Blood Eosinophil Levels Research Articles

Clinical features and three-year prognosis of AECOPD patients with different levels of blood eosinophils

BackgroundEosinophils are thought to be associated with the frequency and severity of acute exacerbations of chronic obstructive pulmonary disease (AECOPD); however, the role of eosinophilic inflammation in AECOPD is still incompletely understood. ObjectivesTo investigate the relationship between different levels of blood eosinophils and clinical features, including comorbidities, therapy, and prognosis, and to further explore the optimal eosinophilic cutoff. MethodsWe retrospectively collected and analyzed medical data, laboratory findings, chest CT images, treatment, and three-year follow-up data from 984 AECOPD patients with different blood eosinophil (EOS) levels: EOS%<2%, ≥2%; EOS%<3%, ≥3%; eosinophil counts<100 cells/L, ≥100 cells/L. ResultsThe prevalence of eosinophilia was 36.48% of EOS≥2% (359 cases), 22.87% of EOS≥3% (225 cases), and 48.48% with eosinophil counts≥100 cells/µl (477 cases). EOS was associated with comorbidities, including pulmonary heart disease, arrhythmia (atrial fibrillation), laboratory testing and clinical treatment, including respiratory failure, airway limitation, infectious inflammation, rate of antibiotic use, systemic glucocorticoids, and three mortality rates. The ROC curve showed that the indicators of AUC≥0.5 included chest CT imaging (emphysema 1.8% or ≥100/µl, bronchitis, 1.7% or ≥100/µl), osteoporosis (2.4% or ≥140/µl), mental illness 6.1% (or ≥400/µl), dust exposure (2.2% or ≥240/µl) and ex-smoker (1.3% or ≥100/µl). ConclusionsThe relatively higher EOS group (≥2% or ≥100/µl) was associated with fewer complications, mild airflow limitation, a tendency of noninfectious inflammation, and lower 3-year mortality. Eosinophils can not only guide clinical treatment but also be an indicator of predicting clinical outcome and prognosis in AECOPD patients.

Association of Peripheral Blood and Cutaneous Eosinophils With Bullous Pemphigoid Disease Severity and Treatment Outcomes

Background and aimsA dermal inflammatory infiltrate rich in eosinophils is a prominent histological feature of bullous pemphigoid (BP) and peripheral blood eosinophilia has been documented in 50–60% of BP patients. Nevertheless, the impact of circulating and dermal infiltrate eosinophil levels on BP remains poorly understood. The main objective of this work was to investigate the association of peripheral blood and dermal infiltrate eosinophil levels with clinical and immunological characteristics of the disease. Material and methodsRetrospective cohort study including all patients diagnosed with BP between 2011 and 2020. ResultsThe study cohort included 233 patients with BP. The mean baseline peripheral blood eosinophil count was 956.3±408.6×106/L and the mean number of tissue eosinophils at the dermal hot spot area was 30.5±19.0. Patients with disseminated presentation (i.e. BSA>50%) had significantly higher peripheral blood eosinophil counts (P=0.028). Mucosal involvement was significantly associated with lower dermal eosinophil count (P=0.001). Requiring inpatient care and relapsing were significantly associated with high peripheral blood eosinophil count (P=0.025; P=0.020, respectively). Among the 68 patients who experienced a relapse, 31 had peripheral blood eosinophilia (i.e. >500×106/L) at relapse (44.2%). Peripheral blood eosinophil counts at baseline and at relapse were significantly correlated (r=0.82, P<0.001). ConclusionsPeripheral blood and cutaneous eosinophils levels may be useful biomarkers for disease activity and treatment outcomes in BP. Monitoring peripheral blood eosinophil counts may allow early detection of relapse.

ПРОВОСПАЛИТЕЛЬНЫЕ МАРКЕРЫ РАННИХ РЕПРОДУКТИВНЫХ ПОТЕРЬ

The medical and socio-economic significance of the problem of early reproductive losses is determined by a decrease in the birth rate and a deterioration in the demographic situation. Purpose of the study: To evaluate the diagnostic significance of some laboratory parameters characterizing the inflammatory response and their role in early pregnancy losses. Material and methods. Blood serum, medical records, prenatal records of 94 women. The study of interleukin-6 and tumor necrosis factor-alpha was carried out using enzyme immunoassay. The level of white blood cells, banded neutrophils, segmental leukocytes, eosinophils, basophilis, monocytes, lymphocytes and erythrocyte sedimentation rate was determined by general clinical routine methods. Results. Interleukin-6 in combination with segmental leukocytes, monocytes, erythrocyte sedimentation rate can indicate the formation of pro-inflammatory cascade and can trigger abortion mechanisms.

Clinical and cytokine patterns of uncontrolled asthma with and without comorbid chronic rhinosinusitis: a cross-sectional study

BackgroundAsthma is significantly related to chronic rhinosinusitis (CRS) both in prevalence and severity. However, the clinical patterns of uncontrolled asthma with and without comorbid CRS are still unclear. This study aimed to explore the clinical characteristics and cytokine patterns of patients with uncontrolled asthma, with and without comorbid CRS.Methods22 parameters associated with demographic characteristics, CRS comorbidity, severity of airflow obstruction and airway inflammation, and inflammation type of asthma were collected and assessed in 143 patients with uncontrolled asthma. Different clusters were explored using two-step cluster analysis. Sputum samples were collected for assessment of Th1/Th2/Th17 and epithelium-derived cytokines.ResultsComorbid CRS was identified as the most important variable for prediction of different clusters, followed by pulmonary function parameters and blood eosinophil level. Three clusters of patients were determined: Cluster 1 (n = 46) characterized by non-atopic patients with non-eosinophilic asthma without CRS, demonstrating moderate airflow limitation; Cluster 2 (n = 54) characterized by asthma patients with mild airflow limitation and CRS, demonstrating higher levels of blood eosinophils and immunoglobulin E (IgE) than cluster 1; Cluster 3 (n = 43) characterized by eosinophilic asthma patients with severe airflow limitation and CRS (46.5% with nasal polyps), demonstrating worst lung function, lowest partial pressure of oxygen (PaO2), and highest levels of eosinophils, fraction of exhaled nitric oxide (FeNO) and IgE. Sputum samples from Cluster 3 showed significantly higher levels of Interleukin (IL)-5, IL-13, IL-33, and tumor necrosis factor (TNF)-α than the other two clusters; and remarkably elevated IL-4, IL-17 and interferon (IFN)-γ compared with cluster 2. The levels of IL-10 and IL-25 were not significantly different among the three clusters.ConclusionsUncontrolled asthma may be endotyped into three clusters characterized by CRS comorbidity and inflammatory cytokine patterns. Furthermore, a united-airways approach may be especially necessary for management of asthma patients with Type 2 features.

A critical role for the RNA binding protein HuR in CD4+ T cell-mediated airway inflammation in mouse and human

Abstract The RNA-binding protein HuR (elavl1) positively regulates the expression of its targets by increasing mRNA stability and translation. Th2 and Th17 related genes play critical roles in airway inflammation in both mouse and human. Using in vitro and in vivo studies, we have previously shown that these proinflammatory genes are regulated by HuR. Here, we generated a conditional ablation of HuR in T cells (distal Lck-cre HuRfl/fl). We found significant decreases in Th2 differentiation, cytokine production, and lung inflammation in an alum-emulsified ovalbumin (ova-alum) model of allergic airway inflammation using this novel mouse model. We hypothesized that HuR might similarly regulate lung inflammation in human asthma. Using peripheral CD4+ T cells from 45 asthmatic patients, we found the inhibitory effect of the HuR-specific inhibitor CMLD-2, as well as an AMPK activator (acadesine aka AICAR), on both Th2/Th17 signature cytokines in both protein and mRNA levels. Our asthmatics were classified into type 2 high or non-type 2 high based on their blood eosinophil and FeNO levels. Interestingly, there were significant positive correlations between Th2 cytokine levels in CD4+ cells with levels of eosinophils and FeNO from asthmatics. Surprisingly, IFNγ (protein and mRNA) were also markedly decreased by HuR inhibition. Our bioinformatic studies also revealed proteins with high interaction with HuR including MAPK14/p38α and PTEN, common in the pathways with IFNγ, are affected by HuR inhibitor. Taken together, our mouse and human data suggest that HuR plays a crucial permissive role in both allergen- and nonallergen-driven airway inflammation by regulating key genes and that interfering with its function may be a novel way to treat asthma. Supported by R01: AI080870, R21: AI079341

The Influence of Peripheral Blood Eosinophil Counts in Asthma Comorbidities in Adults: A Real Life Study

Asthma and eosinophilia are two closely related pathologies whose interaction is key in the era of precision medicine. However, this relationship is rarely taken into account without the influence of therapeutic prescriptions. In this study involving 1296 subjects, the relationship between eosinophilia and asthma was analyzed without taking into account other biases. We observed that rhinitis only appears in non-asthmatic patients with elevated blood eosinophil levels, while atopy was elevated in parallel to eosinophilia regardless of whether the patients were asthmatic or not. In terms of lung function, a decrease was observed for higher blood eosinophil levels, which is especially relevant in the FEV1/FVC ratio. FENO is elevated in relation to higher eosinophilia, but total IgE is only elevated in patients with high peripheral blood eosinophil levels and asthma. Finally, the only feature of asthma that is altered by increased peripheral eosinophilia is persistent asthma, with all other features remaining unchanged.

Effects of anti-IL5 biological treatments on blood IgE levels in severe asthmatic patients: A real-life multicentre study (BIONIGE).

BackgroundMepolizumab and benralizumab are clinically effective biological treatments for severe eosinophilic asthmatic patients by hampering eosinophilic inflammation. The effects of these compound on the immunoglobulin (Ig)E T2 component are virtually unknown.ObjectivesTo evaluate the change in total IgE levels at 4 ± 2 months after initiation of the mepolizumab (primary outcome) or benralizumab. When available, the changes of blood inflammatory cell counts, lung function and asthma control test (ACT) were also assessed and correlated with changes in total IgE levels.MethodsObservational, retrospective, multicentre, cohort study. Severe eosinophilic atopic asthmatic patients treated with mepolizumab or benralizumab were included in the analysis.ResultsThree‐month treatment (on average) with mepolizumab (n = 104) or benralizumab (n = 82) resulted in significantly higher reduction of blood eosinophil and basophil levels in patients treated with benralizumab compared to mepolizumab. Mepolizumab did not significantly modified the levels of blood total IgE during the study period, whereas benralizumab significantly reduced (−35%, p < 0.001) total blood IgE levels. In patients treated with benralizumab the reduction of blood total Ig‐E levels correlated with the reduction of blood basophils (but not eosinophils) and weakly with the improvement of asthma control.ConclusionBenralizumab but not mepolizumab, treatment led to a significant reduction of circulating IgE level. The study provides different and specific mechanisms of action for anti‐IL5‐pathway treatments.

Determinants of blood eosinophil levels in the general population and patients with COPD: a population-based, epidemiological study

BackgroundBlood eosinophils are considered a biomarker for the treatment of chronic obstructive pulmonary disease (COPD). Population-based studies are needed to better understand the determinants of the blood eosinophil count (BEC) in individuals with and without COPD.MethodsEPISCAN II is a multicentre, cross-sectional, population-based epidemiological study aimed at investigating the prevalence and determinants of COPD in Spain. Study subjects were randomly selected from the general population, and COPD was defined by a post-bronchodilator FEV1/FVC < 0.7. For the pre-specified outcomes related to BEC, the first 35 COPD and 35 non-COPD subjects were consecutively recruited in 12 of the participating centres with the objective of analysing 400 individuals in each group. Baseline BEC and its association with demographic, clinical and functional variables were analysed.ResultsA total of 326 COPD and 399 non-COPD subjects were included in the analysis. The mean age (standard deviation [SD]) was 63.2 years (11.0), 46.3% were male, and 27.6% were active smokers. BEC was significantly higher in individuals with COPD [192 cells/μL (SD: 125) vs. 160 cells/μL (SD: 114); p = 0.0003]. In a stepwise multivariate model, being male, active smoker and having a previous diagnosis of asthma were independently associated with having a higher BEC.ConclusionsThis population-based study estimated the distribution of eosinophils in the healthy adult population and concluded that COPD patients have a significantly higher BEC. Male sex, active smoking and concomitant asthma were significantly associated with a higher BEC.

FeNO in Asthma.

Asthma is a common disease affecting 350 million people worldwide, which is characterized by airways inflammation and hyperreactivity. Historically diagnosis and treatment have been mainly based on symptoms, which have the potential to result in misdiagnosis and inappropriate treatment. Nitric oxide (NO) is exhaled in human breath and is a marker of airways inflammation. Levels of NO are increased in the exhaled breath of patients with type 2 asthma and fractional exhaled nitric oxide (FeNO) provides an objective biomarker of airway inflammation. FeNO testing is an accessible, noninvasive, and easy-to-use test. Cut-off values have been established by the American Thoracic Society (ATS), the Global Initiative for Asthma (GINA), and the National Institute for Health and Care Excellence (NICE) but vary between guidance. FeNO levels have been shown to be predictive of blood and sputum eosinophil levels but should not be used in isolation and current guidance emphasizes the importance of incorporating clinical symptoms and testing when utilizing FeNO results. The inclusion of FeNO testing can increase diagnostic accuracy of asthma, while high levels in asthmatic patients can help predict response to inhaled corticosteroids (ICS) and suppression of levels with ICS to monitor adherence. FeNO levels are also a predictor of asthma risk with increased exacerbation rates and accelerated decline in lung function associated with high levels as well as having an emerging role in predicting response to some biologic therapies in severe asthma. FeNO testing is cost-effective and has been shown, when combined with clinical assessment, to improve asthma management.

COVID-19 infection in hypereosinophilic syndrome: A survey-based analysis

COVID-19 infection in hypereosinophilic syndrome: A survey-based analysis

Results of a Phase 2b Trial With GB001, a Prostaglandin D2 Receptor 2 Antagonist, in Moderate to Severe Eosinophilic Asthma

Prostaglandin D2 receptor 2 (DP2) antagonists inhibit prostaglandin D2-induced effects, including recruitment and activation of cells driving asthma pathogenesis. However, challenges identifying target population and end points persist. What is the effect of the DP2 antagonist GB001 on asthma worsening in patients with moderate to severe eosinophilic asthma? In this phase IIb, randomized, double-blind, placebo-controlled, dose-ranging, parallel-group, multicenter study, GB001 or placebo was added to standard-of-care treatment in patients with moderate to severe asthma with a blood eosinophil count≥ 250 cells/μL. Patients aged≥ 18 years to< 75 years received one of four once-daily treatments (GB001 20mg, 40mg, or 60mg or placebo). The primary end point was the proportion of patients who experienced asthma worsening by 24weeks. Efficacy analyses were performed for the intention-to-treat population and safety analyses for patients who received at least one dose of study treatment. A total of 480 patients were treated. The ORs for asthma worsening for GB001 20mg, 40mg, and 60mg vsplacebo were 0.674 (95%CI, 0.398-1.142), 0.677 (95%CI, 0.399-1.149), and 0.651 (95%CI, 0.385-1.100), respectively. Analysis according to baseline blood eosinophil levels and/or fractional exhaled nitric oxide did not show greater treatment effects with higher values. Elevated liver aminotransferase levels and adverse events leading to discontinuation were more frequent for GB001 60mg than with placebo, GB001 20mg, and GB001 40mg. Although GB001 did not significantly reduce the odds of asthma worsening, reductions favoring GB001 were observed. Treatment effects were consistent regardless of high/low type 2 phenotype. The overall safety profile was acceptable, although GB001 60mg was associated with risk of liver injury. ClinicalTrials.gov; No.: NCT03683576; URL: www. gov.

IGE АНТИТЕЛА К МАЖОРНЫМ КОМПОНЕНТАМ АЛЛЕРГЕНА КЛЕЩА ДОМАШНЕЙ ПЫЛИ DER P1 И DER P2 У ДЕТЕЙ С АЛЛЕРГИЕЙ

Background. House dust mite allergy is widespread throughout the world. Analysis of the immune response to D. pteronyssinus contributes to understanding the patterns of IgE-mediated response in patients with house dust mite allergy living in different geographic regions. Objective. To establish serum sIgE levels to the major components of the house dust mite allergen Der p1 and Der p2 in children with allergies. Material and methods. We examined 61 children aged 4 to 17 years with symptoms of allergy associated with house dust mite in the period from September 2020 to July 2021. The level of sIgE to rDer p1 and rDer p2 was determined by the ImmunoCAP method. Results. In the study group boys dominated (χ2=11.84, p=0.0006). In the age structure school-age children dominated (χ2=19.74, p&lt;0.00001): up to 6 years old – 5 children (8.2%, CI: 1.31–15.09), 7-12 and over 12 years old – 28 children (45.9%, CI: 33.39–58.41) in each age group. The majority of children had a positive family history of allergies (χ2=20.49, p&lt;0.0001). The average level of eosinophils in the peripheral blood was 6.8 [2–9.5] %, in the nasal secretions – 24.5 [19.0– 32.0]%. The average level of total IgE in the blood serum was 314.5 [132.0–691.0] IU/ml. An increased level of sIgE antibodies to Der p1 and/or Der p2 was found in 83.6% of children, to Der p1 in 75.4% of children, and to Der p2 in 70.5% of children. sIgE antibodies simultaneously to two molecular components of the dust mite (Der p1 + Der p2) were detected in 62.3% of children. The sIgE level to Der p1 was 12.5 [0.56–31.0] kUA/l, to Der p2 – 14.0 [0.04–43.3] kUA/l). The severity of the sIgE immune response to Der p2 in all children in general and in boys in particular, regardless of age, was slightly higher, than to Der p1 (p&gt;0.05). In children aged 6-12 years, the level of sIgE to Der p1 was higher in girls than in boys (p=0.045). A direct correlation was established between the level of sIgE to Der p1 and Der p2 in all children (r=0.56, p&lt;0.00001): boys (r=0.52, p=0.001), girls (r=0.63 , p=0.002); in children aged 6-12 years old (r=0.56, p=0.001): boys (r=0.61, p=0.003); children over 12 years old (r=0.69, p&lt;0.0001): boys (r=0.68, p=0.007), girls (r=0.8, p=0.001). The level of sIgE to Der p1 in the group of children with the results of the skin prick tests «++» and «+++» was higher than in the group of children with the results of the prick tests «+» (p&lt;0.05). The level of sIgE to Der p2 in the group of children with the results of the skin prick tests «++» was higher than in the group of children with the results of the prick tests «+» (p&lt;0.05). In children (9.8%) with «-» skin prick test results (but with an increased level of sIgE to the extract of the house dust mite), the level of sIgE to Der p1 and Der p2 did not differ from the level of sIgE to Der p1 and Der p2 in the group of children with the results of skin prick tests «++», «++» (p&gt;0.05), but exceeded that in children with the results of skin prick tests «+» (p&lt;0.05). Conclusion. The determination of sIgE levels to the allergenic components of the house dust mite Der p1 and Der p2 is a method for the accurate molecular diagnosis of the house dust mite allergy, allowing for better management of allergic diseases in children.

The German severe asthma patient: Baseline characteristics of patients in the German Severe Asthma Registry, and relationship with exacerbations and control

Introduction.The German Asthma Net Severe Asthma Registry is collecting long-term data from a large cohort of patients aged ≥6 years with severe asthma. This manuscript presents their baseline characteristics, and identifies relationships with exacerbations and/or poor asthma control.Methods.The registry is collecting routine clinical parameters including: demographics and medical history; disease characteristics (Asthma Control Questionnaire [ACQ]-5, forced expiratory volume in 1 s [FEV1]); exacerbations; and biomarkers (eosinophils, immunoglobulin E [IgE], fractional exhaled nitric oxide [FeNO]).Results.These analyses include data from 2011 patients at 72 sites (91.9% adult). Children (6–17 years) were more likely to be male, whereas more adults were female (males: children/adults 62%/41%). Most were receiving inhaled corticosteroid/long-acting β2-agonist combinations (78%/81%); 38.0% of adults were receiving systemic steroids. Asthma control was suboptimal in both groups: 21.5%/13.3% were controlled; 10.4%/49.1% were symptomatic; 33.1%/37.2% received emergency asthma treatment in the previous year. Median blood eosinophil (400/238 cells/μL) and IgE levels (494/186 IU/mL) were higher in children; FeNO was lower (19/35 ppb). Patients with ≥2 exacerbations in the previous year had lower FEV1 (absolute and % predicted) and IgE, and higher ACQ-5, FeNO and blood eosinophil levels (all p < 0.05). There was a weak, negative correlation between ACQ-5 and FEV1% predicted in adults (p < 0.001).Conclusions.These analyses characterise the typical German patient with severe asthma, and provide information on their overall care. Their planned long-term follow-up will assess whether asthma control can be optimised, how best to do so, and most importantly how such optimisation can benefit patients.

Effects of substituting soybean meal with corn on immune function and gene expression of gut TLR4 pathway of growing goats.

BackgroundProtein malnutrition remains a severe problem in ruminant production and can increase susceptibility to infection, especially during the growth stage. This study aimed to explore substituting soybean meal with corn on activation of the TLR pathway and potential impact on immune response bias towards Type 1 or Type 2 using growing female goats as experimental animals.MethodsTwenty-four Xiangdong black goats (initial BW = 19.83 ± 0.53 kg, about 8 ± 0.3 months old) were selected and randomly divided into the corn-soybean meal basal diet group (CON, 10.77% protein) and replacing soybean meal with 100% of corn group (CRS, 5.52% protein). EDTA whole blood and serum samples were collected prior to slaughter for determinations of blood cell counts, anti-inflammatory cytokines and antibodies. The duodenum, jejunum, ileum and colon tissues were collected after formal trial to study the effect of CRS diet on the expression of TLR4 pathway.ResultsOur results showed CRS diet did not induce a significant change in immune function, as evidenced by the observations that white blood cell (WBC), neutrophil (Neu), lymphocyte (Lym), monocyte (Mon), eosinophil (Eos), interleukin-4 (IL-4), IL-5, IL-13, immunoglobin G (IgG), IgA, and IgM levels in serum were similar between the two groups. RT-PCR results showed the expression of tumor necrosis factor-α (TNF-α) (P < 0.01) and interferon-β (IFN-β) (P < 0.01) were up-regulated in the colon of goats in the CRS group. No differences in the expression of myeloid differentiation factor 88 (MyD88) adaptor-like protein (TIRAP), IL-1 receptor–associated kinase 1 (IRAK1), TNF receptor related factor 6 (TRAF6), NF-kappa B (NF-κB), mitogen-activated protein kinase 1 (MAPK1) or activator protein-1 (AP-1) in the TLR4/MyD88 dependent pathway were observed between the two groups for any of the tested tissue. However, the expression of NF-κB activator (TANK) binding kinase 1 (TBK1) in TLR4/MyD88 independent pathway was up-regulated in the duodenum and colon (P < 0.01), and the expression of interferon regulatory factor-3 (IRF3) was up-regulated (P < 0.01) in colon.ConclusionsOur results suggested that the CRS diet failed to induce a significant change in innate immunity and adaptive immunity in growing goats. However, the up-regulated TBK1 and IRF3 in the colon from the CRS goats suggests that the CRS diet may induce the expression of Th1-type proinflammatory cytokines and inflammatory response through a TLR4-MyD88-independent pathway, and the colon may be the easiest targeted section in the intestinal tract.

Predicting the course of asthma from childhood until early adulthood.

Purpose of reviewTo communicate recent insights about the natural history of childhood asthma, with a focus on prediction of persistence and remission of childhood asthma, up to early adulthood.Recent findingsLung function around the age of 8–9 years is the strongest predictor: obstructive lung function predicts asthma persistence up to early adulthood, whereas normal lung function predicts remission. The ability to predict asthma remission improves when lung function is combined with blood eosinophil levels and degree of bronchial hyperresponsiveness. Interventions, such as inhaled corticosteroids and immunotherapy do not appear to alter the course of asthma. Epigenetic studies have revealed potential novel biomarkers of asthma remission, such as micro-RNA patterns in blood. Specifically, lower serum levels of mi-R221-5p, which is associated with lower IL-6 release and eosinophilic inflammation, predict remission. Higher levels of blood DNA-methylation of a CpG site in Peroxisomal Biogenesis Factor 11 Beta were associated with asthma remission.SummaryLung function, allergic comorbidity and polysensitization in childhood predict the course of asthma. Recent epigenetic studies have provided a better understanding of underlying pathological processes in asthma remission, which may be used to improve prediction or develop novel treatments aimed at altering the course of asthma.

Imatinib-associated skin rash is related to treatment outcome in patients with unresectable and/or metastatic gastrointestinal stromal tumor.

Imatinib-associated skin rash in gastrointestinal stromal tumor (GIST) patients is one of the most troublesome adverse effects, and can reduce imatinib adherence and persistence. However, the relationship between skin rash and adherence is unknown, and there are few published studies on the clinical outcomes of patients with severe skin rash. Adult patients (≥18 years) who were treated with 400 mg/day imatinib for unresectable or metastatic GIST were enrolled in this retrospective study. The skin rash was graded by physicians according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Progression-free survival (PFS) was compared using the Kaplan-Meier method between groups with and without skin rash. The risk factors for GIST progression were investigated by Cox regression analysis. A total of 125 GIST patients were finally included. Among them, 43 (34.4%) patients developed skin rash during imatinib treatment. Serial blood eosinophil levels were associated with skin rash and severity (P<0.001). Patients with skin rash tended to have poorer PFS than patients with no rash (P=0.035). Moreover, patients with rash had a significantly higher prevalence of non-adherence compared with patients without rash [odds ratio (OR): 3.42, 95% confidence interval (CI): 1.36-8.61, P=0.009 for grades 1-2; OR: 6.07, 95% CI: 1.42-26.11, P=0.015 for grades 3-4). Cox regression analysis indicated that the independent risk factors for GIST progression were non-adherence (OR: 4.20, 95% CI: 1.57-11.25, P=0.004) and medium- and high-risk GIST (OR: 5.38, 95% CI: 1.15-25.09, P=0.032). Non-adherence and medium- and high-risk GIST are independent risk factors for GIST progression. Skin rash can be associated with treatment adherence, which can in turn be associated with poor outcomes of GIST treatment. Measuring the blood eosinophil levels could be helpful in predicting risk of skin rash during imatinib treatment.

Efficacy of Dupilumab in Quadrants of Elevated- vs Low- Type 2 Biomarkers in Children With Uncontrolled, Moderate-to-Severe Asthma: LIBERTY ASTHMA VOYAGE

Dupilumab, a human mAb, blocks the shared receptor component for IL-4/13, key and central drivers of type 2 inflammation. In VOYAGE (NCT02948959), dupilumab 100/200mg vs placebo every 2 weeks for 52 weeks reduced severe asthma annualized exacerbation rate (AER) and improved percent predicted pre-bronchodilator FEV1 (ppFEV1) in children aged 6-11 years with uncontrolled, moderate-to-severe asthma. We evaluated the predictive value of baseline blood eosinophil and FeNO levels as biomarkers for dupilumab response.

The levels and correlations of FeNO, blood eosinophils and lung function in well-controlled asthma.

Whether biomarkers (i.e., fractional exhaled nitric oxide (FeNO) and blood eosinophils) or lung function are additional ultimate outcomes in asthma treatment among patients with clinical remission has been the subject of previous research, the study of the correlations between FeNO, blood eosinophils and lung function among well-controlled asthmatic patients is less clear. To investigate the clinical application of the correlation between FeNO, blood eosinophils and lung function parameters in well-controlled asthmatic patients. This was a prospective cross-sectional study. We measured FeNO, blood eosinophil and lung function in 84 asthmatic patients with clinical remission who were assessed by asthma control questionnaires. The correlation coefficient was used to ascertain among those parameters. The diagnostic accuracy of blood eosinophil to identify low FeNO (< 25 ppb) was calculated using the area under the receiver operating characteristics (AUROC). Of 84 patients analyzed, the median ACT was 25 and the median ACQ-7 was 0.43. The median duration of being well-controlled asthma was 14.5 months. The median FeNo was 23 ppb and the median blood eosinophils was 375 cell/mm³. A significant positive correlation was found between FeNo and blood eosinophil (r = 0.310, p = 0.004). No correlation was detected between either FeNO or blood eosinophil and all lung function parameters. The AUROC results for blood eosinophils was 64.4% (p = 0.024) to detect FeNO < 25 ppb at a cutoff point of 295 cell/mm3 (sens tivity = 83.5%, specificity = 50%). Measuring FeNO and blood eosinophils in patients with a clinical remission of asthma may determine which of those patients have achieved complete remission. As the level of blood eosinophils has a significant correlation with FeNO, it may easily be a feasible biomarker to evaluate inactive airway inflammation before stepping down asthma treatment.

Predictors of a Minimal Clinically Important Difference Following Omalizumab Treatment in Adult Patients With Severe Allergic Asthma.

Several factors have been found to be predictors of a good response following omalizumab treatment in patients with severe allergic asthma (SAA). However, it remains unclear whether clinical characteristics can predict a minimal clinically important difference (MCID) following omalizumab treatment in this population. Therefore, the aim of this study was to investigate the features associated with an MCID following omalizumab treatment in adult patients with SAA. Of the 124 participants enrolled in this retrospective, cross-sectional study, 94, 103, 20 and 53 achieved the MCID following treatment with omalizumab and were considered to be responders of exacerbation reduction (no exacerbation during the 1-year follow-up period or ≧50% reduction in exacerbations from baseline), oral corticosteroid (OCS) sparing (no use of OCS to control asthma during the study period or a reduction of the monthly OCS maintenance dose to <50% of baseline), lung function (an increase of ≧230 ml in the forced expiratory volume in 1 s from baseline) and asthma control (an increase of ≧3 points in the asthma control test score from baseline), respectively. Normal weight [<25 vs. ≧30 kg/m2, odds ratio (OR) = 3.86, p = 0.024] was predictive of a responder of reduction in exacerbations following omalizumab treatment while subjects with a blood eosinophil level of <300 cells/μL (<300 vs. ≧300 cells/μL, OR = 5.81, p = 0.001) were more likely to exhibit an MCID in OCS sparing. No factor was found to be a predictor of lung function or asthma control. When choosing treatment for adult patients with SAA, our findings may help to select those who may benefit the most from omalizumab treatment.

Association Between Clinical Burden and Blood Eosinophil Counts in Asthma: Findings From a Korean Adult Asthma Cohort.

BackgroundSome reports have suggested that the clinical and economic burdens of asthma are associated with blood eosinophil levels. The association between clinical burden and blood eosinophil counts were evaluated in a Korean adult asthma cohort.MethodsClinical information including blood eosinophil counts that were not affected by systemic corticosteroids were extracted from the Cohort for Reality and Evolution of Adult Asthma in Korea database. Clinical burden was defined as 1) asthma control status, 2) medication demand and 3) acute exacerbation (AE) events during 1 consecutive year after enrollment. All patients were divided into atopic and non-atopic asthmatics. The associations between asthma outcomes and the blood eosinophil count were evaluated.ResultsIn total, 302 patients (124 atopic and 178 non-atopic asthmatics) were enrolled. In all asthmatics, the risk of severe AE was higher in patients with blood eosinophil levels < 100 cells/µL than in patients with levels ≥ 100 cells/µL (odds ratio [OR], 5.406; 95% confidence interval [CI], 1.266–23.078; adjusted P = 0.023). Among atopic asthmatics, the risk of moderate AE was higher in patients with blood eosinophil levels ≥ 300 cells/µL than in patients with levels < 300 cells/µL (OR, 3.558; 95% CI, 1.083–11.686; adjusted P = 0.036). Among non-atopic asthmatics, the risk of medication of Global Initiative for Asthma (GINA) steps 4 or 5 was higher in patients with high blood eosinophil levels than in patients with low blood eosinophil levels at cutoffs of 100, 200, 300, 400, and 500 cells/µL.ConclusionThe baseline blood eosinophil count may predict the future clinical burden of asthma.