Eosinophilic Protein Research Articles

Features of mammary gland morphology in domestic carnivores

The mammary gland is a target organ for hormones in the hypothalamus, pituitary gland, thyroid gland, and ovaries. In the postnatal period of animal ontogenesis, breast growth, and development are determined by the estrous cycle and pregnancy. One of the most pressing problems in morphology, mammology, and reproductology of animals is the study of the structure of the breast at the macro and microscopic levels. However, modern studies on the morphology of animals' breasts are mainly devoted to the features of pathomorphological changes in the breast during carcinogenesis. The work aims to conduct a scientific review of the study of normal breast morphology in domestic carnivores. Electronic publication searches have been conducted in the Web of Science, Scopus, PubMed, and Google Scholar databases over the past 20 years. The principles of objectivity and a comprehensive attitude to studying the chosen problem are used. The authors of the review article review the current scientific literature and summarize current knowledge on the features of dog and cat breast morphology. The anatomical structure of the breast of animals is presented with an emphasis on its topography. According to the description of the microscopic structure of the breast, its main structural components are characterized by secretory parts (alveoli and tubes) and intraparticle excretory ducts. Anatomical characteristics of the nerves, blood, and lymphatic vessels of the mammary glands of dogs and cats are presented. Morphological changes in the mammary gland of dogs and cats at different stages of the estrus cycle and during pregnancy are described; in particular, the mammary gland is at rest (inactive) during proestrus and estrus. According to diestrus, due to an increase in progesterone levels, successive morphological changes occur, in particular, stromal and ductal proliferation; early development of lobules with branching ducts and proliferation of alveoli; the dominance of glandular tissue with large lobules containing secretory material; early regression, an increase in interparticle connective tissue, eosinophilic protein secretion in dilated ducts and alveoli. Complete involution of the alveoli and tubes of the breast is recorded at the end of the anestrus. The described anatomical and microscopic features of the structure of the mammary glands of dogs and cats are relevant for the comparative morphology of carnivores at different stages of the sexual cycle and during pregnancy. Data on blood supply, lymphatic drainage, and innervation of the breast are essential for its functional characteristics in normal and pathological conditions, particularly for developing a reasonable model of breast extirpation in malignant tumors.

Walking a thin line between fixation and epitope binding - characterization of antigen retrieval methods suitable for eosinophil and HSV-2 staining in formalin-fixed female reproductive tissue.

Antibody-based fluorescence analysis of female reproductive tissues in research of sexually transmitted diseases allows for an in-depth understanding of protein localization, interactions, and pathogenesis. However, in many cases, cryosectioning is not compatible with biosafety regulations; at all times, exposure of lab personnel and the public to potentially harmful pathogens from biological infectious material must be avoided; thus, formaldehyde fixation is essential. Due to formaldehyde's cross-linking properties, protein detection with antibodies can be impeded. To allow effective epitope binding during immunofluorescence of formalin-fixed paraffin-embedded vaginal tissue, we investigated two antigen retrieval methods. We tested these methods regarding their suitability for automated image analysis, facilitating reproducible quantitative microscopic data acquisition in sexually transmitted disease research. Heat-based retrieval at 80°C in citrate buffer proved to increase antibody binding to eosinophil protein and HSV-2 visibly and tissue morphology best, and was the most efficient for sample processing and quantitative analysis.

Compilation of Evidence Supporting the Role of a T Helper 2 Reaction in the Pathogenesis of Acute Appendicitis.

Despite being the most common abdominal surgical emergency, the cause of acute appendicitis (AA) remains unclear, since in recent decades little progress has been made regarding its etiology. Obstruction of the appendicular lumen has been traditionally presented as the initial event of AA; however, this is often the exception rather than the rule, as experimental data suggest that obstruction is not an important causal factor in AA, despite possibly occurring as a consequence of the inflammatory process. Type I hypersensitivity reaction has been extensively studied, involving Th2 lymphocytes, and cytokines such as IL-4, IL-5, IL-9 and IL-13, which have well-defined functions, such as a positive-feedback effect on Th0 for differentiating into Th2 cells, recruitment of eosinophils and the release of eosinophilic proteins and the production of IgE with the activation of mast cells, with the release of proteins from their granules. Cytotoxic activity and tissue damage will be responsible for the clinical manifestation of the allergy. AA histological features are similar to those found in allergic reactions like asthma. The intestine has all the components for an allergic immune response. It has contact with hundreds of antigens daily, most of them harmless, but some can potentially induce an allergic response. In recent years, researchers have been trying to assess if allergy is a component of AA, with their latest advances in the understanding of AA as a Th2 reaction shown by the authors of this article.

Eosinophilic globules (syn. hyaline inclusions) and protein crystalloids in the nasal mucosa of rats treated with synthetic amorphous silica, an unspecific chitinase-like-protein-positive background lesion

In a 13-week inhalation toxicity study with three recovery periods (3, 6, and 12 months), Crl: WI rats were allocated to nine groups, each containing 25 animals per sex. Eight groups were treated daily by inhalation with the test items at concentrations of 0.5, 1.0, 2.5, or 5.0 mg/m3 (SAS 1 groups 2, 3, 4, or 5, respectively; SAS 2 groups 6, 7, 8, or 9, respectively). Controls (group 1) were treated with air only.In nasal cavities, the major lesions consisted of increased eosinophilic globules and chitinase-3-like-protein-positive crystalloids* in the nasal mucosa, mainly in nasal cavity levels 2–4 up to week 26 of recovery without any further injury in olfactory mucosa, mainly in SAS 1-treated animals. Eosinophilic globules in the rodent nasal cavity are common and increase with age; they represent a particular finding of the rodent nasal mucosa. The relevance of chitinase-3-like protein (Ym1 + Ym2) expression in the rodent nasal mucosa is unknown but is normal in control animals. Both findings developed without any indicator for inflammatory processes. The increase of these unspecific background findings is considered an indicator of minor irritative effects.Due to the clear lack of nasal tissue injury or concurrent changes (degeneration, necrosis, inflammatory infiltrate, dysplasia, and/or neoplasia) following repeated inhalation exposure to SAS, it is deemed that the eosinophilic globules (hyaline inclusions) combined with the formation of eosinophilic protein crystalloids in this study represent an adaptive response.

Presence of sputum IgG against eosinophilic inflammatory proteins in asthma.

Sputum immunoglobulin G (Sp-IgG) has been discovered to induce cytolytic extracellular trap cell death in eosinophils, suggesting a potential autoimmune mechanism contributing to asthma. This study aimed to explore the potential origin of Sp-IgG and identify clinically relevant subtypes of Sp-IgG that may indicate autoimmune events in asthma. This study included 165 asthmatic patients and 38 healthy volunteers. We measured Sp-IgG and its five subtypes against eosinophil inflammatory proteins (Sp-IgGEPs), including eosinophil peroxidase, eosinophil major basic protein, eosinophil-derived neurotoxin, eosinophil cationic protein, and Charcot-Leyden Crystal protein in varying asthma severity. Clinical and Mendelian randomization (MR) analyses were conducted. A positive Sp-IgGEPs signature (Sp-IgGEPs+) was defined when any of the five Sp-IgGEPs values exceeded the predefined cutoff thresholds, calculated as the mean values of healthy controls plus twice the standard deviation. The levels of Sp-IgG and Sp-IgGEPs were significantly elevated in moderate/severe asthma than those in mild asthma/healthy groups (all p < 0.05). Sp-IgG levels were positively correlated with airway eosinophil and Sp-IgGEPs. MR analysis showed causality between eosinophil and IgG (OR = 1.02, 95%CI = 1.00-1.04, p = 0.020), and elevated IgG was a risk factor for asthma (OR = 2.05, 95%CI = 1.00-4.17, p = 0.049). Subjects with Sp-IgGEPs+ exhibited worse disease severity and served as an independent risk factor contributing to severe asthma (adjusted-OR = 5.818, adjusted-95% CI = 2.193-15.431, adjusted-p < 0.001). Receiver operating characteristic curve analysis demonstrated that the combination of Sp-IgGEPs+ with non-allergic status, an ACT score < 15, and age ≥ 45 years, effectively predicted severe asthma (AUC = 0.84, sensitivity = 86.20%, specificity = 67.80%). This study identifies a significant association between airway eosinophilic inflammation, Sp-IgG, and asthma severity. The Sp-IgGEPs panel potentially serves as the specific biomarker reflecting airway autoimmune events in asthma.

Non-Invasive and Minimally Invasive Biomarkers for the Management of Eosinophilic Esophagitis beyond Peak Eosinophil Counts: Filling the Gap in Clinical Practice.

Eosinophilic esophagitis (EoE) is a chronic esophageal disease that needs lifelong management and follow-up. The diagnosis requires an upper endoscopy with at least one esophageal biopsy demonstrating >15 eosinophils/high-power field, and often occurs with a diagnostic delay of up to ten years, partly due to the absence of valid non-invasive screening tools. In addition, serial upper endoscopies with esophageal biopsies are mandatory to assess the efficacy of any ongoing treatment in patients with EoE. These procedures are invasive, costly, and, when performed without sedation, are often poorly tolerated by patients. Therefore, there is the clinical need to identify reliable non-invasive or minimally invasive biomarkers that could be used to assess disease activity in clinical practice as a surrogate of peak eosinophil counts on esophageal biopsies. This review summarizes evidence on investigational non-invasive or minimally invasive biomarkers for the diagnosis and follow-up of EoE to report on the state of the art in the field and support future research. We discussed eosinophil-derived mediators including eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN, also known as eosinophil protein X), eosinophil peroxidase (EPO), and major basic protein (MBP) as well as other promising non-eosinophil-derived biomarkers. Although several studies have shown the utility of most biomarkers collected from the serum, esophageal luminal secretions, and feces of EoE patients, numerous limitations currently hamper the integration of such biomarkers in clinical practice. Future studies should aim at validating the utility of non-invasive and minimally invasive biomarkers using rigorous protocols and updated consensus criteria for EoE.

A Rapid Sputum‐based Lateral Flow Assay for Airway Eosinophilia using an RNA‐cleaving DNAzyme Selected for Eosinophil Peroxidase

AbstractThe first protein‐binding allosteric RNA‐cleaving DNAzyme (RCD) obtained by direct in vitro selection against eosinophil peroxidase (EPX), a validated marker for airway eosinophilia, is described. The RCD has nanomolar affinity for EPX, shows high selectivity against related peroxidases and other eosinophil proteins, and is resistant to degradation by mammalian nucleases. An optimized RCD was used to develop both fluorescence and lateral flow assays, which were evaluated using 38 minimally processed patient sputum samples (23 non‐eosinophilic, 15 eosinophilic), producing a clinical sensitivity of 100 % and specificity of 96 %. This RCD‐based lateral flow assay should allow for rapid evaluation of airway eosinophilia as an aid for guiding asthma therapy.

A Rapid Sputum-based Lateral Flow Assay for Airway Eosinophilia using an RNA-cleaving DNAzyme Selected for Eosinophil Peroxidase.

The first protein-binding allosteric RNA-cleaving DNAzyme (RCD) obtained by direct in vitro selection against eosinophil peroxidase (EPX), a validated marker for airway eosinophilia, is described. The RCD has nanomolar affinity for EPX, shows high selectivity against related peroxidases and other eosinophil proteins, and is resistant to degradation by mammalian nucleases. An optimized RCD was used to develop both fluorescence and lateral flow assays, which were evaluated using 38 minimally processed patient sputum samples (23 non-eosinophilic, 15 eosinophilic), producing a clinical sensitivity of 100 % and specificity of 96 %. This RCD-based lateral flow assay should allow for rapid evaluation of airway eosinophilia as an aid for guiding asthma therapy.

Morphological Features and Morphometric Parameters of Peripheral Blood Eosinophiles in Raccoon Dogs &lt;i&gt;Nyctereutes procyonoides&lt;/i&gt; (Grey, 1834)

The aim of this work was to analyze the morphology and morphometric parameters of peripheral blood eosinophils and eosinophilic granules in raccoon dogs Nyctereutes procyonoides (Grey, 1834). On blood smears stained by Pappenheim, the composition of the leukocyte formula was determined, the morphological features and morphometric parameters of eosinophils and their granules were evaluated. Cytochemical methods revealed the localization of peroxidase and cationic proteins in eosinophils. ANOVA was used to assess the effect of sex. As a result of the study, it was found that raccoon dogs are characterized by a high relative content of eosinophils (7–10%), as well as the presence of large secretory granules in them. Along with the common eosinophils, there were cells with abnormal granularity (low number of secretory granules, the presence of vacuole-like granules that did not stain with the dyes used). The influence of sex was expressed in a higher proportion of eosinophils with abnormal granularity in males compared to females, while the latter had higher morphometric parameters (the number and average area of granules in one cell, the ratio of the area occupied by granules to the area of the cell). Since the causes of abnormally granular eosinophils in raccoon dogs are not completely clear, there is a need for further research into this issue.

MiR-223-3p regulates the eosinophil degranulation and enhances the inflammation in allergic rhinitis by targeting FBXW7.

MiR-223-3p is a multifunctional microRNA regulated by multiple transcription factors and plays a critical role in inflammation. This paper was designed to investigate the regulatory role and mechanism of miR-223-3p in eosinophils degranulation and allergic rhinitis (AR) inflammation. OVA sensitized AR mouse model and EOL-1 cells model were established. RT-qPCR and FISH were performed to detect the miR-223-3p expression. ELISA and WB were utilized to evaluate mRNA and protein expression. HE staining and transmission electron microscopy were applied to observe the morphological changes in nasal mucosa. Flow cytometry and immunofluorescence staining were performed to measure the proportion of eosinophils and eosinophilic major basic protein expression. The targeting relationship between miR-223-3p and FBXW7 was verified by bioinformatic analysis and dual-luciferase reporter gene assay. The expression of FBXW7 was detected by immunohistochemistry. The level of miR-223-3p in nasal mucosa was significantly up-regulated in AR group. The expression of miR-223-3p, ECP, MBP, and EPO were increased in EOL-1 cells, further increasing the miR-223-3p level could promote the ECP and EPO mRNA expression. Upregulation of miR-223-3p increased eosinophils granule protein expression, aggravated mucosal destruction and enhanced AR inflammation. Luciferase assay verified miR-223-3p directly target the 3'-UTR of FBXW7. In vitro, overexpression of FBXW7 could reverse the increase in MBP expression caused by the up-regulation of miR-223-3p. In vivo, knockdown of FBXW7 could reverse the down-regulation in granule protein level caused by the down-regulation of miR-223-3p, thereby aggravating AR inflammation. Collected evidence elucidated that miR-223-3p could regulate the eosinophil degranulation and enhances the inflammation in AR by targeting FBXW7. The miR-223-3p/FBXW7 axis may provide a novel approach for AR treatment.

СОДЕРЖАНИЕ КАЛЬПРОТЕКТИНА В СТУЛЕ И ЭОЗИНОФИЛЬНОГО ПРОТЕИНА Х В МОЧЕ У МЛАДЕНЦЕВ В ЗАВИСИМОСТИ ОТ ПОЛИМОРФИЗМА ГЕНОВ ИНТЕРЛЕЙКИНА-10 (G1082A, C592A) И ТОЛЛ-ПОДОБНОГО РЕЦЕПТОРА 4 (ASP299GLY)

Background. Cytokine and toll-like receptor gene polymorphisms may impact oral tolerance formation in infants. Objective: To determine the genotype distribution of IL-10 (G1082A, C592A) and TLR 4 (Asp299Gly) gene polymorphisms in children with different family history of allergy residing in Grodno region; to analyze the association between gene polymorphisms and concentrations of fecal calprotectin (FCP) and urine eosinophil protein X (UEoPX) in infants. Material and Methods. 92 infants were recruited and analyzed for IL-10 (G1082A, C592A) and TLR 4 (Asp299Gly) gene polymorphisms. Concentrations of FCP and UEoPX were examined in dynamics in children aged 1 and 3 months. Results. 80.4% and 48.9% of infants were carriers of the mutant allele of the G1082A and C592A polymorphisms respectively. 70.5% of children with negative family history of allergy were carriers of the wild G allele of G1082A polymorphism. Carriage of the mutant A allele of G1082A polymorphism is associated with lower FCP concentration in infants aged 1 month (AA: 1.9 ng/mL [1.9; 3.1], GA: 15.9 ng/mL [1.9; 93.8]) and GG: 88.3 ng/mL [2.4; 230.1]). The level of UEoPX in 3 months old infants with homozygote AA genotype was significantly (p=0.019) higher than in infants with heterozygote CA genotype (3.2 ng/ml [2.4; 4.5] and 2.3 ng/ml [1.3; 3.3] respectively). Conclusion. Carriage of the wild G allele of G1082A polymorphism is associated with higher fecal calprotectin concentration in one month old infants and significantly lower level of urine eosinophil protein X in 3 months old infants.

House Dust Mite Exposure: Can It Be A Severe COVID-19 Prevention?

Background: In the midst of the ongoing COVID-19 pandemic, many studies are looking for treatment to suppress viral replication and prevention through vaccination. However, to this day the number of incidences and deaths due to COVID-19 is still increasing. Objective: The purpose of this article is to review theoretically the alleged increase in eosinophils in house dust mite exposure can prevent the severity of COVID-19 symptoms. Methods: This article was compiled through a literature search in reputable international journals by the time 2020-2021. Result: The severity of symptoms that arise due to COVID-19 infection is one of them caused by eosinophenia. On the other hand, the host immune response to house dust mite exposure can increase the number of eosinophils through stimulation of IL-6, IL-8, GM-CSF, IL-5 and IL-33. These eosinophils will then express TLR-7 on the cell surface which makes them able to recognize SARS-CoV-2. Stimulation of this eosinophil receptor triggers the production of cytokines, degranulation, superoxide, and nitric oxide (NO) through NO synthase which has a direct antiviral effect. EDN and ECP of human eosinophils can decrease viral infectivity through a ribonuclease-dependent mechanism. Eosinophils are capable of producing extracellular traps composed of eosinophilic granule proteins bound to mitochondrial DNA in response to viral infection in vitro, especially in an oxidative lung tissue environment. Eosinophils also rapidly mobilize granules of Th1 cytokines, including IL-12 and IFN-g which are important for antiviral immune responses. Conclusion: Although available data are still limited, there are indications that eosinophils have a protective effect during SARS-CoV-2 infection. Therefore, biological agents such as exposure to house dust mites targeting eosinophils may be useful to help clarify the role of eosinophils in their antiviral response.

Immunoglobulin E and G autoantibodies against eosinophil proteins in children and adults with asthma and healthy subjects

BackgroundAutoimmune IgG response has been described in the pathogenesis of asthma in adults, but IgE autoimmunity has been little explored. Considering high levels of blood eosinophils and immunoglobulin E in asthmatic patients, the possibility of IgE autoantibody response to eosinophil proteins arises. ObjectiveTo explore the presence of IgE and IgG autoantibodies against Eosinophil peroxidase (EPX) and Eosinophil cationic protein (ECP). MethodsThree steps were followed: 1) The frequency of IgE and IgG autoantibodies against EPX and ECP was investigated among asthmatic and healthy subjects. 2) The ability of IgE autoantibodies to induce an inflammatory response (basophil activation) was performed. 3) The capacity of autoantibodies to identify patients with severe asthma was evaluated. ResultsAsthmatic and healthy subjects had IgE and IgG autoantibodies against EPX and ECP. Anti-EPX IgE was significantly higher in asthmatic patients. Severe asthmatic patients had a higher frequency and higher levels of IgE and IgG autoantibodies compared to healthy subjects. There was not a correlation between autoantibodies and blood eosinophils. Children younger than 14 years of age had IgE and IgG autoantibodies against to EPX and ECP. IgE autoantibodies to EPX and ECP induced basophil activation in asthmatic patients. ConclusionIn this study, we identify for the first time IgE autoantibodies against EPX and ECP in adults and children patients with asthma; IgE and IgG autoantibodies against EPX and ECP could serve as a predictive biomarker of the clinical severity.

Лимфангиома вульвы у молодой женщины, диагностированная ранее как аногенитальные бородавки

Lymphangioma of the vulva is a rare benign tumor. Clinical manifestations in the form of papillomatous growths make differential diagnosis difficult and are often regarded as a herpes virus or papillomavirus infection. We present a clinical case of vulvar lymphangioma in a 19-year-old patient with an 8-year history of the disease, previously diagnosed as papillomavirus infection, for which cryodestruction was repeatedly performed without any visible effect. Clinically, the disease was manifested by multiple verrucous growths on the labia majora. A skin biopsy showed hyperplastic epidermis with hyperkeratosis, cavities lined with endothelium and filled with eosinophilic protein fluid. To date, there is no consensus on the optimal therapy for vulvar lymphangioma. The use of destructive methods is not always effective and the recurrence, rate remains high enough.

Abstract 14113: Atrial Fibrillation Associated With Differences in Proteomic Composition of Retrieved Acute Ischemic Stroke Emboli

Introduction: Study of the composition of acute ischemic stroke emboli is still in infancy, though recent literature has begun to demonstrate remarkable heterogeneity in the composition of ischemic stroke emboli from different etiologies. Atrial fibrillation (AF) is a significant risk factor for stroke, and so in this study we investigate differences in proteomic composition between retrieved stroke emboli from patients with and without AF. Methods: The full proteomic composition of retrieved thromboembolic material from 24 patients with AIS was evaluated by mass spectrometry. The abundance of individual proteins in patients with AF was compared to that of patients without AF using Mann-Whitney U-tests, with significant differences described by the fold change (FC) in abundance. Cut-offs for significance were set at p = 0.05 and an FC difference of 2x. Descriptive heatmaps with sorted dendrograms were generated using the proteins with significant FC differences between patients with and without AF. Results: Proteins with the greatest FC enrichment in emboli from patients with AF included ferritin light chain (p = 0.006), ferritin heavy chain (p = 0.003), eosinophil peroxidase (p = 0.01), eosinophil lysophospholipase (p = 0.02), eosinophil-derived neurotoxin (p = 0.02), the neprilysin modulator nicastrin (p = 0.0007), HLA class I B α chain (p = 0.02), among others. Notably, neutrophil and histone proteins were also significantly enriched in emboli from patients with AF (p &amp;lt; 0.05 for all). Proteins with the greatest FC enrichment in emboli from patients without AF included interferon-induced GTP-binding protein Mx1 (p78) (p = 0.04) and mitsugumin-53 (p = 0.03). Conclusions: This data demonstrates that clot composition may directly reflect underlying stroke etiology. More specifically, the enrichment of eosinophil, neutrophil, and histone proteins in emboli from patients with AF points to significant immunothrombosis in emboli from this patient population. These findings may underlie distinct mechanisms in clot formation or maintenance in AF, and inform not only future studies on stroke pathophysiology, but also future work on novel pharmacotherapies for acute ischemic stroke in this patient population.

Galectin-10 as a Potential Biomarker for Eosinophilic Diseases.

Galectin-10 is a member of the lectin family and one of the most abundant cytoplasmic proteins in human eosinophils. Except for some myeloid leukemia cells, basophils, and minor T cell populations, galectin-10 is exclusively present in eosinophils in the human body. Galectin-10 forms Charcot–Leyden crystals, which are observed in various eosinophilic diseases. Accumulating studies have indicated that galectin-10 acts as a new biomarker for disease activity, diagnosis, and treatment effectiveness in asthma, eosinophilic esophagitis, rhinitis, sinusitis, atopic dermatitis, and eosinophilic granulomatosis with polyangiitis. The extracellular release of galectin-10 is not mediated through conventional secretory processes (piecemeal degranulation or exocytosis), but rather by extracellular trap cell death (ETosis), which is an active cell death program. Eosinophils undergoing ETosis rapidly disintegrate their plasma membranes to release the majority of galectin-10. Therefore, elevated galectin-10 levels in serum and tissue suggest a high degree of eosinophil ETosis. To date, several studies have shown that galectin-10/Charcot–Leyden crystals are more than just markers for eosinophilic inflammation, but play functional roles in immunity. In this review, we focus on the close relationship between eosinophils and galectin-10, highlighting this protein as a potential new biomarker in eosinophilic diseases.

Pilot study for immunoglobulin E as a prognostic biomarker in coronavirus disease 2019.

BackgroundLaboratory biomarkers to estimate the severity of COVID‐19 are crucial during the pandemic, since resource allocation must be carefully planned.AimIn the present study, we aim to evaluate the effects of basal serum total immunoglobulin E (IgE) levels and changes in inflammatory parameters on the clinical progression of patients hospitalized with COVID‐19.MethodsPatients hospitalized with confirmed COVID‐19 were included in the study. Laboratory data and total IgE levels were measured upon admission. Lymphocyte, eosinophil, ferritin, d‐dimer and CRP parameters were recorded on the baseline and on the 3rd and 14th days of hospitalization.ResultsThe study enrolled 202 patients, of which 102(50.5%) were males. The average age was 50.17 ± 19.68. Of the COVID‐19 patients, 41 (20.3%) showed clinical progression. Serum total IgE concentrations were markedly higher (172.90 [0‐2124] vs 38.70 [0‐912], p<0.001) and serum eosinophil levels were significantly lower (0.015 [0‐1.200] vs 0.040 [0‐1.360], p=0.002) in clinically worsened COVID‐19 patients when compared to stable patients. The optimal cut‐off for predicting clinical worsening was 105.2 ng/L; with 61% sensitivity, 82% specificity, 46.3% positive predictive value and 89.2% negative predictive value (area under the curve=0.729). Multivariable analysis to define risk factors for disease progression identified higher total IgE and CRP levels as independent predictors.ConclusionsOur single‐center pilot study determined that total IgE levels may be a negative prognostic factor for clinical progression in patients hospitalized due to COVID‐19 infection. Future studies are required to determine the impact of individuals' underlying immune predispositions on outcomes of COVID‐19 infections.This article is protected by copyright. All rights reserved.

The Beneficial Effects of Hydrogen-Rich Saline Irrigation on Chronic Rhinitis: A Randomized, Double-Blind Clinical Trial

PurposeChronic rhinitis (CR) is a common chronic inflammation of the nasal mucosa. Nasal saline irrigation has been demonstrated to be an effective treatment for CR. In this study, we investigated the beneficial effects of hydrogen-rich saline irrigation as an anti-inflammatory irrigation therapy for CR and compared its effectiveness over saline irrigation. Hydrogen-rich saline (HRS) was investigated due to its antioxidant and anti-inflammatory properties.MethodsA total of 120 patients with CR were randomly divided into two groups, patients irrigated with HR (HRS group) and the control group irrigated with saline (NS group). A randomized, double-blind control study was performed. The main observation index in this study was the total score of nasal symptoms (TNSS). In addition, eosinophilic protein (ECP) of the nasal secretions, nasal nitric oxide (nNO) levels, and levels of regulatory T cells (Treg) and regulatory B cells (Breg) were also compared between the two groups. Furthermore, patients with allergic rhinitis (AR) and non-allergic rhinitis (NAR) were also evaluated based on serum-specific IgE positivity.ResultsAfter treatment, TNSS and nasal ECP in the two groups decreased significantly (P<0.05), with patients in the HRS group showing significantly lower levels compared to the NS group (P<0.05). There were no significant differences in Treg and Breg levels between the two groups. Subgroup analysis showed that TNSS in the AR-HRS group showed a more significant reduction compared to the AR-NS group (P<0.05); however, there were no significant differences for the other inflammatory biomarkers (P>0.05). ECP levels were reduced significantly in the NAR subgroup compared to NS irrigation (P<0.05). There were no obvious adverse events observed in patients during the entire treatment period.ConclusionCompared to saline irrigation, HRS nasal irrigation was found to improve CR clinical symptoms, especially in patients with AR. HRS could effectively be used for the clinical treatment of patients with CR.

Benralizumab reduces eosinophils and inflammatory markers in patients with severe eosinophilic asthma and chronic rhinosinusitis with nasal polyps: A pilot real-life study.

Chronic rhinosinusitis with nasal polyps (CRSwNP) and Severe Eosinophilic Asthma (SEA) are both frequently sustained by eosinophilic inflammation and are probably the manifestation of a unique disease of upper and lower respiratory tract.We retrospectively observed 11 patients with severe CRSwNP and concomitant SEA under add-on therapy with benralizumab evaluating symptoms using Sino Nasal Outcome Test-22 (SNOT-22), Visual Analogue Scale (VAS), and Asthma Control Test (ACT) and Nasal polyp size by endoscopic and radiological score by Nasal Polyp Score (NPS) and Lund-Mackay Score (LMS). At 6 and 12 months, the expression of cationic eosinophil protein (ECP), Interleukin 17 (IL-17), Interferon gamma (INF-γ), and vascular endothelial growth factor (VEGF) was measured by nasal scraping to assess mucosal inflammation.After 12 months of benralizumab treatment, SNOT-22 decreased from 45 (23–97) to 14 (5–53) (p < 0.05), total VAS of rhinologic symptoms decreased from 30 (17–44) to 9 (5–37) (p ≤ 0.01) and ACT score increased from 10 (5–15) to 24 (20–25) (p ≤ 0.01).NPS decreased from 5 (3–6) to 3 (2–4) after 6 months (p < 0.05) and to 2 (2–3) after one year respectively (p < 0.05) and LMS total score from 21 (15–24) to 17 (8–21) (p ≤ 0.01) after 12 months from starting treatment.Nasal mucosa scraping found differences in INF-γ and VEGF expression in patients compared to 10 healthy subjects, with a normalization of these markers during eosinophils depletion induced by benralizumab.This is the first pilot real-life study conducted with an anti-IL5R monoclonal antibody in severe eosinophilic asthma and severe CRSwNP patients showing that this treatment can induce benefit both diseases not only from the clinical, but also from the inflammatory point of view. Moreover, our research pointed out that INF-γ and VEGF may represent potential response biomarker.

Asthma and COVID-19 in the elderly: course, survival, predictors of mortality

Bronchial asthma occurs in 0.9 – 17% of patients hospitalized with COVID-19. However, it is not clear whether asthma is a risk factor for the development and severity of COVID-19. Studies have shown that patients with asthma appear to be more susceptible to COVID-19 infection, but severe disease progression is not related to medication use, including asthma biologics, but rather to older age and comorbidities.Aim.To evaluate the clinical course of SARS-CoV-2 infection in elderly patients with asthma, to examine the effect of asthma and comorbidities on COVID-19related outcomes, and to determine predictors of mortality.Methods.Elderly patients [WHO, 2020] (&gt; 60 years,n= 131, median age 74 (67; 80) years; 59 men, 72 women) with asthma hospitalized for COVID-19 were included in the study. COVID-19 was confirmed by laboratory tests (PCR smear) and/or clinical and radiological examinations. All patients had a history of a documented diagnosis of asthma (GINA, 2020).Results.Out of 131 patients, 30 (22.9%) died in the hospital, and 15 (14.9%) died after discharge from the hospital (within 90 days). The group of patients with lethal outcome showed the following differences from those who recovered: values of Charlson index, respiration rate, degree of lung damage on CT scan, absolute number of leukocytes, neutrophils and neutrophils-to-lymphocytes ratio, C-reactive protein on the 5th day of hospitalization, and LDH were statistically significantly higher, while absolute number of eosinophils, total protein content, SpO2and SpO2/FiO2levels were lower; steroid intake during the year and non-atopic asthma were more common. Multivariate and ROC analysis revealed the most significant predictors of hospital mortality and their thresholds: Charlson comorbidity index ≥ 6 points, neutrophil/lymphocyte ratio ≥ 4.5, total protein ≤ 60 g/l, eosinophil level ≤ 100 cells/μL.Conclusion.The most significant predictors of hospital mortality in elderly patients with severe COVID-19 against asthma are Charlson comorbidity, neutrophil/lymphocyte ratio; lower eosinophil and total protein levels. Survival time of patients has an inverse correlation with the number of mortality risk factors present.