Eosinophil Count Research Articles

Twice-Yearly Depemokimab in Severe Asthma with an Eosinophilic Phenotype.

Depemokimab is an ultra-long-acting biologic therapy with enhanced binding affinity for interleukin-5 that may enable effective 6-month dosing intervals. In these phase 3A, randomized, placebo-controlled replicate trials, we evaluated the efficacy and safety of depemokimab in patients with severe asthma and an eosinophilic phenotype characterized by a high eosinophil count (≥300 cells per microliter in the previous 12 months or ≥150 cells per microliter at screening) and a history of exacerbations despite the receipt of medium- or high-dose inhaled glucocorticoids. Patients were randomly assigned in a 2:1 ratio to receive either depemokimab (at a dose of 100 mg subcutaneously) or placebo at weeks 0 and 26, plus standard care. The primary end point was the annualized rate of exacerbations at 52 weeks. Secondary end points, which were analyzed in a hierarchical manner to adjust for multiplicity, included the change from baseline in the score on the St. George's Respiratory Questionnaire (SGRQ), the forced expiratory volume in 1 second, and asthma symptom reports at 52 weeks. Across the two trials, 792 patients underwent randomization and 762 were included in the full analysis; 502 were assigned to receive depemokimab and 260 to receive placebo. The annualized rate of exacerbations was 0.46 (95% confidence interval [CI]), 0.36 to 0.58) with depemokimab and 1.11 (95% CI, 0.86 to 1.43) with placebo (rate ratio, 0.42; 95% CI, 0.30 to 0.59; P<0.001) in SWIFT-1 and 0.56 (95% CI, 0.44 to 0.70) with depemokimab and 1.08 (95% CI, 0.83 to 1.41) with placebo (rate ratio, 0.52; 95% CI, 0.36 to 0.73; P<0.001) in SWIFT-2. No significant between-group difference in the change from baseline in the SGRQ score was observed in either trial, so no statistical inference was drawn on subsequent secondary end points. The proportion of patients with any adverse event was similar in the two groups in both trials. Depemokimab reduced the annualized rate of exacerbations among patients with severe asthma with an eosinophilic phenotype. (Funded by GSK; SWIFT-1 and SWIFT-2 ClinicalTrials.gov numbers, NCT04719832 and NCT04718103.).

Food-Protein-Induced Proctocolitis in Pre-Term Newborns with Bloody Stools in a Neonatal Intensive Care Unit.

The bloody stools of newborns may be a clue for several clinical entities of varying severity, ranging from idiopathic neonatal transient colitis to food-protein-induced allergic proctocolitis (FPIAP) or necrotizing enterocolitis (NEC). Distinguishing among them at an early stage is challenging but crucial, as the treatments and prognoses are different. We conducted a monocentric retrospective study including all pre-term infants with bloody stools admitted to the Neonatal Intensive Care Unit (NICU) of the Vittore Buzzi Children's Hospital (Milan) from December 2022 to May 2024. Patients diagnosed with NEC exhibited significantly lower eosinophil counts and higher procalcitonin levels than both patients with FPIAP and patients with idiopathic neonatal transient colitis, as well as a statistically significant increase in pathological features from abdomen ultrasounds and abdominal X-rays. In contrast, no lab markers or imaging techniques have been demonstrated to be useful in distinguishing between idiopathic neonatal transient colitis and FPIAP. Thus, after excluding a diagnosis of NEC, the only way to confirm FPIAP is through the oral food challenge, which can be performed in premature newborns presenting with bloody stools who are otherwise healthy and under medical supervision, in order to identify infants who may benefit from a cow's-milk-free diet.

Immunologic mediators profile in COVID-19 convalescence

SARS-CoV-2 caused the pandemic situation experienced since the beginning of 2020, and many countries faced the rapid spread and severe form of the disease. Mechanisms of interaction between the virus and the host were observed during acute phase, but few data are available when related to immunity dynamics in convalescents. We conducted a longitudinal study, with 51 healthy donors and 62 COVID-19 convalescent patients, which these had a 2-month follow-up after symptoms recovery. Venous blood sample was obtained from all participants to measure blood count, subpopulations of monocytes, lymphocytes, natural killer cells and dendritic cells. Serum was used to measure cytokines, chemokines, growth factors, anti-N IgG and anti-S IgG/IgM antibodies. Statistic was performed by Kruskal–Wallis test, and linear regression with days post symptoms and antibody titers. All analysis had confidence interval of 95%. Less than 35% of convalescents were anti-S IgM+, while more than 80% were IgG+ in D30. Anti-N IgG decreased along time, with loss of seroreactivity of 13%. Eosinophil count played a distinct role on both antibodies during all study, and the convalescence was orchestrated by higher neutrophil-to-lymphocyte ratio and IL-15, but initial stages were marked by increase in myeloid DCs, B1 lymphocytes, inflammatory and patrolling monocytes, G-CSF and IL-2. Later convalescence seemed to change to cytotoxicity mediated by T lymphocytes, plasmacytoid DCs, VEGF, IL-9 and CXCL10. Anti-S IgG antibodies showed the longest perseverance and may be a better option for diagnosis. The inflammatory pattern is yet present on initial stage of convalescence, but quickly shifts to a reparative dynamic. Meanwhile eosinophils seem to play a role on anti-N levels in convalescence, although may not be the major causative agent. We must highlight the importance of immunological markers on acute clinical outcomes, but their comprehension to potentialize adaptive system must be explored to improve immunizations and further preventive policies.

Clinical characteristics and risk factors for antituberculosis drug-induced hypersensitivity.

The aim of this study was to explore the clinical characteristics and risk factors for hypersensitivity reactions induced by antituberculosis drugs. A retrospective analysis was conducted on the medical records of patients with active tuberculosis (TB) treated in the TB ward at West China Hospital, Sichuan University, from November 2010 to April 2020. Out of 7106 patients with active tuberculosis, 205 experienced hypersensitivity reactions to antituberculosis drugs; the incidence of hypersensitivity was 2.9%. The predominant clinical manifestation was a rash, observed in 57.1% (117/205) of these cases. Additionally, 19.0% (39/205) of patients presented with concurrent liver injury. The laboratory parameters white blood cell count, total lymphocyte count, monocyte count, eosinophil count, basophil count, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase were significantly elevated in patients with hypersensitivity compared to those without. In 38 patients who tested positive for oral antituberculosis drug provocation, 14 (36.8%) were allergic to more than two antituberculosis drugs. Significant risk factors included being female (odds ratio [OR] = 1.387, 95% confidence intervals [CI]: 1.016-1.894), under 65 years of age (OR = 1.826, 95% CI: 1.145-2.913), existing liver disease (OR = 2.464, 95% CI: 1.822-3.333) and a history of allergic diseases (OR = 6.633, 95% CI: 2.681-16.406) and were significantly correlated with hypersensitivity to antituberculosis drugs. Hypersensitivity reactions to antituberculosis drugs primarily affect the skin, with significant associations observed with liver injury. Females, individuals younger than 65 years, those with pre-existing liver disease and patients with a history of allergic diseases are at elevated risk for hypersensitivity.

Prevalence and CCR3-T51C genotype–phenotype correlation of bronchial asthma among basic education school children: an observational study

BackgroundBronchial asthma (BA) is a chronic inflammatory disorder identified by different endotypes and phenotypes. Chemokine receptor 3 (CCR3) is one of the essential chemokine receptors that have a crucial role in asthma development by activating the migration of eosinophils through eotaxin production. We aimed to determine asthma prevalence among school children and to investigate the association between CCR3-T51C gene polymorphisms and the symptom-based clinical asthma phenotypes.MethodsThis study employed a hybrid design, conducted at a single center in Egypt from 2020 to 2021, to explore the relationship between asthma, its clinical phenotypes, and the CCR3-T51C gene polymorphism. Initially, a cross-sectional analysis was performed, utilizing a modified version of the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire to determine the prevalence of asthma in a cohort of 60 children, who presented with diverse clinical phenotypes, alongside 100 healthy controls. Subsequently, in the case–control phase of the study, we focused on examining the association between asthma (and its clinical phenotypes) and the CCR3-T51C gene polymorphism. For both groups, serum immunoglobulin E (IgE) levels and eosinophil counts were assessed, and the genotypes and alleles of the CCR3-T51C gene polymorphism were identified using the polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) technique.ResultsA total of 600 children aged (6 to 16 years old) were enrolled. Out of these, 72 children (12%) were diagnosed with bronchial asthma in the basic education schools in El Manzala City, Egypt. Also, 72 (12%) of the studied children had wheezes, and 48 (8%) had night cough. Children with asthma had significantly higher relative eosinophil count and serum IgE levels than the control group. In terms of CCR3-T51C genotypes analysis, the TT genotype was the most prevalent in both patient and control groups, with 63.3% and 64%, respectively, but the difference was not statistically significant (P > 0.05). Also, there were no significant associations between CCR3-T51C genotypes and laboratory biomarkers among cough, wheezy, and cough and wheezy groups, except for the CT genotype in the cough group that had a lower eosinophil count than the wheezy group (P = 0.04).ConclusionAsthma affects 12% of the school-aged children. The CCR3-T51C genotype or allelic polymorphism frequency did not differ between asthmatics and controls; however, the TT genotype was more frequent in asthmatic children. Eosinophil count, serum IgE and gene polymorphism of CCR3-T51C appeared similar among different asthmatic phenotypes.

The Uselessness of Anaerobic Antibiotic Coverage in Aspiration Pneumonia: A Systematic Review and Meta-Analysis

Introduction: Asthma is a prevalent respiratory condition, and biologic agents have proven effective in managing moderate to severe asthma. However, the role of biomarkers in guiding the use of biologic agents remains unclear. Method: On July 30, 2024, a systematic review and subsequent meta-analysis were conducted by searching three major online databases: PubMed, Web of Science, and Cochrane. Results: The final analysis included 10 studies with a total of 6,709 patients with moderate to severe asthma. The overall pooled effect across all ages demonstrated a rate ratio (RR) reduction of 0.61 (95% CI: 0.46 to 0.80; p &lt; 0.01; I² = 71%). Subgroup analysis revealed an onset or treated age of less than 18 years with RRs of 0.79 (95% CI: 0.62 to 1.02; p = 0.07; I² = 0%) and 0.88 (95% CI: 0.42 to 1.84; p = 0.73; I² = 14%), respectively. Patients with varying blood eosinophil levels showed a pooled RR of 0.51 (95% CI: 0.38 to 0.69; p &lt; 0.01; I² = 82.7%). However, blood eosinophil levels below 150/μL demonstrated a limited effect of biologic agents, with an RR of 0.77 (95% CI: 0.35 to 1.67; p = 0.50; I² = 87%). For patients with all levels of fraction of exhaled nitric oxide (FeNO), the RR was 0.43 (95% CI: 0.30 to 0.62; p &lt; 0.01; I² = 84%). The test for subgroup differences yielded a p-value of &lt; 0.001, indicating that patients with higher FeNO levels experienced a more significant reduction in RR. Conclusion: Patients with asthma onset or treatment before age 18 may benefit less from biologics. Blood eosinophil counts and FeNO levels aid in selecting these therapies.

Saffron (Crocus sativus) and its constituents in ovalbumin-induced asthma model: a preclinical systematic review and meta-analysis.

Animal and human studies have demonstrated that the saffron and the active components of saffron, including crocin, crocetin, and safranal, possess anti-inflammatory, antioxidant, and immunomodulatory properties. In this meta-analysis, the preclinical evidence and potential mechanism of saffron were explored in an animal model of ovalbumin-induced asthma. Studies related to saffron and its constituents in an animal model of ovalbumin-induced asthma from the beginning to March 2024 were searched from Scopus, PubMed, and Web of Science databases. The methodological quality of the studies was evaluated using the 15-item CAMARADES checklist. Data analysis was performed using STATA software version 17. Thirteen studies with 536 animals (268 animals in the intervention group and 268 animals in the ovalbumin-induced group) were analyzed. The meta-analysis findings demonstrated that saffron and its constituents played a significant role in reducing total WBC, eosinophil, lymphocyte, and monocyte counts. Moreover, saffron showed a significant decrease in the levels of IL-4, IL-5, IL-13, IgE, histamine, endothelin, nitric oxide, and nitrite. Moreover, saffron was found to elevate EC50 thresholds and lower maximum response rates in experimental animals. The analysis revealed a significant identification of modulation in endoplasmic reticulum (ER) stress markers and miRNAs pathways. Saffron and its components may impact ovalbumin-induced asthma model in animals through anti-inflammatory, antioxidant, and immunomodulatory pathways, as well as improving pulmonary function and modulating ER stress markers and miRNAs pathways. As a result, saffron should be considered for further clinical trials in individuals suffering from asthma.

Exploring the mechanisms and relationship between body mass index and asthma: findings from Mendelian randomization

Background The mechanism linking BMI and asthma remains unclear. Method Mendelian Randomization (MR) analysis was conducted using summary-level GWAS data from the FinnGen Biobank and the Open GWAS project. The analysis considering potential variables as mediators, including blood cell counts, blood pressure, and blood biomarkers. Three commonly used MR methods—the inverse-variance-weighted (IVW) method, weighted median (WM) method, and MR-Egger method—were employed to infer causal links. A two-step approach was used in mediation analysis to evaluate the causal links among BMI, candidate mediators, and asthma. Result Elevated BMI demonstrated a substantial correlation with increased asthma risk. Thirteen biomarkers mediated the relationship between BMI and asthma, mainly including leukocyte count (5.070%), apolipoprotein A levels (7.395%), cystatin C levels (5.345%), urate levels (9.057%), diastolic blood pressure (7.365%), and albumin levels (10.888%). These factors collectively explained over 50% of the increased asthma risk associated with BMI elevation. Additionally, eosinophil count and C-reactive protein were also identified as important mediators using the WM method. Conclusion This study highlights the complex relationship between obesity, blood biomarkers, and asthma risk. Additional studies are required to validate these results and investigate causal relationships in various populations.

Back to Basics: The Diagnostic Value of a Complete Blood Count in the Clinical Management of COVID-19.

Since the beginning of the COVID-19 pandemic, scientists have struggled significantly to understand the complexity of COVID-19 pathophysiology. COVID-19 has demonstrated a notoriously unpredictable clinical course. This unpredictability constituted a significant obstacle to clinicians in predicting the disease course among COVID-19 patients, more specifically, in predicting who would develop severe cases and possibly die from the infection. This brief report aims to assess the diagnostic value of using a complete blood count (CBC) and applying high-dimensional analysis, i.e., principal component analysis (PCA), on it to differentiate between patients with mild and severe COVID-19 infection. The data of 855 patients were retrieved from multiple centres in Saudi Arabia. Descriptive statistics, such as counts, percentages, and medians (interquartile ranges) were used to describe patients' characteristics and CBC parameters. Analytical statistics, such as the Mann-Whitney U test, were used to compare between survivors and non-survivors. PCA was applied using the CBC parameters, and the results were compared between survivors and non-survivors. Patients in this study had a median age of 41, with an almost equal ratio of men to women. Most participants were Saudis, and non-survivors were 13.22% of the total cohort. The median values of all CBC indices were within reference ranges; however, some statistically significant differences were observed between survivors and non-survivors. Non-survivors had lower hemoglobin levels and lower hematocrit, lymphocyte, and eosinophil counts but higher WBC and neutrophil counts compared to survivors. PCA on the CBC results of survivors yielded a significantly different profile than non-survivors, indicating the possibility of its use in the context of COVID-19. The diagnostic value of CBC in the clinical management of COVID-19 should be utilized in clinical guidelines for managing COVID-19 cases.

The Enhanced Role of Eosinophils in Radiomics-Based Diagnosis of Microvascular Invasion and Its Association with the Immune Microenvironment in Hepatocellular Carcinoma.

To investigate the role of eosinophil counts (EC) in microvascular invasion (MVI) for enhancing the radiomics based diagnostic model. Additionally, its correlation with early recurrence and tumor immune microenvironment was explored. Propensity score matching was employed to evaluate on 462 cases whether EC was an independent risk factor for MVI. Subgroup analyses examined EC's effect on MVI across varying hypersplenism degrees. Univariate-multivariate logistic regression identified MVI's independent factors to develop a diagnostic model. Univariate-multivariate COX regression determined early recurrence factors. Co-detection by indexing (CODEX) constructed the immune score (IS), and Spearman correlation analyzed its association with peripheral immunity. EC was an independent risk factor for MVI (p=0.038, OR=1.304 (95% CI: 1.014-1.677)), and its effect on MVI disappeared with the severity of hypersplenism. The diagnostic model with EC was significantly improved (AUC=0.787 (95% CI: 0.737-0.836) vs AUC=0.748(95% CI: 0.694-0.802, p=0.005)). MVI was an independent risk factor for early recurrence (p<0.001, HR = 2.254 (95% CI: 1.557-3.263)). IS was negatively correlated with lymphocyte counts (R=-0.311, p=0.022), and positively correlated with EC (R=0.301, p=0.027) and RS (R = 0.315, p = 0.018). EC was an independent risk factor for MVI and was related to the tumor immune microenvironment. EC should be included in the diagnosis of MVI to improve diagnostic efficiency.

Allergo-immunopathology mechanism of thymol-inhibiting airway remodeling in asthmatic mice by regulating TGF-β/Smad3 pathway.

Allergic asthma is an important public health problem and is a complicated respiratory sickness that is characterized by bronchial inflammation, bronchoconstriction, and breathlessness. Asthma is orchestrated by type 2 immune response and remodeling is one of the important outputted problem in chronic asthma. Thymol is a naturally occurring monocyclic phenolic, it has a series of biological properties, and its immunomodulatory and anti-remodeling effects on allergic asthma were evaluated. The OVA-LPS-induced asthmatic mice were treated with thymol. Methacholine challenge test, eosinophil count, and levels of IL-4, IL-5, IL-13, and IL-33 in bronchoalveolar lavage fluid, total and OVA-specific IgE levels in serum, remodeling factors, gene expression of TGF-β, Smad2, Smad3, and lung histopathology were done. Treatment with thymol could control AHR, eosinophil percentage levels of Th2 cytokines and Igs, remodeling factors, expression of TGF-β, Smad2 and Smad3 genes, inflammation, goblet cell hyperplasia, and mucus production in asthmatic mice. Thymol can control asthma pathogens and related remodeling and fibrosis bio-factors and can be a potential treatment of asthma.

265. INITIAL RESULTS FROM RESOLVE, A PHASE 1B DOSE-ESCALATION STUDY OF EP-104GI (EXTENDED-RELEASE FLUTICASONE PROPIONATE INTRA-ESOPHAGEAL INJECTION) FOR EOSINOPHILIC ESOPHAGITIS

Abstract Background Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease characterized by inflammation, influx of eosinophils and esophageal remodeling. Therapy for EoE includes swallowed/topical corticosteroids, dupilumab, and dietary elimination; but these are not always effective. EP-104GI is an extended-release fluticasone propionate (FP) intra-esophageal injection being developed as a novel treatment for EoE. EP-104GI consists of coated FP crystals that release locally via diffusion at a pre-defined rate to reduce peak concentrations and prolong therapeutic window. RESOLVE (NCT05608681) is a Phase 1b, multicenter, open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of EP-104GI in patients with EoE. Methods The conservative starting dose of EP-104GI consisted of 1 mg injected at each of 4 sites in 4 quadrants over two ‘rings’ in the esophagus. Dose escalations increase the dose per site and/or number of sites; the second cohort received 1 mg at each of 8 sites. After a single administration of EP-104GI, participants are assessed for up to 24 weeks including adverse events (AEs) and laboratory tests. Efficacy assessments include histological endpoints and patient-reported symptom outcomes including the Straumann Dysphagia Index (SDI). Esophageal biopsies are collected at baseline, Week 4 and Week 12. Results All subjects demonstrated decreased symptom scores compared to baseline, with generally greater responses at the higher EP-104GI dose in Cohort 2 (Fig 1). Histologically, all Cohort 2 patients showed decreases in EoEHSS scores with 2/3 having ≈50% decrease in total grade score and ≈35% decrease in total stage score at Week 4, also, eosinophil counts were reduced by ≈35% at Week 4 and ≈40% at Week 12. Findings from Cohorts 1 and 2 of the ongoing trial include mild-moderate treatment-emergent AEs, the majority occurring on the day of treatment. No AEs were related to EP-104GI. Conclusions The initial results presented here indicate that the novel diffusion-based localized delivery of FP via EP-104GI injection into the esophagus is feasible and safe in patients with EoE and could avoid the side-effects typically associated with swallowed/topical corticosteroids. Efficacy data from the doses studied, although limited at this point, suggest a dose-response relationship with symptom outcomes and also show histologic improvements. These findings support the potential for an interval of at least 6 months between inter-esophageal injections, which may be further extended at the higher doses to be investigated in this study. Recruitment is ongoing.

Acute Liver Injury and Bilateral Pulmonary Artery Thrombosis Due to Hypereosinophilic Syndrome.

A 46-year-old Japanese man was referred to our hospital because of a marked increase in his eosinophil count (22,870/μL) and elevated liver enzyme levels. Computed tomography (CT) showed thrombi measuring approximately 8 cm in both femoral veins. A liver biopsy revealed eosinophilic infiltration, hepatocyte necrosis, fibrosis, and multiple thrombi. We suspected acute liver injury and deep vein thrombosis associated with hypereosinophilic syndrome and initiated steroids and heparin treatment. Four days after starting treatment, the patient experienced sudden chest pain and cardiopulmonary arrest. CT revealed bilateral pulmonary artery thrombosis, and despite administration of a tissue plasminogen activator, the patient died.

Rheumatoid Arthritis Exacerbates Eosinophilic Inflammation Contributing to Postoperative Recurrence in Chronic Rhinosinusitis with Nasal Polyps.

To assess the impact of rheumatoid arthritis (RA) on histopathological features and the risk of postoperative recurrence in chronic rhinosinusitis with nasal polyps (CRSwNP) patients. A retrospective cohort study of CRSwNP patients who underwent functional endoscopic sinus surgery was performed. Patients were followed up for more than two years, and classified into RA and Non-RA groups, recurrent and non-recurrent groups. The influence of RA on histopathological features and the risk of CRSwNP recurrence was explored. A total of 517 CRSwNP patients were finally recruited, including 78 RA patients. The RA group exhibited a higher recurrence rate, tissue eosinophil counts and percentages compared to the non-RA group (P < 0.05). Tissue eosinophil count and percentage, and the prevalence of allergic rhinitis were significantly higher in the recurrent group in compared to the non-recurrent group (P < 0.05). Multivariate logistic regression analysis identified tissue eosinophil count and percentage, RA, and allergic rhinitis as significant predictors of increased recurrence risk (P < 0.05). Both adjusted and unadjusted models affirmed RA as an independent risk factor for CRSwNP postoperative recurrence (P < 0.05). Kaplan-Meier curves further indicated a higher recurrence risk in CRSwNP patients with RA than those without (P < 0.05). Our findings suggest that RA significantly exacerbates tissue eosinophilic inflammation and independently heightens the risk of postoperative recurrence in CRSwNP patients. These insights underscore the need for tailored therapeutic strategies addressing the complex interplay between CRSwNP and RA to mitigate recurrence risks and improve clinical outcomes.

Disease Burden, Treatment Patterns and Asthma Control in Adult Patients with Asthma in China: A Real-World Study.

To inform better asthma management in China, this study aimed to comprehensively investigate clinical characteristics, treatment patterns, asthma control status, exacerbations, and humanistic burden among adult patients seeking hospital-based asthma care by analyzing data from Adelphi Asthma Disease Specific Program conducted in China. All information was collected on survey date (August-December 2018) from medical records, physicians, or patients, without follow-up being conducted. Results are summarized descriptively for the overall population as well as subgroups defined by GINA 2018 treatment step. Of the included 765 patients, 46.0%, 40.4%, and 29.2% had undergone lung function, blood eosinophil count, and specific immunoglobulin E/radioallergosorbent testing, and 17.2%, 24.1%, and 58.7% were managed at GINA Steps 1-2, 3, and 4-5, respectively. Asthma was not well controlled in 57.3% of patients based on definitions adapted from the ERS/ATS and 10.7% of patients had experienced ≥1 severe exacerbation in the preceding year. According to patient self-reporting (n=603), the mean (SD) was 0.9 (0.1) for utility on EQ-5D-3L and was 7.8% (10.4%), 36.9% (20.0%), 40.8% (22.2%), and 37.9% (22.3%) for absenteeism, presenteeism, work productivity loss, and activity impairment, respectively, on WPAI. Both asthma control and humanistic burden worsened with progressive GINA treatment steps. In patients seeking hospital-based asthma care in China, lung function and biomarker tests were underutilized, impairment in productivity and quality of life was observed, and more than half did not achieve well-controlled asthma despite approximately 60% being managed at GINA treatment Steps 4-5. These findings highlight the urgent need for optimizing asthma management in China.

Interleukin 16 and 25 (IL-17E) and Clinical Outcomes in Exacerbation of COPD-A Pilot Study.

Background: Exacerbation of chronic obstructive pulmonary disease (ECOPD) significantly impact health status, hospitalization rates, and disease progression, and are linked to increased mortality. Predictive factors for ECOPD are therefore of considerable interest. The limited understanding of interleukin 16 (IL-16) and IL-25 role in ECOPD provided the rationale for this study. Methods: Fifty ex-smokers diagnosed with COPD (22 ECOPD and 28 patients in the stable phase of the disease) underwent prospective analysis to evaluate the role of I IL-25 as predictive markers of clinical outcomes in ECOPD. Results: We observed a significantly lower IL-16 and higher IL-25 concentrations among ECOPD patients (p = 0.002 and p = 0.01 respectively). We also detected a significant negative correlation between IL-16 and neutrophil-to-lymphocyte ratio (NLR) (p = 0.04) and a significant negative correlation between IL-25 concentration and absolute eosinophil count (p = 0.04). In the entire group, we observed a positive correlation between IL-16 and both FEV1 and FVC, both expressed as a percentage of reference value, (p = 0.002 and p = 0.0004 respectively). However, after stratification to ECOPD and stable COPD group, significance maintained for FVC (p = 0.045 for ECOPD and p = 0.02 for stable COPD). In survival analysis, we detected significantly lower all-cause mortality for 3rd tertile of IL-16 concentrations, with a hazard ratio of 0.33 (95%CI: 0.11-0.98; p = 0.04). Conclusions: Lower IL-16 levels among ECOPD patients may indicate a feedback mechanism linked to heightened Th1 response activation. Observed correlations with ventilatory parameters and survival also seems to reflect this mechanism. The higher IL-25 concentrations observed in ECOPD patients, along with the negative correlation with absolute eosinophil count and eosinopenia, suggest multifactorial regulation and independent functions of eosinophils and IL-25. Hypothetically, this paradox may be related to the Th1/Th2 imbalance favoring Th1 response. Obtained results should be reproduced in larger size samples.

One-food versus 4-food elimination diet for pediatric eosinophilic esophagitis: A multisite randomized trial

BackgroundA 6-food elimination diet in pediatric eosinophilic esophagitis (EoE) is difficult to implement and may negatively impact quality of life (QoL). Less restrictive elimination diets may balance QoL and efficacy. ObjectiveWe performed a multi-site, randomized comparative efficacy trial of a 1-food (milk) elimination diet (1FED) versus 4-food (milk, egg, wheat, soy) elimination diet (4FED) in pediatric EoE. MethodsPatients aged 6 to 17 years with histologically active and symptomatic EoE were randomized 1:1 to 1FED or 4FED for 12 weeks. Primary endpoint was symptom improvement by Pediatric EoE Symptom Score (PEESSv2.0). Secondary endpoints were proportion achieving histologic remission (<15 eosinophils/high-power field [eos/hpf]); change in histologic features (histology scoring system [HSS]), endoscopic severity (endoscopic reference score [EREFS]), transcriptome (EoE diagnostic panel [EDP]), and QoL scores; and predictors of remission. Results63 patients were randomly assigned to 1FED (n=38) and 4FED (n=25). In 4FED versus 1FED, mean PEESSv2.0 improved -25.0 versus -14.5 (p=0.04) but remission rates (41% versus 44%; p=1.00), HSS (-0.25 versus -0.29; p=0.77), EREFS (-1.10 versus -0.58; p=0.47) and QoL scores were similar between groups. The EoE transcriptome normalized in histologic responders to both diets. Baseline peak eosinophil count predicted remission (OR 0.975, 95% CI 0.953–0.999, p=0.04; cut-off ≤42 eos/hpf). The 4FED withdrawal rate (32%) exceeded 1FED (11%) (p=0.0496). ConclusionsAlthough 4FED moderately improved symptoms compared to 1FED, the histologic, endoscopic, QoL, and transcriptomic outcomes were similar in both groups. 1FED is a reasonable first choice therapy for pediatric EoE given its effects, tolerability, and relative simplicity.

578. DUPILUMAB EFFICACY IN EOSINOPHILIC OESOPHAGITIS PATIENTS TREATED WITH PRIOR THERAPY AND INADEQUATE RESPONSE, INTOLERANCE, OR CONTRAINDICATION TO SWALLOWED TOPICAL CORTICOSTEROIDS

Abstract Background Improvements in histologic, symptomatic, and endoscopic aspects of eosinophilic oesophagitis (EoE) were observed in patients treated with dupilumab weekly (qw) enrolled in the 3-part, phase 3 LIBERTY EoE TREET study (NCT03633617), regardless of prior inadequate response, intolerance, and/or contraindication to swallowed topical corticosteroids (STC). Here we assess the efficacy of dupilumab qw versus placebo in this STC non-responsive/intolerant subgroup, stratifying further by those with/without history of food elimination diets, proton pump inhibitor (PPI) use at randomisation, or history of oesophageal dilation. Methods This analysis includes patients who received dupilumab 300 mg qw or placebo for 24 weeks in Part B and an additional 28 weeks dupilumab in Part C. Co-primary endpoints (Weeks 24 and 52) include: proportions of patients achieving peak eosinophil count (PEC) ≤6 eosinophils/high-power field (eos/hpf) and absolute change in Dysphagia Symptom Questionnaire (DSQ) score. Secondary endpoints assessed included proportions of patients achieving PEC ≤1 eos/hpf, &amp;lt;15 eos/hpf, % change in PEC, and absolute change in Endoscopic Reference Score, and EoE-Histologic Scoring System grade/stage scores. Results Dupilumab 300 mg qw improved proportions of patients achieving co-primary endpoints, ≤6 eos/hpf and absolute change in DSQ score, and secondary endpoints, ≤1 eos/hpf and &amp;lt;15 eos/hpf at Week 24 versus placebo, regardless of history of food elimination diets, PPI use at randomisation, or history of dilation (Table). Improvements were maintained or continued to improve at Week 52. A similar trend was observed for other secondary endpoints assessed. Placebo-treated patients who switched to dupilumab in Part C demonstrated similar efficacy to patients treated with dupilumab in Part B. Dupilumab safety was consistent with the known dupilumab safety profile. Conclusion Dupilumab qw demonstrated sustained improvements in histologic and symptomatic aspects of EoE up to 52 weeks in adults and adolescents with an inadequate response, intolerance, and/or contraindication to STC, regardless of history of food elimination diets, PPI use, or history of oesophageal dilation. Improvements in endoscopic aspects of EoE up to 52 weeks were also observed.

Eosinophilia and Adverse Effects of Dupilumab for Respiratory Indications: A Real-World Setting

BackgroundDupilumab has been used with significant benefit in the treatment of asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). Phase 3 clinical trials have demonstrated transient eosinophilia and rare eosinophil-related and other adverse effects. ObjectiveTo characterize dupilumab-associated eosinophilia (absolute eosinophil count [AEC] ≥ 1.5 x 103/μL within 36 weeks of dupilumab initiation) and adverse effects associated in real-world patients with asthma and CRSwNP in the United States. MethodsRetrospective chart review of 251 patients on dupilumab for asthma and/or CRSwNP seen at a single institution. ResultsAmong the 142 patients who had AECs checked before and after treatment, 16 (11.3%) patients had post-treatment eosinophilia, including 11 (7.7%) patients who had new eosinophilia upon dupilumab initiation. Thirteen patients with post-treatment eosinophilia remained on dupilumab, 10 of whom had resolution of eosinophilia. Eosinophil-related adverse effects were rare and cases of eosinophilic granulomatous polyangiitis (EGPA) were limited to 1 patient with eosinophilia and 1 patient with normal eosinophil levels on systemic steroids. Other adverse effects included arthralgias (13/251, 5.2%), rash (8/251, 3.2%), and conjunctivitis (7/251, 2.8%). All patients with pre-treatment eosinophilia and the majority of patients with post-treatment eosinophilia received significant treatment benefit for their respiratory disease with dupilumab. ConclusionWhile dupilumab-associated eosinophilia is seen in a subset of patients, persistent eosinophilia or eosinophil-related adverse effects are rare. Furthermore, treatment benefit on dupilumab despite eosinophilia supports its continued use in both asthma and CRSwNP.

Real-World Effectiveness of Mepolizumab in Severe Asthma: Results from the Multi-country, Self-controlled Nucala Effectiveness Study (NEST).

The Nucala Effectiveness Study (NEST) assessed the effectiveness of mepolizumab in patients with severe asthma (SA) in countries previously underrepresented in real-world studies. A multi-country, bi-directional, self-controlled, observational cohort study conducted in Colombia, Chile, India, Türkiye, Saudi Arabia, United Arab Emirates, Kuwait, Oman, and Qatar. Historical and/or prospective data from patients with SA were assessed 12months pre- and post-mepolizumab initiation. incident rate ratio (IRR) of clinically significant exacerbations (CSEs). Key secondary endpoints: healthcare resource utilisation (HCRU), oral corticosteroid (OCS) use, lung function and symptom control (Asthma Control Test [ACT] scores). Overall, 525 patients with SA burden pre-initiation (geometric mean blood eosinophil count [BEC] 490.7 cells/µl; 31.4% prior biologic use; 37.3% obese) received at least one dose of mepolizumab 100mg subcutaneously. Post-initiation, a significant reduction in CSEs was observed (76% [p < 0.001]; IRR [95% confidence interval] 0.24 [0.19-0.30]); 72.0% of patients had no CSEs. Mepolizumab treatment led to a reduction in OCS use (52.8% pre-initiation vs. 16.6% post-initiation) and a mean (standard deviation [SD]) change in OCS dose of -18.1 (20.7) mg post-initiation; 36.1% of patients became OCS-free. Fewer patients were hospitalised post-initiation (22.5% pre-initiation vs. 6.9% post-initiation). Improvements in mean (SD) forced expiratory volume in 1s (62.8 [20.2]% pre-initiation vs. 73.0 [22.7]% post-initiation) and ACT scores (15.0% pre-initiation vs. 64.5% of patients post-initiation with well-controlled asthma) were observed. Proportion of patients with BEC ≥ 500 cells/µl decreased from 84.4% pre-initiation to 18.1% post-initiation. Mepolizumab was effective in reducing the burden of SA by significantly reducing CSEs, reducing OCS use and HCRU, and improving lung function and asthma control, which could translate to improvements in health-related quality of life in patients with SA and high OCS dependency in the countries studied. A graphical abstract is available with this article.