Eosinophilic Tissue Infiltration Research Articles

High-CBD Extract (CBD-X) in Asthma Management: Reducing Th2-Driven Cytokine Secretion and Neutrophil/Eosinophil Activity.

Asthma is a chronic inflammatory disorder of the airways affecting over 10% of the global population. It is characterized by airway inflammation, mucus hypersecretion, and bronchial hyperresponsiveness, driven predominantly by type 2 helper T cells (Th2) and type 2 innate lymphoid cells (ILC2s) in a subset of patients. However, a significant portion of asthmatic individuals present with "type 2-low" asthma that is often refractory to standard inhaled corticosteroid (ICS) therapy. Therefore, developing innovative therapeutic strategies has become essential. Recent studies have highlighted cannabidiol (CBD) as a promising anti-inflammatory agent capable of modulating immune responses. This study investigates the therapeutic potential of a high-CBD extract (CBD-X) in asthma. We evaluated the effects of CBD-X on cells involved in asthma pathogenesis using primary human Th2 cells, neutrophils, and asthma mouse model. Our findings indicate that CBD-X extract inhibits Th2 differentiation and reduces the secretion of IL-5 and IL-13, which are crucial cytokines in asthma. Additionally, CBD-X significantly reduces pro-inflammatory cytokines IL-8 and IL-6 in neutrophils and impairs their migration, a critical step in airway inflammation. In a murine asthma model, CBD-X administration led to marked downregulation of IgE and pro-asthmatic cytokines, along with reduced leukocyte, eosinophil, and neutrophil infiltration in lung tissues. These results suggest that CBD-X extract could offer a novel and complementary approach to managing both type 2-high and type 2-low asthma by targeting key inflammatory pathways and modulating immune cell behavior.

Clinical and Histological Differences Between Choanal Polyps in Children and Adults: A 15-Year Retrospective Study.

Choanal polyps (CPs) are benign, inflammatory, solitary lesions extending toward the junction between the nasal cavity/paranasal sinus and the nasopharynx through the choana. This study aimed to evaluate the clinical and histological characteristics of CPs in children compared to adult patients. Characteristics of patients (demography, main complaints, side, localization, surgical approach, histological characteristics, accompanying chronic rhinosinusitis [CRS], association with allergic rhinitis [AR] and aspirin sensitivity, postoperative follow-up period, recurrence rates) were retrospectively reviewed. The patients were classified into children (<18 years) and adults (≥18 years). Our results suggest some clinical and histological specificities of CPs in children compared to adults. Epistaxis, oropharyngeal extension, association with AR and ipsilateral CRS, and angiomatous histological subtype of CPs are more frequent in the pediatric population. Also, the level of eosinophil infiltration of polyp tissue and recurrence rates are higher in pediatrics than in adult population.

IL-10+ regulatory B cells mitigate atopic dermatitis by suppressing eosinophil activation

Atopic dermatitis (AD) presents significant therapeutic challenges due to its poorly understood etiology. Eosinophilia, a hallmark of allergic inflammation, is implicated in AD pathogenesis. Interleukin-10 (IL-10)-producing regulatory B (Breg) cells exhibit potent anti-inflammatory effects. However, their role in controlling AD-related eosinophilia is not well understood. To investigate the impact of eosinophils on AD, we employed IL-5Rα-deficient (Il5ra−/−) mice, which lack functional eosinophils. Induction of AD in these mice resulted in attenuated disease symptoms, underscoring the critical role of eosinophils in AD development. Additionally, the adoptive transfer of purified Breg cells into mice with AD significantly alleviated disease severity. Mechanistic studies revealed that IL-10 produced by Breg cells directly inhibits eosinophil activation and infiltration into the skin. In vitro experiments further confirmed that Breg cells inhibited eosinophil peroxidase secretion in an IL-10-dependent manner. Our collective findings demonstrate that IL-10 from Breg cells alleviates AD by suppressing eosinophil activation and tissue infiltration. This study elucidates a novel regulatory mechanism of Breg cells, providing a foundation for future Breg-mediated therapeutic strategies for AD.

Oral and topical administration of a geranyl acetophenone attenuates DNCB-induced atopic dermatitis-like skin lesions in BALB/c mice

Atopic dermatitis (AD) is a chronic, allergic inflammatory skin disorder that lacks a definite cure. Using a mouse DNCB-induced AD-like skin lesions model, this study evaluated the potential therapeutic utility of tHGA as an oral and topical treatment for AD. Male BALB/c mice were sensitised and challenged with 1% and 0.5% DNCB on their shaved dorsal skin. Mice in the treatment group were administered tHGA (20, 40, and 80 mg/kg) orally three times per week for 2 weeks, or tHGA (0.2%, 1%, and 5%) topically once daily for 12 days. On day 34, the mice were euthanized, and blood and dorsal skin samples were obtained for analysis. All doses of orally and topically administered tHGA significantly improved scratching, epidermal thickness, blood eosinophilia and mast cell infiltration. There was a minor discrepancy between the two routes of administration, with orally treated tHGA showing significant reductions in Scoring of Atopic Dermatitis (SCORAD), tissue eosinophil infiltration, serum IgE and skin IL-4 levels with treatment of 40 and 80 mg/kg tHGA, whereas topically applied tHGA showed significant reductions in all dosages. These findings suggest that tHGA exhibited therapeutic potential for AD as both oral and topical treatment ameliorates AD-like symptoms in the murine model.

EOSINOPHILIC MYOPERICARDITIS: A CASE SERIES

Abstract Background Eosinophilic myocarditis is characterized by acute myocardial inflammation due to eosinophilic tissue infiltration. Methods Diagnosis was based on laboratory tests, Echo and CMR; EMB was performed in uncertain cases. Treatment was performed according to the etiology of EM. All patients underwent regular follow–up at our Center. Results This study includes 9 patients (89% Caucasian, 78% women, mean age 48.2±13.6 years), admitted in our Center from February 2021 to November 2023. 66.67% cases occurred in the setting of eosinophilic granulomatosis with polyangiitis, 11% was secondary to B–cell lymphoblastic leukemia, and 22% were labelled as idiopathic EM. All patients presented with high eosinophil count (6133±4893/mcL), elevated CRP (57±66 mg/L) and hs–troponin I (3610±5166 ng/L) levels, and 67% cases NT–proBNP (10751±4038 ng/L) was elevated. 67% patients presented with dyspnea, 56% with chest pain, and 56% with fever. On ECG, sinus tachycardia, low QRS voltages and ST segment depression with negative T–waves were common. Thickening of the myocardial walls with reduction of GLS was seen in all cases; in 44% cases, the EF was below 50%; 56% cases had mild pericardial effusion. 1 patient had intraventricular thrombi at CMR, another one had bilateral pulmonary embolism. On CMR, all patients had areas of hypokinesia, myocardial edema, and myo–pericardial late gadolinium enhancement. EMB was performed in 5 cases, confirming the presence of intramyocardial eosinophilic infiltrates. 7 patients required CICU, and 1 needed inotrope (dobutamine) use. The patient with ALL was treated with combined chemotherapy. The other EM cases were treated with immunosuppressive therapy consisting of corticosteroids and either cyclophosphamide or rituximab or mepolizumab. All patients received cardioprotective therapy with BBs and ACE–inhibitors; in patients with pericardial involvement, colchicine was administered. All patients showed rapid clinical improvement following immunosuppressive therapy initiation, with prompt reduction of circulating eosinophils and hs–troponin I values and normalization of the ejection fraction. On CMR imaging, edema disappeared at follow–up, with LGE replacement in one case. All patients were alive and in good conditions at the last follow–up. Conclusions EM is an underdiagnosed life–threatening disease. A careful assessment of the etiology, as prompt therapy, is mandatory to achieve clinical amelioration and good mid–term prognosis.

Up-regulation of systemic and local BDNF in non-allergic Nasal Polyps in China.

Although the role of brain-derived neurotrophic factor (BDNF) in allergic rhinitis and/or nasal polyps (NPs) development has been studied, the contribution of BDNF in non-allergic NPs has not been evaluated yet. This study was to investigate the possible role of BDNF in non-allergic NPs pathogenesis. The study was carried out at The Second Hospital of Shandong University from December 2020 to November 2021. The non-allergic NPs patients (n=26) and the control group (n=22) were included. Lund-Mackay CT scores, nasal endoscopy scores, and pulmonary function testing were evaluated before surgery. Tissue and serum levels of BDNF, eosinophil cationic protein (ECP), and cytokeratins 5 (CK5) were assessed between different groups. The BDNF level in serum and tissue, CK5 count, and eosinophil infiltration in tissue were higher in non-allergic NPs. The eosinophils infiltration, ECP mRNA expression level, as well as BDNF mRNA level were increased in the BDNFhigh subgroup compared with BDNFlow subgroup. Significantly negative correlations between BDNF count and the situation of airway obstruction were found in non-allergic NPs. BDNF may have both local and systemic effects in non-allergic NPs pathogenesis. BDNF may be a possible therapeutic target or an indicator for eosinophilic NPs management.

Anaphylactic deaths: A retrospective study of forensic autopsy cases from 2009 to 2019 in Shanghai, China

Anaphylaxis is a rare but well-known cause of sudden unexpected death, although data from forensic autopsies in anaphylactic deaths are limited. Herein, a retrospective study of a series of allergic deaths from 2009 through 2019 in Shanghai, China, was conducted to investigate the demographic, medical, and forensic pathological characteristics of fatal anaphylaxis to improve medicolegal understanding on anaphylactic death. Sixty-two autopsy cases of anaphylactic death were registered in this study. Males dominated the cases (74.2%) against females (25.8%), with an average age of 38.8 years. Medications (98.4%), particularly antibiotics (72.6%), were the most frequent cause of anaphylaxis, and 44 cases (71.0%) occurred in clinics administered illegally by unlicensed clinicians. The anaphylactic symptoms began within a few minutes to less than 1 h in 53 cases, with dyspnea (56.5%) and sudden shock (46.8%) being the most common clinical signs. Thirty cases (48.4%) of anaphylaxis resulted in death within 1 h. Laryngeal edema and multiple tissue eosinophil infiltration (85.5%) were the most prevalent autopsy findings, followed by pulmonary edema and congestion (24.2%), which were considered to be non-specific but suggestive. The comorbidities were mainly cardiovascular disease (33.9%), pneumonia (8.1%) and asthma (8.1%). Serum IgE were measured in 11 of 62 cases, ranging from 43.3 to 591 IU/ml, severed as a helpful marker. Therefore, we suggested a thorough analysis of allergen exposure, clinical history and autopsy findings is required for the diagnosis of anaphylactic death currently.

Metabolic syndrome facilitates histopathological changes and the risk of postoperative recurrence in chronic rhinosinusitis with nasal polyps

BackgroundThe relationship between metabolic syndrome (MS) and chronic rhinosinusitis with nasal polyps (CRSwNP) remains unclear. This study aimed to examine the effects of MS on histopathological features and postoperative recurrence in patients with CRSwNP. MethodsWe recruited 529 patients with CRSwNP who underwent functional endoscopic sinus surgery. They were divided into MS and non-MS groups and followed up for 2 years to evaluate postoperative recurrence. Clinical characteristics, histopathological features, the immunoactivity of signature cytokines, and the risk of postoperative recurrence were compared between the two groups. ResultsIn total, 490 patients with CRSwNP were included in the study, 145 of whom experienced postoperative recurrence. The recurrence rate, tissue eosinophil count and percentage, and expression levels of IL-5 and IL-17A were significantly higher in the MS group compared to the non-MS group. Furthermore, within the MS group, patients who experienced recurrence exhibited higher tissue eosinophil counts and IL-5 and IL-17A levels than those in the non-MS group. Notably, the eosinophil count and IL-5 and IL-17A levels were higher in tissues collected during revision surgery than in those collected during primary surgery, particularly in patients with MS. Binary logistic regression analysis and Kaplan-Meier survival curves consistently indicated that MS independently increased the risk of postoperative recurrence in patients with CRSwNP. Furthermore, the risk increased with the number of MS components presented. ConclusionMS promoted tissue eosinophil infiltration, and IL-5 and IL-17A expression, and increased the risk of postoperative recurrence in patients with CRSwNP. MS was identified as an independent risk factor for postoperative recurrence, and the risk increased with an increase in the number of MS components.

Assessment of Tissue Eosinophilic Infiltration in Invasive Mammary Carcinoma.

Background: Stromal inflammatory cells in malignant tissue have recently gained increasing interest. Unlike the extensive research on tumor-infiltrating lymphocytes, published data about tumor-infiltrating eosinophils in breast cancer are scarce. Furthermore, similar studies have yet to be conducted in Iraq. Aims: The objective of this study is to examine the presence of eosinophilic infiltration by direct visualization using light microscopy and to analyze its relationship with other histological parameters in a group of Iraqi women diagnosed with invasive mammary cancer. Methods and material: A retrospective study enrolled 90 histological samples of invasive mammary carcinoma provided by core needle biopsy from a single center, together with their immunohistochemical results for ER and HER2-NEU. Data reviewing, direct morphological visualizations, and counting eosinophilic infiltration in tissue sections were done by two independent pathologists using light microscopy. The results were statistically correlated with the grade, ER, HER2-NEU, calcification, and axillary lymph node status at presentation. Results: Out of the entire sample size (90), 40 (44%) showed the presence of eosinophilic infiltration in the tissue, both intratumoral and stromal. Further analysis revealed that most eosinophilic infiltrates had an intermediate score (4-19) per 10 consecutive high-power fields. A strong and meaningful statistical relationship was seen between tissue eosinophilic infiltration and HER2/NEU status. A statistically insignificant correlation was seen between tissue eosinophilic infiltration and histological grade, ER receptor status, calcification, and axillary lymph node status at presentation. Conclusions: Eosinophils are tumor-infiltrating cells in breast cancer, both intratumoral and stromal. The presence of tissue eosinophilic infiltration can predict HER2/NEU negativity in breast cancer.

Role of peripheral and tissue eosinophils and eosinophil cationic protein in pediatric inflammatory bowel disease.

Inflammatory bowel disease (IBD), eosinophilic gastrointestinal disease (EGID), and functional abdominal pain disorder (FAPD) present with nonspecific gastrointestinal (GI) symptoms clinically and also have some similarities in pathogeneses associated with eosinophils. Therefore, we aimed to evaluate the role of eosinophils in IBD compared to EGID and FAPD by investigating eosinophils in peripheral blood and GI tissue and eosinophil cationic protein (ECP). Pediatric patients with chronic GI symptoms who underwent endoscopic biopsies were enrolled. Complete blood cell counts, inflammatory markers, immunoglobulin E (IgE), serum ECP levels, and endoscopic and histopathologic findings were retrospectively reviewed. A total of 387 patients were included: 179 with EGID, 107 with IBDs, and 82 with FAPD. Peripheral absolute eosinophil count (AEC), total IgE, and serum ECP were significantly higher in both IBD and EGID than in FAPD (all p < 0.05). Statistically significant differences were noted among the three groups in tissue eosinophil counts in each segment of GI tract except for the esophagus (p < 0.05). Significant differences were observed in tissue eosinophil counts in the ascending, sigmoid colon, and rectum between EGID and IBD (p < 0.05). Peripheral and tissue eosinophils in the stomach and duodenum revealed positive correlation in both EGID and IBD (both p < 0.001). Elevated eosinophil-related markers, as well as increased tissue eosinophilic infiltration in the affected areas of the GI tract in both IBD and EGID compared to FAPD, suggest that eosinophils might play a common important role in the pathogeneses of both diseases.

CircMIRLET7BHG, upregulated in an m6A-dependent manner, induces the nasal epithelial barrier dysfunction in allergic rhinitis pathogenesis

ObjectiveAllergic rhinitis (AR) remains a frequent aspiratory allergic inflammatory disorder with a high incidence. Circular RNAs (circRNAs) have been revealed to participate in the pathogenesis of AR. This study investigated the biological function of circMIRLET7BHG (hsa_circ_0008668) in AR progression. MethodsOvalbumin (OVA)-exposed human nasal epithelial cell line (HNEpC) and mice were adopted as the in vitro and in vivo models of AR. Immunofluorescence staining was used to determine epithelial tight junction protein expression. Target molecule levels were assessed by RT-qPCR and Western blotting. Localization of circMIRLET7BHG and IGF2BP1 was observed by RNA-FISH and immunofluorescence. Epithelial barrier damage was determined by transepithelial electrical resistance and fluorescein isothiocyanate-dextran (FD4) permeability. Serum concentrations of IgE, sIgE, IFN-γ, IL-4, and IL-5 were detected by ELISA. Apoptosis, pathological changes, and eosinophil infiltration in nasal mucosa tissues were evaluated by TUNEL, H&E, and Sirius red staining, respectively. Molecular mechanism was analyzed by RNA pull-down, RIP, and MeRIP assays. ResultsAn increased expression of circMIRLET7BHG was found in AR patients and experimental models. Down-regulation of circMIRLET7BHG attenuated OVA-induced allergic symptoms via relieving epithelial thicknesses, eosinophil infiltration, apoptosis, and inflammatory response in mice. Subsequently, circMIRLET7BHG deficiency prevented OVA-induced epithelial barrier dysfunction by reducing epithelial permeability, and inhibiting tight junction proteins. Mechanistically, methyltransferase-like 3 (METTL3) enhanced circMIRLET7BHG expression via m6A methylation, which enhanced ADAM10 mRNA stability via interaction with IGF2BP1. ConclusionMETTL3-mediated m6A modification increased circMIRLET7BHG expression that consequently raised ADAM10 mRNA stability via interplay with IGF2BP1, thereby promoting AR by inducing epithelial barrier dysfunction.

Involvement of CD40-CD40L and ICOS-ICOSL in the development of chronic rhinosinusitis by targeting eosinophils.

Chronic rhinosinusitis (CRS), whose prevalence and pathogenesis are age-related, is characterized by nasal tissue eosinophil infiltration. CD40-CD40 ligand (CD40L) pathway involves in the eosinophil-mediated inflammation, and inducible co-stimulator (ICOS)-ICOS ligand (ICOSL) signal can strengthen CD40-CD40L interaction. Whether CD40-CD40L and ICOS-ICOSL have a role in the development of CRS remains unknown. The aim of this study is to investigate the association of CD40-CD40L and ICOS-ICOSL expression with CRS and underlying mechanisms. Immunohistology detected the expression of CD40, CD40L, ICOS, and ICOSL. Immunofluorescence was performed to evaluate the co-localizations of CD40 or ICOSL with eosinophils. Correlations between CD40-CD40L and ICOS-ICOSL as well as clinical parameters were analyzed. Flow cytometry was used to explore the activation of eosinophils by CD69 expression and the CD40 and ICOSL expression on eosinophils. Compared with the non-eCRS subset, ECRS (eosinophilic CRS) subset showed significantly increased CD40, ICOS, and ICOSL expression. The CD40, CD40L, ICOS, and ICOSL expressions were all positively correlated with eosinophil infiltration in nasal tissues. CD40 and ICOSL were mainly expressed on eosinophils. ICOS expression was significantly correlated with the expression of CD40-CD40L, whereas ICOSL expression was correlated with CD40 expression. ICOS-ICOSL expression positively correlated with blood eosinophils count and disease severity. rhCD40L and rhICOS significantly enhanced the activation of eosinophils from patients with ECRS. Tumor necrosis factor-α (TNF-α) and interleukin-5 (IL-5) obviously upregulated CD40 expression on eosinophils, which was significantly inhibited by the p38 mitogen-activated protein kinase (MAPK) inhibitor. Increased CD40-CD40L and ICOS-ICOSL expressions in nasal tissues are linked to eosinophils infiltration and disease severity of CRS. CD40-CD40L and ICOS-ICOSL signals enhance eosinophils activation of ECRS. TNF-α and IL-5 regulate eosinophils function by increasing CD40 expression partly via p38 MAPK activation in patients with CRS.

Eosinophilic myocarditis as presentation of hypereosinophilic syndrome.

A 67-year-old female with history of eosinophilic gastritis, was admitted with a first episode of heart failure (HF). The X-ray showed a bilateral interstitial infiltrate with a large left pleural effusion (Panel A), with abundant eosinophils in the pleural drainage and eosinophilia in blood stream (22 × 109, normal value 0,5–1 × 109). The transthoracic echocardiogram observed a normal left ventricular function (53%) (see Supplementary Video S1) with restrictive mitral filling pattern (Panel B) and a severely diminished global longitudinal strain of—9.6% (Panel C). The cardiac resonance (see Supplementary Video S2) revealed a septal intramyocardial and anterolateral subepicardial late gadolinium enhancement (Panels D and E) with normal right ventricle function, non-thickened pericardium, and no effusions. Due to high suspicious of a restrictive myocardiopathy (RMC) secondary to a hyperosinophilic syndrome, a right heart catheterization (RHC) and a cardiac biopsy were scheduled. The RHC was compatible with RMC (Panel F), with pulmonary hypertension (mean pulmonary pressure of 28 mmHg), ‘dip & plateau pattern’, and pressure equalization between chambers. Finally, the endomyocardial biopsy (Panel G) revealed an important infiltration of eosinophils in myocardial tissue, confirming the diagnosis of eosinophilic myocarditis (EM), in the context of hypereosinophilic syndrome. High doses of intravenous corticoids plus HF treatment were started, and the patient evolved favourably.

Acute Cholecystitis Associated with Eosinophilic Granulomatosis with Polyangiitis that Responded to Glucocorticoid Therapy.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic disorder characterized by tissue eosinophilic infiltration and vasculitis. Although EGPA causes multiple organ damage, it causes cholecystitis less frequently. We herein report a case of acute cholecystitis associated with EGPA in which successful treatment with glucocorticoid therapy allowed surgery to be avoided. EGPA can present as acute cholecystitis. It is important not to overlook acute cholecystitis associated with EGPA in patients with abdominal pain with peripheral eosinophilia. Furthermore, in cases of mild cholecystitis associated with EGPA that are diagnosed preoperatively, cholecystectomy might be avoided with conservative glucocorticoid treatment.

Prophylactic and therapeutic potential of magnolol-loaded PLGA-PEG nanoparticles in a chronic murine model of allergic asthma.

Magnolol is a chemically defined and active polyphenol extracted from magnolia plants possessing anti-allergic activity, but its low solubility and rapid metabolism dramatically hinder its clinical application. To improve the therapeutic effects, magnolol-encapsulated polymeric poly (DL-lactide-co-glycolide)-poly (ethylene glycol) (PLGA-PEG) nanoparticles were constructed and characterized. The prophylactic and therapeutic efficacy in a chronic murine model of OVA-induced asthma and the mechanisms were investigated. The results showed that administration of magnolol-loaded PLGA-PEG nanoparticles significantly reduced airway hyperresponsiveness, lung tissue eosinophil infiltration, and levels of IL-4, IL-13, TGF-β1, IL-17A, and allergen-specific IgE and IgG1 in OVA-exposed mice compared to their empty nanoparticles-treated mouse counterparts. Magnolol-loaded PLGA-PEG nanoparticles also significantly prevented mouse chronic allergic airway mucus overproduction and collagen deposition. Moreover, magnolol-encapsulated PLGA-PEG nanoparticles showed better therapeutic effects on suppressing allergen-induced airway hyperactivity, airway eosinophilic inflammation, airway collagen deposition, and airway mucus hypersecretion, as compared with magnolol-encapsulated poly (lactic-co-glycolic acid) (PLGA) nanoparticles or magnolol alone. These data demonstrate the protective effect of magnolol-loaded PLGA-PEG nanoparticles against the development of allergic phenotypes, implicating its potential usefulness for the asthma treatment.

SARS-CoV-2 Related Antibody-Dependent Enhancement Phenomena In Vitro and In Vivo.

Antibody-dependent enhancement (ADE) is a phenomenon in which antibodies produced in the body after infection or vaccination may enhance subsequent viral infections in vitro and in vivo. Although rare, symptoms of viral diseases are also enhanced by ADE following infection or vaccination in vivo. This is thought to be due to the production of antibodies with low neutralizing activity that bind to the virus and facilitate viral entry, or antigen-antibody complexes that cause airway inflammation, or a predominance of T-helper 2 cells among the immune system cells which leads to excessive eosinophilic tissue infiltration. Notably, ADE of infection and ADE of disease are different phenomena that overlap. In this article, we will describe the three types of ADE: (1) Fc receptor (FcR)-dependent ADE of infection in macrophages, (2) FcR-independent ADE of infection in other cells, and (3) FcR-dependent ADE of cytokine production in macrophages. We will describe their relationship to vaccination and natural infection, and discuss the possible involvement of ADE phenomena in COVID-19 pathogenesis.

Tissue eosinophilia and computed tomography features in paediatric chronic rhinosinusitis with nasal polyps requiring revision surgery.

Endoscopic sinus surgery (ESS) is an effective and safe treatment modality for medically recalcitrant chronic rhinosinusitis (CRS) in the paediatric population, especially in older children or those with nasal polyposis (CRSwNP). We aimed to elucidate the inflammatory pattern and clinical characteristics of CRSwNP related to revision surgery after ESS in a paediatric population. We retrospectively enrolled 146 patients with bilateral CRSwNP. Twenty-two patients had recurrent nasal polyps that required revision surgery. The clinical characteristics, computed tomography (CT) features, tissue eosinophil count, and immunoactivity of signature cytokines in the two groups were analysed. Tissue eosinophil infiltration and immunoreactivity of eosinophilic cationic protein and IL-5 in the sinus mucosa were higher in patients that required revision surgery. The revision surgery group was significantly younger and had positive aeroallergen test results, higher total Lund-Mackay scores, and ethmoid/maxillary sinus ratio on CT images than those without revision surgery. A nomogram was developed to predict the probability of the requirement of revision surgery according to the logistic regression analysis results. We developed a nomogram model using clinical characteristics, tissue eosinophilia, and CT features for the preoperative identification of patients vulnerable to revision surgery in paediatric CRSwNP. This could help clinicians predict the probability of recurrence and perform intensive postoperative adjunct therapy and follow-up.

Eosinophilic granulomatosis with polyangiitis: case report and literature review.

Eosinophilic granulomatosis with polyangiitis (EGPA), previously known as Churg-Strauss syndrome, is a multisystem disorder characterised by asthma, blood and tissue eosinophilia and small-vessel vasculitis. Eosinophilic tissue infiltration and extravascular granuloma formation can lead to damage in any organ, but it is classically seen to cause pulmonary infiltrates, sino-nasal disease, peripheral neuropathy, renal and cardiac involvement, and rashes. EGPA is part of the anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis syndromes, with the antibody being detected in ∼30-40% of cases and mostly against myeloperoxidase. Two genetically and clinically distinct phenotypes, defined by the presence or absence of ANCA have been identified. Treatment for EGPA focuses on inducing and maintaining disease remission. To date, oral corticosteroids remain first-line agents whilst second-line treatments include immunosuppressants such as cyclophosphamide, azathioprine, methotrexate, rituximab and mycophenolate mofetil. However, long-term steroid usage results in multiple and well-known adverse health effects and new insights into the pathophysiology of EGPA have allowed for the development of targeted biologic therapies, like the anti-eosinophilic, anti-interleukin-5 monoclonal antibodies.

TREATMENT OF HYPEREOSINOPHILIA WITH MEPOLIZUMAB IN A 6-YEAR-OLD BOY

<h3>Introduction</h3> Hypereosinophilic syndrome (HES) is a rare cause of hypereosinophilia among pediatric patients. Mepolizumab, an IL-5 antagonist, is an effective treatment for hypereosinophilia approved for patients ≥12 years of age, but for younger children treatment remains limited to corticosteroids or other cytoreductive agents. This case illustrates successful treatment of hypereosinophilia with mepolizumab in a child. <h3>Case Description</h3> A previously heathy 6-year-old male presented with three days of fatigue, fever, and right cervical lymphadenopathy with an elevated absolute eosinophil count (AEC) that peaked at 83,350 cells/microliter. Work up for infectious disease, end-organ damage, and malignancy with flow cytometry and cytogenetics from blood, bone marrow and lymph node biopsy were negative. Mepolizumab 100 mg injected subcutaneously was given, leading to progressive decline in AEC to 3,370 cells/microliter after 14 days. Fevers, fatigue, and lymphadenopathy resolved. Monthly mepolizumab and close monitoring is planned. <h3>Discussion</h3> HES is a heterogenous group of disorders; of paramount concern is development of malignancy and end-organ damage due to eosinophilic infiltration of tissues. Although effective for hypereosinophilia, long-term treatment with corticosteroids is associated with significant adverse events and may cause diagnostic uncertainty when monitoring pre-malignant conditions. While mepolizumab is approved for children ≥6 years of age for the treatment of asthma, it is not approved for HES in this age group. This case highlights that mepolizumab is an effective steroid-sparing therapy in young children with hypereosinophilia that allows continued monitoring for malignancy without masking or delaying diagnosis from corticosteroid use.

Deep Association between Transglutaminase 1 and Tissue Eosinophil Infiltration Leading to Nasal Polyp Formation and/or Maintenance with Fibrin Polymerization in Chronic Rhinosinusitis with Nasal Polyps.

Transglutaminase (TGM) isoform catalyze the cross-linking reaction of identical or different substrate proteins. Eosinophil has been recognized in chronic rhinosinusitis with nasal polyps (CRSwNP) forming tissue eosinophil in nasal polyp (NP), and TGM isoforms are suggested to be associated with a critical role in asthma and other allergic conditions. The aim of this study was to reveal the association of specific TGM isoform with both the tissue eosinophil infiltration deeply concerning with the intractable severity of CRSwNP and the fibrin polymerization ability of TGM isoform associated with the tissue eosinophil infiltration, which lead to NP formation and/or maintenance in CRSwNP. NP tissues (CRSwNP group) and uncinate process (UP) (control group) were collected from patients with CRSwNP and control subjects. We examined: (1) the expression level of TGM isoforms by using a real-time polymerase chain reaction (PCR) and the comparison to the issue eosinophil count in the CRSwNP group, (2) the location of specific TGM isoform in the mucosal tissue using immunohistochemistry, (3) the inflammatory cell showing the colocalization of specific TGM isoform in Laser Scanning Confocal Microscopy (LSCM) imaging, and (4) the fibrin polymerase activity of specific TGM isoform using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). A certain level of TGM 1, 2, 3, 5 expression was present in both the CRSwNP group and the control group. Only TGM 1 expression showed a positive significant correlation with the tissue eosinophil count in the CRSwNP group. The localization of TGM 1 in NP (CRSwNP) laid mainly in a submucosal layer as inflammatory cells and was at the cytoplasm in the tissue eosinophil. Fibrin polymerase activity of TGM 1 showed the same polymerase ability of factor XIIIA. TGM 1 might influence the NP formation and/or maintenance in CRSwNP related to the tissue eosinophil infiltration, which formed fibrin mesh composing NP stroma.