[Basics in diagnostics and therapy of allergic diseases for ENT consultations]. / Grundlagen der Allergologie für die HNO-Sprechstunde.

Allergies play a pivotal role in the daily practice of ENT specialists. Allergic symptoms induced by inhalant allergens are widespread in the population and can manifest through a wide range of symptoms, including rhinorrhea, sneezing, conjunctival redness, cough and dyspnea. Inconsistent diagnosis and treatment of allergic conditions can lead to reduced quality of life, decreased work performance, and socioeconomically significant secondary diseases. In addition to the medical history, the skin prick test and serological IgE diagnostics are the most important diagnostic procedure for detecting type-I allergies. To clarify clinical relevance, molecular diagnostics and nasal provocation testing may be employed. The key to effective treatment lies in a comprehensive allergological diagnosis coupled with a detailed patient history. General treatment recommendations such as allergen avoidance and nasal irrigation should complement pharmacological therapy. In the treatment of allergic rhinitis topical steroids are first line treatment options. The primary goal of treatment is symptom control, and if control is insufficient, causal therapy through specific allergen immunotherapy is recommended. Challenges in the ENT clinic involve selecting the necessary diagnostics and appropriate, effective treatments. Hence, using diagnostic and treatment algorithms, as well as standardized patient history questionnaires, can serve as invaluable tools in daily patient interactions, especially considering limited time availability.

[Interpretation of 2023 EAACI guidelines on the diagnosis of IgE-mediated food allergy].

The prevalence of food allergy is increasing globally, becoming a significant public health issue that greatly impacts the quality of life for patients and their families. However, there is currently a problem with both underdiagnosis and overdiagnosis of food allergy. Therefore, accurate diagnosis of food allergy and personalized management based on accurate diagnosis are crucial. Over the past 10 years, there has been relevant research on food allergy diagnosis, particularly focusing on IgE-mediated food allergy diagnostic methods such as component resolved diagnosis and basophil activation test, since the launch of the European Academy of Allergy and Clinical Immunology(EAACI) Food Allergy Guidelines in 2014. In October 2023, EAACI published updated diagnostic guidelines for IgE-mediated food allergy. To help allergists and other medical professionals stay informed about the latest EAACI recommendations on the diagnosis of IgE-mediated food allergy, this guideline is now being interpreted.

[Current status and progress on in vitro diagnosis of allergic diseases].

Allergic diseases are immune disorders caused by allergens, leading to inflammation or organ dysfunction. In the past decade, the prevalence of allergic diseases in China has increased dramatically, imposing a heavy economic burden on the health care system and society. In vitro diagnosis of allergic diseases plays a crucial role in the diagnosis, treatment, and prevention of such diseases. This article enumerates the in vitro tests and diagnostic techniques of allergic diseases, gives an advocacy for quality management of IgE-related tests, summarizes the clinical interpretation and relevant research progress, aiming to provide a reference for improving laboratory diagnosis of allergic diseases.

[Analysis of the effect of early subcutaneous specific immunotherapy on the levels of dust mite allergen-specific antibodies and polyunsaturated fatty acid metabolism].

Objective: To investigate the effects of subcutaneous immunotherapy (SCIT) on patients' immune markers and metabolic levels in the early stage of allergen treatment, and to gain insight into the role of SCIT in regulating immune responses and metabolic levels, so as to provide reference data for the further discovery of potential biomarkers. Methods: A longitudinal study was used to include 40 subjects who underwent SCIT with dust mite allergens in the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University between November 2017 and February 2022, including 20 subjects each of single mite subcutaneous immunotherapy (SM-SCIT) and double mite subcutaneous immunotherapy (DM-SCIT). In this study, levels of dust mite allergen-specific antibodies and polyunsaturated fatty acid metabolism were measured before and 12 months after treatment, while pulmonary function tests were performed. The therapeutic effects of the patients were followed up by visual analogue scale (VAS), asthma control test (ACT) and total medication scores (TMS). The results were statistically analyzed using t-test and Mann-Whitney U-test. Results: After 12 months of treatment with SCIT, both groups showed a significant decrease in total VAS score (SM-SCIT:Z=-2.298, P<0.05; DM-SCIT:Z=-3.411, P<0.001); total ACT score (SM-SCIT:Z=-2.054, P<0.05; DM-SCIT:Z=-2.014, P<0.05) and total medication scores (SM-SCIT:Z=-3.799, P<0.000 1; DM-SCIT:Z=-3.474, P<0.001) were significantly higher, in addition to significantly higher MMEF75/25 values in the DM-SCIT group (t=-2.253, P<0.05). There was no significant change in sIgE in the SM-SCIT group (P>0.05), and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 2, and p 21 fractions were significantly elevated (Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, and -3.285, respectively, all P<0.05); The sIgE of Der p 2, f 2, p 7 and p 23 fractions(Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, -3.285, all P<0.05) and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 1, f 2, p 10, p 21 and p 23 fractions (Z=-3.808, -3.845, -3.061, -2.688, -2.464, -3.211, -2.371, -2.091, -2.427, all P<0.05) of the DM-SCIT group were significantly elevated. Metabolomics analysis showed that arachidonic acid, docosahexaenoic acid, docosapentaenoic acid, eicosapentaenoic acid, 5, 9, 12-octadecatrienoic acid, 5(S)-hydroxylated eicosatetraenoic acid, and dihomo-gamma-linolenic acid were significantly elevated at the beginning of the treatment period after SM-SCIT treatment (Z of -2.191, -2.497, -1.988, -2.090, -2.19, -2.803, -2.073, all P<0.05); 5(S)-hydroxylated eicosatetraenoic acid showed elevated and alpha-linolenic acid, eicosadienoic acid, and eicosapentaenoic acid were significantly decreased in the DM-SCIT group after treatment (Z=-1.988, -2.090, -2.497, -1.988, respectively, all P<0.05). Correlation analysis showed that arachidonic acid was significantly negatively correlated with changes in dust mite-specific IgG4 (r=-0.499, P<0.05), and that alpha-linolenic acid, 5, 9, 12-octadecatrienoic acid, and eicosapentaenoic acid were positively correlated with the ΔsIgG4 of the dust mite der p 2 (r=0.451, 0.420, 0.474, respectively; all P<0.05). Conclusion: Significant changes in allergen-specific antibody levels and polyunsaturated fatty acid metabolism levels occur during SCIT, and the two may interact and influence each other.

[Analysis of allergen-specific IgE in children with atopic dermatitis from 2021 to 2023 in a hospital of pediatric in Tianjin City].

Objective: To explore the distribution of allergen-specific IgE (sIgE) for children with atopic dermatitis in Tianjin City and provide the evidences of clinical diagnosis and treatment. Methods: A retrospective cross-sectional study was conducted to analyze the children who were suspected of atopic dermatitis and tested for serum sIgE in the Tianjin Children's Hospital from March 2021 to February 2023. Using first detection results only, a total of 1 841 serum samples were tested for twenty common allergens. The method was the enzyme-linked immune capture assay. The allergen epidemiological characteristics were statistically analyzed by Chi square test based on the children's characteristics and factors such as different sexes, ages and seasons by the mass data. Results: Among the 1 841 cases, the results showed that 1 247 (67.73%) were sensitized to at least 1 allergen-sIgE, comprising to 49.86% (918/1 841) to food allergen-sIgE and 47.96% (883/1 841) to aeroallergen-sIgE. The top three food allergens-sIgE were egg 32.10% (591/1 841), milk 25.91% (477/1 841) and wheat flour 14.61% (269/1 841); the top three positive rates of aeroallergens-sIgE were house dust 24.33% (448/1 841), alternaria 20.59% (379/1 841) and dermatophagoides farinae 14.83% (273/1 841). The positive rates of food allergens-sIgE were the highest in the 1-3 years old group (64.11%, 434/677) (χ2=122.854, P<0.001), while the positive rates of aeroallergens-sIgE were higher in the 11-14 years old group (71.26%, 62/87) (χ2=134.968, P<0.001). No seasonal difference was revealed in the overall positive rate of food allergen-sIgE and aeroallergen-sIgE (χ2=4.047, P=0.256; χ2=7.549, P=0.056). The positive rates of soybean-sIgE and milk-sIgE were the highest in summer (χ2=11.329, P=0.010; χ2=28.720, P<0.001), whereas alternaria-sIgE and mugwort-sIgE were the highest in summer and autumn, respectively (χ2=8.462, P=0.037; χ2=10.641, P=0.014). Among the 1 841 cases, 32.21% were sensitized to three or more allergens-sIgE. The sIgE concentration levels of egg, milk and house dust were mainly level 1 to 2, and the proportions of level 3 and above were all under 15%; although the positive rates of crab, shrimp, and peanut were low, the proportions of grade 3 and above were all beyond 30%. Children sensitized to alternaria, dermatophagoides farinae, mugwort, and cat dander had higher sIgE concentration levels, which were 68.07%, 49.45%, 56.57% and 47.83% respectively. Conclusions: This study can reflect the epidemic characteristics of allergen-sIgE in children with atopic dermatitis in Tianjin region to a certain extent. Allergen-sIgE positivity in patients differed by age, and there were seasonal differences and grade distribution differences in the positive rates of some allergens-sIgE. It is necessary to reasonably avoid the high-risk allergens according to the epidemiological characteristics and clinical symptoms, which provide valuable information for the prevention, diagnosis and treatment of atopic dermatitis.

[Efficacy and safety study of standardized mite allergen specific immunotherapy with no reduction during maintenance in children with respiratory allergic disease].

Objective: To explore the optimal regimen of standardized mite allergen immunotherapy for airway allergic diseases in children, and to observe the clinical efficacy, safety and compliance. Method: Use a retrospective real-world study, clinical data from 156 children aged 5-16 years who received subcutaneous immunotherapy (SCIT) with double mite allergen preparation in the pediatrics department of the Third Affiliated Hospital of Sun Yat sen University from June 2019 to September 2020 were selected for allergic rhinitis (AR) and/or allergic asthma (bronchial asthma, BA), including gender, age, total VAS(visual analogue scale) score and CSMS(combined symptom and medication scores) score at different time points (before treatment, 4-6 months, 1 year, and 2 years after initiation of desensitization), peripheral blood eosinophil counts (EOS), serum total IgE (tIgE), specific IgE (tIgE), and serum IgE (tIgE), specific IgE (sIgE), tIgG4, and incidence of local and systemic adverse reactions. All patients had a consistent regimen during the initial treatment phase (dose-escalation phase), which was performed as directed. Among them, 81 cases (observation group) continued to continue subcutaneous injection of 1 ml of vial No. 3 every 4-6 weeks during the dose maintenance phase, while 75 cases (control group) followed the old traditional regimen during the maintenance phase (i.e., change to a new vial to halve the amount of vial No. 3 by 0.5 ml, and then 0.75 ml after 1-2 weeks, and 1 ml in a further interval of 1-2 weeks). The clinical efficacy, safety and adherence to the treatment were compared between the two groups. Results: A total of 81 cases of 156 children were included in the observation group, of which 58 children with AR, 15 children with BA, and 8 children with AR combined with BA; 75 cases were included in the conventional control group, of which 52 children with AR, 16 children with BA, and 7 children with AR combined with BA. In terms of safety, the difference in the incidence of local and systemic adverse reactions between the two groups was not statistically significant (χ2=1.541 for local adverse reactions in the control group, χ2=0.718 for the observation group; χ2=0.483 for systemic adverse reactions in the control group, χ2=0.179 for the observation group, P value >0.05 for all of these), and there were no grade Ⅱ or higher systemic adverse reactions in any of them. In the control group, there were 15 cases of dropout at 2 years of follow-up, with a dropout rate of 20.0%; in the observation group, there were 7 cases of dropout at 2 years of follow-up, with a dropout rate of 8.6%, and there was a statistically significant difference in the dropout rates of the patients in the two groups (χ2=4.147, P<0.05). Comparison of serological indexes and efficacy (compared with baseline at 3 different time points after treatment, i.e., 4-6 months, 1 year and 2 years after treatment), CSMS scores of the observation group and the conventional control group at 4-6 months, 1 year and 2 years after treatment were significantly decreased compared with the baseline status (t-values of the conventional group were 13.783, 20.086 and 20.384, respectively, all P-values <0.001, and t-values of the observation group were 15.480, 27.087, 28.938, all P-values <0.001), and VAS scores also decreased significantly from baseline status in both groups at 4-6 months, 1 year, and 2 years of treatment (t-values of 14.008, 17.963, and 27.512 in the conventional control group, respectively, with all P-values <0.001, and t-values of 9.436, 13.184, and 22.377 in the observation group, respectively; all P-values <0.001). Intergroup comparisons showed no statistically significant differences in CSMS at baseline status, 4-6 months, 1 year and 2 years (t-values 0.621, 0.473, 1.825, and 0.342, respectively, and P-values 0.536, 0.637, 0.070, and 0.733, respectively), and VAS was no statistically significant difference in comparison between groups at different time points (t-values of 1.663, 0.095, 0.305, 0.951, P-values of 0.099, 0.925, 0.761, 0.343, respectively); suggesting that the treatment regimens of the observation group and the conventional control group were clinically effective, and that the two regimens were comparable in terms of efficacy. The peripheral blood eosinophil counts of the observation group and the conventional control group decreased significantly from the baseline status at 4-6 months, 1 year and 2 years of treatment (t-values of the conventional group were 3.453, 5.469, 6.273, P-values <0.05, and the t-values of the observation group were 2.900, 4.575, 5.988, P-values <0.05, respectively). 4-6 months, 1 year and 2 years compared with the baseline status tIgE showed a trend of increasing and then decreasing (t-value in the conventional group was -5.328, -4.254, -0.690, P-value was 0.000, 0.000, 0.492, respectively, and t-value in the observation group was -6.087, -5.087, -0.324, P-value was 0.000, 0.000, 0.745, respectively). However, the results of intergroup comparisons showed no statistically significant differences in serological indices and efficacy between the two groups in terms of peripheral blood eosinophil counts at baseline status, 4-6 months, 1 year and 2 years (t-values of 0.723, 1.553, 0.766, and 0.234, respectively; P-values of 0.471, 0.122, 0.445, and 0.815, respectively), tIgE (t-values of 0.170, -0.166, -0.449, 0.839, P-values 0.865, 0.868, 0.654, 0.403, respectively), tIgG4 (t-values 1.507, 1.467, -0.337, 0.804, P-values 0.134, 0.145, 0.737, 0.422, respectively). Conclusion: Both immunotherapy regimens for airway allergic diseases with double mite allergen subcutaneous immunotherapy have significant clinical efficacy, low incidence of adverse reactions, and the observation group has better patient compliance than the control group.

[Correlation between the distribution of airborne pollen and the positive sIgE test in patients with allergic rhinitis in Taiyuan City in spring from 2022 to 2023].

This study was to investigate the relationship between spring pollen distribution concentration, species and the detection results of air-borne pollen allergens in Taiyuan City, Shanxi Province during March to May 2022 and March to May 2023.A retrospective study was conducted in the Otorhinolaryngology Head and Neck Surgery Clinic of the First Hospital of Shanxi Medical University.Pollen particles will be monitored by gravity sedimentation method on the roof of the outpatient department of the First Hospital of Shanxi Medical University in downtown Taiyuan from March to May 2022-2023, and pollen species and quantity will be observed and recorded under an optical microscope.The air-borne pollen allergen detection results of all allergic rhinitis patients in the otolaryngology Head and Neck surgery Department of the First Hospital of Shanxi Medical University were extracted from the relevant outpatient system. SPSS software and Pearson correlation analysis were used to compare the correlation between the allergens and the dominant air-borne pollen monitoring results. Results are as follows: (1)A total of 18 species of spring pollen in Taiyuan City were monitored in 2022-2023, with 101 177.5 grains, and the dominant airborne pollen was poplar (16.69%) and pine (29.06%) pollen. The pollen of poplar (11.96%), elm (7.89%) and cypress (8.68%) were dominant in early spring; Pine (25.16%) pollen predominated in late spring. The two peaks of pollen dispersal in Taiyuan were in late March (15 479 grains) and early and mid May (15 094/15 343 grains).(2) The positive rates of allergens in serum specific IgE detection were: wormwood (46%, 248/541 cases), tree combination (26%, 143/541 cases), ragweed (19%, 101/541 cases), humulus scandens (9%, 49/541 cases).(3)There was a linear positive correlation between the positive rate of air-borne pollen allergens in allergic rhinitis patients in the Department of Otolaryngology Head and Neck Surgery in the First Hospital of Shanxi Medical University and the dominant air-borne pollen concentration in the same period (P<0.05, r=0.999). In conclusion, two spring pollen dispersal peaks were formed in late March and early to mid May in Taiyuan City, and the dominant air-borne pollens were poplar and pine pollens. The positive rate of air borne pollen allergen sIgE showed that wormwood allergy was the highest.There was a positive correlation between the concentration of air-borne pollen and the positive rate of air-borne pollen allergens in patients with allergic rhinitis in the Department of otorhinolaryngology and head and neck surgery in Taiyuan in 2022 and 2023.The monitoring of pollen distribution in spring can provide an important scientific basis for clinical workers to formulate prevention and treatment plans for patients with allergic rhinitis in the season, and provide data reference for the epidemiological investigation of allergic diseases in Taiyuan in the future.

[Allergic bronchopulmonary aspergillosis with low serum IgE: a case report].

Here, we reported a case of delayed diagnosis of allergic bronchopulmonary aspergillosis (ABPA) with low serum IgE and normal Aspergillus fumigatus-specific IgE levels. During the course of the disease, the patient (female, 55 years old) had imaging manifestation of mass shadow and significant elevation of carcinoembryonic antigen, leading to suspicion of a lung tumor. Later, transbronchial lung biopsy tissue culture showed Aspergillus fumigatus. Combined with the history, clinical characteristics and imaging, she was diagnosed with allergic bronchopulmonary aspergillosis combined with invasive pulmonary aspergillosis. As the diagnostic criteria for ABPA do not cover all patients with ABPA, in rare cases where immunological evidence is insufficient, a combination of clinical and imaging features is required for early diagnosis and treatment.

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

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

Aspergillus fumigatus binding IgA and IgG1 are increased in bronchoalveolar lavage fluid of horses with neutrophilic asthma.

Introduction: Equine asthma (EA) is a common lower airway disease in horses, but whether its pathogenesis is allergic is ambiguous. Extrinsic stimuli like hay dust induce acute exacerbation of clinical signs and sustained local neutrophilic inflammation in susceptible horses. Aspergillus fumigatus is an EA stimulus, but it is unclear if it merely acts as an IgE-provoking allergen. We aimed to comprehensively analyze immunoglobulin (Ig) isotypes in EA, elucidating their binding to different A. fumigatus antigens, and their quantities systemically in serum and locally in bronchoalveolar lavage fluid (BALF). Methods: Serum and BALF from healthy horses (HE, n = 18) and horses with mild-moderate asthma (MEA, n = 20) or severe asthma (SEA, n = 24) were compared. Ig isotype (IgG1, IgG3/5, IgG4/7, IgG6, IgA, and IgE) binding to nine antigens (A. fumigatus lysate, and recombinant Asp f 1, Asp f 7, Asp f 8, dipeptidyl-peptidase 5, class II aldolase/adducin domain protein, glucoamylase, beta-hexosaminidase, and peptide hydrolase) was compared by enzyme-linked immunosorbent assays. Total Ig isotype contents were determined by bead-based assays. Results: MEA and SEA differed from HE but hardly from each other. Compared to HE, asthmatic horses showed increased anti-A. fumigatus binding of IgG (BALF and serum) and IgA (BALF). Serum and BALF IgE binding and total IgE contents were similar between HE and EA. Single antigens, as well as A. fumigatus lysate, yielded similar Ig binding patterns. Serum and BALF IgG1 binding to all antigens was increased in SEA and to several antigens in MEA. Serum IgG4/7 binding to two antigens was increased in SEA. BALF IgA binding to all antigens was increased in SEA and MEA. Total BALF IgG1 and IgG4/7 contents were increased in SEA, and serum IgG4/7 content was increased in MEA compared to HE. Yet, total isotype contents differentiated EA and HE less clearly than antigen-binding Ig. Discussion: A. fumigatus immunogenicity was confirmed without identification of single dominant antigens here. A. fumigatus provoked elevated BALF IgG1 and IgA binding, and these isotypes appear relevant for neutrophilic EA, which does not support allergy. BALF Ig isotype differentiation beyond IgE is crucial for a comprehensive analysis of immune responses to fungi in EA pathogenesis.

Clinical and serological characteristics of patients allergic to LTP.

BACKGROUND: Allergy to lipid transfer proteins (LPT) is common in Mediterranean Europe, and it causes severe reactions in patients and affects multiple foods, impairing the quality of life. OBJECTIVE: This study aimed to describe the clinical and sensitization profile of patients with LTP syndrome and to determine a clinical pattern of severity. Molecular diagnosis is shown in a broad population through microarrays. MATERIAL AND METHODS: This study was performed at the LTP Allergy Consultation of the Reina Sofia Hospital in Murcia, Spain. We analyzed the patients' characteristics, reactions, cofactors, food implicated, quality of life, skin prick test to food and aeroallergens, and serologic parameters, such as total immunoglobulin E, peach LTP (Pru p 3 IgE) and immunoglobulin G4, and microarray Immuno Solid-phase Allergen Chip (ISAC). We related the severity of the reactions with other variables. RESULTS: We presented a series of 236 patients diagnosed with LTP allergy, 54.66% suffering from anaphylaxis, 36.02% from urticaria angioedema, and 9.32% from oral allergy syndrome. The most frequently implicated food was peach, producing symptoms in 70% of patients, followed by walnut in 55%, peanut in 45%, hazelnut in 44%, and apple in 38% patients. Regarding the food that provoked anaphylaxis, walnut was the most frequent instigator, along with peach, peanut, hazelnut, almond, sunflower seed, and apple. According to the severity of LPT reaction, we did not discover significant differences in gender, age, food group involved, and serologic parameters. We found differences in the presence of cofactors, with 48.84% of cofactors in patients with anaphylaxis, compared to 27.1% in patients without anaphylaxis and in family allergy background (P < 0.0001). CONCLUSION: In our series of patients, 54% presented anaphylaxis, and the foods that most frequently produced symptoms were peaches, apples, and nuts. Cofactors and family allergy backgrounds were associated with the severity of LPT reaction.

A real-life ImmunoCAT study: impact of molecular diagnosis through ImmunoCAPTM ISAC 112 on immunotherapy prescription in pollen-polysensitized patients in Catalonia, Spain.

BACKGROUND: Molecular diagnosis in allergology helps to identify multiple allergenic molecules simultaneously. The use of purified and/or recombinant allergens increases the accuracy of individual sensitization profiles in allergic patients. OBJECTIVE: To assess the impact of molecular diagnosis through the ImmunoCAPTM ISAC 112 microarray on etiological diagnosis and specific immunotherapy (SIT) prescription. This was compared to the use of conventional diagnoses in pediatric, adolescent, and young adult patients with rhinitis or rhinoconjunctivitis and/or allergic asthma, sensitized to three or more pollen allergens of different botanical species. METHODS: A multicenter, prospective, observational study was conducted in patients aged 3-25 years who received care at the Allergology service of 14 hospitals in Catalonia from 2017 to 2020. Allergology diagnosis was established based on the patient's clinical assessment and the results of the skin prick test and specific immunoglobulin E assays. Subsequently, molecular diagnosis was conducted using ImmunoCAPTM ISAC® 112 to recombinant and/or purified allergen components. RESULTS: A total of 109 patients were included; 35 (32.1%) were pediatric patients and 74 (67.9%) were adolescents or young adults (mean age: 18 years), with 58.0% being females. A change of 51.0% was observed in SIT prescription following molecular etiological diagnosis by means of a multi-parameter microarray. CONCLUSIONS: Molecular diagnosis by means of multi-parameter tests increases the accuracy of etiological diagnosis and helps to define an accurate composition of SIT.

Multiarray screening identifies plasma proteins associated with Th17 cell differentiation and viral defense in coincident asthma and obesity.

BACKGROUND: The immunological mechanisms behind the clinical association between asthma and obesity in adolescence are not fully understood. This study aimed to find new plasma protein biomarkers associated specifically with coincident asthma and obesity in adolescents. METHODS: This was a cross-sectional study in children and adolescents 10-19 years old (N = 390). Relative plasma concentrations of 113 protein biomarkers related to inflammation and immune response were determined by proximity extension assay (Target 96; Olink, Uppsala, Sweden). Differences in protein concentrations between healthy controls (n = 84), subjects with asthma (n = 138), subjects with obesity (n = 107), and subjects with both asthma and obesity (AO; n = 58) were analyzed by ANCOVA, adjusting for age and sex, and in a separate model adjusting also for the sum of specific IgE antibody concentrations to a mix of food allergens (fx5) and aeroallergens (Phadiatop). Proteins elevated in the AO group but not in the obesity or asthma groups were considered specifically elevated in asthma and obesity. RESULTS: Five proteins were elevated specifically in the AO group compared to controls (here sorted from largest to smallest effect of asthma and obesity combined): CCL8, IL-33, IL-17C, FGF-23, and CLEC7A. The effects of adjusting also for specific IgE were small but IL-33, IL-17C, and FGF-23 were no longer statistically significant. CONCLUSION: We identified several new potential plasma biomarkers specifically elevated in coincident asthma and obesity in adolescents. Four of the proteins, CCL8, IL-33, IL-17C, and CLEC7A, have previously been associated with viral mucosal host defense and Th17 cell differentiation.

What can be learned from real-world data about chronic spontaneous urticaria?

Background: Chronic spontaneous urticaria (CSU) is a common disease with complex pathogenesis. Patients' clinical characteristics and responses to treatment vary. Objective: We aimed to investigate the role of data obtained from routinely recommended tests in predicting the response to omalizumab, the only biologic agent approved for treatment, and in defining the clinical characteristics of the patients. Methods: A retrospective study of patients who started omalizumab treatment for CSU between 2015 and 2022 at the Department of Dermatology, Pamukkale University, was conducted. Response criteria were based on the urticaria control test, and patients with a urticaria control test score <12 at 6 months were considered treatment non-responders. Eosinophil and basophil counts, neutrophil-lymphocyte ratio (NLR), systemic immune inflammation index (SII), systemic inflammation response index (SIRI), and total immunoglobulin E (IgE) levels of the patients were evaluated before treatment and at the sixth month of treatment. Results: A total of 23.1% of the patients were unresponsive to omalizumab. The response rate to the omalizumab treatment of the patients with a total IgE level ≤ 30 IU/L (n = 4 [5.7%]) was significantly lower than patients with total IgE level > 30 IU/L (n = 66 [94.3%]) (p = 0.015). The mean ± standard deviation SIRI levels were significantly higher in non-responders versus responders (1.53 ± 1.03 versus 1.15 ± 7.76; p = 0.026). Eosinophil counts positively correlated with basophil counts (r = 587; p < 0.001) and IgE levels (r = 0.290; p = 0.005) but a negative correlation was found with levels of NLR (r = -0.475; p < 0.001), SIRI (r = -0.259; p = 0.013), and SII (r = -0.285; p = 0.006). NLR levels were lower in CSU patients with atopy, than in those without atopy (1.9 ± 0.9 vs 2.9 ± 2.1, p = 0.022). Conclusion: We suggest that eosinopenia and high NLR levels are linked to autoimmune CSU. Predicting a poor response to omalizumab seems possible with total IgE levels < 30 IU/L and high SIRI levels.

Clinical features, severity, and immunological changes during venom immunotherapy in children and adults.

Background: Hymenoptera venom allergy (HVA) is among the most common causes of severe allergic reactions worldwide. Objective: To investigate clinical features and factors that affect the severity of HVA and to determine the alterations in immunologic biomarkers after venom immunotherapy (VIT). Methods: Seventy-six adults and 36 children were prospectively investigated. We analyzed specific immunoglobulin E (sIgE) and sIgG4 levels of venom extracts and components (rApi m1, rApi m10, rVes v1, rVes v5, rPol d5) before and after the first year of VIT. Results: Although cardiovascular symptoms were more common in adults (p < 0.001), the skin was the most affected organ in children (p = 0.009). Serum basal tryptase (sBT) levels were higher in the adults than the children (p < 0.001). The absence of urticaria (odds ratio [OR] 4.208 [95% confidence interval {CI}, 1.395-12.688]; p = 0.011) and sBT ≥ 5.2 ng/mL (OR 11.941 [95% CI, 5.220-39.733]; p < 0.001) were found as the risk factors for grade IV reactions. During VIT, changes in sIgE levels were variable. In the Apis VIT group, we observed remarkable increases in sIgG4 levels in Apis extract and rApi m1 but not in Api m10. Vespula extract, rVes v1, and rVes v5 sIgG4 levels were significantly increased in Vespula VIT group, we also detected significant increases in the Polistes extract and rPol d5 sIgG4 levels, which were not observed in the Apis VIT group. In the patients who received both Apis and Vespula VIT, increases in sIgG4 levels were observed for both venoms. Conclusion: Adults and children can have different clinical patterns. After 1 year, VIT induced a strong IgG4 response. Although Apis immunotherapy (IT) induced Apis sIgG4, excluding Api m10, Vespula IT induced both Vespula and Polistes sIgG4.

Grass pollen allergoids conjugated with mannan for subcutaneous and sublingual immunotherapy: a dose-finding study.

Background: Polymerized allergoids conjugated with mannan represent a novel approach of allergen immunotherapy targeting dendritic cells. In this study, we aimed to determine the optimal dose of mannan-allergoid conjugates derived from grass pollen (Phleum pratense and Dactylis glomerata) administered via either the subcutaneous or sublingual route. Methods: A randomized, double-blind, placebo-controlled trial with a double-dummy design was conducted, involving 162 participants across 12 centers in Spain. Subjects were randomly allocated to one of nine different treatment groups, each receiving either placebo or active treatment at doses of 500, 1,000, 3,000, or 5,000 mTU/mL over four months. Each participant received five subcutaneous (SC) doses of 0.5 mL each, every 30 days, and a daily sublingual (SL) dose of 0.2 mL. Participants who received active treatment through SC, received placebo through SL. Participants who received active treatment through SL, received placebo SC. One Group, as control, received bot SC and SL placebo. The primary efficacy outcome was the improvement in titrated nasal provocation tests (NPT) at the end of the study compared to baseline. Secondary outcomes included specific antibody (IgG4, IgE) and cellular (IL-10 producing and regulatory T cell) responses. All adverse events and side reactions were recorded and assessed. Results: Post-treatment, the active groups showed improvements in NPT ranging from 33% to 53%, with the highest doses showing the greatest improvements regardless of the administration route. In comparison, the placebo group showed a 12% improvement. Significant differences over placebo were observed at doses of 3,000 mTU/mL (p=0.049 for SL, p=0.015 for SC) and 5,000 mTU/mL (p=0.011 for SL, p=0.015 for SC). A dose-dependent increase in IgG4 was observed following SC administration, and an increase in IL-10 producing cells for both routes of administration. No serious systemic or local adverse reactions were recorded, and no adrenaline was required. Conclusion: Grass pollen immunotherapy with mannan-allergoid conjugates was found to be safe and efficacious in achieving the primary outcome, whether administered via the subcutaneous or sublingual routes, at doses of 3,000 and 5,000 mTU/mL. Clinical trial registration: https://www.clinicaltrialsregister.eu/ctr-search (EudraCT), identifier 2014-005471-88; https://www.clinicaltrials.gov, identifier NCT02654223.

12,13-diHOME Promotes Inflammatory Macrophages and Epigenetically Modifies Their Capacity to Respond to Microbes and Allergens.

Elevated infant fecal concentrations of the bacterial-derived lipid 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) increase the risk for childhood atopy and asthma. However, the mechanisms by which this lipid contributes to disease development are largely unknown. We hypothesized that macrophages, which are key to both antimicrobial and antigen responses, are functionally and epigenetically modified by 12,13-diHOME leading to short- and long-term dysfunction with consequences for both antimicrobial and antigenic responses. Macrophages exposed to 12,13-diHOME are skewed toward inflammatory IL-1ß highCD206low cells, a phenomenon that is further amplified in the presence of common microbial-, aero-, and food-allergens. These IL-1ß highCD206low macrophages also exhibit reduced bacterial phagocytic capacity. In primary immune cell coculture assays involving peanut allergen stimulation, 12,13-diHOME promotes both IL-1ß and IL-6 production, memory B cell expansion, and increased IgE production. Exposure to 12,13-diHOME also induces macrophage chromatin remodeling, specifically diminishing access to interferon-stimulated response elements resulting in reduced interferon-regulated gene expression upon bacterial lipopolysaccharide stimulation. Thus 12,13-diHOME reprograms macrophage effector function, B-cell interactions and promotes epigenetic modifications that exacerbate inflammatory response to allergens and mutes antimicrobial response along the interferon axis. These observations offer plausible mechanisms by which this lipid promotes early-life pathogenic microbiome development and innate immune dysfunction associated with childhood allergic sensitization.

A retrospective comparison of IgE-mediated cow's milk protein allergy management strategies in pediatric cohorts.

BACKGROUND: Complete avoidance of milk is the usual management for IgE-mediated cow's milk protein allergy (CMPA). A baked milk ladder is a method of dietary advancement therapy in IgE-mediated CMPA in Ireland, while in Spain, avoidance of milk awaiting natural tolerance acquisition through an oral food challenge (OFC) is employed. The aim of this study was to evaluate the use of dietary advancement therapy using a milk ladder compared with complete avoidance of milk for managing IgE-mediated CMPA. METHODS: This is a retrospective chart review of 371 pediatric patients from the population who have been treated for IgE-mediated CMPA between 2011 and 2020, with the milk ladder (Ireland) or complete avoidance followed by an OFC (Spain). The main outcome was the introduction of cow's milk. RESULTS: Milk ladder patients were 3.67 times more likely to succeed in comparison with milk avoidance (p < .001). Anaphylaxis during the treatment period occurred in 34 patients in the milk avoidance groups, while three patients in the milk ladder group experienced anaphylaxis due to accidental exposure to milk (p < .001). Failure to complete treatment was associated with a higher skin prick test in the milk avoidance group and a raised specific IgE in the milk ladder group. CONCLUSION: This is the first study that compares outcomes of dietary advancement therapy to complete avoidance for CMPA management, demonstrating that cow's milk can be successfully and safely reintroduced using dietary advancement therapy using a milk ladder.

Glutenin from the Ancient Wheat Progenitor Is Intrinsically Allergenic as It Can Clinically Sensitize Mice for Systemic Anaphylaxis by Activating Th2 Immune Pathway.

Wheat allergy is a major type of food allergy with the potential for life-threatening anaphylactic reactions. Common wheat, Triticum aestivum (hexaploid, AABBDD genome), was developed using tetraploid wheat (AABB genome) and the ancient diploid wheat progenitor (DD genome)-Aegilops tauschii. The potential allergenicity of gluten from ancient diploid wheat is unknown. In this study, using a novel adjuvant-free gluten allergy mouse model, we tested the hypothesis that the glutenin extract from this ancient wheat progenitor will be intrinsically allergenic in this model. The ancient wheat was grown, and wheat berries were used to extract the glutenin for testing. A plant protein-free colony of Balb/c mice was established and used in this study. The intrinsic allergic sensitization potential of the glutenin was determined by measuring IgE response upon transdermal exposure without the use of an adjuvant. Clinical sensitization for eliciting systemic anaphylaxis (SA) was determined by quantifying the hypothermic shock response (HSR) and the mucosal mast cell response (MMCR) upon intraperitoneal injection. Glutenin extract elicited a robust and specific IgE response. Life-threatening SA associated and a significant MMCR were induced by the glutenin challenge. Furthermore, proteomic analysis of the spleen tissue revealed evidence of in vivo Th2 pathway activation. In addition, using a recently published fold-change analysis method, several immune markers positively and negatively associated with SA were identified. These results demonstrate for the first time that the glutenin from the ancient wheat progenitor is intrinsically allergenic, as it has the capacity to elicit clinical sensitization for anaphylaxis via activation of the Th2 pathway in vivo in mice.