Higher Eosinophil Counts Research Articles

High eosinophil counts predict decline in FEV1: results from the CanCOLD study.

The aim of this study was to examine the association between blood eosinophil levels and the decline in lung function in individuals aged >40 years from the general population. The study evaluated the eosinophil counts from thawed blood in 1120 participants (mean age 65 years) from the prospective population-based Canadian Cohort of Obstructive Lung Disease (CanCOLD) study. Participants answered interviewer-administered respiratory questionnaires and performed pre-/post-bronchodilator spirometric tests at 18-month intervals; computed tomography (CT) imaging was performed at baseline. Statistical analyses to describe the relationship between eosinophil levels and decline in forced expiratory volume in 1 s (FEV1) were performed using random mixed-effects regression models with adjustments for demographics, smoking, baseline FEV1, ever-asthma and history of exacerbations in the previous 12 months. CT measurements were compared between eosinophil subgroups using ANOVA. Participants who had a peripheral eosinophil count of ≥300 cells·µL-1 (n=273) had a greater decline in FEV1 compared with those with eosinophil counts of <150 cells·µL-1 (n=430; p=0.003) (reference group) and 150-<300 cells·µL-1 (n=417; p=0.003). The absolute change in FEV1 was -32.99 mL·year-1 for participants with eosinophil counts <150 cells·µL-1; -38.78 mL·year-1 for those with 150-<300 cells·µL-1 and -67.30 mL·year-1 for participants with ≥300 cells·µL-1. In COPD, higher eosinophil count was associated with quantitative CT measurements reflecting both small and large airway abnormalities. A blood eosinophil count of ≥300 cells·µL-1 is an independent risk factor for accelerated lung function decline in older adults and is related to undetected structural airway abnormalities.

COPD patients with chronic bronchitis and higher sputum eosinophil counts show increased type‐2 and PDE4 gene expression in sputum

Chronic obstructive pulmonary disease (COPD) patients with higher eosinophil counts are associated with increased clinical response to phosphodiesterase‐4‐inhibitors (PDE4i). However, the underlying inflammatory mechanisms associated with this increased response is not yet elucidated. This post hoc analysis focused on sputum gene expression in patients with chronic bronchitis who underwent 32‐day treatment with two doses of the inhaled PDE4i CHF6001 (tanimilast) or placebo on top of triple therapy. Biological characterization and treatment effects were assessed between patients with different sputum eosinophil levels (eosinophilhigh ≥ 3%; eosinophillow < 3%) at baseline (primary samples) or at the end of the treatment of the placebo arm (validation samples). Forty‐one genes were differentially expressed in primary samples (p‐adjusted for false discovery rate < 0.05); all up‐regulated in eosinophilhigh patients and functionally enriched for type‐2 and PDE4 inflammatory processes. Eleven out of nineteen genes having immune system biological processes annotations including IL5RA, ALOX15, IL1RL1, CLC, GATA1 and PDE4D were replicated using validation samples. The expression of a number of these inflammatory mediators was reduced by tanimilast treatment, with greater effects observed in eosinophilhigh patients. These findings suggest that type‐2 and PDE4 overexpression in COPD patients with higher sputum eosinophil counts contribute to the differential clinical response to PDE4i observed in previous clinical trials.

Blood eosinophil count as predictor of asthma exacerbation. A meta-analysis.

Evidence about the association of high blood eosinophil count with asthma exacerbation is inconsistent and unclear. The objective of this meta-analysis was to determine whether elevated blood eosinophil count predicts asthma exacerbation. We searched MEDLINE, EMBASE, and additional databases, without any language restriction. We also checked the reference lists of the included studies and of relevant systematic reviews. The main outcome was the occurrence of asthma exacerbation. We calculated global pooled odds ratios (ORs) and their 95% confidence intervals (CIs) and performed predefined subgroup analyses. We appraised the quality of the studies using Newcastle-Ottawa Scale, examined the heterogeneity between studies, assessed publication bias, and carried out sensitivity analyses. Among 1567 retrieved publications, 23 observational studies comprising 155,772 participants met the inclusion criteria. High blood eosinophil count was associated with higher odds of asthma exacerbation [OR: 1.31 (95% CI: 1.16, 1.49)], specifically with asthma-related outpatient visits [OR: 1.46 (95% CI: 1.25, 1.70)] and emergency department visits [OR: 1.63 (95% CI: 1.29, 2.07)]. A significant association was observed starting from an eosinophils' cutoff value of 200 cells/μl. The association was observed for cohort studies [OR: 1.30 (95%CI: 1.13, 1.49)], North American studies [OR: 1.43 (95%CI: 1.31, 1.57)], Asian populations [OR: 1.67 (95%CI: 1.34, 2.08)], children [OR: 1.38 (95%CI: 1.22, 1.56)], and studies that adjusted for inhaled corticosteroids therapy [OR: 1.42 (95%CI: 1.28, 1.56)]. Blood eosinophil counts≥200cells/µL are associated with asthma exacerbation. Blood eosinophil count is a modifiable factor that could be addressed in asthma management strategies.

Genomics and Pharmacogenomics of Rhinosinusitis

Background: Polymorphisms of selected inflammatory and metabolic genes have been described in the etiology of chronic rhinosinusitis, and these effects can be explained on a pharmacogenetic basis. Objective: The purpose of this study was to examine whether there is an association between inflammatory factors and some of these alleles, by associating these genetic variables with each other. Methods: CYP1A2, CYP2D6, CYP2C19, CYP2C9, CYP3A4, CYP3A5, G6PD, NAT2, UGT1A1, VKORC1, ABCB1, SLCO1B1, APOE, TNF, IL1B, IL6 and IL6R gene polymorphisms were analyzed by PCR. Drug-metabolizing enzymes were classified according to their phenotype. Blood cell counts and biochemical parameters were also considered. Results: Significant differences were found in the CYP1A2 phenotype, with fewer CYP1A2 normal metabolizers (NMs) expressing sinusitis (14.3% vs 30%) and a greater number of CYP1A2 ultra-rapid-metabolizers (UMs)(85% vs 69%); and in TNF, affecting TNF-A/A (4% vs 2%) and TNF-G/G (78% vs 66%) compared with TNF-G/A (19% vs 32%) carriers. 96% of patients with CRS had at least one G allele. When trigenic variables involved in sinusitis were analyzed, statistical differences were found in SLCO1B1-TNFCYP1A2, with a higher proportion of subjects with 1/1-GG-UM (44.3%); and IL1B-TNFCYP1A2 with CC-GG-UM (26%), CT-GG-UM (19.8%) and CC-GG-NM (13.7%) genophenotypes, respectively. Subjects with sinusitis had a higher eosinophil count (308.80 cel/mcL vs 263.14 cel/mcL) and lower HDL levels (265.34 vs 297.85 mg/dL). Conclusion: SLCO1B1-TNF-CYP1A2 and IL1B-TNF-CYP1A2 trigenic clusters may condition the chronicity of sinusitis. Eosinophilia and HDL are factors involved in inflammation, and thus in the development of CRS.

NAVIGATOR: a phase 3 multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the efficacy and safety of tezepelumab in adults and adolescents with severe, uncontrolled asthma

BackgroundPatients with severe, uncontrolled asthma have a significant unmet need for new treatments that have broader effects on airway inflammation, and that provide greater improvements in asthma outcomes than currently approved biologics and standard-of-care therapies. Tezepelumab is a human monoclonal antibody that blocks the activity of the epithelial cytokine thymic stromal lymphopoietin. In the PATHWAY phase 2b study (NCT02054130), tezepelumab significantly reduced exacerbations by up to 71% in adults with severe, uncontrolled asthma, irrespective of baseline disease phenotype. This article reports the design and objectives of the pivotal phase 3 NAVIGATOR study.MethodsNAVIGATOR (NCT03347279) is an ongoing randomized, double-blind, placebo-controlled trial in adults (18–80 years old) and adolescents (12–17 years old) with severe, uncontrolled asthma, who are receiving treatment with medium- or high-dose inhaled corticosteroids plus at least one additional controller medication with or without oral corticosteroids (N = 1061). The study population includes approximately equal proportions of patients with high (≥ 300 cells/μL) and low (< 300 cells/μL) blood eosinophil counts. The study comprises a 5–6-week screening period, a 52-week treatment period and a 12-week post-treatment follow-up period. All patients will receive their prescribed controller medications without change throughout the study. The primary efficacy endpoint is the annualized asthma exacerbation rate during the 52-week treatment period. Key secondary endpoints include the effect of tezepelumab on lung function, asthma control and health-related quality of life.DiscussionNAVIGATOR is evaluating the effect of tezepelumab in patients with a broad range of severe asthma phenotypes at baseline, including those with low blood eosinophil counts. The target sample size for NAVIGATOR (N = 1060) was achieved, and it is the largest clinical study of tezepelumab in severe, uncontrolled asthma to date. NAVIGATOR aims to further investigate the effect of tezepelumab on exacerbations and build on observations from the phase 2b PATHWAY study, and to demonstrate further the potential of tezepelumab to provide patients with severe, uncontrolled asthma with improvements in lung function, asthma control and health-related quality of life.Trial registrationNCT03347279 (ClinicalTrials.gov). Registered 20 November 2017.

Prognostic Role of Blood Eosinophil Count in Patients with Sorafenib-Treated Hepatocellular Carcinoma.

Inflammation is a long-established hallmark of liver fibrosis and carcinogenesis. Eosinophils are emerging as crucial components of the inflammatory process influencing cancer development. The role of blood eosinophils in patients with hepatocellular carcinoma receiving systemic treatment is an unexplored field. The objective of this study was to analyse the prognostic role of the baseline eosinophil count in patients with sorafenib-treated hepatocellular carcinoma. A training cohort of 92 patients with advanced- or intermediate-stage sorafenib-treated hepatocellular carcinoma and two validation cohorts of 65 and 180 patients were analysed. Overall survival and progression-free survival in relation to baseline eosinophil counts were estimated by the Kaplan-Meier method. Univariate and multivariate analyses were performed. A negative prognostic impact of low baseline eosinophil counts (< 50*109/L) was demonstrated in all cohorts (training cohort: hazard ratio = 50.1, 95% confidence interval 11.6-216.5, p < 0.0001 for low vs high eosinophil counts; first validation cohort: hazard ratio = 4.55, 95% confidence interval 1.24-16.65, p = 0.022; second validation cohort: hazard ratio = 3.21, 95% confidence interval 1.83-5.64, p < 0.0001). Moreover, low eosinophil counts had a negative prognostic role in patients progressing on or intolerant to sorafenib who received second-line regorafenib, but not capecitabine or best supportive care. Our analysis identified baseline blood eosinophil counts as a new prognostic factor in patients with sorafenib-treated hepatocellular carcinoma. Concerning second-line therapies, eosinophil counts were associated with survival outcomes only in regorafenib-treated patients, suggesting a possible predictive role in this setting.

Eosinophil Count Variation among Histopathological Features of Appendectomy Specimens at Birat Medical College Teaching Hospital

Introduction: The histopathological examination of appendectomy specimens is the gold standard method for diagnosis. The presence of eosinophil besides other inflammatory cells like neutrophils and mature lymphocytes within different histological layers of appendectomy specimens are common findings for labeling it under various groups. This finding supports the assumption that appendicitis is triggered by Type 1 hypersensitivity reaction. &#x0D; Objective: To evaluate the eosinophil count variation in appendectomy specimens in patients with the clinical diagnosis of appendicitis. &#x0D; Methodology: This is a cross sectional hospital based study of 144 appendectomy specimens obtained in Department of Pathology, Birat Medical College Teaching Hospital from January 2019 to December 2019. Socio-demographic data, association of histopathological patterns with age groups, gender and eosinophil count in various histopathological groups was compared and cross-tabulated using SPSS version 16. &#x0D; Result: Among 144 appendectomy specimens, male gender (50.70%) of 15-24 years age group (36.80%) was predominant. The commonest histopathological diagnosis was acute appendicitis (31.25%) with highest eosinophil count in all of its histological layers. The association of various histopathological patterns with age groups and gender were not statistically significant, whereas it revealed statistically significant correlation between eosinophil counts in all histological layers.&#x0D; Conclusion: Findings suggest that the eosinophil count variation in the entire histological layers correlate well among different histopathological patterns of appendectomy specimens. This reflects the high diagnostic value of evaluating the eosinophil count in appendectomy specimens.

GENETIC VARIANTS DO NOT PREDICT ACUTE COPD EXACERBATIONS OR TREATMENT RESPONSE TO FLUTICASONE FUROATE/UMECLIDINIUM/VILANTEROL (FF/UMEC/VI) AND ITS COMPONENTS

SESSION TITLE: Obstructive Lung Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Combination treatments, targeting multiple mechanisms, benefit subjects with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, predicting AECOPD and treatment response remains challenging. We investigated genetic effects on AECOPD and response to combination treatment with FF (an inhaled corticosteroid), UMEC (a long-acting muscarinic antagonist), and VI (an ultra-long-acting ß2 adrenoreceptor agonist) and for each component. METHODS: The genetic basis of AECOPD (modelled as rate or risk) was evaluated in samples from 23 clinical studies (n=16,097 subjects) and 2 disease cohort studies (ECLIPSE (n=1,434) and COPDGene (n=2,310)), resulting in a total of 19,841 subjects. Pharmacogenetic (PGx) effects were tested in 8,439 subjects in study NCT02164513 with analysis of 5 co-primary endpoints related to on-treatment exacerbation rate, change from baseline in FEV1 or quality of life score and proportion of subjects with clinically important deterioration. PGx analyses were done within each of 3 treatment arms and 3 molecules. Post-hoc PGx analyses were conducted stratifying by exacerbation history (single moderate, frequent moderate or ≥1 severe exacerbation in the year prior to study). Multiple testing was controlled at the genetic variant level, not by endpoint or arm/molecule. Significance thresholds were 5E-8 in AECOPD, 2.5E-8 in GWAS and 0.001 with candidate variants. Results from the PGx analysis were followed-up in 2,201 subjects from NCT02345161, NCT01009463 and NCT01017952. Endpoints were analyzed using a generalized linear model assuming a negative binomial distribution, linear regression, or logistic regression, as appropriate. RESULTS: Nominal association with an intron variant in SCAPER was observed for AECOPD risk (p=7E-08). In the PGx analysis, rs56195836 (MAPK8) was associated with moderate to severe exacerbation rate in subjects on FF with high baseline blood eosinophil counts (>150cells/µL) (p=1.8E-8). When subjects were stratified by exacerbation history, 3 variants associated with exacerbation endpoints. In subjects with a history of frequent moderate exacerbations treated with FF/VI, rs1962343 (AZUI) associated with moderate to severe exacerbation rate (p=1.1E-8). The ABCB1 variants, rs1128503 and rs2032582, associated with moderate to severe exacerbation rates in white subjects receiving UMEC (p=0.0003) or VI (p=0.0009), respectively, who experienced a single moderate exacrbation the year prior. However, none of these 4 signals replicated in the independent follow-up sample cohort, so are not robust, generalizable effects. CONCLUSIONS: Common genetic variants do not play major roles in exacerbation risk or predict response to FF/UMEC/VI or its components in COPD. CLINICAL IMPLICATIONS: Common genetic variants are unlikely to have clinical utility in predicting FF/UMEC/VI response. DISCLOSURES: Employee relationship with GSK Please note: $5001 - $20000 Added 05/27/2020 by Mathias CHIANO, source=Web Response, value=stock options Employee relationship with Parexel International Please note: >$100000 Added 05/22/2020 by Lynn Condreay, source=Web Response, value=Salary Own stock. relationship with GlaxoSmithKline Please note: $1-$1000 Added 05/22/2020 by Lynn Condreay, source=Web Response, value=Ownership interest Employee relationship with Glaxosmithkline Please note: >$100000 by Charles Cox, source=Admin input, value=Salary Former Employee/Stockholder relationship with Glaxosmithkline Please note: $5001 - $20000 Added 05/22/2020 by Dana Fraser, source=Web Response, value=Stock Employee relationship with GSK Please note: >$100000 by Soumitra Ghosh, source=Admin input, value=Salary No relevant relationships by Joshua Hoffman, source=Admin input recently retired employee relationship with GlaxoSmithKline Please note: $20001 - $100000 by Louise Hosking, source=Admin input, value=shares Employee relationship with GlaxoSmithKline Please note: >$100000 Added 05/22/2020 by David Lipson, source=Web Response, value=Salary Share holder relationship with GSK Please note: >$100000 Added 05/22/2020 by Neil Martin, source=Web Response, value=Salary Employee relationship with Parexel International Please note: >$100000 Added 05/20/2020 by Pamela StJean, source=Web Response, value=Salary Complementary worker relationship with GSK Please note: $1-$1000 Added 05/20/2020 by Pamela StJean, source=Web Response, value=Parexel has a contract with GS Employee relationship with GlaxoSmithKline Please note: $20001 - $100000 Added 05/22/2020 by Astrid Yeo, source=Web Response, value=Salary Stock holder relationship with GlaxoSmithKline Please note: $20001 - $100000 Added 05/22/2020 by Astrid Yeo, source=Web Response, value=Stock

Effectiveness of fevipiprant in reducing exacerbations in patients with severe asthma (LUSTER-1 and LUSTER-2): two phase 3 randomised controlled trials

Fevipiprant, an oral antagonist of the prostaglandin D2 receptor 2, reduced sputum eosinophils and improved lung function in phase 2 trials of patients with asthma. We aimed to investigate whether fevipiprant reduces asthma exacerbations in patients with severe asthma. LUSTER-1 and LUSTER-2 were two phase 3 randomised, double-blind, placebo-controlled, parallel-group, replicate 52-week studies; LUSTER-1 took place at 174 clinical sites in 25 countries and LUSTER 2 took place at 169 clinical sites in 19 countries. Fevipiprant or placebo was added to Global Initiative for Asthma Steps 4 and 5 therapy in adolescents and adults with severe asthma. Patients aged 12 years or older with uncontrolled asthma on dual or triple asthma therapy were randomly assigned by use of interactive response technology to one of three treatment groups (once-daily fevipiprant 150 mg, fevipiprant 450 mg, or placebo) in a 1:1:1 ratio within each of the randomisation strata: peripheral blood eosinophil counts (<250 cells per μL or ≥250 cells per μL), patient age (<18 years or ≥18 years), and use or non-use of oral corticosteroids as part of their standard of care asthma therapy. The primary efficacy endpoint was the annualised rate of moderate to severe asthma exacerbations with 150 mg or 450 mg doses of fevipiprant once daily compared with placebo over 52 weeks, in patients with high blood eosinophil counts (≥250 cells per μL) and in the overall study population. All patients who underwent randomisation and received at least one dose of study medication were included in efficacy and safety analyses. These trials are registered with ClinicalTrials.gov, NCT02555683 (LUSTER-1) and NCT02563067 (LUSTER-2), and are complete and no longer recruiting. Between Dec 11, 2015, and Oct 25, 2018, 894 patients were randomly assigned to fevipiprant 150 mg (n=301), fevipiprant 450 mg (n=295), or placebo (n=298) in LUSTER-1. Between Dec 3, 2015, and July 10, 2018, 877 patients were randomly assigned to fevipiprant 150 mg (n=296), fevipiprant 450 mg (n=294), or placebo (n=287) in LUSTER-2. In the high eosinophil population, in LUSTER-1 the annualised rate ratio of moderate to severe exacerbations compared with placebo was 1·04 (95% CI 0·77-1·41) for fevipiprant 150 mg and 0·83 (0·61-1·14) for fevipiprant 450 mg, and in LUSTER-2 it was 0·69 (0·50-0·96) for fevipiprant 150 mg and 0·72 (0·52-1·01) for fevipiprant 450 mg. In the overall population, in LUSTER-1 the annualised rate ratio of moderate to severe exacerbations compared with placebo was 0·96 (95% CI 0·75-1·22) for fevipiprant 150 mg and 0·78 (0·61-1·01) for fevipiprant 450 mg and in LUSTER-2 it was 0·82 (0·62-1·07) for fevipiprant 150 mg and 0·76 (0·58-1·00) for fevipiprant 450 mg. In the overall pooled population of both studies, serious adverse events occurred in 53 (9%) patients in the fevipiprant 150 mg group, 50 (9%) in the fevipiprant 450 mg group, and 50 (9%) in the placebo group. Adverse events leading to death occurred in two (<1%) patients in the fevipiprant 450 mg group and three (<1%) in the placebo group. Although neither trial showed a statistically significant reduction in asthma exacerbations after adjusting for multiple testing, consistent and modest reductions in exacerbations rates were observed in both studies with the 450 mg dose of fevipiprant. Novartis.

Determination of the cutoff values of Th2 markers for the prediction of future exacerbation in severe asthma: An analysis from the Hokkaido Severe Asthma Cohort Study

BackgroundWe recently reported that severe asthma patients with frequent exacerbations showed high blood eosinophil counts (Eo) and fractions of exhaled nitric oxide (FeNO) compared with non-exacerbators. However, we did not determine exact cutoff values related to exacerbation. The aim of this study was to determine the cutoff values of Eo and FeNO that could be related to the exacerbation of severe asthma. We also aimed to confirm the clinical utility of Th2 markers related to exacerbation. MethodsThis study included 105 severe asthma patients who completed a three-year follow-up of a severe asthma cohort study, including smokers. Three Th2 markers were selected, viz., Eo, FeNO, and positive atopic status. Regarding Eo and FeNO, we determined the cutoff values for the definition of “positive” Th2 features using receiver operating characteristic curve analyses, based on the comparisons between frequent exacerbators and other patients. ResultsThe cutoff values for positive Th2 features were Eo ≥ 250 cells/μL and FeNO ≥31 ppb. Sixteen patients (15.2%) had no Th2 features, 40 (38.1%) had one, 25 (23.8%) had two, and 24 (22.9%) had three. A high number of positive Th2 features was significantly associated with exacerbation frequencies over three years (p < 0.05). Similarly, compared to patients with one or no Th2 features, those with three Th2 features had a significantly higher probability of having more than one exacerbation (p < 0.05). ConclusionsThe cutoff values determined in the current analysis were good predictors of future exacerbations in severe asthma patients.

A report of an unusual case of pediatric eosinophilia associated with platelet-derived growth factor receptor-beta rearrangement

AbstractEosinophilia is a common finding in the pediatric age group. While the majority of mild eosinophilia cases are benign and due to reactive causes, persistent hypereosinophilia is uncommon and requires prompt clinical evaluation because of the potential risk of end-organ damage associated with it. Given the broad differential diagnoses of eosinophilia, it is essential to have a systematic approach to the evaluation of unexplained eosinophilia in children. Here, we discuss the case of a 2-year-old child who presented with very high eosinophil counts. A systematic workup of the case helped us in arriving at a rare diagnosis of platelet-derived growth factor receptor-beta (PDGFRB)-rearranged clonal eosinophilia. Identification of such an entity is important as it has therapeutic implications, and early recognition helps in preventing associated end-organ damage by instituting appropriate therapy. Such cases of eosinophilia associated with platelet-derived growth factor receptor-alpha and PDGFRB rearrangement respond dramatically to imatinib.

Endoscopic and histological characteristics in patients with eosinophilic esophagitis responsive and non‐responsive to proton pump inhibitors

ObjectiveTo compare endoscopic and histologic features of pediatric patients with eosinophilic esophagitis (EoE) responding to proton pump inhibitor (PPI) to those not responding to PPI. MethodsEndoscopic reports and photographs of patients with symptoms of esophageal dysfunction and ≥15 eosinophils per high-powered field (eos/hpf) in esophageal biopsies prior to PPI trial were reviewed. Patients were classified as responsive to PPI (PPIREoE) or non-responsive to PPI (PPINREoE) according to response totreatment (<15 eos/hpf) at second endoscopy after 8 weeks. ResultsOf the 231 patients (72.3% male), 64 (27.7%) were responsive to the proton pump inhibitors. Edema (77.3% vs. 62.5%, p=0.031) and vertical lines (69.5% vs. 51.6%, p=0.014) were more frequent in PPINREoE patients. An eosinophil count in the mid‐esophagus ≥ 35 eos/HPF (25.1% vs. 12.5%) was more frequent in these patients (p=0.001). Those with eosinophil count <15 eos/HPF in the mid‐esophagus at the first endoscopy were more likely to respond to treatment with proton pump inhibitors compared to patients with 15‐34 eos/HPF (p=0.004, OR: 3.26, 95% CI: 1.46‐7.24) and to patients with ≥ 35 eos/HPF (p=0.006, OR: 3.20, 95% CI: 1.39‐7.41). ConclusionEdema and vertical lines at the endoscopy and a higher eosinophil count in the mid‐esophagus were more frequent in patients who were non‐responsive to proton pump inhibitors. As there were no significant differences in the other findings between the groups, it cannot be affirmed that these characteristics are sufficient to differentiate between PPINREoE and PPIREoE patients.

The clinical, immunological and genetic features of 12 Chinese patients with STAT3 mutations

BackgroundLoss-of-function (LOF) mutations in signal transducer and activator of transcription 3 (STAT3) is one of the causes of STAT3 hyperimmunoglobulin E (IgE) syndrome (STAT3-HIES), while gain-of-function (GOF) mutations in STAT3 lead to immune dysregulation diseases. We retrospectively analyzed the age, common clinical symptoms, immunologic and molecular manifestations in 11 patients with LOF STAT3 mutations and 1 patient with a GOF STAT3 mutation.MethodsTwelve patients were enrolled in our study. Serum immunoglobulin measurements, lymphocyte subset detection and whole-exome sequencing were performed.ResultsThe median age at diagnosis of STAT3-HIES patients was 4.74 years. Eczema, recurrent respiratory infections, fevers, abscesses and Staphylococcus aureus infections were the classic manifestations. Elevated serum IgE levels are not always observed in conjunction with high eosinophil counts. A moderate viral DNA load was also measured in peripheral blood mononuclear cells. We noticed that c. 1144C>T was the most common mutation site, followed by c.1311C>A. Additionally, c.1311C>A and c. 1826G>C are two novel mutations. Eight patients achieved notable improvement after receiving intravenous immunoglobulin.ConclusionWe updated the current knowledge of this topic. We found an earlier median age at diagnosis, a higher survival rate, and a general lack of nonimmunological abnormalities; we also described the treatment details and novel mutations involve in STAT3-HIES and compared STAT3 LOF and GOF mutations.

Higher Eosinophils Predict Death-Censored Technique Failure in Peritoneal Dialysis Patients

Introduction: Eosinophilia (eosinophil fraction of leukocytes >5%), an indicative parameter for bioincompatibility in various circumstances, is well established in hemodialysis. However, change in eosinophil count (EOC) and its association with death-censored technique failure among peritoneal dialysis (PD) patients remain unclear. Methods: We compared eosinophils before and after PD initiation among 1,432 eligible continuous ambulatory PD patients regularly followed up in our PD center during 2007–2018. Risk factors of early-stage eosinophilia were examined by the logistic regression test. The relationship of early-stage eosinophilia and EOC with death-censored technique failure was examined using the Cox proportional hazards model for overall patients and for men and women separately. Results: After PD initiation, the EOC and percentage of patients with eosinophilia were significantly increased compared with baseline. Being male (odds ratio [OR]: 2.26; 95% confidence interval [CI]: 1.55–3.31; p < 0.001) and higher EOC at baseline (100 cells/μL increase, OR: 1.62; 95% CI: 1.45–1.82; p < 0.001) were risk factors of early-stage eosinophilia after PD initiation. During follow-up, 204 death-censored technique failures were recorded. In fully adjusted models, each with 100 cells/μL increase in EOC, the adjusted hazard ratios (HRs) of technique failure were 1.11 (95% CI: 1.03–1.20; p = 0.009) in the whole cohort, 1.29 (95% CI: 1.10–1.51; p = 0.002) in women, and 1.07 (95% CI: 0.97–1.17; p = 0.196) in men. Eosinophilia was significantly associated with the risk of technique failure for women (HR: 2.24; 95% CI: 1.07–4.70; p = 0.033), which was especially significant for women aged <55 years (HR: 7.61; 95% CI: 1.88–30.90; p = 0.005). Conclusion: EOC was increased significantly after PD initiation, and increased numbers of eosinophils were associated with higher death-censored technique failure in PD patients, especially women.

Retrospective Study of Dupilumab Treatment for Moderate to Severe Atopic Dermatitis in Korea: Efficacy and Safety of Dupilumab in Real-World Practice.

Among biological agents for the treatment of atopic dermatitis (AD), dupilumab is a front-runner. Although many studies have been conducted on the real-world use of dupilumab, the sample size is often small and data is primarily on Western people. Therefore, we investigated the efficacy and safety of dupilumab in patients with moderate-to-severe AD in Korea. All patients with moderate-to-severe AD treated with dupilumab from September 2018 to June 2019 in this institution were included and analyzed by medical records. They were evaluated using the Eczema Area and Severity Index (EASI), Numerical Rating Scale (NRS), Patient Oriented Eczema Measure (POEM), and Dermatology Quality of Life Index (DLQI), respectively on admission, after two weeks (only EASI and NRS) and after 16 weeks. Laboratory tests were measured before and 16 weeks after treatment. A total of 101 patients were included. All efficacy tools showed a significant decrease after 16 weeks; EASI 77.4%, NRS 70.0%, POEM 60.7%, and DLQI 65.0%. EASI was characterized by a marked improvement of 51.5% in just two weeks. The treatment response was not significantly different according to the interval of treatment. Elevated Lactate Dehydrogenase (LDH) at 16 weeks was associated with poor treatment response. Moreover, a high eosinophil count was related to a lower change in EASI and POEM. In the correlation analysis, EASI was not correlated to DLQI before treatment. For changes after 16 weeks, POEM showed the highest correlation with DLQI. (R = 0.66, p < 0.001) In the additional analysis for factors affecting treatment response, the female gender was associated with good treatment response. (odds ratio = 5.4, p = 0.04) Adverse events from treatment included facial erythema (9.9%) and conjunctivitis (5.0%). Overall, it was confirmed that the efficacy of dupilumab in the real-world is similar to that of the existing clinical trials. We suggest that POEM is a useful tool for identifying the quality of life. The female gender was associated with a good treatment response. Both an elevated LDH and a high eosinophil count could be a therapeutic biomarker. Further research will be needed for a long-term period.

Clinical Features Associated with Strongyloidiasis in Migrants and the Potential Impact of Immunosuppression: A Case Control Study.

Strongyloides stercoralis is a widely distributed nematode more frequent in tropical areas and particularly severe in immunosuppressed patients. The aim of this study was to determine factors associated with strongyloidiasis in migrants living in a non-endemic area and to assess the response to treatment and follow-up in those diagnosed with the infection. We performed a multicenter case-control study with 158 cases and 294 controls matched 1:2 by a department service. Participants were recruited simultaneously at six hospitals or clinics in Spain. A paired-match analysis was then performed looking for associations and odds ratios in sociodemographic characteristics, pathological background, clinical presentation and analytical details. Cases outcomes after a six-month follow-up visit were also registered and their particularities described. Most cases and controls came from Latin America (63%–47%) or sub-Saharan Africa (26%–35%). The number of years residing in Spain (9.9 vs. 9.8, p = 0.9) and immunosuppression status (30% vs. 36.3%, p = 0.2) were also similar in both groups. Clinical symptoms such as diffuse abdominal pain (21% vs. 13%, p = 0.02), and epigastralgia (29% vs. 18%, p < 0.001); along with a higher eosinophil count (483 vs. 224 cells/mL in cases and controls, p < 0.001) and the mean total Immunoglobulin E (IgE) (354 U/L vs. 157.9 U/L; p < 0.001) were associated with having strongyloidiasis. Finally, 98.2% percent of the cases were treated with ivermectin in different schedules, and 94.5% met the cure criteria at least six months after their first consultation. Abdominal pain, epigastralgia, eosinophilia, increased levels of IgE and Latin American origin remain the main features associated with S. stercoralis infection, although this association is less evident in immunosuppressed patients. The appropriate follow-up time to evaluate treatment response based on serology titers should be extended beyond 6 months if the cure criteria are not achieved.

Association Between Immunoglobulin E Levels and Kaposi Sarcoma in African Adults With Human Immunodeficiency Virus Infection.

It has been demonstrated that activated mast cells (MCs) are enriched in Kaposi sarcoma (KS) tumors and contribute to the inflammatory microenvironment. Mechanisms driving MC activation, however, are incompletely understood. We sought to understand whether immunoglobulin E (IgE), a potent activator of MCs, was associated with KS incidence and severity. In a cross-sectional study of untreated human immunodeficiency virus (HIV)-infected adults with or without KS in Uganda, we found that patients with KS had higher plasma IgE levels than those without KS. After adjustment for age, sex, CD4+ T-cell count, and HIV RNA levels, there was a dose-response relationship between plasma IgE levels and the presence and severity of KS. Higher eosinophil counts were also associated with IgE levels, and plasma interleukin 33 concentrations were higher in individuals with KS. These findings suggest that IgE-driven atopic inflammation may contribute the pathogenesis of KS. Therapies targeting IgE-mediated MC activation thus might represent a novel approach for treatment or prevention of KS.

Eosinophilic esophagitis with extremely high esophageal eosinophil counts

Patients with eosinophilic esophagitis (EoE) and extremely high esophageal eosinophilia have a distinct endotype defined by more severe atopic, endoscopic, histologic, and transcriptomic features.

Usefulness of routine blood test-driven clusters for predicting acute exacerbation in patients with asthma

AimAcute exacerbation (AE) is a significant burden in the management of asthma. In this study we aimed to investigate whether routine blood test results predicted AE in asthmatics. MethodsWe applied k-means cluster to routine blood test results which included eosinophil counts, total calcium, phosphorus, uric acid (UA), total cholesterol, total protein, albumin, total bilirubin, alkaline phosphatase, aspartate transaminase (AST), alanine transferase (ALT), gamma-glutamyltransferase, blood urea nitrogen, creatinine, and high-sensitive C-reactive protein (hsCRP) obtained from 590 asthmatics. AEs collected over the prospective follow-up of one-year were used to evaluate clinical trajectories of these clusters. ResultsThree blood clusters were identified. The essential features of each cluster can be characterized as follows: (i) high eosinophil count, UA, total cholesterol, AST, ALT, and hsCRP levels (Cluster 1); (ii) intermediate features (Cluster 2); (iii) low UA, total cholesterol and total bilirubin levels (Cluster 3). Kaplan-Meier analysis confirmed that clusters were strongly predictive of time to the first AE (log-rank P = 0.001). Hazard ratio for each group was as follows: Cluster 2 = 1, Cluster 1 = 2.67 (1 vs. 2, P = 4.68 × 10−4), and Cluster 3 = 1.69 (2 vs. 3, P = 0.021). ConclusionsWe defined three blood clusters in asthmatics. These blood clusters are easily identifiable from routine test results and may help clinicians to predict the future risk of AE in asthmatics.

Prognostic value of baseline complete blood count components in advanced gastric cancer patients: A multicenter retrospective study.

e16528 Background: Gastric cancer (GC) is one of the most prevalent malignant types in the world and an aggressive disease with a poor 5-year survival. Pretreatment CBC-based biomarkers, including blood neutrophil, lymphocyte, monocyte, and platelet counts; hemoglobin (Hb) levels; and their combinations, such as the neutrophil-lymphocyte ratio(NLR), lymphocyte-monocyte ratio (LMR) and platelet-lymphocyte ratio (PLR), have been reported to reflect systemic and local inflammation associated with cancer progression and prognosis. There has been growing interest in using CBC-based measures as biomarkers for GC. Methods: This chart-review study aimed to evaluate the effect of baseline levels of different components of routine CBC examination as well as other patients and disease characteristics on progression free survival (PFS) and overall survival (OS) in metastatic gastric cancer patients. Total 135 metastatic gastric cancer patients who had diagnosed and treated in three oncology centers in Saudi Arabia from 2011 to 2016 were incorporated. Various potential prognostic factors had measured in univariate and multivariate analysis. Results: After a median follow up of 21.4 months, the median OS / PFS were 11.0 and 6.1 months, respectively. Higher albumin level ( &gt; 3g/dl), low neutrophil percentage ≤ 75%, high lymphocyte percentage &gt; 15%, neutrophil /lymphocyte ≤ 2.5, high eosinophil count &gt; 0.4 k/ml, and EOX/EOF chemotherapy vs. doublet chemotherapy were associated with better PFS in univariate analysis. Conversely, in multivariate analysis, only serum albumin and eosinophil levels were related to PFS. In univariate analysis, higher serum albumin (3 g/dl), low neutrophil percentage ≤ 75%, high lymphocyte percentage &gt; 15%, neutrophil/lymphocyte ≤2.5, high eosinophil count &gt; 0.4 k/ml, receiving 1st line chemotherapy vs. no chemotherapy, receiving &gt; 6 cycles of chemotherapy, receiving EOX/EOF chemotherapy vs. doublet chemotherapy, platelet count ≤450 k/ml, male gender were associated with better OS. In multivariate analysis, lower neutrophil percentage, higher serum albumin, male sex and higher number of chemotherapy cycles were independently associated with OS. Conclusions: Higher eosinophil level was associated with improved PFS while lower neutrophil percentage and higher number of chemotherapy cycles were independent predictors of OS. Higher albumin levels independently predicted better OS and PFS.