Elevated Eosinophil Count Research Articles

Benralizumab: Effectiveness in Patients with Uncontrolled Severe Eosinophilic Asthma at 6 and 12 Months at a Third-Level Care Hospital. Capacity for ICS-LABA Therapy Reduction.

Asthma is a health condition with worldwide relevance, evaluated based on the necessary treatment to control symptoms and exacerbations. Severe asthma is uncontrolled despite high doses of ICS-LABA and treatment for triggering factors. Severe eosinophilic asthma is characterized by an increase in eosinophils in the peripheral circulation, walls, and passages of the respiratory tract. Biologic treatments such as benralizumab have demonstrated effectiveness as aids in decreasing respiratory tract inflammation and improving the management of symptoms in patients living with asthma. To assess the efficacy and safety of benralizumab as an add-on therapy for patients with severe, uncontrolled asthma and elevated blood eosinophil counts. Observational, analytic and ambispective study in 21 patients diagnosed with severe eosinophilic asthma treated with benralizumab, to determine the treatment's effectiveness through the change in estimated respiratory function by spirometry through the forced expiratory volume in one second (FEV1) value, reduction in second controlling treatment, serum eosinophil reduction, change in the Asthma Control Test score and the Asthma Control Questionnaire test at 6 and 16 months of treatment. An average difference of 241.43 mL (±461.43) in FEV1 at 6 months was found, as well as an average FeNO reduction of 49.8 ppm and eosinophil reduction of 612.78 cells at 12 months of treatment, additionally, CSI requirements were reduced in 95% of patients. Benralizumab improved respiratory function as well as key biomarkers such as eosinophil count, exhaled nitric oxide fraction (FeNO), which reflected in a decreased requirement of inhaled corticosteroids and improved symptom control.

Severe Uncontrolled Asthma: A Longitudinal Retrospective Study Illustrating the Experience of the Pulmonology Clinic of Târgu-Mureș, Romania.

Introduction: Severe uncontrolled asthma (SUA) affects approximately 5% of asthma patients, leading to frequent exacerbations, reduced lung function, and lower quality of life. Recent biologic therapies target specific inflammatory pathways, offering new options for SUA. Objective: This study aimed to evaluate clinical characteristics, treatment outcomes, and biomarkers in patients with SUA treated with biologics (Omalizumab, Benralizumab, and Dupilumab) at our clinic. Material and Methods: A six-month retrospective longitudinal study was conducted on 28 patients aged 36-83 years with SUA. Patients were divided into three groups: Omalizumab (n = 4), Benralizumab (n = 18), and Dupilumab (n = 6). Lung function tests and biomarkers such as eosinophil and IgE levels were measured over 3-month periods (T0, T1, and T2). Asthma control was assessed using asthma control tests (ACT), and non-parametric statistical methods were applied. Results: The median patient age was 64 years, with 75% showing elevated eosinophil counts (>300 cells/µL). Benralizumab significantly improved lung function (p < 0.05) and ACT scores (p < 0.001), reducing eosinophil counts to zero (p < 0.001). Patients on Dupilumab and Omalizumab showed improved asthma control (p < 0.05) and reduced exacerbations, albeit to a lesser extent (p > 0.05). Conclusions: Biologics, particularly Benralizumab and Dupilumab, improved asthma control, lung function, and quality of life in SUA patients, with improved ACT scores and spirometry values. Some patients remained poorly controlled, emphasizing the need for personalized treatment and regular biomarker monitoring. Multidisciplinary management and lifestyle changes are critical for better outcomes in SUA.

High eosinophil counts aid in diagnosing Kawasaki disease in febrile children

Abstract Background Several recent studies have validated the newfound significance of elevated eosinophils in Kawasaki disease (KD). However, this finding was not incorporated into the suggested laboratory criteria outlined by the Kawasaki Disease Committee of the American Heart Association for assessing children with incomplete KD. Purpose We aimed to determine the potential benefits of including eosinophil levels in the laboratory evaluation of KD. Methods A retrospective cohort study involved 77,934 febrile children (FC, not KD) and 1,970 subjects diagnosed with KD. Participants were recruited from four hospitals, comprising two medical centers and two regional hospitals. The AHA recommends specific laboratory tests—white blood cell count, hemoglobin, platelet count, ALT levels, albumin, and urinalysis—for evaluating incomplete KD in children with a higher CRP than 30mg/dL. The first four items are standard blood assays. Additionally, we introduced high eosinophil counts as a new diagnostic criterion for identifying children with KD. Results All these five laboratory findings (anemia for age defined as below the 5th percentile), platelet count &amp;gt;450,000/mm3, white blood cell&amp;gt;15,000/mm3, ALT&amp;gt;40 U/L, and eosinophil count &amp;gt;190/mm3) are significantly different between KD children and FC. The proportion of having these features is higher in KD children than in FC (19.3% vs. 8.0% in anemia for age, 20.5% vs. 10.3% in thrombocytosis, 37.0% vs. 18.1% in leukocytosis, 45.7% vs. 5.8% in elevated ALT, and 62.6% vs. 29.3% in high eosinophils). Elevated eosinophil counts are most commonly associated with KD among these five parameters. Furthermore, when incorporating the parameter of elevated eosinophil counts, the proportion of KD children with at least two abnormalities rose from 35.4% to 60.7%. In a subgroup analysis of children with KD presenting at least two abnormalities, the proportion rose from 38.7% to 63.5% in the high CRP group (≧ 3.0 mg/L) and 21.6% to 49.0% in the low CRP group (&amp;lt; 3.0 mg/L), respectively. Conclusions Higher eosinophil counts are vital markers in KD children. This aids in the identification of additional potential KD cases, especially in those exhibiting low CRP levels.

A MR-PheWAS and bidirectional Mendelian randomization study: Exploring for causal relationships of pancreatic cancer.

It is unknown what causes pancreatic cancer. We conducted a phenome-wide Mendelian randomization analysis (MR-pheWAS), a bidirectional Mendelian study, and a systematic review of research in order to thoroughly investigate any causal association between pancreatic cancer and Atlas. We used phenome-wide Mendelian randomization analysis to test for associations between pancreatic cancer and 776 phenotypes (n = 452,264) of Atlas in the UK Biobank. Causality is confirmed by two-sample Mendelian randomization (MR) analysis using correlation found by false discovery rate correction. Simultaneously, a comprehensive evaluation of pancreatic cancer MR studies was conducted in order to complement our findings and harmonize the existing evidence. According to the inverse-variance-weighted model, a total of 41 out of 776 phenotypes had a nominal significance level (P < .05) genetic prediction association with pancreatic cancer. Only genetically predicted pancreatic cancer was shown to be linked with elevated eosinophil counts following false discovery rate correction (P = .031) when several tests were taken into account. Pancreatic cancer and eosinophils were shown to be positively causally associated to one another, establishing a self-loop, according to two-sample MR validation in the IEU database (OR = 1.011, 95% CI: 1.002-1.020, P = .010) (OR = 1.229, 95% CI: 1.037-1.458, P = .017). Although MR-pheWAS found a strong causal relationship between eosinophils and pancreatic cancer, it also found a negative exclusion value for each phenotype and a significant number of suggestive association phenotypes that offered guidance for further research.

Aspergillus Serologic Findings and Clinical Outcomes in Patients With Bronchiectasis: Data From the European Bronchiectasis Registry

IntroductionAspergillus sp. cause diverse clinical manifestations in bronchiectasis including Allergic bronchopulmonary aspergillosis (ABPA), Aspergillus sensitization (AS) and raised IgG indicating exposure or infection with Aspergillus. Research QuestionWhat is the prevalence and clinical significance of Aspergillus-associated conditions in individuals with bronchiectasis? MethodsBronchiectasis patients enrolled into the EMBARC registry from 2015 to 2022 with laboratory testing for Aspergillus lung disease (total IgE, specific IgE to Aspergillus or Aspergillus skin test, IgG to Aspergillus and blood eosinophil counts) were included for analysis. Modified-ISHAM-ABPA working group criteria (2021) were used to define ABPA. Results9953 patients were included. 608 (6.1%) were classified as having ABPA, 570 (5.7%) showed Aspergillus sensitization, 806 (8.1%) had raised Aspergillus-specific IgG without sensitisation, 184 (1.8%) were both sensitised to Aspergillus and had raised Aspergillus-specific IgG and 619 (6.2%) had eosinophilic bronchiectasis (elevated eosinophil counts without evidence of Aspergillus lung disease). The remaining 72.0% had negative Aspergillus serology. Patients with ABPA, Aspergillus sensitization, and raised Aspergillus-specific IgG had more severe disease, with worse lung function and more frequent exacerbations at baseline. During long-term follow-up, patients with raised Aspergillus-specific IgG had higher exacerbation frequency and more severe exacerbations. Aspergillus sensitization associated with increased exacerbations and hospitalisations only in patients not receiving inhaled corticosteroids. InterpretationAspergillus lung disease is common in bronchiectasis. Raised IgG to Aspergillus is associated with significantly worse outcomes while ABPA and Aspergillus sensitization are associated with severe disease and exacerbations with a risk that is attenuated by inhaled corticosteroid use.

Type 2 inflammation in COPD: is it just asthma?

COPD is a heterogeneous condition, with tobacco smoking being the main environmental risk factor. The presence of type 2 (T2) inflammation is a well-recognised feature of asthma; however, it is now apparent that a subset of COPD patients also displays evidence of T2 inflammation with respect to elevated eosinophil counts and altered gene and protein expression of several T2 inflammatory mediators. T2 inflammatory mediators represent an attractive therapeutic target in both COPD and asthma; however, the efficacy of pharmaceutical interventions varies between diseases. Furthermore, the nature of some shared clinical features also differs. We provide a narrative review of differences in the nature of T2 inflammation between COPD and asthma, which may partly explain phenotypic differences between diseases. We focus on evidence from studies of pulmonary histopathology, sputum and epithelial gene and protein expression, and response to pharmacological interventions targeted at T2 inflammation.

Silicone allergy manifestation in pediatric ventriculoperitoneal shunting: navigating diagnostic challenges and customizing therapeutic approaches. Illustrative case.

A silicone allergy can significantly impact the efficacy of ventriculoperitoneal shunt devices used in hydrocephalus treatment. Its clinical presentation often resembles infectious ventriculitis, characterized by altered cerebrospinal fluid (CSF) parameters, including low glucose levels, elevated protein concentrations, and increased white blood cell counts predominantly comprising eosinophils. The authors report the case of an 18-month-old male who experienced recurrent shunt malfunction linked to CSF changes indicative of infectious ventriculitis. The patient underwent surgeries for suspected infection management. Notably, he exhibited increased eosinophil counts in both blood and CSF, as well as the development of neoformation tissue. This, along with the absence of microbial infection, indicated silicone hypersensitivity. While navigating medical device scarcity, innovative methods were employed to secure a silicone-free valve, markedly improving the patient's clinical outcome. Clinicians must be vigilant for silicone allergy in patients with ventriculoperitoneal shunts, particularly when elevated serum eosinophil counts and negative microbiological tests are present. This rare condition demands a multidisciplinary approach for timely diagnosis and management to reduce morbidity, unnecessary surgeries, and healthcare costs. The limited availability of non-silicone-based shunts further complicates management. This case emphasizes the need for considering silicone allergy in differential diagnoses, especially in pediatric patients. https://thejns.org/doi/10.3171/CASE2474.

De Novo Deep Intron ELANE Mutation Resulting in Severe Congenital Neutropenia.

Severe congenital neutropenia (SCN) comprises a diverse range of rare hematological disorders characterized by recurrent, often life-threatening infections that manifest within the first months of life. Mutations in the ELANE gene are the most prevalent cause of SCN. While over 230 mutations in ELANE have been documented, including substitutions, frameshifts, nonsense mutations, and splice site alterations, the occurrence of deep intronic mutations has not been previously reported. Herein, we present the case of a young girl who exhibited recurrent fever, respiratory infections, skin abscesses, and gingivitis shortly after birth. Laboratory analysis revealed markedly diminished neutrophil levels alongside elevated monocyte and eosinophil counts. Bone marrow examination disclosed a halt in myelopoiesis maturation. ELANE gene full-length sequencing identified a novel de novo deep intron mutation in ELANE (c.598 + 79G > T), subsequently confirmed by Sanger sequencing. cDNA sequencing of the patient demonstrated aberrant gene splicing. Utilizing a mini-gene splicing assay for ELANE intronic variants, we identified a mutant ELANE allele (c.597 + 1_597 + 83ins) leading to the creation of a premature termination codon (p.Gly200ValfsTer40). Confocal microscopy revealed heightened expression of myeloperoxidase and neutrophil elastase in the patient, suggesting a potential role for the unfolded protein response in the pathogenesis of the deep intron ELANE mutation. In summary, our findings illustrate the first reported instance of de novo deep intron ELANE mutations associated with SCN, underscoring the importance of exploring deep intronic regions in SCN patients lacking identifiable disease-causing gene mutations.

Artemisitene shows superiority over artemisinin in preventing Schistosoma japonica-induced liver disease

BackgroundArtemisinin (ART) analogs, such as dihydroartemisinin, arteether, artemether, and artesunate, all featuring an endoperoxide bridge, have demonstrated efficacy against schistosomiasis. Artemisitene (ATT), which contains an additional α, β-unsaturated carbonyl structure, has shown enhanced biological activities. This study aims to evaluate the anti-schistosomaiasis japonica activity of ATT and compare it with ART.MethodsWe assessed liver inflammation and fibrosis in mice using hematoxylin and eosin staining and Sirius red staining, respectively. RNA sequencing analyzed transcriptomics in female and male Schistosoma japonicum (S. japonicum) adult worms and mice livers, with cytokine profiling and flow cytometry to study immune responses under ART or ATT treatment.ResultsATT exhibits a marked reduction in female S. japonicum adult worms and egg numbers, damaging the adult worms’ surface. It also influences the transcription of genes related to cellular anatomical structures. Notably, ATT treatment resulted in significant reductions in liver granuloma size and collagen area, alongside lowering serum levels of glutamic pyruvic and glutamic oxaloacetic transaminase more effectively than ART. Both ART and ATT markedly decreased neutrophil frequency in the liver and elevated eosinophil counts. However, only ATT treatment significantly reduced the M1/M2 and Th1/Th2 indices, indicating a pronounced shift in immune response profiles. ATT-affected host immunity correlated with the extent of liver fibrosis and the count of single males more strongly than ART.ConclusionATT, as a novel preventive strategy for schistosomiasis japonica in mice, significantly outperforms ART.Graphical

Cholesterol Embolic Renal Disease: Experience of a Large Healthcare System.

Context. To determine the clinical-pathological features associated with cholesterol embolic renal disease, and review of literature. Design. This retrospective case series includes patients with cholesterol embolic renal disease (10 of 3087 kidney biopsies) who were diagnosed at Northwell Health, New York, between July 2017 and October 2022. Results. Cholesterol embolic renal disease is a rare disease with a prevalence of 0.32%. Four of 10 patients had intravascular interventional radiology procedures within 6 months prior to kidney biopsy. Four patients had remote interventional radiology history (6 months to 4 years). Seven patients presented with acute kidney injury; 3 patients underwent renal biopsy due to proteinuria. The average baseline creatinine was 2.0 ± 0.9 mg/dL; the creatinine at kidney biopsy and at follow-up was 4.3 ± 3.0 mg/dL and 2.8 ± 1.3 mg/dL, respectively. Eight patients had elevated serum eosinophil counts. Three patients died (mortality rate 30%) in an average follow-up of 4 months (range: 1-10 months). One patient progressed to end-stage kidney disease. The presence of cholesterol clefts is a hallmark of atherosclerotic emboli. Cholesterol clefts were present on the specimen for light microscopy (H&E and special stains) in 9 biopsies; 7 patients had cholesterol clefts in vascular lumens and/or walls. Cholesterol clefts were present on semi-thin sections for electron microscopy examination in 4 biopsies. One patient had cholesterol clefts present in semi-thin sections only. Conclusions. The clinical manifestation of cholesterol embolic renal disease in patients without recent intravascular interventional radiology history can be indolent but is associated with high mortality. Careful examination of all levels with light microscopy, including the perirenal tissue, and semi-thin sections can increase the detection rate of cholesterol embolic renal disease.

Frequency of Severe Asthma and Its Clinical Phenotypes at the Asthma Clinic in One of the Largest Sudanese Tertiary Pediatric Hospitals: A Cross-Sectional Hospital-Outpatient-Based Study.

Asthma is one of the most common non-communicable diseases. Childhood asthma has been increasing in Sudan, with a 13-16% prevalence among Khartoum school children. To achieve and maintain good asthma control, proper diagnosis, assessment of severity, and appropriate medication administration are crucial, with phenotyping being a key factor in determining patients' specific treatment. To study the frequency of severe asthma and the distribution of its different phenotypes and to investigate associations between age and gender and different phenotypes of asthma. This descriptive cross-sectional hospital-based study was conducted in the Asthma Clinic of Mohamed Al-Amin Hamid Pediatrics Hospital. It included 229 patients who were presented to the clinic from September 2021 to April 2022. Data were collected from the patients and/or their caregivers using a modified validated standard questionnaire and were analyzed using SPSS version 26.0. A p-value of 0.05 or less was considered statistically significant. In this study of 229 participants, 14.4% had severe asthma, with 44.5% and 41% exhibiting mild and moderate asthma, respectively. Most were effectively managed in steps 2 or 3. The cohort, primarily aged 5 or younger (40.2%) with a male majority (62%), showed a mean diagnosis age of 2.9 ± 2.8 years. Impressively, 90% maintained well-controlled asthma. Within severe asthma cases (87% atopic), 39.4% represented a severe allergic asthma phenotype. Elevated eosinophil counts were noted in 45.5% (serum) and 78.8% (sputum cytology), while 57.6% had normal serum IgE levels. The predominant symptom pattern in severe asthma was episodic multi-trigger wheezing (48.5%). Age and gender displayed no significant association with severe asthma phenotype. This study reveals a concerning rise in childhood asthma prevalence in Sudan, emphasizing the importance of tailored treatment strategies. Severe asthma, characterized by atopic eosinophilic involvement, necessitates targeted interventions in pediatric asthma care for specific phenotypes.

Systematic Reporting of Eosinophils in Transbronchial Biopsies After Lung Transplantation Defines a Distinct Inflammatory Response.

Descriptions of eosinophils in transbronchial biopsy (TBBx) pathology reports after lung transplantation (LTx) are associated with poor long-term outcomes. The absence of routine reporting and standardization precludes accurate assessment of this histologic predictor. A systematic reporting scheme for the presence of TBBx eosinophils after LTx was implemented. This report aims to assess this scheme by describing the presence, pattern, and gradation of TBBx eosinophils and clinical associations. A prospective cross-sectional study of all TBBx reports was performed including all patients presenting for a surveillance or diagnostic TBBx between January 2020 and June 2023. Each TBBx was systematically reported in a blinded manner. Mixed-effects logistic regression was performed to measure the association between concurrent clinical and histologic features, and the presence of TBBx eosinophils. A total of 410 TBBx reports from 201 patients were systematically reported. In 43.8% recipients, any TBBx eosinophils were detected and in 17.1% recipients, higher-grade eosinophils (≥3 per high power field) were present. Adjusted analysis showed that retransplantation, A- and B-grade cellular rejection, positive bronchoalveolar lavage (BAL) bacterial microbiology, and elevated blood eosinophil count were independently associated with the presence of any TBBx eosinophils. Diagnostic "for-cause" procedures were independently associated with higher quantities of TBBx eosinophils. Systematic reporting demonstrates that TBBx eosinophils are a distinct inflammatory response associated with rejection, infection, and peripheral eosinophilia. Although these findings require multicenter external validation, standardized reporting for TBBx eosinophils may assist in identifying recipients at risk of poor outcomes and provides a platform for mechanistic research into their role after lung transplantation.

The impact of inflammatory cells on lung function in asthmatics in a cross sectional retrospect study

BackgroundLimited data exists on the impact of inflammatory cells and clinical characteristics on lung function in individuals with asthma. ObjectiveThe objective is to examine the correlation between increased inflammatory cells, asthma symptoms, and lung function in patients with asthma in a clinical setting. MethodsA retrospective cohort study was conducted on 234 individuals suspected of having asthma in Xian, China between January 2008 and December 2021. Of those, 143 patients with complete clinical feature and lung function data were enrolled to examine the relationship between increased inflammatory cells, asthma symptoms, and lung function. Basic characteristics, blood eosinophil count, blood neutrophil count, blood platelet count, blood C-reactive protein (CRP), and comprehensive lung function analysis were evaluated at each inpatient for the 143 adult asthmatics. The association between inflammatory cells and clinical parameters with pulmonary function was compared. ResultsThe results of the study showed that individuals in the alcohol intake group had elevated blood eosinophil count compared to those in the non-alcohol intake group (P = 0.024). Long-acting inhaled beta 2 agonists and antibiotic therapy were associated with lower blood eosinophil count (P = 0.021 and P = 0.049, respectively) compared to other therapy. There was a independent association between blood eosinophil counts and FEV1 pre- and post-therapy in asthma but there was a markedly correlation between blood eosinophil counts and FEV1/FVC pre-and post-therapy in Asthma (P = 0.007). Blood neutrophil counts were inversely correlated with FEV1/FVC after treatment (P = 0.032). Night onset in asthma was positively correlated with blood neutrophil counts, while fever was negatively correlated with blood CRP (P = 0.028). Platelet counts >300 × 109/L after treatment were significantly associated with a decline in FEV (<0.001) in patients with asthma. Elevated blood eosinophil count was independently associated with clinical features in asthma. ConclusionsBased on the study's findings, there is a significant decline in FEV1/FVC among individuals with elevated blood eosinophil count, both pre- and post-bronchodilator while there was a independent relationship between blood eosinophil counts and FEV1 pre-and post-therapy in asthma. This suggests that increased levels of eosinophils may independently associated contribute to reduced lung function in asthma patients.

Analysis of factors affecting complete pathological remission after neoadjuvant immunocombination chemotherapy treatment for locally advanced esophageal squamous carcinoma.

e16061 Background: Chemotherapy combined with immunotherapy for locally advanced esophageal squamous carcinoma has achieved a high rate of complete pathological remission, which is conducive to a better prognosis for patients; however, not all ESCC patients benefit from ICI therapy, so finding validated prognostic markers of efficacy will help us to screen for populations that are superior to neoadjuvant immunotherapy. Methods: Patients with locally advanced esophageal squamous carcinoma treated with neoadjuvant immune-combination chemotherapy followed by radical surgery from January 2019 to June 2023 at our institution were collected. The grouping was based on whether pathologic complete remission (pCR) was achieved after neoadjuvant therapy. Clinical and treatment-related data as well as hematologic, inflammatory, and nutritional indices within 1 week before neoadjuvant therapy and within 1 week after 2 cycles of neoadjuvant immune-combination chemotherapy treatment were collected from all patients, and univariate and multivariate analyses were performed to assess independent predictors of pCR. Results: Patients in both pCR and Non-pCR groups were more likely to obtain pCR if they had pre-treatment BMI &gt; 21Kg/m2 vs BMI ≤21Kg/m2, number of neoadjuvant therapy cycles ≥3 cycles vs number of neoadjuvant therapy cycles = 2 cycles, and CYFRA21-1ng/ml &lt; 3.28 vs ≥3.28 before neoadjuvant therapy (p &lt; 0.05). Patients with albumin ≥40.10g/L vs albumin &lt; 40.10g/L, NLR &lt; 2.50 vs NLR ≥2.50, and NRI ≥98.06 vs NRI &lt; 98.06 were more likely to achieve pCR before treatment in both groups (p &lt; 0.05). SII ≥521.75 VS SII &lt; 521.75 was more likely to achieve pCR after 2 cycles of treatment (p &lt; 0.05). Univariate analysis of the comparison of dynamic changes in nutritional inflammatory indexes during treatment between the two groups of patients showed that pCR was more likely to be achieved in patients with persistently elevated eosinophil counts and NLR after 2 cycles of neoadjuvant immune-combination chemotherapy treatment (p &lt; 0.05). The results of multifactorial analysis showed that pre-treatment BMI, SII after 2 cycles of treatment, and dynamic changes in eosinophils during neoadjuvant therapy were independent influences on complete pathological remission after neoadjuvant immune-combination chemotherapy treatment (p &lt; 0.05). Conclusions: Complete pathological remission after neoadjuvant immune-combination chemotherapy treatment for esophageal squamous carcinoma was significantly correlated with the patient's pre-treatment BMI, Post-treatment SII, and eosinophil dynamics during treatment.

Dupilumab for COPD with Blood Eosinophil Evidence of Type 2 Inflammation

BackgroundDupilumab, a fully human monoclonal antibody that blocks the shared receptor component for interleukin-4 and interleukin-13, key and central drivers of type 2 inflammation, has shown efficacy and safety in a phase 3 trial involving patients with chronic obstructive pulmonary disease (COPD) and type 2 inflammation and an elevated risk of exacerbation. Whether the findings would be confirmed in a second phase 3 trial was unclear.MethodsIn a phase 3, double-blind, randomized trial, we assigned patients with COPD who had a blood eosinophil count of 300 cells per microliter or higher to receive subcutaneous dupilumab (300 mg) or placebo every 2 weeks. The primary end point was the annualized rate of moderate or severe exacerbations. Key secondary end points, analyzed in a hierarchical manner to adjust for multiplicity, included the changes from baseline in the prebronchodilator forced expiratory volume in 1 second (FEV1) at weeks 12 and 52 and in the St. George’s Respiratory Questionnaire (SGRQ; scores range from 0 to 100, with lower scores indicating better quality of life) total score at week 52.ResultsA total of 935 patients underwent randomization: 470 were assigned to the dupilumab group and 465 to the placebo group. As prespecified, the primary analysis was performed after a positive interim analysis and included all available data for the 935 participants, 721 of whom were included in the analysis at week 52. The annualized rate of moderate or severe exacerbations was 0.86 (95% confidence interval [CI], 0.70 to 1.06) with dupilumab and 1.30 (95% CI, 1.05 to 1.60) with placebo; the rate ratio as compared with placebo was 0.66 (95% CI, 0.54 to 0.82; P<0.001). The prebronchodilator FEV1 increased from baseline to week 12 with dupilumab (least-squares mean change, 139 ml [95% CI, 105 to 173]) as compared with placebo (least-squares mean change, 57 ml [95% CI, 23 to 91]), with a significant least-squares mean difference at week 12 of 82 ml (P<0.001) and at week 52 of 62 ml (P=0.02). No significant between-group difference was observed in the change in SGRQ scores from baseline to 52 weeks. The incidence of adverse events was similar in the two groups and consistent with the established profile of dupilumab.ConclusionsIn patients with COPD and type 2 inflammation as indicated by elevated blood eosinophil counts, dupilumab was associated with fewer exacerbations and better lung function than placebo. (Funded by Sanofi and Regeneron Pharmaceuticals; NOTUS ClinicalTrials.gov number, NCT04456673.)

Safety of immune checkpoint inhibitors in patients aged over 80 years: a retrospective cohort study

BackgroundImmuno-oncology (IO) drugs are essential for treating various cancer types; however, safety concerns persist in older patients. Although the incidence of immune-related adverse events (irAEs) is similar among age groups, higher rates of hospitalization or discontinuation of IO therapy have been reported in older patients. Limited research exists on IO drug safety and risk factors in older adults. Our investigation aimed to assess the incidence of irAEs and identify the potential risk factors associated with their development.MethodsThis retrospective analysis reviewed the clinical data extracted from the medical records of patients aged > 80 years who underwent IO treatment at our institution. Univariate and multivariate analyses were performed to assess the incidence of irAEs.ResultsOur study included 181 patients (median age: 82 years, range: 80–94), mostly men (73%), with a performance status of 0–1 in 87% of the cases; 64% received IO monotherapy. irAEs occurred in 35% of patients, contributing to IO therapy discontinuation in 19%. Our analysis highlighted increased body mass index, eosinophil counts, and albumin levels in patients with irAEs. Eosinophil count emerged as a significant risk factor for any grade irAEs, particularly Grade 3 or higher, with a cutoff of 118 (/μL). The group with eosinophil counts > 118 had a higher frequency of irAEs, and Grade 3 or higher events than the group with counts ≤ 118.ConclusionIO therapy is a safe treatment option for patients > 80 years old. Furthermore, patients with elevated eosinophil counts at treatment initiation should be cautiously managed.

The value of biomarkers in the therapy of CRSwNP with biologicals—a long-term follow-up of dupilumab therapy

PurposeSince its release, Dupilumab has shown great results in treating severe uncontrolled CRSwNP. However, there is a lack of real-world data beyond 12 months of follow-up, and it is not clear to what extent biomarkers are appropriate for monitoring and predicting the Dupilumab therapy success. Hence, this study aims to analyze biomarkers for monitoring therapy, predicting therapy success and assess the effect of Dupilumab in real-world settings.MethodsThe follow-up was performed with 104 patients retrospectively up to 22 months, assessing SNOT-22, NPS, olfactometry, ACS, FEV-1, and blood biomarkers (total serum IgE, Eosinophils, ECP). Patients were divided into subgroups depending on their pretherapeutic biomarker levels and subsequent development was analyzed.ResultsThere was substantially improvement in all clinical parameters up to 1 year and then continuously up to month 22. Patients with initially elevated baseline blood eosinophil counts (> 0.5 billion/L) had a trend of better SNOT-22 development after 1 year (− 12.19 points, p = 0.03). The course of total serum IgE showed moderate correlation with almost all clinical variables obtained. Therapy was well tolerated with only mild and transient adverse events.ConclusionDupilumab has considerably reduced symptoms and disease severity even beyond 1 year of treatment, supporting its role as targeted and effective treatment option for CRSwNP. Our data shows that total serum IgE is a promising biomarker for the monitoring during the treatment with Dupilumab. Elevated pre-therapeutic serum eosinophil counts may be a predictor of good subjective response to therapy. Larger cohorts and a long-term-follow-up over years are needed to further consolidate these findings.

A Phase 3 Trial of Dupilumab for People With Chronic Obstructive Pulmonary Disease and Elevated Peripheral Blood Eosinophil Counts

A Phase 3 Trial of Dupilumab for People With Chronic Obstructive Pulmonary Disease and Elevated Peripheral Blood Eosinophil Counts

Kimura's Disease in Unusual Anatomical Locations: Clinical and Radiological Characteristics.

To explore the clinical and imaging features of rare site Kimura's disease (KD). Retrospective analysis was conducted on the clinical manifestations, laboratory examinations, and imaging features of five patients with rare site KD. All imaging data, including the location, quantity, size, uniformity, boundary, and enhanced appearance of the lesion were evaluated by two independent radiologists. Of the five patients, four were asymptomatic, and one experienced localized skin itching. Four cases involved subcutaneous nodules in the upper arm, while one was in the inguinal region. The main manifestations were single (three cases) or multiple (two cases) subcutaneous nodules/masses, with three patients accompanied by local lymph node enlargement. Four patients exhibited elevated eosinophil counts in their peripheral blood. Four patients had lesions with vascular flow voids; in three of these, the lesions also showed prominent enhancement. Notably, the lesion in a 5-year-old did not show vascular flow voids but displayed significant enhancement. Additionally, two patients showed edema around the lesions. The presence of solitary or multiple subcutaneous nodules/masses in the upper arm or inguinal area, accompanied by lymph node enlargement, elevated eosinophils in the peripheral blood, and the observation of internal vascular within the lesion, can aid in the diagnosis of KD occurring in uncommon anatomical locations.

Eosinophils and risk of ulcerative colitis in European population: Evidence from Mendelian randomization study.

Observational studies have indicated that peripheral blood eosinophil count is elevated in individuals diagnosed with ulcerative colitis (UC) and correlates with the disease activity of UC. However, this conclusion contradicts with findings from other studies. Therefore, we employed Mendelian randomization (MR) method to assess the genetic link between eosinophil count and UC. This MR study utilized summary data from genome-wide association studies (GWAS) on eosinophil count and UC. The main approach used for conducting MR analysis was the inverse variance weighted (IVW) method. Meta-analysis of the IVW results was performed alongside multiple sensitivity analyses to confirm the robustness of the MR analysis results. The IVW method unveiled a causal relationship between eosinophil count and UC (OR = 1.18, 95% CI: 1.04-1.33, p = .01) in the discovery cohort. This finding was further corroborated by the replication cohorts (OR = 1.16, 95% CI: 1.04-1.29, p = .01; OR = 1.12, 95% CI: 1.01-1.24, p = .03). The meta-analysis indicated that the overall odds ratio (OR) for all studies was 1.15 (common effect model, 95% CI: 1.08-1.23, p < .01). Sensitivity analysis suggested the absence of heterogeneity and horizontal pleiotropy in all MR analyses. Based on bidirectional two-sample MR analysis, there is an indication that elevated eosinophil count may increase the risk of UC. However, potential confounding factors cannot be ruled out, and further research is necessary to explore how eosinophils contribute to the onset and progression of UC.