High Total Serum IgE Levels Research Articles

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.

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.

Levels of Galectin-7 in serum and sputum in children with asthma

Objective: To observe the expression of Galectin-7 in the serum and sputum of asthmatic children and to explore its significance in asthmatic children. Methods: The study prospectively case-control selected 183 children diagnosed with bronchial asthma at Department Ⅱ of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Beijing Children's Hospital of Capital Medical University. The control group consisted of 41 children with other bronchial diseases and 43 healthy children. Children in the asthma group were divided into acute and non-acute exacerbation groups. Acute exacerbation group was divided as mild acute, moderate acute and severe acute groups; non-acute exacerbation group was divided as mild persistent, moderate persistent and severe persistent groups. Children without acute exacerbation asthma in the asthma group were divided into high and low Galectin-7 groups based on median serum Galectin-7 levels. Serum and sputum were collected, Galectin-7 levels were measured using enzyme-linked immunosorbent assay. The study compared and analyzed the differences in Galectin-7 levels between children with asthma and the control groups using Mann-Whitney U test or the Kruskal-Wallis or the Chi-square test for inter-group comparisons. Results: Among 183 children, 61 cases had acute asthma exacerbation, and 122 cases had persistent asthma without acute exacerbation. The asthma group comprised 110 males and 73 females. The control group consisted of 41 children with other bronchial diseases, including 24 cases of bronchiectasis and 17 cases of obliterans bronchitis. The control group comprised 26 males and 15 females. Forty-three healthy children who underwent physical examination, including 22 males and 21 females. The levels of Galectin-7 in serum were significantly higher in children with an acute asthma exacerbation than that of healthy children (0.1 (0, 0.7) vs. 0 (0, 0.2) μg/L, Z=2.09, P=0.001). Galectin-7 levels in sputum were higher in children with an acute asthma exacerbation than that in children with other bronchial diseases (1.2 (0.1,3.7) vs. 0.4 (0.1, 1.5) μg/L, Z=2.20, P<0.001). Serum Galectin-7 levels were significantly higher in children with persistent asthma compared to children with other bronchial diseases and healthy children (0.6 (0.3, 1.2) vs. 0.1 (0, 0.5) and 0 (0, 0.2) μg/L, Z=-6.12,-7.63, both P<0.001), and the levels were significantly and positively correlated with asthma severity (r=0.77, P<0.001), disease duration (r=0.34, P=0.001), and number of previous attacks (r=0.51, P<0.001). There were 61 children in the high-Galectin-7 group and 61 children in the low-Galectin-7 group. Children with high Galectin-7 had more asthma triggers, a greater proportion with a positive family history, more previous asthma attacks, longer duration of asthma, and higher serum total IgE levels compared to those with low Galectin-7 (χ2=9.30, 22.46, Z=5.06, 3.57, 2.31, all P<0.05). Conclusion: The expression of Galectin-7 is found to be elevated in the serum and sputum of asthmatic children and correlated with asthma conditions.

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.

Association Between Serum Total IgE Levels and Clinical Response to Omalizumab for Chronic Spontaneous Urticaria: A Systematic Review and Meta-Analysis.

Omalizumab is the only biological agent approved for patients with chronic spontaneous urticaria (CSU), but no biomarker is well established for predicting clinical response to omalizumab. We aimed to determine the association between baseline total serum IgE levels and the effects of omalizumab in patients with CSU. PubMed, Web of Science, Scopus, and Cochrane Library were systematically searched for relevant studies from inception to August 23, 2022. The research protocol was registered on PROSPERO (CRD42022355592). No language restrictions were applied. A random-effects model was used for meta-analysis. Ten interventional studies, including 1 randomized controlled trial, were included in the final meta-analysis, and a total of 866 patients with CSU were included. A pooled analysis showed significantly higher serum total IgE levels in complete responders (CRs) than in nonresponders (NRs) (mean difference [MD]: 56.509 IU/mL; 95% confidence interval [CI]: 24.230-88.789) and in partial responders (PRs) than in NRs (MD: 62.688 IU/mL; 95% CI: 32.949-92.427), but no significant difference was detected between CRs and PRs. The mean total IgE levels for CRs, PRs, and NRs were 163.154, 179.926, and 51.535 IU/mL, respectively. Further, the serum total IgE levels in early CRs were significantly higher compared with late CRs (MD: 55.194 IU/mL; 95% CI: 13.402-96.986). The sensitivity analyses with the leave-one-out method validated the robustness of all findings. This systematic review and meta-analysis provide convincing evidence that pretreatment total serum IgE levels in patients with CSU are associated with clinical responses to omalizumab.

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 prevalence of ultra-low total IgE level among Egyptian population: impact of age, sex, and socioeconomic class

BackgroundImmunoglobulin E (IgE) is the least prevalent antibody type; it plays a key role in host immunity against parasitic infections and allergic diseases. Association between IgE deficiency and higher malignancy rates has been suggested in many studies.ObjectivesThe goal of our study was to determine the prevalence of ultra-low total IgE levels and their variations according to sex and age among the Egyptian population.MethodologyThis multicenter retrospective cross-sectional study included serum total IgE and CBC records of 1099 children and 993 adults recruited from private and public hospitals in Egypt between 2015 and 2021. Total IgE levels were classified into ultra-low, normal, high, and very high.ResultsOf all included subjects, 0.8% had ultra-low IgE levels and 74.4% had normal IgE levels. High and very high serum total IgE levels were 24.1% and 0.7%, respectively. IgE levels were significantly higher among adults than children 45 (16.5–113.25) IU/ml vs. 20 (10–75) IU/ml; p < 0.001and among private hospital’s patients than the public one (40 (15–98.4) IU/ml vs. 25 (10–98.4) IU/ml; p = 0.002. No significant difference between total IgE serum levels regarding gender (p = 0.825). Total IgE levels were higher among young adults, with a gradual decline among older patients and a peak among the 50 s and 60 s patients. Pearson correlation between IgE and absolute eosinophilic count showed positive correlation but did not reach significant level r = 0.04, p = 0.367.ConclusionAge and socioeconomic class have impacts on total IgE levels with a relatively low prevalence of ultra-low IgE among the Egyptian population.

A Study on Correlation of Serum IGE Levels with Diagnosis and Management of Bronchial Asthma in Children

Introduction: Traditional methods for identifying atopic individuals in allergy and respiratory illness studies include the responsiveness of allergy skin tests, serum IgE levels, and peripheral blood eosinophilia. Objectives: The main objective of the study is to find the association between Raised Serum IgE levels and bronchial asthma in children. Material and methods: This cross sectional study was conducted in Mayo Hospital Lahore during May 2021 till November 2021. The data was collected from 140 patients of age range 2 to 12 years. The doctor conducted a thorough examination of each patient, after which the required paperwork was completed. Results: 140 patients provided the data for this study. Gender, a family history of asthma, breastfeeding exclusively for the first six months, or living in a residential setting were not shown to have a significant impact on the amount of total serum IgE. Higher total serum IgE levels in asthmatics and older age groups, cigarette smoke exposure, and higher eosinophil counts are correlated. Asthmatics had higher IgE levels. Conclusion: It is concluded that there is a correlation between total serum IgE levels and a child's propensity for wheeze and early sensitivity to local aeroallergens. Allergy in children can be accurately predicted by measuring the serum total IgE level.

Alveolar Nitric Oxide and Peripheral Oxygen Saturation in Frequent Exacerbators with Asthma: A Pilot Study

Introduction: Asthmatics can experience recurrent exacerbations (AEs), irrespectively of asthma severity. Airway inflammatory monitoring could be fundamental to optimize the asthma management. The present study evaluated whether exhaled NO concentrations in proximal and distal respiratory compartments are different in AE-prone patients in combination with T2 blood biomarkers and resting oxygen saturation (SpO₂). Methods: In this observational cross-sectional study, 91 mild-to-severe asthmatics were enrolled. Clinical characteristics, blood and lung function parameters including SpO₂, and F_ENO were evaluated. On 50 randomly selected patients, C_ANO and J_awNO were also analyzed. Then, patients were stratified in frequent exacerbators (FEs) or non-frequent exacerbators (nFEs), according to AE frequency in the previous year (phase I). Chart data were re-evaluated through a 12-month follow-up period post exhaled NO measurement to detect occurrence of novel AE (phase II). Results: FE asthmatics had poorer asthma control and required higher therapeutic intensity (p < 0.05). F_ENO, C_ANO, and J_awNO were similar between FE and nFE. FE exhibited higher total serum IgE levels and residual volume values but reduced SpO₂ than nFE (p < 0.05); SpO₂<96.5% characterized the FE patient (odds ratio = 2.94). In phase II, C_ANO was higher in the group with novel AE at 1-month post-NO measurement (p < 0.05), but not afterward. A higher prevalence of C_ANO >6 ppb was detected in asthmatics who developed AE within 1 month, suggesting its potential clinical use as biomarker in predicting near-future AE (RR = 11.20). Conclusion: AE-susceptible asthmatics are characterized by air trapping and distal airway inflammation in conjunction with lower oxygen saturation. C_ANO and SpO₂ could exert specific roles, respectively, in predicting AE and monitoring FE asthmatics.

Genome-wide association study of asthma, total IgE, and lung function in a cohort of Peruvian children

Genetic ancestry plays a role in asthma health disparities. Our aim was to evaluate the impact of ancestry on and identify genetic variants associated with asthma, total serum IgE level, and lung function. A total of 436 Peruvian children (aged 9-19 years) with asthma and 291 without asthma were genotyped by using the Illumina Multi-Ethnic Global Array. Genome-wide proportions of indigenous ancestry populations from continental America (NAT) and European ancestry from the Iberian populations in Spain (IBS) were estimated by using ADMIXTURE. We assessed the relationship between ancestry and the phenotypes and performed a genome-wide association study. The mean ancestry proportions were 84.7% NAT (case patients, 84.2%; controls, 85.4%) and 15.3% IBS (15.8%; 14.6%). With adjustment for asthma, NAT was associated with higher total serum IgE levels (P< .001) and IBS was associated with lower total serum IgE levels (P< .001). NAT was associated with higher FEV1 percent predicted values (P< .001), whereas IBS was associated with lower FEV1 values in the controls but not in the case patients. The HLA-DR/DQ region on chromosome 6 (Chr6) was strongly associated with total serum IgE (rs3135348; P= 3.438×10-10) and was independent of an association with the haplotype HLA-DQA1∼HLA-DQB1:04.01∼04.02 (P= 1.55×10-05). For lung function, we identified a locus (rs4410198; P= 5.536×10-11) mapping to Chr19, near a cluster of zinc finger interacting genes that colocalizes to the long noncoding RNA CTD-2537I9.5. This novel locus was replicated in an independent sample of pediatric case patients with asthma with similar admixture from Brazil (P= .005). This study confirms the role of HLA in atopy, and identifies a novel locus mapping to a long noncoding RNA for lung function that may be specific to children with NAT.

Primary Immun Deficiency in Patients with Non-Cystic Fibrosis Bronchiectasis and Its Relationship with Clinical Parameters.

Bronchiectasis is characterized by chronic respiratory infection. The role of immunodeficiency in this disease is poorly studied in relation to clinical indices. The primary aim of this study was to determine the frequency of these neglected altered immune status by evaluating immunoglobulins, lymphocyte subsets, complement levels, and neutrophil function, and to assess its relationship with clinical parameters in adult patients with non-cystic fibrosis bronchiectasis (NCFB). A total of 74 (30 men and 44 women with a mean age of 47±17 years) adult patients with stable NCFB were enrolled in this study. The bronchiectasis severity index (BSI) and FACED (F:FEV1, A: Age, C: Chronic colonization, E: Extension, D: Dyspnea) scores were assessed. Peripheral blood samples were collected for the detection of total IgG, IgA, IgM, IgE, and IgG subclasses and C3 and C4 levels. The counts of CD3, CD4, CD8, CD19, CD16/56 expressing peripheral blood lymphocytes and neutrophil oxidative function were evaluated. In the study population, BSI and FACED severity index scores increased with longer duration of the disease (p=0.01 and p=0.040, respectively). Of the 74 patients, 27 (37%) showed humoral aberrations. The number of male patients were higher in this group (p=0.03). High serum total IgE levels were associated with high scores in BSI (moderate-severe group versus mild group, p=0.030). Patients with bronchiectasis demonstrated lower CD3+ T cell count, lower CD4+ T helper cell percentage, and lower CD4+ T cell count (p=0.031, p=0.030, p=0.029, respectively) than healthy subjects. A significant negative correlation was found between the percentage and count of CD16/56+ natural killer (NK) cells and the number of exacerbations within the past year (r=-0.230, p=0.049 and r=-0.264, p=0.023, respectively). Humoral aberrations in adult patients with NCFB were found to be frequent. IgE levels were related to high scores for disease severity indices. Furthermore, patients with low percentage and counts of NK cells had higher rates of exacerbations. These results emphasize the importance of immune function assessment in adult patients with NCFB.

Hypersensitivity to dipyrone in aspirin-exacerbated respiratory disease patients is associated with urticaria

ObjectiveTo phenotype patients with aspirin-exacerbated respiratory disease (AERD) according to the presence of atopy, urticaria and level of peripheral eosinophils. MethodsThis study included adult asthmatic patients with AERD followed up at a tertiary hospital. They were classified according to atopy and/or urticaria, assessing clinical and laboratorial differences among the groups in order to identify possible aggravating factors of the disease. ResultsWe included 73 patients, 78.1% being female with a mean age of 54.0 years. Severe asthma was observed in 68.5% and respiratory exacerbation with dipyrone in 67.1% of these patients. They had median total serum IgE of 191.6 IU/mL, mean peripheral eosinophils of 718.5 cells/mm3, and 50.7% were atopic. Urticaria was observed in 32.9% of them, and exacerbations were more often triggered by dipyrone (p = .016). Atopic patients were younger than nonatopic patients (p = .023), and had, on average, higher total serum IgE levels (p = .022). We observed a good correlation between asthma severity and peripheral eosinophils count (r2 = 026; p = .021). ConclusionsIn this study, severe asthma was highly prevalent in AERD patients. Likewise, urticaria was quite prevalent and its presence was associated with dipyrone induced hypersensitivity reaction. Atopy was found in half of the patients, with no association with asthma severity. Patients with higher levels of peripheral eosinophils had more severe asthma. Dypirone hypersensitivity may be a marker for concomitant respiratory and cutaneous hypersensitivity reactions.

Clinical utility of serum specific IgE food testing in general practice: A tertiary care experience

Serum Specific IgE (SSIgE) testing is the preferred method for diagnosis of food allergy by Primary Care Physicians(PCPs). However, the diagnostic value of such tests, without a valid history, is questionable due to high false positive results. We tested the hypothesis that greater than 50% of positive food allergens according to Serum Specific Immunoassays do not correlate with a definitive food allergy. We performed a medical record review on 336 patients previously diagnosed with “food allergies” based on positive SSIgE ordered by PCPs. We compared these SSIgE results with an assessment from our tertiary care center Allergy specialists which included detailed history, skin prick testing and home/in office oral challenges. The top 10 foods tested by PCPs were milk, peanut, wheat, shrimp, soybean, codfish, walnut, egg, sesame, and scallop. 167 (49.7%) subjects had positive skin testing to one or more foods. Only 41(12.20%) had positive oral food challenges. Average total serum IgE per patient was 581IU/ml (ref: 100-300IU/ml). SSIgE assay was obtained only on 71 subjects in 2008 compared to 240 in 2018. False positive rate in our study is >80 % compared to >50% in the previous studies.A high average total serum IgE level/ patient related to nonspecific IgE and cross-reactive but clinically irrelevant allergen SSIgE might be a reason for false-positive IgE values for the specific food allergen.A rising trend for indiscriminate ordering of SSIgE in the last 10 years has caused not only the over diagnosis of food allergy but also an unnecessary cost of evaluation.

Characterization of tenascin-C as a novel biomarker for asthma: utility of tenascin-C in combination with periostin or immunoglobulin E

BackgroundExtracellular matrix proteins tenascin-C (TNC) and periostin, which were identified as T-helper cell type 2 cytokine-induced genes in human bronchial epithelial cells, accumulate in the airway basement membrane of asthmatic patients. Although serum periostin has been accepted as a type 2 biomarker, serum TNC has not been evaluated as a systemic biomarker in asthma. Therefore, the objective of this study was to evaluate whether serum TNC can serve as a novel biomarker for asthma.MethodsWe evaluated 126 adult patients with mild to severe asthma. Serum TNC, periostin, and total IgE concentrations were quantified using enzyme-linked immunosorbent assays.ResultsSerum TNC levels were significantly higher in patients with severe asthma and high serum total IgE levels. Patients with both high serum TNC (> 37.16 ng/mL) and high serum periostin (> 95 ng/mL) levels (n = 20) or patients with both high serum TNC and high serum total IgE (> 100 IU/mL) levels (n = 36) presented higher disease severity and more severe airflow limitation than patients in other subpopulations.ConclusionsTo our knowledge, this is the first study to show that serum TNC levels in asthmatic patients are associated with clinical features of asthma and that the combination of serum TNC and periostin levels or combination of serum TNC and total IgE levels were more useful for asthma than each single marker, suggesting that serum TNC can serve as a novel biomarker for asthma.

The characterization of asthma with blood eosinophilia in adults in Latin America

Objective: To identify and characterize asthma with blood eosinophilia in adults. Methods: This cross-sectional study consisted of 164 asthma patients, aged 18 years or older. Multivariate analyses by logistic regression were performed to identify clinical characteristics and biomarkers associated with asthma with blood eosinophilia (defined as asthma and a peripheral blood eosinophil count ≥400 cells/mm3). To evaluate the diagnostic accuracy of these biomarkers, the sensitivity, specificity and predictive values were calculated. Additionally, the area under the receiver operating characteristic (ROC) curve (AUC) was estimated for each biomarker. Results: Overall, 37.8% (95%CI: 30.7–45.4%) of asthma patients had blood eosinophilia. The following factors were associated with this characteristic: patient age <50 years (OR 3.25; 95% CI: 1.33–7.94), a serum level of IgE ≥300 UI/mL (OR 2.32; 95%CI: 1.14–4.75), and an Asthma Control Test (ACT) score <20 points (OR 3.10; 95%CI: 1.35–4.75); asthma with blood eosinophilia was also associated with a baseline FEV1/FVC <70% (OR 2.68; 95%CI: 1.28–5.59). On the other hand, age <50 years and ACT score <20 showed the highest sensitivity (above 80% each). Serum IgE level ≥300 UI/mL had the highest specificity (almost 68%). Finally, those with an ACT score <20 had the highest AUC (68%). Conclusions: In our study population, one-third of asthmatic adults had asthma with blood eosinophilia. Furthermore, the prevalence was greater in those ≤50 years of age; these patients experienced more severe, more poorly controlled asthma and had higher total serum IgE levels.

The Severe Asthma Network in Italy: Findings and Perspectives

Severe Asthma Network in Italy (SANI) is a registry of patients recruited by accredited centers on severe asthma. To analyze epidemiological, clinical, inflammatory, functional, and treatment characteristics of severe asthmatics from the SANI registry. All consecutive patients with severe asthma were included into the registry, without exclusion criteria to have real-life data on demographics, asthma control, treatments (including biologics), inflammatory biomarkers, and comorbidities. A total of 437 patients (mean age: 54.1 years, 57.2% females, 70.7% atopics, 94.5% in Global Initiative for Asthma severity step V) were enrolled into the study. The mean annual exacerbation rate was 3.75. The mean blood eosinophil level was 536.7 cells/mcL, and the average serum total IgE was 470.3 kU/L. Approximately 64% of patients were on regular oral corticosteroid treatment, 57% with omalizumab and 11.2% with mepolizumab. Most common comorbidities were rhinitis, nasal polyposis, and bronchiectasis. Patients with nasal polyposis had higher age of disease onset, higher blood eosinophil count, and lower frequency of atopy and atopic eczema. Bronchiectasis was associated with more frequent severe exacerbations, higher blood eosinophils, and total IgE. Stratifying patients, those with late-onset asthma were less frequently atopic (with less frequent allergic rhinitis and food allergy), and more frequently with nasal polyposis and higher serum total IgE levels. This study revealed a high frequency of relevant comorbidities and that a substantial proportion of patients have late-onset asthma; all these features define specific different disease phenotypes. Severe asthma complexity and comorbidities require multidisciplinary approaches, led by specifically trained pulmonologists and allergists.

Severe/uncontrolled asthma and overall survival in atopic patients with eosinophilic granulomatosis with polyangiitis.

Although asthma, rhinitis/rhinosinusitis and peripheral eosinophilia are present in virtually all patients with eosinophilic granulomatosis with polyangiitis (EGPA), the role of atopy in these patients is not well defined. To clarify the role of atopy in patients affected with EGPA. Clinical, laboratory and standard spirometry data have been abstracted from medical records. Only patients who underwent skin and/or specific IgE testing for common aeroallergens before the vasculitic phase were included. Overall, 33.5% (63) of our patients underwent skin and/or specific IgE testing to aeroallergens. Atopy related to aeroallergens was confirmed in 22.3% (two-third of those tested), and was associated with more severe/uncontrolled asthma (p < 0.001), including a greater use of oral glucocorticoids for respiratory manifestations the year before the diagnosis of EGPA (p = 0.013). Atopic patients with EGPA had higher total serum IgE levels and less renal disease at EGPA diagnosis compared to non-atopic patients (p < 0.05). Among atopic patients, the majority had multiple sensitizations (76%); dust mite and grass pollen were the most common respiratory allergens identified. The number of allergens did not correlate with peripheral eosinophilia, total serum IgE, ESR, or measures of airway obstruction (p > 0.05 in all cases). The presence of atopy increased the risk of severe/uncontrolled asthma, but not the risk of severe vasculitis (Five Factor Score≥1). Atopic patients had a better overall survival (p = 0.027). In EGPA, atopy is associated with better prognosis and more severe/uncontrolled asthma manifestations in the year before the development of vasculitis, but not with more severe vasculitis at presentation.

Neither self-reported atopy nor IgE-mediated allergy are linked to gastrointestinal symptoms in patients with irritable bowel syndrome.

Among patients with irritable bowel syndrome (IBS), atopic disease has been proposed as a common comorbidity increasing the IBS symptom burden. We therefore assessed the prevalence of self-reported atopy among patients with IBS as compared to non-IBS controls, and whether atopy and higher serum IgE levels were associated with increased IBS symptom severity. Levels of total and specific IgE in serum were measured and questionnaires assessing the presence of atopic disease (ie, eczema, asthma, rhinoconjunctivitis, and pollen allergy), gastrointestinal symptom burden, food intolerance, somatic, and psychological symptoms were completed. In total, 223 patients with IBS and 47 controls participated. Presence of atopic disease was reported in 55% of patients with IBS compared to 40% of controls (P=.07). IBS patients with atopic manifestations (N=123) had higher total serum IgE levels (median 31 vs 16 kUA /L, P<.001) and higher prevalence of self-reported food intolerance (28% vs 9%, P=.002) than non-atopic IBS patients (N=100), respectively, but no major difference in gastrointestinal or psychological symptom burden was noted. However, severe somatic symptoms were more common among atopic than non-atopic patients with IBS (38% vs 27%, P=.028). We found no associations between self-reported atopy and IBS symptom severity using linear regression models. Atopic disease is common in patients with IBS, but that is also true for subjects without IBS. The presence of atopic disease in IBS is associated with self-reported food intolerance and somatic symptom severity, but unrelated to IBS symptom severity.

Dysbiosis of Inferior Turbinate Microbiota Is Associated with High Total IgE Levels in Patients with Allergic Rhinitis.

Abnormalities in the human microbiota are associated with the etiology of allergic diseases. Although disease site-specific microbiota may be associated with disease pathophysiology, the role of the nasal microbiota is unclear. We sought to characterize the microbiota of the site of allergic rhinitis, the inferior turbinate, in subjects with allergic rhinitis (n = 20) and healthy controls (n = 12) and to examine the relationship of mucosal microbiota with disease occurrence, sensitized allergen number, and allergen-specific and total IgE levels. Microbial dysbiosis correlated significantly with total IgE levels representing combined allergic responses but not with disease occurrence, the number of sensitized allergens, or house dust mite allergen-specific IgE levels. Compared to the populations in individuals with low total IgE levels (group IgElow), low microbial biodiversity with a high relative abundance of Firmicutes phylum (Staphylococcus aureus) and a low relative abundance of Actinobacteria phylum (Propionibacterium acnes) was observed in individuals with high total serum IgE levels (group IgEhigh). Phylogeny-based microbial functional potential predicted by the 16S rRNA gene indicated an increase in signal transduction-related genes and a decrease in energy metabolism-related genes in group IgEhigh as shown in the microbial features with atopic and/or inflammatory diseases. Thus, dysbiosis of the inferior turbinate mucosa microbiota, particularly an increase in S. aureus and a decrease in P. acnes, is linked to high total IgE levels in allergic rhinitis, suggesting that inferior turbinate microbiota may be affected by accumulated allergic responses against sensitized allergens and that site-specific microbial alterations play a potential role in disease pathophysiology.

Targeting IgE Antibodies by Immunoadsorption in Atopic Dermatitis.

One major hallmark of atopic dermatitis (AD) is the elevated level of total serum IgE, which has been reported to be partly of the autoreactive type in a subset of patients. Immunoadsorption (IA) has been successfully applied in various classical autoantibody-mediated diseases such as pemphigus. Recent reports proposed the use of IA also for patients with severe AD and high total serum IgE levels. In this mini-review, we summarize the current knowledge about this novel treatment approach for AD and briefly discuss the so far incompletely known role of autoreactive IgE as potential target of IA therapy in this common inflammatory skin disorder.