High Total IgE Levels Research Articles

Nebulized Budesonide Prevents Airway Inflammation in Children with High Total IgE Levels After Open Heart Surgery with Cardiopulmonary Bypass: A Prospective Randomized Controlled Trial.

Cardiopulmonary bypass (CPB) is a crucial technique used to repair congenital heart defects (CHD); however, it may induce inflammatory response, leading to airway inflammation and need for prolonged mechanical ventilation. In this study, we aimed to evaluate the effect of budesonide nebulization in children with high serum total immunoglobulin E (tIgE) levels undergoing surgical repair of CHD via CPB. We conducted a randomized, single-center, controlled trial at a tertiary teaching hospital. One-hundred and one children with high tIgE were enrolled and randomized into the budesonide nebulization group (BUD group, n = 50) or the normal saline nebulization group (NS group, n = 51) between January 2020 and December 2020. Budesonide or normal saline was administered through a vibrating mesh nebulizer during mechanical ventilation every 8h. Blood and bronchoalveolar lavage fluid (BALF) samples were examined and data on airway mechanics and clinical outcomes were recorded. IL-6 and IL-8 levels in the blood and BALF samples significantly increased after CPB in both groups. Budesonide inhalation reduced IL-6 and IL-8 levels in the blood and BALF samples in children with high tIgE (P < 0.05). The mean airway pressure, PCO2, and oxygen index in the BUD group were significantly lower than those in the NS group after the first inhalation dose and persisted until almost 24h after surgery. The peak inspiratory pressure and drive pressure were lower in the BUD group than in the NS group at nearly 24h after surgery, with no significant difference at other time points. Additionally, the duration of mechanical ventilation, number of noninvasive ventilations after extubation, and number of patients using aerosol-inhaled bronchodilators after CICU in the BUD group were significantly lower than those in the NS group (P < 0.05). Children with high preoperative tIgE levels are at risk of airway inflammation after cardiopulmonary bypass. Inhaling budesonide during postoperative mechanical ventilation can reduce the intensity of inflammatory reactions, shorten the duration of mechanical ventilation, reduce airway pressure and the utilization of NIV after extubation.

High serum total IgE levels correlate with urticarial lesions and IgE deposition in perilesional skin of bullous pemphigoid patients: An observational study.

Background In the pathophysiology of bullous pemphigoid, besides IgG, there has been evidence that supports the role of IgE antibodies. However, there have been no studies to evaluate total serum IgE levels or detect IgE deposits in the skin of Vietnamese patients. Aim To analyse the association between IgE levels in the serum and disease severity as well as eosinophils and IgE basement membrane zone (BMZ) deposition in Vietnamese bullous bullous pemphigoid patients. Methods A single-centre observational research on 35 newly diagnosed and untreated bullous bullous pemphigoid patients. Total serum IgE levels were analysed using enzyme-linked immunosorbent assay (ELISA). For controls, we collected sera of 30 pemphigus patients and 30 elderly patients with pruritus. Perilesional skin biopsies underwent direct immunofluorescence (DIF) staining, with biopsies of pemphigus patients as controls. Results Elevated total serum IgE was observed in 60% of bullous pemphigoid patients, the percentage in the pemphigus group and pruritus group was 20% and 40%, respectively. The mean total serum IgE level among the bullous pemphigoid group was higher than that of the pemphigus group (123.3 ± 102.4 IU/mL vs. 64.3 ± 45.1 IU/mL, p = 0.010). Total serum IgE levels of bullous pemphigoid patients correlated with higher eosinophil counts (r = 0.61; p = 0.018) and urticaria/erythema (U/E) Bullous Pemphigoid Disease Area Index (BPDAI) score (r = 0.50; p = 0.035). Among 35 bullous pemphigoid patients, 5 patients showed positive IgE DIF staining, accounting for 14.3%. Higher serum IgE levels correlated with the deposition of IgE in patients' perilesional skin (p = 0.037). Limitations Due to the rarity of bullous pemphigoid, the effect of the COVID-19 pandemic, and self-treatment issues in Vietnam, we could not recruit a larger number of participants. Conclusions Total serum IgE values correlated with urticarial lesions and IgE deposition in perilesional skin of Vietnamese bullous pemphigoid patients. IgE autoantibodies present in the skin of bullous pemphigoid patients support the role of IgE in bullous pemphigoid pathogenesis.

Mammalian Meat Allergy and IgE to Alpha-Gal in Central Virginia: Findings From a COVID-19 Vaccine and Patient Cohort

IgE to galactose-alpha-1,3-galactose (alpha-gal) is linked to tick bites and an important cause of anaphylaxis and urticarial reactions to mammalian meat. The alpha-gal syndrome (AGS) is recognized as being common in the southeastern United States. However, prevalence studies are lacking and open questions remain about risk factors and clinical presentation of alpha-gal sensitization. Here we characterized the prevalence as well as the presentation and risk factors of AGS and alpha-gal IgE sensitization in adults in central Virginia recruited without regard to the history of allergic disease. Adults in central Virginia, primarily University of Virginia Health employees, were recruited as part of a COVID-19 vaccine study. Subjects provided at least one blood sample and answered questionnaires about medical and dietary history. We used ImmunoCAP for IgE assays and assessed the ABO blood group by reverse typing using stored serum. We also investigated biobanked serum from COVID-19 patients. Median age of the 267 enrollees was 42 years, 76% were female, and 43 (16%) were sensitized to alpha-gal (cutoff of 0.1 IU/mL), of which mammalian meat allergy was reported by seven (2.6%). Sensitized subjects (1) were older, (2) had higher total IgE levels but a similar frequency of IgE to common respiratory allergens, and (3) were more likely to report tick bites than were nonsensitized subjects. Among those who were sensitized, alpha-gal IgE levels were higher among meat-allergic than nonallergic subjects (geometric mean, 9.0 vs 0.5 IU/mL; P< .001). Mammalian meat and dairy consumption was common in individuals with low-level sensitization. In central Virginia, AGS is a dominant cause ofadult food allergy with a prevalence approaching or exceeding2%.

Manifestation and associated factors of systemic and local allergy among patients with allergic fungal rhinosinusitis: An observational study.

Allergic fungal rhinosinusitis (AFRS) is a subtype of chronic rhinosinusitis, characterized by excessive immune responses to environmental molds or fungi. The diagnosis and classification of AFRS into systemic and local types remain clinically challenging due to overlapping characteristics. This study investigated the prevalence of AFRS, its manifestation and associated factors in systemic and local AFRS. A total of 200 patients diagnosed with fungal rhinosinusitis underwent both skin provocation tests (SPT) and nasal provocation tests (NPT) to confirm AFRS and classify systemic and local types. Patients were considered to have AFRS if either the SPT or NPT was positive. Among these, patients with systemic AFRS were those who had a SPT positive. Local AFRS was when patients had a negative SPT and a positive NPT. Medical history, serum total IgE level, nasal endoscopy examinations, and CT scans were also recorded. Most patients were female (65.8%), with a mean age of 55.6 years (SD = 14.4). Based on the SPT and NPT results, 31% of patients (n = 62) were diagnosed with AFRS. Among these, 54.8% (n = 34) had systemic AFRS, while 45.2% (n = 28) had local AFRS. Patients with AFRS exhibited significantly higher levels of total IgE, eosinophils, and more pronounced signs and symptoms compared to those without AFRS. However, no statistically significant differences were observed between patients with systemic AFRS and those with local AFRS. AFRS was prevalent in our study. Among patients with AFRS, both systemic AFRS and local AFRS were also prevalent. While allergic indicators and clinical presentations can aid in AFRS diagnosis, minimal distinctions were observed between systemic and local AFRS. A comprehensive assessment incorporating both local and systemic allergic responses through provocation tests, such as a combination of skin and nasal tests, is imperative for optimizing AFRS diagnosis and management.

Association between single nucleotide polymorphisms of interleukin-35 genes and atopic dermatitis.

The pathogenesis of atopic dermatitis (AD) involves complex interactions between environmental factors, the skin microbiome, epidermal barrier defects, and altered immune responses that develop on a not fully understood specific genetic background. We aimed to evaluate the contribution of single nucleotide polymorphisms (SNPs) in the IL-35 genes (IL-12A and EBI3) towards AD susceptibility and clinical characteristics of AD in the Polish population. Two SNPs (rs568408, rs582054) in IL-12A and one SNP (rs428253) in EBI3 were selected. Blood samples were collected from 202 AD patients and 178 healthy individuals. SNPs in IL-35 genes were analysed by the polymerase chain reaction with sequence-specific primers (SSP-PCR) method. For IL-12A rs568408, the AA genotype was significantly linked to increased odds of AD (OR = 34.61; 95% CI: 2.06-579.97, p = 0.0137) and marginally associated with normal total serum IgE levels (OR = 2.82; 95% CI: 0.97-8.16; p = 0.05), while the GA genotype showed significantly reduced odds of AD (OR = 0.53; 95% CI: 0.34-0.81; p = 0.0035). In the context of IL-12A rs582054, TT genotype carriers had increased odds of AD (OR = 2.05; 95% CI: 1.08-3.85; p = 0.03). Patients with the GG genotype of EBI3 rs428253 had decreased odds of high total serum IgE levels (OR = 0.42; 95% CI: 0.20-0.86; p = 0.02) and milder pruritus severity compared to CC genotype carriers (4.12 vs. 7.50; p = 0.02). IL-35 genetic variations appear to play a role in AD pathogenesis.

Reliability of Total Serum IgE Levels to Define Type 2 High and Low Asthma Phenotypes.

Background: High total IgE levels are weak predictors of T2High and have been reported in nonallergic asthma. Therefore, the role of total serum IgE (IgE) in the T2High phenotype is still debated. Objective: This study investigated the reliability of stratifying asthmatics into IgEHigh and IgELow within the T2High and T2Low phenotypes. Methods: This cross-sectional single-center study investigated the association of clinical, functional, and bio-humoral parameters in a large asthmatic population stratified by IgE ≥ 100 kU/L, allergen sensitization, B-EOS ≥ 300/µL, and FENO ≥ 30 ppb. Results: Combining T2 biomarkers and IgE identifies (1) T2Low-IgELow (15.5%); (2) T2Low-IgEHigh (5.1%); (3) T2High-IgELow (33.6%); and T2High-IgEHigh (45.7%). T2Low-IgELow patients have more frequent cardiovascular and metabolic comorbidities, a higher prevalence of emphysema, and higher LAMA use than the two T2High subgroups. Higher exacerbation rates, rhinitis, and anxiety/depression syndrome characterize the T2Low-IgEHigh phenotype vs. the T2Low-IgELow phenotype. Within the T2High, low IgE was associated with female sex, obesity, and anxiety/depression. Conclusions: High IgE in T2Low patients is associated with a peculiar clinical phenotype, similar to T2High in terms of disease severity and nasal comorbidities, while retaining the T2Low features. IgE may represent an additional biomarker for clustering asthma in both T2High and T2Low phenotypes rather than a predictor of T2High asthma "per se".

Comorbid food allergy in patients with congenital epidermolysis bullosa

Introduction. Inherited epidermolysis bullosa belongs to the group of severe rare hereditary mechanobullous diseases. Often, the skin pathological process is difficult to treat, which leads to a decrease in the quality of life of such patients. The mechanism of development of transcutaneous sensitization in this category of patients is not excluded. This issue remains a very relevant area for study, given the characteristic nutritional deficiency and the difficulties that arise in the formation of the diet.The aim: to assess the frequency of occurrence and characteristics of food sensitization in children with epidermolysis bullosa.Materials and methods: the group included 164 children with epidermolysis bullosa (45 with rapid detection and 119 with dystrophic). For all patients, an assessment of the risk of an allergic history, determination of the total level of IgE and specific IgE of blood serum to the most significant food allergens (UniCAP system, Thermo Fisher Scientific). Results: food sensitization was detected in 34.1 % of children with epidermolysis bullosa (in 38.7 % of cases with dystrophic and in 24.4 % with a simple form of epidermolysis bullosa). Among the manifestations of food allergy in both groups, skin symptoms were more common. The most common etiological factors were products containing cow’s milk protein, eggs, and cereals. In the group of children with comorbid food allergies and epidermolysis bullosa, high and extremely high levels of total IgE were most common.Conclusion: a high frequency of food sensitization in patients with epidermolysis bullosa, was shown, which is important not only from a scientific, but also from a practical point of view. Given the nutritional deficiency characteristic of this disease, the complexity of nutritional support, the presence of comorbid food allergies should be taken into account when recommending nutrition and selecting therapeutic products for this category of patients.

Perinatal Characteristics and the Sensitization to Cow Milk, Egg Whites and Wheat in Children up to 3 Years of Age.

Food sensitization in early life identifies children at risk of developing allergic diseases. We investigated the sensitization to cow milk (CM), egg whites, and wheat. Newborns and infants under 3 years of age with available specific immunoglobulin E (sIgE) data were identified. A retrospective survey was conducted using data from the Chang Gung Research Database. Perinatal characteristics, such as singleton or multiples in a single pregnancy, parity, meconium staining, maternal age, spontaneous delivery or cesarean section, meconium passage, weeks of gestation, birth length, body weight, head and chest circumferences, and season, were obtained. The data on sIgE were collected, and a logistic regression model was used to determine the odds of sensitization. Positive sIgE for CM and egg whites was more likely to occur in boys than in girls. Early-life egg white and wheat sensitization was associated with increased birth body length and weight. A multivariate analysis indicated an association between egg white sIgE positivity and logarithmic total IgE. Higher total IgE levels and younger age were associated with egg white sensitization, and elevated weight and length at birth were linked to food sensitization, particularly to egg whites and wheat.

Bloody Stool in Infants: A Pediatric Allergy View

Objective: The prevalence of food allergy (FA) has gradually increased. Bloody stool is among the symptoms associated with non-immunoglobulin E (IgE) mediated FA in infants. In our study, we shared the clinical characteristics of the patients who applied to our clinic with bloody stool. Material and Methods: The data of the patients with bloody stool were reviewed. Patients’ characteristics and the time of onset of tolerance in patients with FA were recorded, retrospectively. Results: The 110 patient files were reviewed. 68% of the patients were diagnosed with FA (63 proctocolitis/12 enterocolitis), 22% with an anal fissure, and 9% with nonspecific colitis. The most common causative food was cow milk (57%), the second was the combination of egg and milk (24.2%), and the third was egg (18.2%). The presence of atopic dermatitis (AD) and eosinophil count at the time of admission did not affect tolerance development time but it was shown that skin prick test (SPT) positivity and the high level of total IgE at the time of admission delayed the development of tolerance [(p=0.02), (r=0.510, p=0.009)]. Conclusion: Bloody stool is one of the common complaints in infants. It does not always indicate a FA. The clinic is mild when the underlying disease is non-IgE mediated FA. However, accompanying IgE-type sensitivities negatively affect the prognosis. Elevated total IgE and SPT positivity at the time of diagnosis may give an impression that tolerance of baked products could be delayed in this type of allergy.

Allergic sensitisation and type-2 inflammation is associated with new-onset and persistent allergic disease.

Allergic disease is common. The aim of this study was to look at the change in asthma and rhinitis over time and to characterise factors contributing to remission and persistence of disease. This cohort study included 255 individuals with or without asthma and or rhinitis that participated in a population survey and a follow-up 10years later. The participants were tested for allergic sensitisation, total IgE, multiplex allergen component analysis and type-2 inflammatory markers: exhaled nitric oxide (FE NO), eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN). Of the 132 healthy individuals, 112 remained healthy, 16 developed rhinitis, 4 asthma and rhinitis over the 10years. Out of 82 subjects with rhinitis, 26 went into remission, 53 remained unchanged and 3 developed asthma in addition to rhinitis. None of the 41 participants with asthma and rhinitis went into remission. Subjects with persistent rhinitis and asthma had higher levels of total IgE (odds ratio [OR]95% confidence interval [CI]: 6.16 [3.05-12.5]) at baseline and after 10years, and FE NO and ECP at baseline (OR per log unit increase, 95% CI 5.21 [1.20-22.7] and 6.32 [1.52-26.4], respectively), compared with those that remained healthy. Subjects with persistent rhinitis were more likely to be sensitised to grass pollen and had higher total IgE levels than those that went into remission. Individuals with persistent asthma were more likely to be sensitised to tree pollen and furry animals than those with only persistent rhinitis (OR 95% CI: 3.50 [1.29-9.49] and 6.73 [2.00-22.6], respectively). IgE sensitisation and total IgE levels are associated with the persistence of rhinitis and asthma. Participants with persistent allergic disease had higher levels of allergen sensitisation and type 2 inflammation markers at baseline than those who remained healthy.

Asthma with recurrent middle lobe syndrome in children: Clinical features and lung function patterns.

Middle lobe syndrome (MLS) is a complication of childhood asthma. This study aimed to compare the clinical features and lung function between asthmatic children with recurrent MLS and transient right middle lobe (RML) and/or lingula atelectasis. This study retrospectively analyzed asthmatic children with RML and/or lingula atelectasis between 2010 and 2020 using data from the pediatric pulmonary department. According to the episodes of atelectasis, children were divided into recurrent (≥2 episodes) and non-recurrent (only 1 episode) MLS groups, to compare clinical features and lung function. Spirometry during acute asthma exacerbation and stable stages were recorded, and variations were calculated. A total of 35 children with asthma and RML and/or lingula atelectasis were included, 15 of whom had recurrent MLS. The recurrent MLS group had a higher proportion of girls, infections, family allergy history, severe asthma, severe exacerbation, and higher levels of total IgE than the non-recurrent MLS group (P < 0.05). The recurrent MLS group had a significantly higher % predicted and z-scores for forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), a greater proportion of high FEV1 and higher variations in FEV1 and FVC than that in the non-recurrent group (P < 0.05). After excluding children with mild to moderate asthma in the recurrent MLS group, the differences in clinical features disappeared, but the results regarding lung function remained similar, when compared to severe asthma patients without RML and/or lingula atelectasis. Childhood asthma with recurrent MLS has more frequent severe asthma and exacerbation but high lung function and variations.

IgE-immunoadsorption for severe allergy to multiple foods: A case series of five children

BackgroundChildren with severe food allergy may present high risk of fatal anaphylaxis and a highly impaired quality of life. Anti IgE-treatment has been shown to be a promising approach as monotherapy for severe allergy to multiple foods. However, very high serum total IgE levels may limit its use.This study aims to assess the efficacy of IgE-selective immunoadsorption (IgE-IA) on total IgE levels and threshold of reactivity to the culprit foods in children with history of severe anaphylaxis due to multiple foods and allergic comorbidities. MethodsIn this single-center, prospective, open-label efficacy study we evaluated children with severe asthma, allergy to 2+foods and total IgE levels >2300 kUI/L. To establish the food reactivity threshold, each patient underwent oral food challenges (OFCs) before and after IgE-IA. ResultsFive patients (4 males; age, 12.2 ± 5 years, mean ± SD) underwent an average of 3 (range 2–4) sessions of IgE-IA. Each session reduced IgE levels by a mean of 1958.87 kUI/L. After the IgE-IA cycle, serum total IgE dropped from 3948 ± 1652.7 (mean ± SD) to 360.8 ± 71.9 kUI/L (−10.9 folds; p = 0.01). The threshold of reactivity (No Observed Adverse Effect Level, NOAEL) tested at OFCs for the culprit foods (4 baked-milk + 2 baked-egg + 1 lentil + 2 hazelnut + 1 wheat) increased overall from 21.5 (median, IQR 1.5–82.6) protein milligrams to 1115 (837.2–4222.8) milligrams (p < 0.001), ie, up to 51.8 times higher than baseline. 8/10 OFCs were negative after IgE-IA. ConclusionsIgE-IA increased food threshold quickly. It can be considered in well-selected patients with severe food allergies and high IgE-levels especially if otherwise eligible to anti IgE treatment.

The role of fine suspended particles of atmospheric air in the formation of eosinophilic inflammation in T2-endotype of asthma

BACKGROUND: Allergens induce eosinophilic inflammation in the T2 endotype of asthma. However, much less is known about the role of non-specific factors (suspended particles in the atmospheric air-PM).&#x0D; AIMS: To define eosinophilic inflammation on the basis of several biomarkers in the T2 endotype of asthma exposed to PM.&#x0D; MATERIALS AND METHODS: We studied 150 patients with asthma, and 61 patients with T2 endotype of asthma (ages 1865 years) were enrolled. Group 1 included 34 patients with allergic asthma, and group 2 included 27 patients with non-allergic asthma. Moreover, 30 healthy matched controls without asthma and other allergic diseases were enrolled in the study. Clinical examination and allergy testing were performed. Additionally, serum levels of IL-33, IL-25, IL-4, IL-5, IL-13, DPP4 (multiplex assay), and periostin (ELISA) were evaluated. The analyses of the average annual concentrations (Avr) and the maximal annual concentrations (MaxAvr) of PM2.5 and PM10 in Kazan were conducted using the database of the Center for Hygiene and Epidemiology in the Republic of Tatarstan, being averaged over the period from 2014 to 2020 years in monitoring points at residential areas. Statistical analyses were performed using R version 4.0.5. The study was funded by RFBR (Project no. 19-05-50094).&#x0D; RESULTS: We detected increased blood eosinophil count and IL-5 levels in patients with asthma. High levels of total IgE (p=0.0001) that correlated with IL-4 levels were observed only in patients with allergic asthma (rS=0.38; p=0.045). Moreover, elevated IL-25 levels were found in patients with allergic asthma (p=0.009). No significant differences in IL-13 levels in patient with asthma were found. The regression analysis revealed that the PM2.5Avr increase by 1 mcg/m3 increases IL-33 and IL-25 levels, but the PM10Avr increase raises the IL-25 levels only in patients with non-allergic asthma. No significant increase in IL-25 and IL-33 levels under exposure to PM2.5Avr and PM 10Avr was detected in patients with allergic asthma.&#x0D; CONCLUSIONS: The results of this study indicate the pivotal role of fine suspended particles in the development and maintenance of eosinophilic inflammation in patients with non-allergic asthma.

Оценка иммунного статуса у беременных женщин с отягощенным аллергологическим анамнезом

Most researchers emphasize that in the structure of diseases of infants, there is a predominance of pathological conditions that occur precisely in the perinatal period, which indicate the correlation of these diseases with the health of the mother and the course of her pregnancy. Objective. Assessment of the immune status and effectiveness of diet therapy in pregnant women with burdened allergic history. Patients and methods. The observation groups consisted of 118 pregnant women. The first group included 83 pregnant women who received a hypoallergenic diet with the exclusion of main allergens, with the replacement of cow's milk with goat's milk, or the exclusion of dairy products as a causally significant allergen. The second group consisted of 35 pregnant women who followed the usual dietary recommendations offered in women's consultations, with the inclusion of cow's milk in the diet. The content of total IgE and allergen-specific IgE antibodies to food proteins in blood serum was determined by the immunoblot method using PROTIA Allergy-Q diagnostic panels. Results. 71.1% of pregnant women of the first group and 40% of women of the second group had the history of allergic diseases. According to skin scarification tests, these women had polyvalent sensitization. When studying the immunological status of pregnant women, attention was drawn to the fact that high levels of total serum IgE were in patients with allergies, with diseases of the gastrointestinal tract, as well as with a combination of these pathologies. 37.3% of the observed pregnant women of the first group, both with and without allergies, had high levels of total serum IgE. At the same time, the level of total IgE was higher in pregnant women suffering from allergic diseases. In addition, IgE sensitization to milk proteins was found in women with normal and high levels of total IgE in the blood. The concentration of allergen-specific IgE antibodies to cow's milk proteins was higher in women with IgE-mediated allergies. The use of a hypoallergenic diet in pregnant women caused the most pronounced decrease in the total IgE content in the blood compared with the indicators before treatment. The majority of the observed women showed a positive trend towards a decrease in IgE sensitization to milk proteins against the background of dietary therapy. Conclusion. All pregnant women with allergic diseases had food sensitization. Gastrointestinal pathology was observed in 34.7% of pregnant women, and its frequency in women with clinically confirmed allergies was 2.3 times higher than in women without allergies. A highly sensitive method for diagnosing food sensitization using PROTIA Allergy-Q panels has made it possible to most accurately identify causally significant allergen products, develop and effectively use personalized hypoallergenic diets for pregnant women. Considering the concept of food programming, the use of hypoallergenic diets in the diet of pregnant women with allergic diseases is one of the options for the prevention of allergic diseases in the future in children born to such mothers. Key words: pregnant women, allergy, food IgE sensitization, diet therapy

Биомаркеры воспаления и контроль бронхиальной астмы у детей

Asthma is the heterogeneous lung disease, caused by a chronic inflammation, characterized by various phenotypes, for the identification of which biomarkers can be used. However, most biomarkers are still experimental and have limitations for clinical practice. Objective. To study the link between the values of T2-inflammatory biomarkers in children with poor asthma control and features of asthma treatment. Patients and methods. The study included 100 patients aged 5 to 17 years (average age 13 years) with an established diagnosis of asthma. The level of asthma control of patient was assessed using asthma control tests and asthma control tests in children (ACT and C-ACT). The following markers were studied: the level of total immunoglobulin E (total IgE), peripheral blood eosinophils, fractional exhaled nitric oxide (FeNO), the number of eosinophils in nasal smears. The significance of the marker was determined by statistical data analysis methods used in medicine. Results. Despite the prescribed basic therapy, most children do not achieve normal asthma control. It was revealed that 43% of patients had one or more elevated markers of T2 inflammation. Children with partially controlled and uncontrolled asthma had high levels of total IgE (≥100 IU/ml), elevated levels of eosinophils in the blood (≥400 cells/ml) and high FeNO values (≥20 parts per billion). The most significant biomarker of poor asthma control in children is the level of total serum IgE ≥100 IU/ml. It has been established that allergic asthma in children is usually combined with the predominance of Th2 lymphocytes and eosinophilic inflammation of the respiratory tract. Conclusion. T2-inflammation biomarkers can be used as indicators of respiratory tract inflammation activity and to assess asthma control in children. Key words: biomarkers, asthma, children, asthma control, T2-inflammation

A Multi-Center Study of the Prevalence and Characteristics of Eosinophilic Phenotype and High IgE Levels Among Chinese Patients with Severe Asthma.

Patients with severe asthma have higher total- and asthma-related health burden than those whose disease is not severe. Recent medical advances in biologic therapies allow better control of asthma characterized by type 2 inflammation. To study the prevalence of eosinophilic phenotype and IgE levels in Chinese with severe asthma, and the relationship of these type 2 characteristics with asthma control, exacerbations and lung function. This was a multicenter cross-sectional observational study in Hong Kong, in Chinese adults with asthma on Step 4 or 5 of GINA treatment. Their blood eosinophil counts and total IgE levels were measured, and the relationship of these phenotypic parameters to the number of exacerbations in the past 12 months, and to symptom control in the past 4 weeks, were investigated. A total of 232 subjects were recruited from 6 centers. The mean age was 53.9±12.9 years, with 86 (37.1%) male, and the duration of diagnosed asthma was 26.2±15.7 years. A T-helper 2 (Th2) phenotype indicated by elevated eosinophils and/or IgE was present in 169 (72.8%) of patients. Of 232 patients, 43% had an eosinophilic phenotype (blood eosinophil count ≥300 cell/mm3), while 59% had high total IgE levels of >100 IU/mL (overlap with eosinophilic phenotype in 30%) and 44% had IgE levels of >150 IU/mL (overlap with eosinophilic phenotype in 22%). Subjects with eosinophilic phenotype and IgE >150 IU/mL had a higher rate (1.8 times) of uncontrolled asthma compared with those without such a combination. In Chinese adults with severe asthma defined by the use of conventional maintenance medication regimens, the prevalence of Th2 inflammation is comparable to that reported from other ethnic populations. Those with both eosinophil count ≥300 cell/mm3 and high IgE levels >150 IU/mL had a higher rate of uncontrolled asthma compared with those without a combination of these features.

Successful management of chronic urticaria and food allergies in a pediatric population using integrative traditional Chinese medicine therapy: a case series

BackgroundFood allergy is becoming increasingly common among the pediatric population. Despite strict avoidance of food allergens, a subgroup of sensitive individuals still develops frequent, persistent, and difficult to treat hives (FPDTH) for which there is no curative therapy. Although these cases are rare, these patients are in most need of therapy.Case presentationsThis is a retrospective review of 3 pediatric patients with highly sensitive food allergies who initially presented with hives daily or every other day, or multiple times a day, but achieved marked remission after traditional Chinese medicine (TCM) therapies. Patient 1 (P1) is a 5-year-old who has experienced 140 reactions in his lifetime. Reactions were mostly hives with 4 episodes of anaphylaxis. P1 had used Prednisone 20 times, had an Epinephrine injection 4 times, and had 3 emergency room (ER) visits. Patient 2 (P2) is a 12-year-old who had experienced hives since age 3. Despite daily antihistamine use, P2 had > 730 reactions in his lifetime at the time of presentation including 2 episodes of anaphylaxis. He had been prescribed prednisone 4 times, an Epinephrine injection 2 times, and had 1 ER visit. Patient 3 (P3) is a 20-month-old girl who had experienced > 120 reactions including 1 episode of anaphylaxis. She was on daily desonide and frequently used an antihistamine, yet still had required a course of prednisone once, an Epinephrine injection once, and had 1 ER visit to manage her reaction. After presenting to our clinic, patients received internal and external TCM treatments, including herbal baths and creams (Remedy A-D) as basic remedies to reduce food reactions, including but not limited to frequent hives. Within 7–9 months of TCM treatment, remarkably all patients had complete remission of atopic symptoms. All three patients also experienced an improvement in other conditions including food intolerance, diarrhea, anxiety, eczema, and environmental allergies. After 1 year of treatment, all three patients had reductions in food-specific IgE levels that had been previously elevated, and additionally, P1 and P3, who initially had high total IgE levels, experienced a marked decrease in total IgE levels as well. All three patients continued to introduce foods into their diet that they previously had reactions to, and all 3 patients remain symptom-free.ConclusionsThree pediatric patients with a known history of multiple food sensitivities and physician-diagnosed food allergies that presented with FPDTH underwent a TCM regimen and experienced dramatic improvement in symptoms and reduction in their IgE levels. This regimen appears to be effective in FPDTH population although a further study in a controlled clinical setting is required.

Hypoparathyroidism-Retardation-Dysmorphism Syndrome due to a Variant in the Tubulin-Specific Chaperone E Gene as a Cause of Combined Immune Deficiency.

BackgroundHypoparathyroidism-retardation-dysmorphism (HRD) syndrome is a disease composed of hypoparathyroidism, growth retardation, severe developmental delay, and typical dysmorphic features caused by the tubulin-specific chaperone E gene variant. Many patients succumb in infancy to HRD due to overwhelming infections mainly caused by Pneumococcus spp. Knowledge related to the immune system in these patients is scarce.PurposeTo define the immune phenotype of a cohort of HRD patients including their cellular, humoral, and neutrophil functions.MethodsThe study included HRD patients followed at Soroka University Medical Center. Clinical and immunological data were obtained, including immunoglobulin concentrations, specific antibody titers, lymphocyte subpopulations, lymphocyte proliferation, and neutrophil functions.ResultsNine patients (5 females and 4 males) were enrolled, aged 6 months to 15 years. All received amoxicillin prophylaxis as part of a routine established previously. Three patients had bacteremia with Klebsiella, Shigella spp., and Candida. Three patients had confirmed coronavirus disease 19 (COVID-19), and two of them died from this infection. All patients had normal blood counts. Patients showed high total IgA and IgE levels, low anti-pneumococcal antibodies in spite of a routine vaccination schedule, and reduced frequency of naive B cells with increased frequency of CD21lowCD27- B cells. All patients had abnormal T-cell population distributions, including reduced terminally differentiated effector memory CD8, inverted CD4/CD8 ratios, and impaired phytohemagglutinin (PHA)-induced lymphocyte proliferation. Neutrophil superoxide production and chemotaxis were normal in all patients tested.ConclusionHRD is a combined immunodeficiency disease with syndromic features, manifesting in severe invasive bacterial and viral infections.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10875-022-01380-9.

Comparison of the Patients with Chronic Urticaria Who Responded and Did Not Respond to Omalizumab Treatment: A Single-Center Retrospective Study

Introduction: Chronic urticaria (CU) is a condition usually lasting longer than 6 weeks, with wheals and angioedema, sometimes both. Omalizumab is a recombinant humanized monoclonal IgG antibody developed against IgE. In some patients with CU, treatment response to omalizumab is good, but in some patients, it is poor. We aimed to compare the clinical features and laboratory parameters of the patients who responded and did not respond to omalizumab treatment among patients diagnosed with CU. Methods: Patients treated with omalizumab for the diagnosis of CU were evaluated retrospectively. Treatment response to omaliz­umab was evaluated by urticaria control test (UCT) (responder to omalizumab: UCT score ≥12 at 6 months and an increase of ≥3 compared to baseline). The clinical features and laboratory parameters of the patients who responded and did not respond to treatment were compared. Results: The mean age of the 220 patients, 66 (30%) men and 154 (70%) women, who received 300 mg of sc omalizumab every 4 weeks for CU was 38.89 ± 12.76 years. One hundred eighty-nine (85.9%) patients had good response to omalizumab treatment at the end of 6 months. Atopy (n = 73 [38.6%], p = 0.026), eosinophil count (median = 190 [0–800] [cells/µL], p < 0.001), basophil count (median = 40 [0–100] [cells/µL], p = 0.021), and total IgE (median = 240.5 [45–2,644] [kU/L], p < 0.001) level were significantly higher in the omalizumab responder patients (UCT score ≥12 at 6 months and an increase of ≥3 compared to baseline). Psychiatric disorders (n = 13 [41.9%], p = 0.008) and anti-TG (n = 11 [35.5%] [>2 IU/mL positive], p = 0.024) were significantly higher in the oma­lizumab nonresponder patients (UCT score ≤11 at 6 months). A weak but significant clinical correlation was found between blood eosinophil count (r = 0.168, p = 0.013), blood lymphocyte count (r = −0.149, p = 0.027), total IgE level (r = 0.207, p = 0.002), and increase in UCT score. As a result of the ROC curve analysis, the blood eosinophil count (AUC: 0.763, p < 0.001), total IgE level (AUC: 0.866, p < 0.001), and blood basophil count (AUC: 0.662, p = 0.004) had diagnostic value in predicting the response to omalizumab treatment in patients with CU. Conclusion: The patients with CU who were atopic with high eosinophils, high basophils, and high total IgE levels had good response to omalizumab treatment, but the patients with concomitant psychiatric disease and positive thyroid autoantibodies had poor response to omalizu­mab treatment. These findings obtained in our study should be tested in randomized controlled studies.

REACTION OF NASAL POLYPS IN ALLERGEN-SPECIFIC IMMUNOTHERAPY WITH FUNGAL ALLERGENS IN PATIENTS WITH NASAL POLYPS ON THE BACKGROUND OF FUNGAL SENSITIZATION

Fungal flora is one of the causes of inflammation, including nasal polyposis. Therefore, researches aimed at reducing the impact of fungal sensitization (FS) on the course of chronic rhinosinusitis with nasal polyps (CRSwNP) are relevant.&#x0D; The research included 90 patients with chronic rhinosinusitis with nasal polyps combined with fungal sensitization. The patients were divided into two groups — the first clinical group (G1) and the second clinical group (G2). Group G1 received allergen-specific immunotherapy (ASIT) according to the scheme. Group G2 received basic treatment according to the protocol № 181 of 24.03.2009 (“Protocol for providing medical care to patients with chronic sinusitis”). Indications for allergen-specific therapy were hyperreactivity to fungi (positive allergy history of FS), the presence of specific IgE antibodies to fungal allergens, positive skin tests with fungal allergens, and high levels of total IgE. The research aimed to evaluate the effect of allergen-specific therapy on nasal polyps in patients with CRSwNP on the background of fungal sensitization. The specific oral treatment was carried out in two phases: the first — cumulative or initial, and the second — maintaining, in which the maximum tolerated dose was reached by gradually increasing the allergen concentration. The first phase duration was about 2.5–3 months. In the second phase, which lasted up to 6 months, the patient received the maximum allowable dose of the allergen to achieve a state of persistent hyposensitization. The therapeutic allergen was administered in the morning, 30 minutes before meals. The right amount of drops were dosed per teaspoon from the bottle with the allergen.&#x0D; Treatment was initiated during the period of clinical remission. ASIT was performed with basic anti-inflammatory treatment. The treatment efficiency was evaluated after 3, 6, and 12 months of treatment.&#x0D; Evaluation of the clinical efficiency of allergen-specific immunotherapy was made on the 4-point scale, where excellent results (4 points) — complete remission of the disease during the follow-up period (6-12 months); good results (3 points) — exacerbation of the disease 1-2 times per year, in mild form and removed by expectant treatment; fair results (2 points) — the number of exacerbations did not decrease, poor results (1 point) treatment is stopped due to lack of effect or the patient's symptoms constantly worsen after the introduction of an allergen. The size and distribution of nasal polyps were assessed by the results of nasal endoscopy using the IV-grade scale: I degree - polyps are not visible on endoscopic examination but present on CT scan; II degree - polyps visible in the middle nasal passages; III degree - polyps visible outside the middle nasal passages; IV - degree – nasal polyps obturate the nasal cavity.&#x0D; Improvement of nasal endoscopy picture (the number of G1 patients diagnosed with stage III of nasal polyps after 12 months decreased by 11.1%), reducing the volume of basic therapy. Satisfactory treatment results were determined in 13.8% of patients, in whom the number of exacerbations did not decrease, but the general well-being became much better than before specific immunotherapy, which indicates a stable effect after the treatment.&#x0D; Conclusions. The results conclude that the use of ASIT treatment is pathogenetically justified and significantly improves the clinical condition and quality of life in patients with chronic rhinosinusitis with nasal polyps and fungal sensitization.&#x0D; The severity of the polypous process in G1 patients was 1.6 times lower compared to G2, which contributed to the positive clinical effect of treatment in 86.1% of patients.&#x0D; The conducted research has shown high efficacy, good tolerability, and safety of the non-invasive method of treatment (ASIT) in chronic rhinosinusitis with nasal polyps and fungal sensitization.