Total IgE Levels Research Articles

Omalizumab reduces anaphylactic reactions and allows food introduction in food-allergic in children with severe asthma: An observational study.

In Europe, Omalizumab (anti-IgE) is indicated for the treatment of moderate to severe asthma, but not for IgE-mediated food allergy (FA). We assessed the impact of Omalizumab on efficacy, safety, and quality of life (FA-QoL) in patients with moderate to severe asthma and who have a history of anaphylaxis to peanut, tree nuts, fish, egg, milk, and/or wheat. Food-allergic children (6-18 years) with moderate to severe asthma underwent oral food challenges (OFCs) to establish the threshold of reaction to the culprit food(s) at baseline (T0) and at 4-month intervals (T1, T2, and T3) during their first year of treatment with Omalizumab. We recorded the number and severity of food-allergic reactions, Asthma Control Test (ACT) scores, FA-QoL, and total IgE levels. In 65 patients allergic to 107 foods, the No Observed Adverse Events Level (NOAEL) at T1 increased: 243- and 488-fold for fresh and baked milk, respectively; 172- and 134-fold for raw and baked egg; 245-fold for hazelnut; 55-fold for peanut; 31-fold for wheat; and 10-fold for fish. Full tolerance was achieved in 66.4% of OFCs at T1, 58.3% at T2, and 75% at T3. Ninety-five foods were liberalized in the diet of 55 patients; the remaining 12 were introduced by 10 patients at least in traces. Throughout the study, 40 out of 65 were able to get a free diet. ACT increased from 17 (Q1-Q3: 15-17) to 23.6 (Q1-Q3: 23-25). The FA-QoL score in children ≤12 years decreased from 4.63 ± 0.74 to 2.02 ± 1.13, and in adolescents from 4.68 ± 0.92 to 1.90 ± 1.50. During Omalizumab therapy, a safe reintroduction of allergenic foods is feasible. ClinicalTrials.gov, NCT06316414.

Real-world phenotyping and risk assessment of childhood asthma burden using national registries

BackgroundPhenotype classification contributes to risk assessment of asthma. Previous studies have applied this concept primarily to adult populations and in the setting of research protocol assessments which may not be applicable to clinical settings. ObjectiveExploring the value of routinely collected clinical data for phenotype classification and risk assessment of childhood asthma. MethodsUsing hospital and laboratory data, 29,851 children in a Danish nationwide database aged 2–17 years with ICS-treated asthma in 2015 followed for two years (730 days) were classified to have T2 (elevated blood eosinophils (>300 cells/μL) and/or elevated total- or specific-IgE), and/or non-T2 risk factors (in utero tobacco exposure and/or severe viral infections). Logistic regression was applied to quantify associations of risk factors with asthma severity, control, and exacerbation risk. ResultsIn a complete case analysis, 85.8 % children had at least one T2 risk factor and 29.3 % had mixed T2/non-T2 risk factors. Elevated blood eosinophils and total/specific IgE were associated with exacerbations (ORs 1.55 (1.38–1.73) and 1.41 (1.20–1.66) and higher asthma severity (1.42 (1.24–1.63) and 1.31 (1.08–1.60)), respectively.Dose-dependency was observed between blood eosinophil counts, total IgE levels, and risk of adverse outcomes. Furthermore, accumulation of risk factors demonstrated an increasing risk, with children with all four risk factors having a high risk of any adverse asthma-related outcome (OR 3.13 (2.03–4.82) ConclusionAsthma phenotypic markers defined in research protocols can be reliably applied in real-world settings by utilizing data collected during routine clinical care and enable better classification of risk of adverse asthma outcomes.

Factors Associated With Dupilumab Response in Atopic Dermatitis: A Systematic Review and Meta-Analysis

BackgroundDupilumab was approved for treating moderate-to-severe atopic dermatitis (AD). However, a notable subset of patients remains unresponsive and factors associated with dupilumab response are still limited. ObjectiveTo systematically review and establish factors related to dupilumab response in AD. MethodsWe searched electronic databases, including PubMed/MEDLINE, Embase, Ovid and the Cochrane Center of Controlled Trials, from inception to March 2023. The primary outcome was factors linked to dupilumab response in AD. The odds ratio (OR) and 95% confidence interval (CI) related to a 75% reduction at 12-16 weeks in Eczema Area and Severity Index (EASI) score were synthesized using random-effects meta-analysis. ResultsOf 21 studies involving 5,575 AD patients, 3 were post hoc analyses of phase 3 dupilumab studies, 12 were retrospective, and 6 were prospective studies. Factors associated with favorable responses to dupilumab, defined by the percentage of patients achieving EASI75 at 12-16 weeks, included female with the OR (95% CI) of 2.16 (1.38, 3.38), younger age 2.81 (1.64, 4.81), absence of allergic rhinitis 2.64 (1.07, 6.50), lower body mass index 1.97 (1.18, 3.30), and lower blood eosinophil count 6.47 (3.36, 12.48), with very low certainty of evidence. Age of onset, baseline EASI score, total IgE level, and serum lactate dehydrogenase level were unrelated to dupilumab response. ConclusionFemale, younger age, absence of allergic rhinitis, lower BMI, and lower blood eosinophil count were associated with favorable response to dupilumab in patients with AD. These factors should be taken into account when considering dupilumab therapy in clinical practice.

The triple radiologic asthma phenotype is associated with worse disease control

BackgroundEfforts have been made to combine radiographical biomarkers such as bronchiectasis or bronchial wall thickness (BWT) to identify asthma sub-phenotypes and their clinical implications. ObjectiveTo assess whether a composite triple radiological phenotype measured by high resolution computed tomography comprising BWT, mucus plug score (MPS) and mediastinal lymph node (MLN) size might provide a better insight into sub-phenotypes in persistent asthma. MethodsOne hundred and twelve patients with moderate-to-severe asthma were included in this retrospective observational study. A binary method was used to classify patients according to median values for: pooled MLN≥3.6mm; BWT as pooled wall area ≥50% of the total airway area; and MPS≥1 where a mucus plug was considered positive if complete bronchial obstruction was imaged more than 2 cm from a pleural surface. ResultsPatients with the triple imaging phenotype exhibited significantly worse asthma control questionnaire scores exceeding minimal clinical important difference, a higher prevalence of concomitant chronic rhinosinusitis with nasal polyposis and a greater total IgE level. ConclusionWe have demonstrated an association between poorer symptom control and the triple radiological asthma phenotype.

Prognostic value of serum total IgE and FeNO levels in children with atopic constitution bronchiolitis

Bronchiolitis is a significant factor contributing to bronchial asthma in infants and young children. After treatment, recurrent wheezing symptoms often occur, especially in children with atopic constitution, who tend to have more severe conditions and poorer prognosis. Therefore, exploring the prognostic value of total serum immunoglobulin E (tIgE) and fractional exhaled nitric oxide (FeNO) levels in children with atopic constitution who suffer from bronchiolitis is of great significance. A total of 260 children with bronchiolitis admitted to our hospital from October 2020 to June 2022 were regarded as the research subjects with prospective study, according to whether the children had atopic constitution, they were grouped into non atopic constitution group (n = 156) and atopic constitution group (n = 104); after 6 months of treatment, children with atopic constitution were grouped into a good prognosis group (n = 58) and a poor prognosis group (n = 46) based on their prognosis; in addition, 260 healthy children who underwent physical examination and had clinical data consistent with those of children with bronchiolitis were regarded as the reference group. The serum tIgE and FeNO levels of each group were compared; multivariate Logistic regression was applied to analyze the prognostic factors of children with atopic constitution bronchiolitis; ROC curve was applied to analyze the predictive value of tIgE and FeNO levels after treatment for the prognosis of children with atopic constitution bronchiolitis. The tIgE levels in the control group, non-atopic group, and atopic group [(123.54 ± 29.62) IU/mL, (245.71 ± 30.59) IU/mL, (316.46 ± 31.78) IU/mL, respectively] increased sequentially, with statistically significant differences (F = 1766.954, P = 0.000). The FeNO levels in the control group, non-atopic group, and atopic group [(8.36 ± 3.57) ppb, (15.28 ± 3.69) ppb, (19.84 ± 3.58) ppb, respectively] also increased sequentially, with statistically significant differences (F = 765.622, P = 0.000). The tIgE, FeNO, proportion of patients with asthma family history, and proportion of patients with allergic family history in the poor prognosis group were obviously higher than those in the good prognosis group (P < 0.05). Multivariate Logistic regression analysis showed that family history of asthma, family history of allergies, tIgE, and FeNO were influencing factors for the prognosis of children with atopic bronchiolitis (P < 0.05). The AUC of the combination of tIgE and FeNO in predicting the prognosis of children with atopic constitutional bronchiolitis was 0.910, with a sensitivity of 78.26% and a specificity of 93.10%, which was superior to the independent prediction of tIgE and FeNO (Zcombined detection−tIgE = 2.442, Zcombined detection−FeNO = 3.080, P = 0.015, 0.002). The levels of tIgE and FeNO in children with atopic constitution bronchiolitis are obviously increased, and the combination of the two has high predictive value for the prognosis of atopic constitution bronchiolitis.

Preventive and Therapeutic Effects of Lactiplantibacillus plantarum HD02 and MD159 through Mast Cell Degranulation Inhibition in Mouse Models of Atopic Dermatitis.

As the relationship between the gut microbiome and allergies becomes better understood, targeted strategies to prevent and treat allergies through gut microbiome modulation are being increasingly developed. In the study presented herein, we screened various probiotics for their ability to inhibit mast cell degranulation and identified Lactiplatibacillus plantarum HD02 and MD159 as effective candidates. The two strains significantly attenuated vascular permeability induced by mast cell degranulation in a passive cutaneous anaphylaxis (PCA) model and, in the MC903-induced murine atopic dermatitis (AD) model, demonstrated comparable preventive effects against allergies, reducing blood levels of MCPT-1 (mast cell protease-1) and total IgE. In the house dust mite (HDM)-induced murine AD model, both L. plantarum HD02 and MD159 showed therapeutic effects, with L. plantarum HD02 demonstrating superior efficacy. Nevertheless, L. plantarum MD159 better suppressed transepidermal water loss (TEWL). Furthermore, L. plantarum HD02 and MD159 significantly increased the number of splenic Foxp3+ regulatory T cells, with L. plantarum MD159 having a more pronounced effect. However, only L. plantarum HD02 achieved a reduction in immune cells in the draining lymph nodes. Our findings highlight L. plantarum HD02 and MD159 as promising candidates for the prevention and treatment of allergies, demonstrating significant efficacy in suppressing mast cell degranulation, reducing the number of allergy biomarkers, and modulating immune responses in experimental models of AD. Their distinct mechanisms of action suggest potential complementary roles in addressing allergic diseases, underscoring their therapeutic promise in clinical applications.

Changes in Circulating CD44+CD62L− Treg Subsets and CD44−CD62L+ Treg Subsets Reflect the Clinical Status of Patients with Allergic Rhinitis

Introduction: This study clarified the expression changes and clinical significance of CD44+CD62L− Treg and CD44−CD62L+ Treg subsets in the peripheral blood of patients with allergic rhinitis (AR). Methods: The peripheral blood of 39 patients with AR and 42 healthy controls was collected. Clinical data, such as sex, age, IgE titer, allergen screening information and visual analogue scale (VAS) score, were recorded. Changes in serum IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ were detected using the cytometric bead array method. Flow cytometry was used to detect the proportions of Th1, Th2, Th17, TFH, and Th9 cells and the proportions of CD44+CD62L− Treg and CD44−CD62L+ Treg subsets. Correlation analysis was performed between the CD44+CD62L− Treg subsets and the CD44−CD62L+ Treg subsets with clinical indicators (VAS score, total IgE titer), cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ), and Th1/Th2/Th17/TFH/Th9 cell proportions. Results: Compared to the control group, the proportion of total Treg cells and CD44+CD62L− Treg cells in the AR group decreased, and the proportion of CD44−CD62L+ Treg cells increased (p < 0.05). The proportions of CD44+CD62L− Treg cells significantly negatively correlated with Th2 cells (R = −0.5270, p < 0.05) and positively correlated with Treg cytokine IL-10 (R = 0.6447, p < 0.05). In addition, CD44+CD62L− Treg cells negatively correlated with the VAS score (R = −0.4956, p < 0.05), total IgE level (R = −0.4177, p < 0.05) and Th2 cytokine IL-6 level (R = −0.3034, p < 0.05) but positively correlated with the Th1 cytokine IL-2 (R = 0.4331, p < 0.05). In contrast, the proportion of CD44+CD62L− Treg cells significantly positively correlated with the Th2 cells (R = 0.6187, p < 0.05). Moreover, the proportion of CD44−CD62L+ Treg cells positively correlated with the VAS score (R = 0.4060, p < 0.05), total IgE level (R = 0.5224, p < 0.05) and Th2 cytokine IL-4 (R = 0.2647, p < 0.05) and IL-6 levels (R = 0.3824, p < 0.05) but negatively correlated with Th1 cytokine IL-2 (R = −0.3451, p < 0.05) and IL-10 (R = −0.3277, p < 0.05). Conclusion: A greater proportion of CD44+CD62L− Tregs correlated with better reversal of the Th1/Th2 imbalance and milder clinical symptoms in AR patients. The presence of more CD44−CD62L+ Tregs correlated with a weaker immunosuppressive effect on Th2 cells and more severe clinical symptoms in AR patients. These findings provide new perspectives for the treatment and disease monitoring of AR.

Venom immunotherapy in clinical practice: comparison of two ultra-rush protocols.

Background. Ultra-rush venom immunotherapy protocols have shown to be a safe and effective approach to prevent the occurrence of systemic reactions after hymenoptera stings. The aim was to describe our experience with two ultra-rush protocols - a five-step with 1 µg starting dose and a six-step with 0.1 µg starting dose, as well as to compare their safety profile. Methods. This is a retrospective study of all the patients who underwent VIT with honey bee or wasp venom between January 2008 and December 2021, in our department. Results. A total of 110 patients was included, with 109 patients (99%) completing the protocol. A total of 63 (57%) patients had no local or systemic reactions. Most systemic reactions occurred with 20 µg or higher doses (24, 83%). There were no documented grade IV systemic reactions (Mueller grading). No differences were found in local or systemic reactions regarding sex, atopy, β-blocker medication, the severity of the index reaction, ID test positivity, levels of total IgE, specific IgE and tryptase (all p > 0.05). Younger age, treatment with bee VIT or being a beekeeper were associated with more systemic reactions (p = 0.035, 0.006 and 0.047, respectively). No statistical differences in the number of local and systemic reactions were found when comparing both protocols (p = 1.000). Conclusions. Ultra-rush protocols are safe and effective, but systemic reactions are to be expected, especially with honeybee. Our data supports that ACE inhibitors do not compromise safety. Beginning with 1 µg is safe and can save time and resources.

Allergo-immunopathology mechanism of thymol-inhibiting airway remodeling in asthmatic mice by regulating TGF-β/Smad3 pathway.

Allergic asthma is an important public health problem and is a complicated respiratory sickness that is characterized by bronchial inflammation, bronchoconstriction, and breathlessness. Asthma is orchestrated by type 2 immune response and remodeling is one of the important outputted problem in chronic asthma. Thymol is a naturally occurring monocyclic phenolic, it has a series of biological properties, and its immunomodulatory and anti-remodeling effects on allergic asthma were evaluated. The OVA-LPS-induced asthmatic mice were treated with thymol. Methacholine challenge test, eosinophil count, and levels of IL-4, IL-5, IL-13, and IL-33 in bronchoalveolar lavage fluid, total and OVA-specific IgE levels in serum, remodeling factors, gene expression of TGF-β, Smad2, Smad3, and lung histopathology were done. Treatment with thymol could control AHR, eosinophil percentage levels of Th2 cytokines and Igs, remodeling factors, expression of TGF-β, Smad2 and Smad3 genes, inflammation, goblet cell hyperplasia, and mucus production in asthmatic mice. Thymol can control asthma pathogens and related remodeling and fibrosis bio-factors and can be a potential treatment of asthma.

Gynostemma pentaphyllum saponins shield mice from peanut allergy by modulation of gut microbiota: A novel approach for peanut allergy management

BackgroundFood allergies, particularly peanut (PN) allergies, are a growing concern, with fatal anaphylaxis incidents often reported. While palforzia is the sole FDA-approved drug for managing PN allergies, it is not universally effective. PurposeThis study aimed to investigate the potential of Gynostemma pentaphyllum saponins (GpS) as a novel therapeutic agent for PN allergy through modulation of gut microbiota, addressing the limitations of current treatments. MethodsTo elucidate the role of GpS on peanut allergy, we first built a PN-sensitized C57BL/6J model mice. Through comprehensive sequencing analysis, we identified Parabacteroides distasonis as a key bacterium triggering PN sensitization. Employing the same mouse model, GpS was evaluated for its effects on anaphylactic symptoms, serum immunoglobulin levels, and allergy-related biomarkers. 16S rRNA sequencing and transcriptomic analysis were applied to investigate the impact of GpS on the host's gut epithelium and microbiome. ResultsGpS treatment effectively reduced anaphylactic symptoms in PN-sensitized mice, as shown by decreased IgG1, total IgE, and PN-specific IgE levels. It also modulated the immune response by suppressing proinflammatory cytokines (IL-1β, IFN-γ, IL-21) and chemokines (CCL5, CCL12, CCL17, CCL22), while enhancing anti-inflammatory cytokines (IL-4, IL-10, IL-12, IL-13). Fecal microbial transplant from GpS-treated Model mice to PN-sensitized mice displayed anti-peanut allergy effects. Additionally, the administration of GpS-enhanced bacteria (Clostridium aldenese or Lactobacillus murinus), alleviated anaphylactic symptoms and reduced serum allergy markers in PN-sensitized mice. ConclusionTo conclude, we revealed the intestinal environment, signaling molecules, mucosal cytokines, and commensal microbial profiles in the peanut-sensitized mouse model. We further presented evidence for the protective effect of GpS against PN allergen sensitization by downregulating a series of food-allergy-associated biomarkers and cytokines via the modulation of gut bacteria. More importantly, supported by both in vitro and in vivo experiments, we demonstrated that the protective effect of GpS against PN-allergy is through the enhancement of two commensal bacteria, Clostridium aldenese, and Lactobacillus murinus.

Anti-Allergic and Anti-Inflammatory Effects of Lidocaine-Derived Organic Compounds in a House Dust Mite-Induced Allergic Rhinitis Mouse Model.

Allergic rhinitis (AR) is a common chronic disease that significantly impacts the quality of life. Lidocaine is known to have anti-inflammatory and immunomodulatory effects. This study evaluated the effect of lidocaine analogs in a Dermatophagoides pteronyssinus (DP)-induced AR mouse model. An AR model was developed using BALB/c mice via intraperitoneal sensitization with DP and intranasal challenge with DP. One hour before stimulation with DP, lidocaine analogs, EI137 and EI341 (at a dose of 0.5 or 5 ug/g), were administered intranasally. Nasal symptoms and serum total IgE, interleukin (IL)-4, IL-10, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α levels were evaluated. Reverse-transcription polymerase chain reaction was used to determine IL-4, IL-10, and IFN-γ, as well as the expression of their mRNA transcription factors in the sinonasal mucosa. Histologic changes were evaluated using hematoxylin and eosin and periodic acid-Schiff staining. The DP-induced AR mouse model had increased serum levels of total IgE and cytokines. EI137 and EI341 significantly suppressed the levels of total IgE, IL-4, and TNF-α. Intranasal instillation of EI137 and EI341 significantly inhibited IL-4, IL-10, and IFN-γ mRNA expression, as well as inflammatory cells and mucus-producing goblet cells. Lidocaine analogs also suppressed DP-stimulated IL-4, IFN-γ, and IFN-γ production by splenocytes. Intranasal instillation of EI137 and EI341 exhibited anti-allergic and anti-inflammatory effects, influenced by Th1 and Th2 inflammatory cytokines. These lidocaine analogs suppressed DP-induced sinonasal mucosal inflammation, inflammatory cell infiltration, and mucus hypersecretion.

Study of the role of genes involved in the metabolism of histamine in the development of allergic respiratory diseases

The interaction of genetic, epigenetic and environmental factors underlies the pathogenesis of allergic diseases. Allergic rhinitis and atopic bronchial asthma are closely related and often concurrent respiratory allergic diseases. The chronic recurrent course of these diseases establishes the importance of further and more profound studies of the mechanisms underlying the development of these pathologies. Histamine is one of the most significant inflammatory mediators secreted during allergic reactions. The aim of the research was to study the role of polymorphic variants of AOC1, HRH2, HRH3, ALDH7A1, ADCYAP1, HNMT, PSAP, SCG3, genes involved in the histamine metabolism in the development of different endophenotypes of the allergic airway diseases in individuals living in the Republic of Bashkortostan. DNA samples of 358 individuals with allergic diseases of the respiratory tract of different ethnicity (Russians – 165, Tatars – 143, Bashkirs – 50) and 200 controls with unweighted heredity in allergic diseases (Russians – 75, Tatars – 83, Bashkirs – 42). Genotyping of polymorphic variants was performed by real-time PCR and PCR-RFLP analysis. It was revealed that the rs104979793*CC genotype and the rs104979793*C allele of the AOC1 gene were associated with allergic diseases of the respiratory tract and asthma with concomitant allergic rhinitis in Russians. A significant increase of total IgE level was revealed in Russian patients with allergic diseases of the respiratory tract with the rs1049793*CC genotype of the AOC1 gene compared to carriers of the rs1049793*CG and rs1049793*GG genotypes. The association of the C allele of the rs17525472 polymorphic variant localized near the SCG3 gene with allergic rhinitis in Russians was established. The results revealed that AOC1 and SCG3 genes involved in the metabolism of histamine are related to the development of different endophenotypes of airway diseases in children.

The function and mechanism of Human nasal mucosa-derived mesenchymal stem cells in allergic rhinitis in mice.

To investigate the immunomodulatory effects and potential mechanisms of human nasal mucosa-derived mesenchymal stem cells(hNMSCs) on mouse allergic rhinitis, and to compare them with human umbilical cord-derived mesenchymal stem cells (hUCMSCs). hNMSCs and hUCMSCs were isolated and cultured for identification from human nasal mucosa and umbilical cord tissues. A co-culture system of LPS-stimulated RAW264.7 cells/mouse peritoneal macrophages and MSCs was employed.Changes in inflammatory factors in RAW264.7 cells and the culture medium as well as the expression of NF-κB signaling pathway in RAW264.7 cells were detected. Forty-eight BALB/c mice were randomly divided into control, OVA, hNMSCs, and hUCMSCs groups. An allergic rhinitis (AR) model was established through ovalbumin (OVA) stimulation and treated with hNMSCs and hUCMSCs. Subsequent assessments included related symptoms, biological changes, and the expression of the NF-κB signaling pathway in the nasal mucosa of mice. MSCs can be successfully isolated from human nasal mucosa. Both hNMSCs and hUCMSCs interventions significantly reverseed the inflammation induced by LPS and suppressed the upregulation of the NF-κB signaling pathway in RAW264.7 cells. Treatment with hNMSCs and hUCMSCs alleviated mouse allergic symptoms, reduced levels of total IgE, OVA-specific IgE and IgG1 in mouse serum, TH2-type cytokines and chemokines in mouse nasal mucosa, and TH2-type cytokines in mouse spleen culture medium, while also inhibiting the expression of the NF-κB signaling pathway in the nasal mucosa of mice. moreover, the hNMSCs group showed a more significant reduction in OVA-specific IgG1 in serum and IL-4 expression levels in mouse spleen culture medium compared to the hUCMSCs group. Our findings suggest that hNMSCs can ameliorate allergic rhinitis in mice, with a certain advantage in anti-inflammatory effects compared to hUCMSCs. The NF-κB pathway is likely involved in the anti-inflammatory regulation process by hNMSCs.Therefore, hNMSCs might represent a novel therapeutic approach for allergic rhinitis.

The impact of adverse reactions on adherence to sublingual immunotherapy for Japanese cedar pollinosis and house dust mite allergy in Japan

Background Allergen immunotherapy is the only treatment that can achieve remission for allergic diseases. Aims/Objectives To investigate the three-year adherence to sublingual immunotherapy for Japanese cedar pollinosis and house dust mite allergy at a clinic in Japan and identify factors that influence adherence and severe adverse reactions. Material and Methods In total, 174 patients aged 12 years or older who started sublingual immunotherapy for Japanese cedar pollinosis (n = 72), house dust mite allergy (n = 55), or both (n = 47) between May 2017 and June 2018. Patient age, sex, type of pharmacotherapy used, adverse reactions, blood test results, and duration of continuous treatment were investigated. Results The three-year treatment continuation rate was 40.8%. Adverse reaction rates were 12.6% for cedar pollinosis and 40.2% for house dust mite allergy. Patients with dose reductions due to severe reactions had lower first-year continuation rates. In the MITICURE® group, patients with severe reactions had significantly higher serum total IgE levels. Severe reactions were more common in MITICURE® patients with seven or more positive antigen types. Conclusions and Significance Severe adverse reactions reduced early adherence.

Частота выявления и структура глютензависимых заболеваний среди гастроэнтерологических пациентов детского возраста Республики Узбекистан (когортное проспективное исследование)

Gluten-related disorders (GRDs) are characterized by different pathogenetic development pathways though are having similar clinical manifestations that make its differential diagnosis rather difficult. In the bibliographical sources available currently there were no research works such as a one-time study of the GRDs’ incidence among children. The purpose of this research was to determine the incidence and clinical and laboratory features of celiac disease (CeD), wheat allergy (WA) and non-celiac gluten sensitivity (NCGS) among children with gastroenterological complaints residing in Uzbekistan. Materials and methods used: a single-center cohort prospective study had been carried out in 2021-2022 on the basis of the Uzbekistan Republican Specialized Scientific and Practical Medical Center for Pediatrics of the Ministry of Healthcare of Uzbekistan (Tashkent, Uzbekistan) with 336 children with suspected gluten intolerance aged from 1 to 16 y/o who participated in the study. At the first stage 206 were selected after a short questionnaire developed by the Authors. For the following stage the specific laboratory tests were performed as follows: determination of antibodies (AT) to tissue transglutaminase IgA and total IgA (AT to tissue transglutaminase IgG, total IgG and IgM in IgA deficiency cases), total and specific IgE levels to wheat and gluten, HLA class II genotyping, histological examination of a biopsy specimen of the mucous membrane of the subbulbic part of the duodenum based on indications. The Salerno criteria were used to confirm the NCGS diagnosis. Results: the GRDs incidence among the studied cohort was 17.5% (95% CI: 12.29; 22.6), of which 5.3% (95% CI: 2.27; 8.41) had CeD, 7,3% (95% CI: 3.73; 10.83) had WA and 4.9% (95% CI: 1.92; 7.89) were diagnosed with NCGS. The most significant symptoms in children with GRDs were bloating, diarrhea and abdominal pain. The leading symptom for NCGS was headache. Allergic pinpoint rash with scratching traces were detected in patients with WA. Conclusion: this research was the first to study the GRDs incidence in Central Asia and it had showed that CeD and WA are pretty common among children with gastroenterological complaints in Uzbekistan and that the NCGS incidence does correspond to the average statistical data published priorly.

Heterogeneous IL-9 Production by Circulating Skin-Tropic and Extracutaneous Memory T Cells in Atopic Dermatitis Patients.

Interleukin (IL)-9 is present in atopic dermatitis (AD) lesions and is considered to be mainly produced by skin-homing T cells expressing the cutaneous lymphocyte-associated antigen (CLA). However, its induction by AD-associated triggers remains unexplored. Circulating skin-tropic CLA+ and extracutaneous/systemic CLA- memory T cells cocultured with autologous lesional epidermal cells from AD patients were activated with house dust mite (HDM) and staphylococcal enterotoxin B (SEB). Levels of AD-related mediators in response to both stimuli were measured in supernatants, and the cytokine response was associated with different clinical characteristics. Both HDM and SEB triggered heterogeneous IL-9 production by CLA+ and CLA- T cells in a clinically homogenous group of AD patients, which enabled patient stratification into IL-9 producers and non-producers, with the former group exhibiting heightened HDM-specific and total IgE levels. Upon allergen exposure, IL-9 production depended on the contribution of epidermal cells and class II-mediated presentation; it was the greatest cytokine produced and correlated with HDM-specific IgE levels, whereas SEB mildly induced its release. This study demonstrates that both skin-tropic and extracutaneous memory T cells produce IL-9 and suggests that the degree of allergen sensitization reflects the varied IL-9 responses in vitro, which may allow for patient stratification in a clinically homogenous population.

High-altitude speleotherapy in the treatment of bronchial asthma

The present study concerns clinical effects of speleotherapy in bronchial asthma. The aim of our work was to study the efficiency of speleotherapy in a group of patients with bronchial asthma. We observed a group of 51 patients with bronchial asthma (BA) aged 18 to 50 years, who received a course of treatment at the private center “Solevik” (Yakutsk City), carried out at the Department of Allergology and Immunology. All the examined patients were diagnosed with atopic bronchial asthma, of moderate severity. Basic therapy in all cases included Symbicort and Seretide treatment. The patients were managed and monitored before and after the course of treatment by a therapist, pulmonologist and allergologist-immunologist at the outpatient center. Laboratory parameters included general blood tests and the levels of total serum IgE. Examination of patients after a course of speleotherapy revealed disappearance and reduction of asthma attacks (up to 1 attack per month) in 80% of the examined. General blood testing before and after speleotherapy showed decreased levels of blood eosinophils after the course of treatment. I.e., the average initial level of blood eosinophils before treatment was 12±0.4%, being decreased after the course of speleotherapy to 5.5±0.2%. Measurements of total IgE before and after speleotherapy revealed the following results: in patients before therapy, the average level of this index was 500±0.8 units/mL. After a course of speleotherapy, this parameter decreased to 80±0.3 units/ mL. Speleotherapy shows a positive effect on the clinical course of the patients with bronchial asthma and significantly increases the efficiency of treatment.

Efficacy and safety of dupilumab in the treatment of moderate to severe atopic dermatitis

Objective: To analyse the efficacy and safety of dupilumab in the treatment of moderate to severe atopic dermatitis (AD). Methods: The clinical data of moderate to severe AD patients who received dupilumab therapy in the Department of Dermatology, Xiangya Hospital, Central South University from August 2020 to November 2022 were retrospectively analyzed. The efficacy was evaluated by Eczema Area and Severity Index (EASI), SCORing Atopic Dermatitis (SCORAD), Numerical Rating Scale (NRS), Patient Oriented Eczema Measure (POEM), and Dermatology Quality of Life Index (DLQI) before treatment and 2, 4, 16 and 24 weeks after treatment. Adverse events that occurred during treatment were recorded. Repeated Measures ANOVA and Generalized Estimating Equations were used to compare changes in scores and changes in laboratory indices at different time points before and after treatment. Results: The age of 259 patients was (35.4±25.9) years, the duration of AD was 4.00 (2.00, 9.00) years, and 64.1% (166 patients) were men patients. The scores of EASI, SCORAD, POEM, DLQI and NRS at 2, 4, 16 and 24 weeks after treatment with dupilumab were significantly lower than those before treatment (all P<0.001). The proportions of EASI50, EASI75, and EASI90 were 91.0% (101/111), 71.2% (79/111), and 40.5% (45/111) at 16 weeks, and 95.0% (76/80), 80.0% (64/80) and 45.0% (36/80) at 24 weeks, respectively. Basal total IgE levels (P=0.005) and EOS counts (P<0.001) at Week 24 were significantly lower than those before treatment. Adverse events occurred in 54 patients (20.9%), mainly manifested as intractable erythema of the face and neck (5.0%, 13 patients) and conjunctivitis (1.9%, 5 patients). Conclusions: Dupilumab can effectively improve the rash area, rash severity and itchiness of moderate to severe atopic dermatitis, improve the quality of life of patients, and reduce the incidence of adverse effects.

Allergen Sensitivity Patterns and Their Correlation With Total Serum IgE Levels and Absolute Eosinophil Counts Among Patients With Allergic Rhinitis and Asthma in North Karnataka.

Introduction Respiratory allergies are prevalent across all populations and age groups, with the specific types of allergens varying according to geographic area, climate, location, economic status, and ethnic identity. While skin prick testing is considered the gold standard for assessing specific IgE against particular allergens, several factors can make the test less preferred. Consequently, total serum IgE levels and eosinophil counts are often used instead. Objectives The study aimed to determine allergen sensitivity patterns among patients with allergic rhinitis and/or asthma and to correlate skin prick test (SPT) reactivity with total serum IgE levels and absolute eosinophil count (AECs). This was done to assess the potential use of these measures as screening tests. Materials and methods A cross-sectional study was conducted on 44 patients diagnosed with allergic rhinitis and/or asthma. Each patient underwent an allergen SPT, and measurements were taken for total serum IgE levels and eosinophil counts. The study identified the most common allergens resulting in positive SPTs. Pearson correlation test was used for continuous variables, and a p-value of <0.05 was considered statistically significant. Results The study found that the majority of patients had only allergic rhinitis (17, 38.6%), followed by those with only asthma (12, 27.3%), and those with both allergic rhinitis and asthma (15, 34.1%). The most common allergen was Blomia (house dust mite), affecting 22 (50%) patients, while the least common were honey bee and lemon, each affecting 1 (2.3%) patient. There was a significant correlation between total serum IgE levels and AECs (p < 0.05). Additionally, a statistically significant correlation was found between total serum IgE levels, eosinophil counts, and the number of allergens to which patients were sensitized. Conclusion Blomia (house dust mite) is the most common allergen among patients with respiratory allergies in North Karnataka. While total serum IgE levels and AECs may help identify the extent of allergen sensitivity, the SPT remains the gold standard.

Aspergillus-sensitized asthma in children.

Asthma is the most common chronic respiratory disease in childhood. Aspergillus fumigatus sensitivity may be involved in the pathogenesis of asthma by leading to different clinical presentations. To investigate the demographic, clinical, laboratory, and radiological characteristics of A. fumigatus sensitivity in childhood asthma and identify associated risk factors and diagnostic parameters. A total of 259 children with asthma were included in the study, 7 (2.7%) with allergic bronchopulmonary aspergillosis (ABPA), 84 (32.4%) with A. fumigatus-sensitized asthma (Af-SA), and 168 (64.9%) with A. fumigatus-unsensitized asthma (Af-UA). Aspergillus sensitivity was associated with early asthma onset and longer asthma duration. Total IgE level and asthma severity are highest in ABPA and higher in Af-SA. Absolute eosinophil count was higher, and FEV1 was lower in Af-SA and ABPA. Aspergillus fumigatus was associated with greater odds of being male (odds ratio [OR], 2.45), having atopic dermatitis (OR, 3.159), Alternaria sensitivity (OR, 10.37), and longer asthma duration (OR, 1.266). The best cut-off values for detecting A. fumigatus positivity were 363.5 IU/mL for total IgE and 455 cells/μL for absolute eosinophil count. In Af-SA compared to Af-UA, centrilobular nodules and peribronchial thickening were more common, and the bronchoarterial ratio was higher. Aspergillus sensitivity is a strong allergic stimulus in asthma, leading to laboratory, structural, clinical, and functional consequences. Af-SA is a distinct asthma endotype independent of ABPA that is characterized by increased risk of severe clinical presentations and impaired lung function.