Eosinophilic Disease Research Articles

Elevation of D-dimer in eosinophilic gastrointestinal diseases in the absence of venous thrombosis: A case series and literature review

Abstract Introduction Eosinophilic gastrointestinal diseases (EGIDs) are rare and heterogeneous diseases characterized by excessive eosinophilic infiltration of the digestive system. D-dimer levels and its possible association with disease course were not reported. Case series We reported a series of three EGID cases presenting with high levels of D-dimer. No evidence for potential venous thromboembolism was found through computed tomography pulmonary angiogram and vascular ultrasounds. Moreover, D-dimer levels decreased after short-time systemic prednisolone administration, accompanied by remission of clinical symptoms and decrease of peripheral eosinophil counts and IgE levels. Conclusion Elevation of D-dimer in EGID may not represent thrombotic events but is possibly associated with disease severity. More population-based studies are needed to delineate the potential relationship among D-dimer, thrombosis, and inflammation in EGID.

Clinical and molecular correlates of the Index of Severity for Eosinophilic Esophagitis

The Index of Severity for Eosinophilic Esophagitis (I-SEE) is a new expert-defined clinical tool that classifies disease severity of eosinophilic esophagitis (EoE). We aimed to determine whether I-SEE is associated with patient characteristics, molecular features of EoE, or both. We analyzed a prospective cohort of patients with EoE from the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). Associations between I-SEE and clinical and molecular features (assessed by an EoE diagnostic panel [EDP]) were assessed. In 318 patients with chronic EoE (209 adults, 109 children), median total I-SEE score was 7.0, with a higher symptoms and complications score in children than adults (4.0 vs 1.0; P< .001) and higher inflammatory and fibrostenotic features scores in adults than children (3.0 vs 1.0 and 3.0 vs 0, respectively; both P< .001). Total I-SEE score had a bimodal distribution with the inactive to moderate categories and severe category. EDP score correlated with total I-SEE score (r= -0.352, P< .001) and both inflammatory and fibrostenotic features scores (r= -0.665, P< .001; r= -0.446, P< .001, respectively), but not with symptoms and complications scores (r= 0.047, P= .408). Molecular severity increased from inactive to mild and moderate, but not severe, categories. Longitudinal changes of modified I-SEE scores and inflammatory and fibrostenotic features scores reflected histologic and molecular activity. I-SEE score is associated with select clinical features across severity categories and with EoE molecular features for nonsevere categories, warranting further validation.

Host-related low-prevalence gastritides: Epidemiological and clinical characterization

IntroductionA recent consensus meeting (RE.GA.IN) addressed “host-related, low-prevalence gastritis”: eosinophilic (EoG), lymphocytic (Hp-pos_LyG and Hp-neg_LyG), collagenous (CollG), and granulomatous gastritis (GrG). Our study evaluates their clinico-epidemiological characteristics. Materials and MethodsWe extracted all patients with a diagnosis of EoG, LyG, CollG, and GrG from a clinicopathological database and compared their demographics, clinical and endoscopic characteristics, associated conditions, and clinical awareness to those of all other subjects in the database (controls). ResultsThere were 1,781,005 unique patients (median age 57 years; 55.7 % female). Hispanics were overrepresented amongst those with Hp-pos_LyG. Subjects with GrG had a high prevalence of erosions and ulcers. Clinical awareness of these conditions was dismal (<1:10,000 patients). Some clinical manifestations were more common in patients with certain gastritides (e.g., vomiting and diarrhea in CollG; anemia in LyG), but none were sufficiently distinctive to suggest a clinical diagnosis. EoG was associated with EoE; LyG had a strong association with celiac disease; CollG with microscopic colitis; and GrG with Crohn disease. ConclusionsThe diagnosis of these gastritides (between <1: in 1,000 and 1 in 5000 subjects) rests on histopathology. They remain poorly characterized and clinically neglected. Yet, their associations may herald other conditions: eosinophilic gastrointestinal diseases (EGID), celiac, and Crohn disease. Patients might benefit from increased detection and characterization.

Nonepithelial Gene Expression Correlates With Symptom Severity in Adults With Eosinophilic Esophagitis

BackgroundThe mechanistic basis of the variable symptomatology seen in eosinophilic esophagitis (EoE) remains poorly understood. ObjectiveWe examined the correlation of a validated, patient-reported outcome (PRO) metric with a broad spectrum of esophageal transcripts to uncover potential symptom pathogenesis. MethodsData were extracted from 146 adults with EoE through the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). Patients were subgrouped by esophageal dilation history. We compared a validated PRO metric, the EoE Activity Index (EEsAI), with a set of transcripts expressed in the esophagus of patients with EoE, the EoE Diagnostic Panel (EDP). We utilized single-cell RNA sequencing data to identify the cellular source of EEsAI-related EDP genes and further analyzed patients with mild and severe symptoms. ResultsThe EEsAI correlated with the EDP total score, especially in patients without recent esophageal dilation (r = -0.31, P = .003). We identified 14 EDP genes that correlated with EEsAI scores (r ≥ 0.3, P < .05). Of these, 11 were expressed in non-epithelial cells and 3 in epithelial cells; during histologic remission, only 4/11 (36%) non-epithelial versus 3/3 (100%) epithelial genes had decreased expression to <50% of that in active EoE. Fibroblasts expressed 5/11 (45%) non-epithelial EEsAI-associated EDP genes. A subset of non-epithelial (8/11, 73%), but not EoE-representative (0/4, 0%; CCL26, CAPN14, DSG1, SPINK7), genes was upregulated in patients with EoE with the highest versus lowest symptom burden. ConclusionThe correlation of symptoms and non-epithelial esophageal gene expression substantiates that non-epithelial cells (e.g., fibroblasts) likely contribute to symptom severity.

Causal relationship between eosinophilic esophagitis and inflammatory bowel disease: a bidirectional two-sample Mendelian randomization study.

Eosinophilic esophagitis (EoE) and inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis (UC), are immune-mediated gastrointestinal diseases with overlapped pathogenesis and are sometimes concurrently diagnosed, but their causal relationship remains unclear. We investigated the causal relationship between EoE and IBD and its subtypes via a two-sample bidirectional Mendelian randomization (MR) approach. MR analyses were performed using summary data of a genome-wide association study (GWAS) on individuals of European ancestry. Independent single-nucleotide polymorphisms correlated with EoE (from a GWAS meta-analysis containing 1,930 cases and 13,634 controls) and IBD (from FinnGen GWASs containing 9,083 IBD, 2,033 CD, and 5,931 UC cases, and GWASs of IBD genetic consortium containing 12,882 IBD, 6,968 UC, and 5,956 CD cases) were selected as instruments. We applied the inverse variance weighted (IVW) method as the primary analysis followed by several sensitivity analyses. For the forward MR study, estimates from IVW methods were subsequently meta-analyzed using a random-effect model. Our results suggested a causal effect of EoE on IBD [pooled odds ratio (OR), 1.07; 95% confidence interval (CI), 1.02-1.13] and EoE on UC (pooled OR, 1.09, 95% CI, 1.04-1.14). No causal link between EoE and CD was observed (pooled OR, 1.05; 95% CI, 0.96-1.16). The reverse MR analyses revealed no causal effect of IBD (and its subtypes) on EoE. Sensitivity analyses confirmed the robustness of primary results. Our findings provided evidence of a suggestive causal effect of EoE on IBD (specifically on UC) in the European population. Increased awareness of concurrent or subsequent IBD in patients with EoE is called for. Still, the present evidence is not adequate enough and ought to be validated by further investigations.

Ophthalmic vascular manifestations in eosinophil-associated diseases: a comprehensive analysis of 57 patients from the CEREO and EESG networks and a literature review.

Eosinophils have widespread procoagulant effects. In daily practice, eosinophil-related cardiovascular toxicity consists of endomyocardial damage, eosinophilic vasculitis and arterial or venous thrombosis. Here we aim to report on the clinical features and treatment outcomes of patients with unexplained ophthalmic vascular manifestations and eosinophilia. We conducted a retrospective, multicenter, observational study and a literature review of patients with eosinophilia (≥0.5 x109/L) and concomitant ophthalmic vascular manifestations independent of the underlying eosinophilic disease but with no alternative cause for ophthalmic manifestations. Fifty-seven patients were included (20 from the observational study and 37 from the literature review). Ophthalmic vascular features were the initial manifestation of eosinophil-related disease in 34 (59%) patients and consisted of 29 central retinal artery occlusions, six branch retinal artery occlusions, five central retinal vein occlusions, two branch retinal vein occlusions, seven retinal vasculitides, two retinal vasospasms, 12 Purtscher's retinopathies, 13 anterior ischemic optic neuropathies and two posterior ischemic optic neuropathies. The median [IQR] absolute eosinophil count at onset of ophthalmic vascular manifestations was 3.5 [1.7-7.8] x109/L. Underlying eosinophil-related diseases included eosinophilic granulomatosis with polyangiitis (n=32), clonal hypereosinophilic syndrome (HES) (n=1), idiopathic HES (n=13), lymphocytic HES (n=2), adverse drug reactions (n=3), parasitosis (n=2), polyarteritis nodosa (n=1), IgG4-related disease (n=1), eosinophilic fasciitis (n=1) and primary sclerosing cholangitis (n=1). Other extra-ophthalmologic arterial or venous thromboses related to eosinophilia were reported in four (7%) and nine (16%) patients, respectively. Visual prognosis was poor: only eight (10%) patients achieved full recovery of ophthalmologic symptoms. After a median follow-up of 10.5 [1-18] months, one patient (3%) had a recurrence of an ophthalmic vascular manifestation, and three patients (10%) had a recurrence of other vascular symptoms (deep vein thrombosis in two and pulmonary embolism in one patient). At the time of recurrence, absolute eosinophil counts were above 0.5 x109/L in all cases (n=4). This study broadens the spectrum of vascular manifestations associated with hypereosinophilia by adding ophthalmic vascular manifestations. In patients with ophthalmological vascular manifestations and hypereosinophilia, aggressive treatment of the underlying pathology (and normalization of blood count) should be implemented.

Challenging assumptions about the demographics of eosinophilic gastrointestinal diseases: A systematic review

BackgroundThe demographic characteristics of patients with eosinophilic gastrointestinal diseases (EGIDs) are poorly understood. Population-based assessments of EGID demographics may indicate health disparities in diagnosis. ObjectivesWe aimed to characterize the demographic distribution of EGIDs and evaluate the potential for bias in reporting patient characteristics. MethodsWe conducted a systematic review, extracting data on age, sex, gender, race, ethnicity, body mass index (BMI), insurance, and urban/rural residence on EGID patients and the source population. Differences in proportions were assessed using Chi-squared tests. Demographic reporting was compared to recent guidelines. ResultsAmong 50 studies that met inclusion/exclusion criteria, 12 reported ≥1 demographic feature in both EGID and source populations. Except for age and sex or gender, demographics were rarely described (race [n=4], ethnicity [n=1], insurance [n=1]) or not described (BMI, urban/rural residence). A higher proportion of males was observed for EoE or esophageal eosinophilia relative to the source population, but no difference in gender or sex distribution was observed for other EGIDs. Sex and gender were used interchangeably, and frequently only the male proportion was reported. Reporting of race and ethnicity was inconsistent with guidelines. ConclusionCurrent data support a male predominance for EoE only. Evidence was insufficient to support enrichment of EGIDs in any particular racial, ethnic or other demographic group. Population-based studies presenting demographics on both cases and source populations are needed. Implementation of guidelines for more inclusive reporting of demographic characteristics is crucial to prevent disparities in timely diagnosis and management of patients with EGIDs.

Exploring the immunopathology of type 2 inflammatory airway diseases.

Significant advancements have been achieved in understanding the roles of different immune cells, as well as cytokines and chemokines, in the pathogenesis of eosinophilic airway conditions. This review examines the pathogenesis of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), marked by complex immune dysregulation, with major contributions from type 2 inflammation and dysfunctional airway epithelium. The presence of eosinophils and the role of T-cell subsets, particularly an imbalance between Treg and Th17 cells, are crucial to the disease's pathogenesis. The review also investigates the pathogenesis of eosinophilic asthma, a unique asthma subtype. It is characterized by inflammation and high eosinophil levels, with eosinophils playing a pivotal role in triggering type 2 inflammation. The immune response involves Th2 cells, eosinophils, and IgE, among others, all activated by genetic and environmental factors. The intricate interplay among these elements, chemokines, and innate lymphoid cells results in airway inflammation and hyper-responsiveness, contributing to the pathogenesis of eosinophilic asthma. Another scope of this review is the pathogenesis of Eosinophilic Granulomatosis with Polyangiitis (EGPA); a complex inflammatory disease that commonly affects the respiratory tract and small to medium-sized blood vessels. It is characterized by elevated eosinophil levels in blood and tissues. The pathogenesis involves the activation of adaptive immune responses by antigens leading to T and B cell activation and eosinophil stimulation, which causes tissue and vessel damage. On the other hand, Allergic Bronchopulmonary Aspergillosis (ABPA) is a hypersensitive response that occurs when the airways become colonized by aspergillus fungus, with the pathogenesis involving activation of Th2 immune responses, production of IgE antibodies, and eosinophilic action leading to bronchial inflammation and subsequent lung damage. This analysis scrutinizes how an imbalanced immune system contributes to these eosinophilic diseases. The understanding derived from this assessment can steer researchers toward designing new potential therapeutic targets for efficient control of these disorders.

Dupilumab in adolescent eosinophilic esophagitis: Experience with fibrostenosis and EGID with esophageal involvement.

We evaluated patients aged 12-20 on dupilumab 300 mg weekly for treatment of eosinophilic esophagitis (EoE) who had ≥1 follow-up endoscopy at a tertiary care pediatric hospital (n = 18). Fifty percent had inflammatory EoE (n = 9), 22% had fibrostenotic EoE (n = 4), and 28% had non-EoE eosinophilic gastrointestinal disease (EGID) with esophageal involvement (n = 5). Ninety-four percent discontinued topical corticosteroids (TCS) 2-4 weeks after starting dupilumab. Eighty-nine percent of inflammatory EoE patients had histological response (<15 eosinophils/high-powered field) after an average of 19.1 weeks. One hundred percent of patients with fibrostenotic disease exhibited histological response after 16.8 weeks. Of patients with non-EoE EGID, 60% achieved esophageal histological response after an average of 40.1 weeks. In a small cohort, dupilumab was very effective for adolescent inflammatory and fibrostenotic EoE despite rapid weaning of TCS. Dupilumab was also somewhat effective for non-EoE EGID with esophageal involvement; however, a longer duration of therapy was required.

Autism in patients with eosinophilic gastrointestinal disease: A systematic review with meta-analysis.

Neurodevelopmental disorders, such as autism spectrum disorder (ASD), have been increasingly associated with eosinophilic gastrointestinal disorders (EGID). However, the relationship between these diseases remains unclear. We performed a systematic review with meta-analysis to address this issue. The search was performed according to the PRISMA guidelines using descriptors for ASD and EGIDs from the MEDLINE, Embase, PsycInfo, LILACS, and Web of Science databases. Observational studies with the prevalence of ASD in any EGID were included. The study protocol was registered on the PROSPERO platform under the number CRD42023455177. The total dataset comprised 766,082 participants. The result of the single-arm meta-analysis showed an overall prevalence of ASD in the population with EGID of 21.59% (95% CI: 10.73-38.67). There was an association between EGID and ASD (OR: 3.44; 95% CI: 1.25-2.21), also significant when restricted only to EoE (OR: 3.70; 95% CI: 2.71-5.70). Recent studies have implicated the influence of an inadequate epithelial barrier integrity in the pathogenesis of several diseases. The role of this mechanism can be extended to situations beyond allergic reactions, including other conditions with underlying immunological mechanisms. Several diseases are potentially related to the systemic effect of bacterial translocation in tissues with defective epithelial barriers. Our meta-analysis provides evidence that supports the consideration of EGID in patients with ASD and ASD in patients with EGID. Despite its limitations, the results should also be validated by future studies, preferably using multicenter prospective designs in populations with low referral bias.

Symptoms and treatment of eosinophilic esophagitis prior to, during, and after pregnancy

Eosinophilic esophagitis disease course varies during pregnancy. Many patients' symptoms improve during pregnancy and worsen after. Pregnant patients often opt to decrease pharmacotherapy, highlighting the importance of discussing medication safety data, adverse outcomes associated with diet restriction, and close follow-up.

Minimally Invasive Approaches to Diagnose and Monitor Eosinophilic GI Diseases.

This review seeks to understand novel avenues for eosinophilic GI disease management. Biomarkers offer a unique and non-invasive approach to tracking EoE disease progression. While no biomarkers have definitively met the diagnostic criteria for eosinophilic GI diseases, some biomarkers have been shown to be associated with disease activity. Here, we examine the potential of recently studied biomarkers. Current research shows advancements in blood, luminal fluid, and breath testing. Particular areas of interest include mRNA analyses, protein fingerprinting, amplicon sequence variants (ASVs), T cells and IgE receptors, eosinophilic cationic proteins, cytokines, and nitric oxide exhalation. Preliminary results showed that mucosal biomarkers, directly captured from the esophagus, may reflect the best representation of biopsy-based results, in contrast to biomarkers obtained from indirect or peripheral (blood, breath) methods. However, this is based on limited clinical studies without sufficient numbers to evaluate true diagnostic accuracy. Large-scale randomized trials are needed to fully ascertain both the optimal sampling technique and the specific biomarkers that reflect diagnostic status of the disease.

Prevalence of eosinophilic gastrointestinal diseases in children with short bowel syndrome: A single center study.

Patients with short bowel syndrome (SBS) have multiple risk factors for eosinophilic gastrointestinal diseases (EGIDs) including increased risk for intestinal dysbiosis and food allergy compared to their counterparts with normal anatomy. However, there is limited data on the prevalence of EGIDs in children with SBS. We aimed to define the prevalence of EGIDs in an SBS cohort and its association with different risk factors via a retrospective chart review of patients with SBSat Children's National Hospital. The prevalence of eosinophilic esophagitis in our SBS cohort was 10%, eosinophilic gastritis was 4.9%, and eosinophilic enteritis was 4.9%. SBS patients with history of allergy or atopy were more likely to have esophageal and intestinal eosinophilia on biopsy than patients without allergy. The prevalence of EGIDs in our SBS cohort is significantly higher than in the general population and may be associated with allergic polarization.

Evidence for 2 clusters among patients with noneosinophilic asthma

BackgroundAlthough asthma is often seen as an eosinophilic disease associated with atopy, patients with noneosinophilic asthma represent a substantial part of the population with asthma. ObjectiveTo apply an unsupervised clustering method in a cohort of 588 patients with noneosinophilic asthma (sputum eosinophils < 3%) recruited from an asthma clinic of a secondary care center. MethodsOur cluster analysis of the whole cohort identified 2 subgroups as cluster 1 (n = 417) and cluster 2 (n = 171). ResultsCluster 1 comprised a predominantly female group with late disease onset, a low proportion of atopy (24%), and a substantial smoking history (53%). In this cluster, treatment burden was low (<50% of inhaled corticosteroid users); asthma control and quality of life were poor, with median Asthma Control Test, Asthma Control Questionnaire, and Asthma Quality of Life scores of 16, 1.7, and 4.5, respectively, whereas lung function was preserved with a median postbronchodilation forced expiratory volume in 1 second of 93% predicted. Cluster 2 was a predominantly male group, almost exclusively comprising patients with atopy (99%) with early disease onset and a moderate treatment burden (median inhaled corticosteroids dose 800 µg/d equivalent beclomethasone). In cluster 2, asthma was partially controlled, with median Asthma Control Test and Asthma Control Questionnaire scores reaching 18 and 1.3, respectively, and lung function well preserved with a median postbronchodilation of 95% predicted. Although systemic and airway neutrophilic inflammation was the dominant pattern in cluster 1, cluster 2 essentially comprised paucigranulocytic asthma with moderately elevated fraction exhaled nitric oxide. ConclusionNoneosinophilic asthma splits into 2 clusters distinguishing by disease onset, atopic status, smoking history, systemic and airway inflammation, and disease control and quality of life.

Sensitization with Fungal Protease Allergen Establishes Long-Lived, Allergenic Th Cell Memory in the Lung.

Allergic asthma is a chronic inflammatory disease that affects millions of individuals worldwide. Exposure to allergens produced by a variety of otherwise harmless microbes, including fungi, predisposes individuals to immunopathologic disease upon subsequent encounters with allergen. We developed a mouse model that employs a purified protease produced by Aspergillus (Asp f 13) to investigate the contributions of CD4+ Th cells to recurrent lung inflammation. Notably, memory CD4+ T cells enhanced the eosinophil response of sensitized/rechallenged animals. In addition, memory CD4+ T cells maintained allergenic features, including expression of GATA-binding protein 3 and IL-5. Th2 memory T cells persisted in the peribronchiolar interstitium of the lung and expressed markers of tissue residence, such as CD69, CCR8, and IL-33R. Lastly, we identified a peptide epitope contained within Asp f 13 and generated a peptide-MHC class II tetramer. Using these tools, we further demonstrated the durability and exquisite sensitivity of memory T cells in promoting lung eosinophilia. Our data highlight important features of memory T cells that strengthen the notion that memory T cells are principal drivers of eosinophilic disease in murine models of allergic sensitization and episodic airway inflammation.

A Classification for Gastric Outlet Obstruction in Childhood: Extending Beyond Infantile Hypertrophic Pyloric Stenosis.

Gastric outlet obstruction (GOO) is a rare condition in childhood, with the exception of infantile hypertrophic pyloric stenosis (IHPS). However, no classification exists from a pediatric gastroenterologist's perspective. The patients with a diagnosis of GOO between 2009 and 2020 were reviewed retrospectively. We classified the patients according to GOO: presence of clinical findings accompanied by radiological and/or endoscopic findings; clinical status: intractable nonbilious postprandial vomiting alone or with abdominal pain, early satiety, weight loss, postprandial abdominal distension, and malnutrition; radiology: delayed gastric emptying and dilated stomach; endoscopy: nonbilious gastric contents after 6-8 hours of emptying and/or failed pyloric intubation; physical examination: visible gastric peristalsis. A total of 30 GOO patients (15 patients with IHPS, 1 patient with annular pancreas, 4 patients with gastric volvulus, 2 patients with duodenal atresia, 2 patients with antral web, 1 patient with late-onset hypertrophic pyloric stenosis (LHPS) had surgical treatment, and remaining 5 patients had medical treatment) were enrolled to the study. The median age was 8 months (range: 3 months-16 years), and 14 patients were female. Mitochondrial disorders, LHPS, metabolic disorders, and eosinophilic gastrointestinal system diseases were added to Sharma's GOO classification, and the classification has been expanded. This is the first and largest study of GOO in children. From the perspective of pediatric gastroenterology, new diseases will be addressed, and definitions will be highlighted with our classification for GOO in childhood.

Clinical evaluation of pulmonary quantitative computed tomography parameters for diagnosing eosinophilic chronic obstructive pulmonary disease: Characteristics and diagnostic performance.

To investigate the characteristics and diagnostic performance of quantitativecomputed tomography (QCT) parameters in eosinophilic chronic obstructive pulmonary disease (COPD) patients. High-resolution CT scans of COPD patients were retrospectively analyzed, and various emphysematous parenchyma measurements, including lung volume (LC), lung mean density (LMD), lung standard deviation (LSD), full-width half maximum (FWHM), and lung relative voxel number (LRVN) were performed. The QCT parameters were compared between eosinophilic and noneosinophilic COPD patients, using a definition of eosinophilic COPD as blood eosinophil values ≥ 300 cells·µL-1 on at least three times. Receiver operating characteristic curves and area under the curve (ROC-AUC) and python were used to evaluate discriminative efficacy of QCT. Noneosinophilic COPD patients had a significantly lower TLMD (-846.3 ± 47.9 Hounsfield Unit[HU]) and TFWHM(162.5 ± 30.6 HU) compared to eosinophilic COPD patients (-817.8 ± 54.4, 177.3 ± 33.1 HU, respectively) (p = 0.018, 0.03, respectively). Moreover, the total LC (TLC) and TLSD were significantly lower in eosinophilic COPD group (3234.4 ± 1145.8, 183.8 ± 33.9 HU, respectively) than the noneosinophilic COPD group (5600.2 ± 1248.4, 203.5 ± 20.4 HU, respectively) (p = 0.009, 0.002, respectively). The ROC-AUC values for TLC, TLMD, TLSD, and TFWHM were 0.91 (95% confidence interval [CI], 0.828-0.936), 0.66 (95% CI, 0.546-0.761), 0.64 (95% CI, 0.524-0.742), and 0.63 (95% CI, 0.511-0.731), respectively. When the TLC value was 4110 mL, the sensitivity was 90.7% (95% CI, 79.7-96.9), specificity was 77.8% (95% CI, 57.7-91.4) and accuracy was 86.4%. Notably, TLC demonstrated the highest discriminative efficiency with an F1 Score of 0.79, diagnostic Odds Ratio of 34.3 and Matthews Correlation Coefficient of 0.69, surpassing TLMD (0.55, 3.66, 0.25), TLSD (0.56, 3.95, 0.26), and TFWHM (0.56, 4.16, 0.33). Eosinophilic COPD patients exhibit lower levels of emphysema and a more uniform density distribution throughout the lungs compared to noneosinophilic COPD patients. Furthermore, TLC demonstrated the highest diagnostic efficiency and may serve as a valuable diagnostic marker for distinguishing between the two groups.

In-Depth Review of Loeffler Endocarditis: What Have We Learned?

Loeffler endocarditis, eosinophilic endocarditis or eosinophilic endomyocardial disease are conditions associated with hypereosinophilia and they affect the heart function. Loeffler endocarditis is a rare endomyocardial disorder thought to be caused by eosinophilic damage. The disorder is characterized by inflammatory infiltration, formation of thrombus within cardiovascular system, and ultimately fibrosis of the afflicted area. It can lead to multiple severe complications, including thromboembolic disease, thickening of fibrous tissue in the endocardium of ventricles, valve involvement, apical obliteration, and various heart disorders. Although early clinical intervention can lead to remission, the underlying mechanisms of the disorder remain unresolved. In the present article, we summarise the existing literature concerning Loeffler endocarditis based on PubMed, Web of Science, and other medical databases to conduct an in-depth review of the epidemiology, etiology, pathophysiological mechanisms, staging, diagnosis, treatment and prognosis of Loeffler endocarditis. Meanwhile, we provide novel patients data and clinical figures of Loeffler endocarditis to supplement the understanding of this cardiac disorder. The findings presented in this article provide a basis for further studies and can be used to improve management of the disorder.

ANCA-associated Vasculitis: The Focus is on Eosinophilic Granulomatosis With Polyangiitis (Eosinophilic Vasculitis of Charge-Strauss)

Eosinophilic granulomatosis with polyangiitis (Charge-Strauss syndrome) is an eosinophilic granulomatous disease characterized by small caliber vascular lesions and is autoimmune in nature. Patients with this syndrome experience weight loss, fever, arthralgias, and myalgias. The disease most often begins with respiratory tract involvement, including infectious allergic rhinitis, bronchial asthma, symmetric eosinophilic pulmonary infiltrates, and eosinophilic pneumonia. In older individuals, the syndrome manifests with multiple mononeuritis, asymmetric polyneuropathy, anemia, and muscle weakness. This scientific review presents the main aspects of the prevalence, mechanisms of development, spectrum of clinical manifestations, diagnosis and differential diagnosis of eosinophilic granulomatosis with polyangiitis.

The last step to achieve barrier damage control.

Heterogeneity characterises inflammatory diseases and different phenotypes and endotypes have been identified. Both innate and adaptive immunity contribute to the immunopathological mechanism of these diseases and barrier damage plays a prominent role triggering type 2 inflammation through the alarmins system, such as anti-Thymic Stromal Lymphopoietin (TSLP). Treatment with anti-TSLP monoclonal antibodies showed efficacy in severe asthma and clinical trials for other eosinophilic diseases are ongoing. The aim of this perspective review is to analyse current advances and future applications of TSLP inhibition to control barrier damage.