research supports dupilumab as another candidate that possesses potential benefits for AA. High levels of IgE may be not prerequisites for dupilumab’s successful treatment response.

Background: Total immunoglobulin E (IgE) analysis is a common tool in allergy diagnosis. Suggested reference values for IgE are divergent and sometimes based on outdated assay methods. We aimed to validate the published reference values (geometric mean [GM]: 13.2 kU/L, upper limit of normal [ULN], 114 kU/L) shown in an Uppsala cohort from 1974 using Phadebas IgE PRIST, and the suggested clinical threshold of 100 kU/L (Zetterström and Johansson 1981). Methods: Immunoglobulin E was measured in two Uppsala cohorts from 1997 (Blood bank) and 2011 to 2013 (the European community respiratory health survey part III [ECRHS III]) using ImmunoCAP™ Total IgE. For the reference value calculations, exclusion criteria were atopy (both cohorts), doctor’s diagnosis of asthma and self-reported allergy (hay fever, rhinitis, rash) (only ECRHS III). Upper limit of normal was defined as mean + 2 standard deviations (SD) calculated using log-transformed values and back-transformation of the ULN prior to presentation. Common imputation methods for results below the assay range were evaluated. Results: The average GM was 14.2 kU/L (Blood bank, n = 63; imputation method range: 16.9–17.4 kU/L; ECRHS III, n = 113: 10.7–11.6 kU/L) and the overall mean ULN was 118 kU/L (Blood bank: 113–130 kU/L; ECRHS III: 104–128 kU/L). The clinical sensitivity and specificity of the 100 kU/L IgE threshold were 37.8 and 94.3% for atopy, 34.9 and 89.5% for doctor’s diagnosis of asthma, and 24.5 and 97.3% for any self-reported allergy (ECRHS III). Conclusion: The calculated ULN values were similar between the cohorts. We conclude that the total IgE reference values shown for Uppsala subjects from 1974 are still valid and suitable also for the ImmunoCAP Total IgE assay. The 100 kU/L threshold for total IgE had a low sensitivity but high specificity for atopy, asthma, and allergy.

Wan Zhen Janice Ng,1,* James van Hasselt,2,* Bhumika Aggarwal,3 Anand Manoharan4 1School of Biological Sciences, Nanyang Technological University, Singapore, Singapore; 2GSK, Regional Medical Affairs, Bryanston, Gauteng, South Africa; 3Regional Respiratory Medical Affairs, GSK Plc, Singapore, Singapore; 4Infectious Diseases Medical & Scientific Affairs, GSK, Mumbai, India*These authors contributed equally to this workCorrespondence: James van Hasselt, GSK, The Campus, Flushing Meadows, 57 Sloane Street, Bryanston, Gauteng, 2021, South Africa, Tel +27-82-330-8489, Email james.d.van-hasselt@gsk.comBackground: Strong associations between early antibiotic exposure and increased risk of childhood allergies have been established. Antibiotics have the potential to induce microbial dysbiosis that may be linked to allergic conditions. This review examines the limited available evidence on the associations between adult antibiotic use, microbial dysbiosis and atopic conditions.Methods: A systematic literature search was conducted using PubMed and Embase for relevant studies, published between 01– 01– 2000 and 08– 17– 2022. We searched for associations between antibiotic use, microbial dysbiosis, and allergic conditions in adults, defined as over 13 years of age for the purposes of this review.Results: Twenty-one studies were analyzed, with the inclusion of four narrative reviews as scarce relevant literature was found when stricter selection criteria were employed. Relevant studies predominantly focused on asthma. Significant microbial differences were observed in most measures between healthy subjects and subjects with allergic conditions. However, no system-wise and strain-wise associations were evident. Notably, at the phyla level, the Bacillota and Pseudomonadota phyla were associated with asthmatics, while the Actinobacteria phylum was linked to healthy controls. Asthmatics tends to reflect upregulation in the Bacillota and Pseudomonadota phyla in both airway and gut microbiomes.Conclusion: No compelling evidence could be found between adult antibiotic exposure, consequent microbial dysbiosis, and allergic conditions in adults. Our review is limited by scarce literature and therefore remains inconclusive. However, potential implications of antibiotic use impacting on allergic conditions justify additional research and heightened pharmacovigilance in this area.Keywords: atopy, allergic, asthma, microbiome

Introduction: Eosinophilic esophagitis (EoE) is a chronic, allergic inflammatory disease of the esophagus. It has a peak incidence in the 2nd and 3rd decades of life. Despite this, little is known about pregnancy outcomes in patients with EoE. Methods: Using a validated histopathologic and nationwide population-based cohort for the diagnosis of EoE, we examined maternal and fetal outcomes, with preterm birth as the primary outcome, in females with EoE compared to matched controls. Odds ratios (ORs) were calculated using logistic regression. Results: Between 1992 and 2016, we identified 19 females with EoE who gave birth to 23 children (reference births: n = 115). There was 1 (4.3%) preterm birth in the EoE cohort versus 8 (7.0%) in the reference cohort (OR = 0.60; 95% CI = 0.07–5.14). Secondary fetal outcomes included stillbirth, neonatal death, small for gestational age, low birth weight (LBW), and low Apgar score. Of these, LBW (

Atopic diseases, including atopic dermatitis (AD) and allergic asthma (AA), are characterized by complex immune responses involving various T cells subsets and their cytokine profiles. It is assumed that single nucleotide polymorphisms (SNPs) in the Vitamin D receptor (VDR) gene and the Vitamin D-binding protein (GC) gene are related to the action of Vitamin D and, consequently, play a role in regulating the immune response. However, there is not enough data to unequivocally support the hypothesis about the relationship between T cells profile and VDR or GC SNPs. Two hundred sixty-six subjects (aged > 18 years) were involved in the study: 100 patients with mild or moderate AD, 85 patients with mild or moderate AA, and 81 healthy individuals. Blood cell counts were determined by standard methods. Flow cytometric analysis was used to evaluate CD4+ T-helper (Th) cell subtypes: Th2, Th1, Th17, and T regulatory (Treg) cells in peripheral blood. Measurements of cytokines, total immunoglobulin E (IgE), and Vitamin D levels in serum were evaluated by ELISA. Significantly higher levels of Th1, Th2, and Th17 cells, along with lower levels of Tregs, were found in patients with atopic diseases compared to healthy individuals. Additionally, higher serum levels of interleukin (IL) 5, IL-17A, and transforming growth factor-β1 (TGF-β1), as well as lower levels of IL-10, were observed in patients with atopic diseases than in control. The study established associations between VDR SNPs and immune profiles: the AA genotype of rs731236 was associated with increased Th2 and Th17 cells and a higher Th1/Th2 ratio; the GG genotype of rs731236 was linked to decreased serum IL-10 and TGF-β1 levels; and the TT genotype of rs11168293 was associated with increased IL-10 levels. Additionally, the GG genotype of GC gene SNP rs4588 was associated with reduced Th2 and Th17 lymphocytes, while the TT genotype of rs4588 was linked to decreased IL-10 levels. Furthermore, the CC genotype of rs7041 was associated with higher levels of Th2, Th17, IL-10, and IL-35, as well as reduced levels of TGF-β1, while the GG genotype of rs3733359 was associated with reduced IL-10 levels. In conclusion, our study demonstrates that the Vitamin D receptor gene single nucleotide polymorphisms rs731236 and rs11168293, along with polymorphisms in the Vitamin D-binding protein gene (rs4588, rs7041, rs3733359), are significantly associated with variations in T cell profiles in atopy. These variations may play a crucial role in promoting inflammation and provide insight into the genetic factors contributing to the pathogenesis of atopy.

(1) Background: Food allergy (FA) is an immune-mediated hypersensitivity to foods, significantly contributing to childhood morbidity and mortality. This study aimed to assess the prevalence, characteristics, and influencing factors of parent-reported FAs among children in Saudi Arabia. (2) Methods: This cross-sectional study utilized a validated parental questionnaire distributed across all regions of Saudi Arabia. Data from 2130 participants were collected and analyzed using SPSS v. 26 and Prism software v. 10.3.0. (3) Results: Parent-reported FA prevalence was 15.2%. Egg was the most common allergen (6.2%), followed by tree nuts (4.1%), peanuts (4.0%), milk (3.8%), and sesame (3.2%). Significant geographical variations were observed, with the western region having the highest burden (p < 0.001). Older children had higher rates of shellfish and fish allergies. Parental allergies and co-existing asthma/drug allergies were positively associated with childhood FAs. (4) Conclusions: This study highlights a substantial burden of parent-reported FAs in Saudi Arabia, with regional variations in food allergen distribution. Parental allergies and co-existing allergic conditions may influence FA risk.

Abstract 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.

Food protein-induced allergic proctocolitis (FPIAP) is a non-IgE-mediated allergic condition that presents with hematochezia in otherwise healthy infants. It is most commonly induced by cow's milk protein via breast milk or formula. The prognosis for FPIAP is generally considered favorable with most infants achieving symptomatic resolution after diet modification. Most infants go on to tolerate the offending foods by 1–3 years of age. Over 8 years at our institution, five patients were identified and noted to have FPIAP to cow's milk during infancy with subsequent development of IgE-mediated allergic reaction to cow's milk and other foods. All five cases developed other atopic disorders (atopic dermatitis in four cases). IgE-mediated cow's milk allergy has persisted beyond the preschool years in at least two patients (currently 8 and 16 years old). For three of the patients, the IgE-mediated reaction to cow's milk was severe with development of anaphylaxis or angioedema. In addition, three patients experienced anaphylaxis or angioedema to allergens other than milk. While FPIAP is a non-IgE-mediated process traditionally thought not to progress past the first year of life, some infants with FPIAP develop severe, persistent IgE-mediated cow's milk allergy. To our knowledge, this is the first detailed clinical description of such patients.

The prevalence and severity of allergic diseases have increased over the last 30 years. Understanding the mechanisms responsible for these diseases is a major challenge in current allergology, as it is crucial for the transition towards precision medicine, which encompasses predictive, preventive, and personalized strategies. The urge to identify predictive biomarkers of allergy at early stages of life is crucial, especially in the context of major allergic diseases such as food allergy and atopic dermatitis. Identifying these biomarkers could enhance our understanding of the immature immune responses, improve allergy handling at early ages and pave the way for preventive and therapeutic approaches. This minireview aims to explore the relevance of three biomarker categories (proteome, microbiome, and metabolome) in early life. First, levels of some proteins emerge as potential indicators of mucosal health and metabolic status in certain allergic diseases. Second, bacterial taxonomy provides insight into the composition of the microbiota through high-throughput sequencing methods. Finally, metabolites, representing the end products of bacterial and host metabolic activity, serve as early indicators of changes in microbiota and host metabolism. This information could help to develop an extensive identification of biomarkers in AD and FA and their potential in translational personalized medicine in early life.

Chronic urticaria (CU) is one of the most common dermatological diseases and has a significant impact on the quality of life of patients. However, the pathogenesis of this disease remains unclear. Autoimmunity in chronic spontaneous urticaria (CSU) has received considerable attention and has been studied previously. Atopy is an important characteristic of CU; however, it has not been fully recognized. Atopy predisposes individuals to immune responses to allergens, leading to type 2 inflammation and immunoglobulin E (IgE) overproduction. Compared with healthy individuals, patients with CU have a higher proportion of atopy, and an atopic background is correlated with the clinical characteristics of CU. The total IgE levels in patients with CU is significantly higher than those in healthy individuals. Although its level is not higher than that in classic allergic diseases, it is closely related to CU. Exogenous allergens, auto-allergens, and specific IgEs, which are closely related to atopy, have been reported, and their roles in CU pathogenesis are also being studied. Local and systemic atopic inflammation is present in patients with CU. This review summarizes the current knowledge regarding atopy and CU, speculating that there are CU subtypes, such as atopic CSU or atopic chronic inducible urticaria (CIndU) and that atopy may be involved in the pathogenesis of CU. These findings provide a new perspective for a comprehensive understanding of the clinical features of CU and further research regarding its pathogenesis.

Allergy is a conundrum lacking satisfactory answers despite its global prevalence. Traditional systems of medicine may contain sustainable and effective solutions for the same. For mainstreaming them, an evaluation based on the system's own methods is inevitable rather than symptom-based correlations. Atopy is a novel entity in Ayurveda, but the methods of tripartite delineation (disease pattern, disease targets and influencing factors) of novel diseases and multifactorial approach to diagnosis and management in Ayurveda can bring about comprehensiveness in collection and categorization of data regarding the entity. This in turn can make the prediction, prevention and management of the same more precise, effective and sustainable. The article provides a template for the application of Ayurvedic biological framework in the diagnosis and management of novel diseases, with special reference to childhood allergic disorders.

Introduction. Pediatric asthma is predominantly atopic, but no data are found on atopy in obese asthmatic child in the literature. In addition, the increased obesity rates, sensitization to airborne allergens are a risk factor for asthma. Objective. To determine whether elevation of body mass index (BMI) was associated with asthma severity or with sensitization to inhalation allergens in adolescents in the wilaya of Constantine. Material and methods. This was a prospective, descriptive and cross-sectional study, carried out during the 2017-2018 school year, on 104 asthmatic adolescents, aged between 13 and 14, in schools in Constantine. The weight status of the patients was assessed using the 2012 thresholds of the International Obesity Task Force (IOTF), and a BMI ≥ 25 kg/m2 defined overweight or obesity. Asthmatics obese and non-obese groups were compared for the prevalence of severe asthma and sensitization using the Chi-square test, at the 95% confidence interval. Results. Twenty-five per cent of asthmatics were overweight or obese with an average BMI of 28,20±3,80. Asthma symptoms were persistent in 66%, and uncontrolled in 40% of cases. Almost 70% of the population were atopic, and 50% were poly-sensitized. Sensitization occurred in both groups with a significant positive ratio (p=0.03). No association was observed between obesity and prevalence of severe asthma (p=0.5), or poly-sensitizations. Conclusion. The quarter of adolescents is overweight or obese, and tends to present an atopy. However, no positive association is found between obesity and prevalence of severe asthma symptoms. Further prospective studies are needed for a better understanding of this obese asthmatics group. [Résumé Introduction. L’asthme pédiatrique est majoritairement atopique, mais aucune donnée n’existe sur l’atopie de l’enfant asthmatique obèse dans la littérature. En outre, l’élévation du taux d’obésité, la sensibilisation aux pneumallergènes sont un facteur de risque pour l’asthme. Objectif. Déterminer si l’élévation de l’indice de masse corporelle (IMC) est associée à la sévérité de l’asthme ou à la sensibilisation aux pneumallergènes, chez des adolescents asthmatiques dans la wilaya de Constantine. Matériel et méthodes. Une étude prospective, descriptive et transversale est réalisée durant l’année scolaire 2017-2018, et a porté sur 104 adolescents asthmatiques, âgés entre 13 et 14 ans, au sein des établissements scolaires de Constantine. Le statut pondéral des malades a été évalué en utilisant les seuils de l’International Obesity Task Force (IOTF), avec un indice de masse corporelle (IMC) ≥ 25 kg/m² définissant le surpoids ou l’obésité. Des groupes d’asthmatiques obèses et non obèses ont été comparés afin de noter la prévalence de l’asthme sévère et la sensibilisation en utilisant le test de Chi-deux à l’intervalle de confiance de 95 %. Résultats. Un quart des asthmatiques étaient en surpoids ou obèses avec un IMC moyen de 28,20±3,80. Les symptômes d’asthme étaient persistants chez 66%, et non contrôlés chez 40% des cas. Près de 70% de la population était atopique et 50 % étaient polysensibilisés. La sensibilisation s’est produite dans les deux groupes avec un rapport positif significatif (p=0,03). Aucune association n’est observée entre l’obésité et la prévalence de l’asthme sévère ou les poly-sensibilisations. Conclusion. Le quart des adolescents sont en surpoids ou obèses et ont tendance à présenter une atopie. Cependant, aucune association n’est notée entre l’obésité et la prévalence des symptômes sévères d’asthme. D’autres études prospectives sont nécessaires pour une meilleure compréhension du groupe d’asthmatiques obèses.]

Gut bacterial alterations have been previously linked to several non-communicable diseases in adults, while the association of mycobiome is not well understood in these diseases, especially in infants and children. Few studies have been conducted on the association between gut mycobiome and non-communicable diseases in children. We investigated gut mycobiome composition using 194 faecal samples collected at birth, 6 months after birth, and 18 months after birth in relation to atopic dermatitis (AD) and overweight diagnoses at the age of 18 or 36 months. The mycobiome exhibited distinct patterns, with Truncatella prevalent in the meconium samples of both overweight and non-overweight groups. Saccharomyces took precedence in overweight cases at 6 and 18 months, while Malassezia dominated non-overweight samples at 6 months. Saccharomyces emerged as a consistent high-abundance taxon across groups that had dermatitis and were overweight. We found a weak association between gut mycobiome and AD at birth and overweight at 18 months when using machine learning (ML) analyses. In ML, unidentified fungi, Alternaria, Rhodotorula, and Saccharomyces, were important for classifying AD, while Saccharomyces, Thelebolus, and Dothideomycetes were important for classifying overweight. Gut mycobiome might be associated with the development of AD and overweight in children.

As the burden of mild asthma is not well understood, the significance of expanding research in the group of patients with mild asthma is emphasized. Thymic stromal lymphopoietin (TSLP) and interleukin 33 (IL-33) are involved in the pathogenesis of atopy and the immune response to inhaled environmental insults, such as allergens, in asthmatic patients. Objectives: The objective of this study was to explore the correlation between specific polymorphisms within the genes encoding TSLP and IL-33, as well as the concentrations of TSLP and IL-33 in the serum, and the occurrence of pediatric mild asthma. Methods: The analysis encompassed 52 pediatric patients diagnosed with mild bronchial asthma, including both atopic and non-atopic cases, and a control group of 26 non-asthmatic children. Recruitment was conducted through a comprehensive questionnaire. Parameters such as allergic sensitization, serum levels of circulating TSLP and IL-33, and the identification of single-nucleotide polymorphisms in TSLP (rs11466750 and rs2289277) and IL-33 (rs992969 and rs1888909) were assessed for all participants. Results: Significantly lower mean serum TSLP concentrations were observed in asthmatic subjects compared to the control group, with atopic asthma patients showing even lower TSLP levels than non-atopic counterparts. No significant differences were found in mean serum IL-33 concentrations between the two groups. Considering the allele model, for both tested SNPs of IL-33, we observed that patients with asthma, atopic asthma, and atopy statistically less frequently possess the risk allele. Conclusions: Our study findings suggest that IL-33 and TSLP do not serve as ideal biomarkers for mild asthma in children. Their effectiveness as biomarkers might be more relevant for assessing disease severity rather than identifying asthma in pediatric patients. Further research focusing on the association between TSLP and IL-33 gene polymorphisms and asthma is expected to significantly advance disease management.

Evodiamine is an alkaloid found in Evodia fruits, a traditional Chinese medicine. Preclinical studies have demonstrated its anti-inflammatory and neuroprotective properties. The 2,4-dinitro-1-chloro-benzene (DNCB) was used to test the effects of evodiamine on a chemically induced atopic dermatitis-like model in BALB/c mice. Evodiamine significantly lowered serum immunoglobulin E levels, which increased as an immune response to the long-term application of DNCB. Several atopic dermatitis-like skin symptoms induced by DNCB, including skin thickening and mast cell accumulation, were suppressed by evodiamine therapy. DNCB induced higher levels of pro-inflammatory cytokines in type 2 helper T (Th2) cells (IL-4 and IL-13), Th1 cells (IFN-γ and IL-12A), Th17 cells (IL-17A), Th22 cells (IL-22), and chemokines (IL-6 and IL-8). These increases were suppressed in the lymph nodes and skin following evodiamine treatment. The results of our study indicate that evodiamine suppresses atopic dermatitis-like responses in mice and may therefore be useful in treating these conditions.

Introduction: Measuring soluble interleukin-2 receptor (sIL-2R) might be useful for diagnosis and monitoring of immune-mediated diseases. The study investigated factors associated with serum sIL-2R concentrations in adults. Methods: Serum sIL-2R concentrations were measured in 1499 randomly selected individuals (44.6% male, median age 52 years, range 18–91 years). Lifestyle factors (alcohol consumption, smoking, and physical activity) were assessed by questionnaire. Body mass index and data defining metabolic syndrome were measured in all participants. Atopy was defined by skin tests to aeroallergens. Results: Serum sIL-2R concentrations displayed wide variation (2.5–97.5 percentile range, 209–950 U/mL). A total of 230 (15.3%) individuals showed values higher than the standard reference range (158–623 U/mL). After adjusting for covariates, sIL-2R concentrations increased with age, particularly after 65 years. Serum sIL-2R concentrations were higher in males than in females, were higher in smokers than in never smokers, and were higher in atopic than in non-atopic individuals. Serum sIL-2R concentrations were positively associated with metabolic syndrome, particularly with abdominal obesity, and with a history of ischemic heart disease. Light alcohol drinkers showed lower sIL-2R concentrations than abstainers. Conclusion: Aging, sex, lifestyle factors, atopy, metabolic abnormalities, and ischemic heart disease might influence serum sIL-2R concentrations in adults.

Introduction: Cow’s milk allergy (CMA) is a common complication and one of the most common food allergies in infants, and it is estimated that this disease affects 2-3% of children under five years old. Objectives: This study investigated the factors associated with developing immune tolerance in children with CMA in Gorgan. Patients and Methods: In this cross-sectional study, 50 children with CMA referred to the asthma and allergy clinic of Taleghani Hospital in Gorgan during 2019-2020 were investigated. Multiple logistic regression was applied to measure odds ratios (ORs) and 95% confidence intervals (CIs) of the associations between the selected factors and tolerance to cow’s milk. Results: The results suggested that factors including standard delivery (P=0.024, OR=4.03, 95% CI: 1.20-13.53) and breastfeeding in the first month of birth (P=0.003, OR=6.73, 95% CI:1.94-23.36), and gastrointestinal symptoms (P=0.026, OR=3.78, 95% CI: 1.17-12.19) were associated with immune tolerance to CMA. Younger age of starting complementary feeding (P

Maysoun Al Rushood,1,2 Wafaa AL-Qabandi,1,3 Amani AL-Fadhli,1 Suha Atyani,4 Abrar AL-Abdulghafour,5 Ahmed Hussain6 1Department of Pediatrics, College of Medicine, Kuwait University, Kuwait City, Kuwait; 2Allergy and Clinical Immunology Unit, Department of Pediatrics, Mubarak Al Kabir Hospital, Kuwait City, Kuwait; 3Gastroenterology Unit, Department of Pediatrics, Amiri Hospital, Kuwait City, Kuwait; 4Department of Pediatrics, Jaber Hospital, Kuwait City, Kuwait; 5Department of Pediatrics, Amiri Hospital, Kuwait City, Kuwait; 6Allergy and Clinical Immunology Unit, Department of Pediatrics, Amiri Hospital, Kuwait City, KuwaitCorrespondence: Maysoun Al Rushood, Email maysoun.alrushood@ku.edu.kwBackground: Cow’s Milk Protein Allergy (CMPA) is the most common food allergy in children. The reaction is classified into IgE-mediated immediate reaction and delayed-onset, according to the underlying immune mechanism, and hence, the timing of the symptoms. Case reports suggest that children, with delayed CMPA reactions on elimination diet, may develop severe immediate reactions on reintroduction.Aim: The objective of this study was to evaluate the incidence and the risk factors of developing immediate reactions to milk and dairy products in children with CMPA whose initial presentations were of delayed type.Methods: A retrospective chart review of children, aged 0– 12 years, presented with delayed type CMPA reactions to the allergy-clinical immunology clinics, was performed. The diagnosis was made clinically, and with appropriate allergy tests when indicated.Results: Sixty children were included. Males:female ratio was 1.7:1. Family history of atopy was in 72%, and 57% had personal history of atopy. Sixty percent were not breast fed. The most common concomitant food allergy was egg. The most common initial presentation was diarrhea without protein loss or bleeding followed by exacerbation of atopic dermatitis upon exposure to dairy products. Immediate reactions developed in 21.6% upon re-exposure. There were significant associations with concomitant food allergy (OR 56.6 (3.15– 1016.1) P< 0.0001), especially eggs (OR 12.85 (3.09– 53.5) P< 0.01).Conclusion: Children with CMPA, who present with delayed-type allergic reactions, may be at a significant risk of developing immediate reactions upon reintroduction. Evaluation of possible IgE-mediated allergic reactions before reintroduction may be advisable.Keywords: atopy, cow’s milk protein allergy, food allergy, proctocolitis, eczema, allergy

Abstract Atopic dermatitis (AD) as a chronic inflammatory systemic condition is far more than skin deep. Co-morbidities such as asthma and allergic rhinitis as well as the psychological impact influence seriously the quality of life of the patients. Recent studies have shown that only 10% of atopic patients undergo full manifestation of the atopic march, while 40% demonstrate concomitant food allergy. Exposure to food allergens in the environment causes sensitization and food allergy through the disruption of the skin barrier, as in AD. Food allergy and AD are closely related. While not all AD patients have a food allergy, 20–40% of children with moderate to severe AD will have an IgE-mediated food allergy. It is known that they may coexist but it is unclear if food allergy worsens the course of AD. Experimental, clinical, and epidemiological studies have provided evidence of the primary role of an epidermal barrier defect in the development of sensitization to environmental allergens and that this process occurs in the damaged skin barrier rather than the gastrointestinal or respiratory tract. There is strong evidence for a connection between early AD onset and the development of other allergic diseases later in life.

Abstract Background The gastrointestinal (GI) microbiota has been linked to health consequences throughout life, from early life illnesses (e.g. sepsis and necrotising enterocolitis) to lifelong chronic conditions such as obesity and inflammatory bowel disease. It has also been observed that events in early life can lead to shifts in the microbiota, with some of these changes having been documented to persist into adulthood. A particularly extreme example of a divergent early GI microbiota occurs in premature neonates, who display a very different GI community to term infants. Certain characteristic patterns have been associated with negative health outcomes during the neonatal period, and these patterns may prove to have continual damaging effects if not resolved. Results In this study we compared a set of premature infants with a paired set of term infants (n = 37 pairs) at 6 weeks of age and at 2 years of age. In the samples taken at 6 weeks of age we found microbial communities differing in both diversity and specific bacterial groups between the two infant cohorts. We identified clinical factors associated with over-abundance of potentially pathogenic organisms (e.g. Enterobacteriaceae) and reduced abundances of some beneficial organisms (e.g. Bifidobacterium). We contrasted these findings with samples taken at 2 years of age, which indicated that despite a very different initial gut microbiota, the two infant groups converged to a similar, more adult-like state. We identified clinical factors, including both prematurity and delivery method, which remain associated with components of the gut microbiota. Both clinical factors and microbial characteristics are compared to the occurrence of childhood wheeze and eczema, revealing associations between components of the GI microbiota and the development of these allergic conditions. Conclusions The faecal microbiota differs greatly between infants born at term and those born prematurely during early life, yet it converges over time. Despite this, early clinical factors remain significantly associated with the abundance of some bacterial groups at 2 years of age. Given the associations made between health conditions and the microbiota, factors that alter the makeup of the gut microbiota, and potentially its trajectory through life, could have important lifelong consequences.

Human metapneumovirus (hMPV) is an important pathogen that causes both upper (URTIs) and lower respiratory tract infections (LRTIs) in children. The virus can be implicated in severe bronchiolitis and pneumonia, necessitating hospitalization, with certain cases requiring intensive care unit intervention. As part of a retrospective observational study, we aimed to identify indicators of severe hMPV respiratory tract infections in children referred to the University Children’s Hospital Ljubljana and the Department of Infectious Diseases Ljubljana, Slovenia, during a recent outbreak. We analyzed clinical data from November 2022 to January 2023 and compared the characteristics of children presenting with URTIs and LRTIs. We also examined the characteristics of children with hMPV LRTIs, distinguishing between children with and without LRTI-associated hypoxemia. Of 78 hMPV-PCR-positive pediatric patients (mean age 3.1 years; 60.3% boys), 36% had a URTI, and 64% had an LRTI. Hospitalization was required in 64% (50/78), with 42% (21/50) requiring oxygen therapy. LRTI-associated hypoxemia was more common in patients with atopy who showed dyspnea, tachypnea, crackles, and wheezing on lung auscultation. In a multivariable logistic regression analysis, wheezing detected on lung auscultation was a significant predictive factor for hypoxemic hMPV-LRTI. Specifically, children presenting with wheezing were found to be ten times more likely to experience hypoxemia. Prematurity and chronic conditions did not influence the presentation or severity of hMPV infection. This study highlights wheezing and atopy as crucial indicators of severe hMPV LRTI in children, emphasizing the importance of early recognition and intervention.

The gut microbiota plays an important role in maintaining human health, as well as in the development of various pathologies, as indicated by a large amount of research. One of the manifestations of an imbalance in the gut microbiome composition is the appearance of various diseases or immune reactions, in particular, atopic dermatitis (AD) and/or food allergies (FA). In this research, using 16S NGS sequencing, it was found that the gut microbiome of children with food allergies and children with atopic dermatitis can be characterized as having higher inflammatory potential. Both groups exhibited an abundance of representatives from the Pasteurellaceae and Erysipelotrichaceae families, as well as a decrease in the relative number of representatives from the Barnesiellaceae family compared to healthy participants. In the group of participants with food allergies, there was a decrease in the relative number of Desulfovibrionaceae representatives and Bifidobacteriaceae family enrichment in relatively healthy participants. In addition, when comparing this group with patients with atopic dermatitis, it was revealed that a number of representatives of such families as Erysipelotrichaceae, Ruminococcaceae and Sutterellaceae prevailed. This information confirms that AD and FA correlate with changes in the composition of the gut microbiota. Further research is needed to determine the cause–effect connections and the effect of compounds derived from the microbiota on the AD and FA development and progression, as well as to create new probiotic drugs to prevent and modulate immune responses, including at an early age.

In traditional Korean medicines, Magnolia officinalis is commonly included for the remedy of atopic dermatitis, and magnolol is a major constituent of Magnolia officinalis. Its pharmacological effects include anti-inflammatory, hepatoprotective, and antioxidant effects. Using BALB/c mice repeatedly exposed to 1-chloro-2,4-dinitrobenzene (DNCB), magnolol was evaluated in atopic dermatitis-like lesions. Administration of magnolol (10 mg/kg, intraperitoneal injection) markedly relieved the skin lesion severity including cracking, edema, erythema, and excoriation, and significantly inhibited the increase in IgE levels in the peripheral blood. A DNCB-induced increase in mast cell accumulation in atopic dermatitis skin lesions was reversed by magnolol administration, as well as a rise in expression levels of pro-inflammatory Th2/Th17/Th1 cytokines’ (IL-4, IL-13, IL-17A, IFN-γ, IL-12A, TARC, IL-8, and IL-6) mRNAs in the lymph nodes and skin (n = 5 per group). In lymph nodes, magnolol reversed DNCB’s increase in CD4+RORγt+ Th17 cell fraction and decrease in CD4+FoxP3+ regulatory T cell fraction. The results also showed that magnolol suppressed T cell differentiation into Th17 and Th2 cells, but not Th1 cells. Magnolol suppresses atopic dermatitis-like responses in the lymph nodes and skin, suggesting that it may be feasible to use it as a treatment for atopic dermatitis through its suppression of Th2/Th17 differentiation.

Background: In order to improve the control of atopic diseases, it is important to clarify the pathogenesis of atopy and identify its various triggers. Single nucleotide polymorphisms (SNPs) of the vitamin D receptor gene (VDR) may impact atopy. The aim of this study was to investigate the possible associations between VDR SNPs and vitamin D, total IgE, and eosinophils in atopy. Methods: In total, 203 adults, including 122 patients with atopic diseases (45 with atopic dermatitis, 77 with allergic asthma) and 81 healthy controls, were involved in the study. The blood eosinophil count was determined with an automated hematology analyzer. Vitamin D and total immunoglobulin E (IgE) levels were evaluated using the ELISA method. Polymorphisms in the VDR gene were analyzed with real-time PCR using TaqMan probes. Results: We analyzed six VDR single nucleotide polymorphisms and found a significant association between VDR rs731236 GG genotype and normal vitamin D levels in atopic patients and healthy subjects (OR 11.33; 95% CI: 1.049–122.388 and OR 4.04; 95% CI: 1.117–14.588, respectively, p < 0.05). Additionally, the study results revealed a significant relationship between the VDR rs2228570 GG genotype and normal vitamin D levels in patients with atopy and healthy subjects (OR 3.80; 95% CI: 1.190–12.134 and OR 2.09; 95% CI: 1.044–4.194, respectively, p < 0.05). The rs2228570 allele A was associated with decreased vitamin D levels in patients with atopy and healthy subjects (OR 0.28; 95% CI: 0.098–0.804 and OR 0.229; 95% CI: 0.069–0.761, respectively, p < 0.05). The VDR rs3847987 genotypes AA and AC were significantly associated with normal vitamin D levels in healthy subjects (OR 35.99; 95% CI: 6.401–202.446 and OR 4.72; 95% CI: 1.489–15.007, respectively, p < 0.05). In addition, a decreased amount of vitamin D was associated with atopic diseases such as atopic dermatitis and allergic asthma (OR 0.49; 95% CI: 0.439–1.308 and OR 0.58; 95% CI: 0.372–0.908, respectively, p < 0.05). The rs11168293 allele T was associated with the normal range of total IgE in atopy (OR 2.366; 95% CI: 1.133–5.027; p < 0.05). Significant associations were found between VDR rs731263 allele G, rs11168293 allele G, and increased blood eosinophil levels in patients with atopy (OR 0.319; 95% CI: 0.163–0.934 and OR 0.323; 95% CI: 0.112–0.935, respectively, p < 0.05). Conclusions: A decreased vitamin D level showed a significant relationship with atopic diseases (atopic dermatitis and allergic asthma). The association between the VDR gene polymorphisms rs2228570, rs731236, and rs11168293 and vitamin D, total IgE, and blood eosinophils in patients with atopy suggested that VDR polymorphisms and the vitamin D level should be considered when examining the factors associated with atopy.

Asthma is one of the most prevalent chronic lung diseases that afflict genetically predisposed individuals. Certain cytokine gene polymorphisms have been associated with asthma. Tumor necrosis factor-alpha (TNF-α) is a potent inflammatory cytokine that can modulate nonspecific inflammation to influence asthma. This study aimed to define the relationship between the TNF gene polymorphism at position -308 and asthma susceptibility, as well as atopic and non-atopic asthma. Using polymerase chain reaction with sequence-specific primers, we investigated genotype frequencies and alleles of a polymorphic gene coding for TNF-α in 86 pediatric patients with asthma and 470 healthy controls of the same race. Seventy-four patients underwent a skin prick test. The homozygous AA variant (-308, rs1800629) was the most common genotype among patients, accounting for 63.3% of all cases. In contrast, homozygous GG (-308) was significantly less prevalent in the patient group compared to the control group. TNF A (-308) allele frequency was 85.5% among asthma patients and 16.6% among healthy controls. The genotype and allele frequencies of TNF (-308 A>G, rs1800629) did not differ between atopic and non-atopic asthma. In conclusion, TNF (-308) AA and AG genotypes are associated with asthma susceptibility in Iranian children, although there was no significant difference in polymorphism between atopic and non-atopic asthma and no difference in asthma severity groups.

Transcription factors (TFs) are critical components involved in regulating immune system development, maintenance, and function. Monogenic defects in certain TFs can therefore give rise to inborn errors of immunity (IEIs) with profound clinical implications ranging from infections, malignancy, and in some cases severe allergic inflammation. This review examines TF defects underlying IEIs with severe atopy as a defining clinical phenotype, including STAT3 loss-of-function, STAT6 gain-of-function, FOXP3 deficiency, and T-bet deficiency. These disorders offer valuable insights into the pathophysiology of allergic inflammation, expanding our understanding of both rare monogenic and common polygenic allergic diseases. Advances in genetic testing will likely uncover new IEIs associated with atopy, enriching our understanding of molecular pathways involved in allergic inflammation. Identification of monogenic disorders profoundly influences patient prognosis, treatment planning, and genetic counseling. Hence, the consideration of IEIs is essential for patients with severe, early-onset atopy. This review highlights the need for continued investigation into TF defects to enhance our understanding and management of allergic diseases.

Background: Asthma affects 10% of pregnancies and may influence offspring health, including infant size and body composition, through hypoxic and inflammatory pathways. Objective: We sought to determine associations between maternal asthma and asthma phenotypes during pregnancy and infant size and body composition. Methods: The B-WELL-Mom study (2015-19) is a prospective cohort of 418 pregnant persons with and without asthma recruited in the first trimester of pregnancy from 2 US obstetric clinics. Exposures were maternal self-reported active asthma (n = 311) or no asthma (n = 107), and asthma phenotypes were classified on the bases of atopy, onset, exercise induced, control, severity, symptomology, and exacerbations. Outcomes were infant weight, length, head circumference, and skinfold measurements at birth and postnatal follow-up, as well as fat and lean mass assessed by air displacement plethysmography at birth. Adjusted multivariable linear regression examined associations of maternal asthma and asthma phenotypes with infant outcomes. Results: Offspring were born at a mean ± SD of 38 ± 2.3 weeks’ gestation and were 18 ± 2.2 weeks of age at postnatal follow-up. Infants of participants with asthma had a mean ± SD fat mass of 11.0 ± 4.2%, birth weight of 3045.8 ± 604.3 g, and postnatal follow-up weight of 6696.4 ± 964.2 g, which were not different from infants of participants without asthma (respectively, β [95% confidence interval]: −0.1 [−1.4, 1.3], −26.7 [−156.9, 103.4], and 107.5 [−117.3, 332.3]). Few associations were observed between asthma or asthma phenotypes and infant size or body composition. Conclusions: In a current obstetric cohort, maternal asthma during pregnancy was not associated with differential infant size or body composition.

Abstract Background Omalizumab is the recommended treatment for antihistamine‐refractory chronic spontaneous urticaria (CSU) and severe allergic asthma. In addition, it has been shown to reduce the frequency of viral respiratory infections in allergic asthma. Respiratory illness is a known trigger for asthma and CSU. Objectives To explore whether the antiviral effect of omalizumab may be extended to CSU patients independent of their atopic status. Methods We conducted a prospective parallel‐group pilot pragmatic trial including 30 non‐allergic and non‐atopic CSU patients (cases) under omalizumab 300 mg Q4‐weeks (due to refractory to H1‐antihistamines) and 30 age‐matched healthy controls. All CSU patients had to have a weekly urticaria activity score UAS7

Abstract Background Atopy varies in people of different ages owing to different physical conditions and exposure to allergens. We aimed to cluster ages based on atopic severity using K‐means cluster analysis and identify atopic incidence, severity, as well as the association among peripheral eosinophils, IgE and sensitisation. Methods Consecutive patients (n = 7654) with allergic symptoms and undergoing allergen‐specific IgE tests were included from 2013 to 2017. Age, sex, specific‐IgE, peripheral eosinophil counts and total‐IgE were collected. Results Five age categories were identified: 1–17, 18–36, 37–52, 53–69 and 70–100 years. The incidences of atopy and poly‐sensitisation decreased with increasing age. Similar trend was observed for aeroallergens, egg and milk but not for peanuts, soy or seafood. Dust mites remain the crucial factor bothering patients with allergic symptoms, especially for children and adolescents. In patients aged

Abstract is missing (Short communication)

Background The skin barrier is important in the pathogenesis of atopic dermatitis and stratum corneum lipids have a critical role. Skin surface lipids have been largely overlooked but also contribute to barrier function. An untargeted approach was used to compare the skin surface lipids from atopic and non-atopic West Highland White terrier dogs (WHWT). Objectives The primary hypothesis was that a difference in the lipidome would exist. The secondary hypothesis was that affected and unaffected skin lipids would differ. Animals and methods This prospective, cross-sectional, case-controlled study included thirty-nine privately owned WHWTs. Dogs were assigned to one of four disease status groups based on strict criteria. Samples for lipid analysis were collected from the skin surface of unaffected and affected sites. Lipid analysis was by untargeted liquid chromatography/mass spectrometry and utilised lipid identification software packages. Principle component analysis (PCA) and partial least-squares discriminant analysis (sPLS-DA) statistical methods analysed the association between the relative lipid abundance and disease status and affected and unaffected skin. Results Samples for lipid analysis found 421 lipid soluble features of which ten lipids were positively identified. Statistical analysis could not distinguish between non-atopic and atopic dogs but did reveal a statistically significant difference in the lipid profiles from affected and non-affected skin irrespective of disease status. Conclusions A large array of unidentified lipids from the skin surface were found with a difference between affected and unaffected skin unrelated to disease status. Investigation into the lipidome of the skin surface is an emerging area of research with clinical and therapeutic applications.

Objective: To assess whether supplementation with long chain n-3 fatty acids during pregnancy, lactation, or infancy reduces the risk of developing asthma or atopic disease during childhood. Methods: Searches were performed in MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus up to 2021-09-20, for randomized controlled trials (RCTs) that investigated the effect of supplemental long chain n-3 fatty acids during pregnancy, lactation, or infancy for the prevention of childhood asthma or allergy. Article selection, data extraction, and risk of bias assessment (Cochrane’s Risk of Bias 2.0) were independently conducted by two assessors. The evidence was synthesized qualitatively according to the criteria of the World Cancer Research Fund and meta-analyzed. Results: A total of nine RCTs met inclusion criteria; six were conducted during pregnancy, two during infancy, and one during both pregnancy and infancy. Meta-analysis showed that long chain n-3 fatty acid supplementation during pregnancy significantly reduced the risk of asthma/wheeze in the child (RR 0.62 [95% confidence interval 0.34–0.91], P = 0.005, I2 = 67.4%), but not other outcomes. Supplementation during lactation of infancy showed no effects on any outcome. The strength of evidence that long chain n-3 fatty acid supplementation during pregnancy reduces risk of asthma/wheeze in the offspring was considered limited – suggestive. No conclusion could be made for the effects of long chain n-3 fatty acid supplementation during pregnancy for other atopic diseases, or for supplementation during lactation or infancy for any outcome. Conclusion: The intake of long chain n-3 fatty acid supplements during pregnancy may reduce the risk of asthma and/or wheeze in the offspring, but the strength of evidence is low. There is inconclusive evidence for the effects of long chain n-3 fatty acid supplements during pregnancy for other outcomes, as well as for supplementation during lactation or infancy.

Himamoni Deka,1 Putul Mahanta,2 Sultana Jesmin Ahmed,3 Madhab Ch Rajbangshi,4 Ranjumoni Konwar,5 Bharati Basumatari5 1Depatment of Anatomy, Gauhati Medical College, Guwahati, Assam, India; 2Department of Forensic Medicine and Toxicology, Assam Medical College, Dibrugarh, Assam, India; 3Department of Community Medicine, Assam Medical College, Dibrugarh, Assam, India; 4Department of Surgery, Tezpur Medical College and Hospital, Tezpur, Assam, India; 5Department of Radiology, Fakhruddin Ali Ahmed Medical College and Hospital, Barpeta, Assam, IndiaCorrespondence: Putul Mahanta, Department of Forensic Medicine and Toxicology, Assam Medical College and Hospital, Dibrugarh, Assam, 786002, India, Tel +919435017802, Email drpmahanta@gmail.comIntroduction: Asthma is a chronic lung illness marked by a reversible airway blockage. Both genetic and environmental factors influence higher asthma rates. The present study aims to assess the various socio-demographic and environmental factors influencing the causation of childhood asthma among patients attending the Paediatric Department of Gauhati Medical College and Hospital (GMCH), Assam.Materials and Methods: A total of 150 clinically diagnosed asthma patients of 3– 12 years as cases and patients of the same age group free from respiratory diseases with no history of asthma in a 1:1 ratio as controls were selected. A predesigned and pretested proforma was used to collect data, and written informed consent was obtained from all the legal guardians of the participants. Data were analyzed by chi-square test and binary logistic regression using SPSS V20, considering a p-value < 0.05 significant.Results: Urban and male children were found to be at higher risk of developing asthma. Children belonging to the urban locality (OR= 4.53; 95% CI: 1.57– 13.09; p< 0.05), damp environment (OR= 5.21; 95% CI: 1.23– 22.10; p< 0.05), lower socioeconomic status (OR= 3.48; 95% CI: 1.34– 9.01; p< 0.05), presence of pets (OR= 6.77; 95% CI: 1.76– 25.99; p< 0.05), family history of atopy/ allergy (OR= 43.29; 95% CI: 5.80– 323.15 p< 0.05), smoking/passive smoking (OR=23.54; 95% CI: 1.41– 394.21 p< 0.05) and mixed feeding (OR= 4.47; 95% CI: 1.46– 13.63 p< 0.05) were the significant risk factors of childhood asthma.Conclusion: Children are vulnerable to environmental-induced asthma. Awareness and preventive measures are necessary to control and reduce the burden of childhood asthma.Keywords: asthma, environmental factors, children, allergy, atopy

Objective: Allergic asthma is the most frequently observed subtype of individuals with asthma. The effects of serotonin plays in the pathophysiology of asthma has not been clearly determined. Thus, this study aimed to investigate the association between the 5HTR2C gene rs 6318 G>C polymorphism and allergic asthma in pediatric patients in Cyprus.

Alopecia areata is an autoimmune disease characterized by non-scarring hair loss with preservation of the hair follicle. Hair loss in alopecia areata can be either focal with the appearance of clearly defined foci of alopecia, or diffuse or complete hair loss in any area of the skin where hair follicles are present. Data on the role of food allergy in the development of alopecia areata and the nature of the sensitization spectrum are extremely scarce. Objective: to study the features of the spectrum of sensitization to food and pollen (cross-reacting) allergens in patients with alopecia areata.The study involved patients with alopecia areata (n = 17), who were divided into groups according to age: group 1 — children (n = 9) and group 2 — adults (n = 8). All patients underwent a specific allergological examination: collection of an allergic history, skin prick testing with food and pollen allergens (Allergopharma, Germany).Analysis of the spectrum of sensitization to food allergens in patients with alopecia areata revealed features depending on their age. Thus, in the group of sick children, the highest frequency of sensitization to whole chicken eggs, food cereals, yeast, soybeans and cow's milk proteins was noted. In the group of sick adults, the most significant food allergens were: egg protein, rye flour, oats. Among the pollen allergens in the first group of patients, the most common allergens were a mixture of weed and grass pollen, in the second group, a mixture of meadow grass pollen. All patients, taking into account allergological testing, were administered an individual elimination diet with the exclusion of causally significant allergens, taking into account crossreacting allergens. The elimination effect was assessed 2 months after the start of the elimination diet. 70% of patients showed a clinical improvement, i.e., the growth of vellus was noted (vellus depigmented hair) in the foci of alopecia, as well as terminal pigmented hair. Complete regression of alopecia foci occurred on average within 3-6 months from the start of therapy.The sensitization to food and pollen (cross-reacting) allergens in patients with alopecia areata and the positive effect of the elimination diet revealed in our study well supports the role of food allergy in the development of this disorder. Therefore, the study of the causal relationship between food allergy and alopecia areata is of particular relevance and creates prerequisites for the discovery of new diagnostic and therapeutic options.

Abstract Background Atopic dermatitis and food allergy are two frequently concomitant manifestations of the presence of atopy. A substantial number of studies have been published on the association of birth order and sibship size (number of siblings) with atopic dermatitis, food allergy, and atopy. The present work is the first systematic synthesis of the existing literature on this topic. Methods Fifteen databases were searched. Screening, data extraction, and quality assessment were performed by independent pairs. Comparable numerical data were statistically synthesized using random‐effects robust variance estimation. Results In total, 114 studies were included out of 8819 papers obtained from database searches. Birth order ≥2 versus 1 was associated with lower risk of ever atopic dermatitis (pooled risk ratio [RR] 0.91, 95% CI 0.84–0.98), current food allergy (RR 0.77, 95% CI 0.66–0.90), and positive skin prick test (SPT) to common aeroallergens (RR 0.86, 95% CI 0.77–0.97). Sibship size ≥2 versus 1 was associated with decreased risk of current atopic dermatitis (RR 0.90, 95% CI 0.83–0.98), ever atopic dermatitis (RR 0.92, 95% CI 0.86–0.97), and positive SPT to common aeroallergens (RR 0.88, 95% CI 0.83–0.92). No putative associations were seen regarding atopy assessed through allergen‐specific immunoglobulin E with common allergens. Conclusion The presence of siblings and being second‐born or later may decrease the lifetime risk of atopic dermatitis and food allergy, albeit marginally. Similar association was seen with SPT sensitization. However, significant protection was not found for IgE sensitization.

IgE antibodies are likely involved in host protection. Trichinella spiralis is a helminth that induces protection through IgE antibodies. The present study examined T. spiralis susceptibility in high and low IgE responder mice, with a specific focus on the inheritance of IgE responsiveness, which controls IgE production specific for the IgE isotype and non-specific for antigens. Furthermore, low IgE responsiveness is inherited as a recessive trait under a single gene, which is not linked to the H-2 gene. This study determined the total IgE and anti-T. spiralis IgE antibody levels after T. spiralis infection in low IgE responder SJL/J mice were several times lower than those in high IgE responders, such as the BALB/c mice. An IgE-dependent susceptibility to T. spiralis, evaluated in mice treated with anti-IgE antibodies and in control mice, was observed in high IgE responder mice but not in low IgE responder mice. The inheritance of IgE responsiveness and susceptibility to T. spiralis was investigated using crosses of SJL/J with high IgE responders. All of the (BALB/c × SJL/J) F1 and half of the (BALB/c × SJL/J) F1 × SJL backcross progenies were high IgE responders after T. spiralis infection. Total IgE and antigen-specific IgE antibody levels were correlated and not linked to H-2. It should be noted that high IgE responders always exhibited low susceptibility, suggesting that the trait of IgE responsiveness functions as a trait of susceptibility to T. spiralis.

The aim Violation of the epidermal barrier can lead to percutaneous sensitization to microbial products or allergens. The interaction between the yeast Malassezia and the skin's immune system contributes to skin inflammation in patients with atopic dermatitis. The aim of this study was to determine the sensitization to the molecular components of the yeast Malassezia (Mala s 5, Mala s 6, Mala s 11) in children with atopy. Methods The study included 333 children aged 1 to 18 with atopy, with symptoms of bronchial obstruction, allergic rhinitis, atopic dermatitis or urticaria. All patients / parents gave informed consent to participate. Spearman's rank test (ρ) was used to assess the correlation between total sIgE, specific sIgE, and age. Results Among 333 children with atopy, specific IgE to Mala s 5 was detected in 20.1 % children, to Mala s 6 in 64.6 %, and to the allergen Mala s 11 in 23.1 % children. The level of antibodies to Mala s 5 and Mala s 6 correlate with total serum IgE (ρ = 0.161 and ρ = 0.112, respectively). The correlation was also found between the level of specific IgE to Mala s 11 and to Mala s 6 (ρ = -0.351), and Mala s 5 and Mala s 6 (ρ = -0.490). Correlation of specific IgE and age was detected for the molecular component Mala s 6 (ρ = -0.126). Conclusions Sensitization to the molecular components of yeast (Mala s 5, Mala s 6, Mala s 11) was quite common among children with allergic diseases. Sensitization to Mala s 6 was most common in children. The highest values of sIgE were observed for Mala s 11 ‒ in 23.9% of patients. For future clinical trials, it is important to consider intrapersonal anatomical variations in skin microbiota, individual susceptibility, sex, age, seasonality, and ethnicity.

IntroductionUnder homeostatic conditions, esophageal epithelium displays a proliferation/differentiation gradient that is generated as proliferative basal cells give rise to suprabasal cells then terminally differentiated superficial cells. This proliferation/differentiation gradient is often perturbed in esophageal pathologies. Basal cell hyperplasia may occur in patients with gastroesophageal reflux disease (GERD), a condition in which acid from the stomach enters the esophagus, or eosinophilic esophagitis (EoE), an emerging form of food allergy. While GERD is a primary risk factor for esophageal cancer, epidemiological data suggests that EoE patients do not develop esophageal cancer.MethodsIn order to investigate the impact of EoE and esophageal cancer specifically on the cellular landscape of esophageal epithelium, we perform single cell RNA-sequencing in murine models of EoE and esophageal cancer, specifically esophageal squamous cell carcinoma (ESCC). We further evaluate modules of co-expressed genes in EoE- and ESCC-enriched epithelial cell clusters. Finally, we pair EoE and ESCC murine models to examine the functional relationship between these pathologies.ResultsIn mice with either EoE or ESCC, we find expansion of cell populations as compared to normal esophageal epithelium. In mice with EoE, we detect distinct expansion of 4 suprabasal populations coupled with depletion of 2 basal populations. By contrast, mice with ESCC display unique expansion of 2 basal populations and 1 suprabasal population, as well as depletion of 2 suprabasal populations. Senescence, glucocorticoid receptor signaling, and granulocyte-macrophage colony-stimulating factor pathways are associated with EoE-enriched clusters while pathways associated with cell proliferation and metabolism are identified in ESCC-enriched clusters. Finally, our in vivo data demonstrate that exposure to EoE inflammation limits tumor burden of esophageal carcinogenesis.DiscussionOur findings provide the first functional investigation of the relationship between EoE and esophageal cancer and suggest that esophageal epithelial remodeling events occurring in response to EoE inflammation may limit esophageal carcinogenesis. This investigation may have future implications for leveraging allergic inflammation-associated alterations in epithelial biology to prevent and/or treat esophageal cancer.

BackgroundDifferences in bronchial microbiota composition have been found to be associated with asthma; however, it is still unclear whether these findings can be applied to recurrent wheezing in infants especially with aeroallergen sensitization.ObjectivesTo determine the pathogenesis of atopic wheezing in infants and to identify diagnostic biomarkers, we analyzed the bronchial bacterial microbiota of infants with recurrent wheezing and with or without atopic diseases using a systems biology approach.MethodsBacterial communities in bronchoalveolar lavage samples from 15 atopic wheezing infants, 15 non-atopic wheezing infants, and 18 foreign body aspiration control infants were characterized using 16S rRNA gene sequencing. The bacterial composition and community-level functions inferred from between-group differences from sequence profiles were analyzed.ResultsBoth α- and β-diversity differed significantly between the groups. Compared to non-atopic wheezing infants, atopic wheezing infants showed a significantly higher abundance in two phyla (Deinococcota and unidentified bacteria) and one genus (Haemophilus) and a significantly lower abundance in one phylum (Actinobacteria). The random forest predictive model of 10 genera based on OTU-based features suggested that airway microbiota has diagnostic value for distinguishing atopic wheezing infants from non-atopic wheezing infants. PICRUSt2 based on KEGG hierarchy (level 3) revealed that atopic wheezing-associated differences in predicted bacterial functions included cytoskeleton proteins, glutamatergic synapses, and porphyrin and chlorophyll metabolism pathways.ConclusionThe differential candidate biomarkers identified by microbiome analysis in our work may have reference value for the diagnosis of wheezing in infants with atopy. To confirm that, airway microbiome combined with metabolomics analysis should be further investigated in the future.