Eosinophil Count Research Articles

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

Serum IgE levels and absolute eosinophil counts with treatment response in patients with allergic rhinitis: A prospective study

: Allergic rhinitis (AR) is a highly prevalent, chronic disease, with variable incidence rates. Clinically manifests as nasal discharge, congestion, nasal itching, sneezing and watery eyes. Treatment approach is based on duration and severity of symptoms. Second generation antihistamines are the drug of choice. Serum Ig E and Absolute Eosinophil Counts (AEC) have the potential to be the viable prognostic markers. The present study aims to assess the relationship of Serum IgE and AEC with treatment response in patients with allergic rhinitis.40 patients of allergic rhinitis were included in the study and were categorized into mild, moderate and severe allergic rhinitis according to ARIA guidelines. Pre-treatment sample for serum IgE and AEC was taken followed by 4 weeks of medical management according to categories. Post- treatment sample was taken and improvement assessed on the basis of fall in serum IgE and AEC levels.A total 40 patients were enrolled ranging from 14-60 years of age (mean age 28.75±11.23years) with female preponderance (52.5%). Most common presenting symptom being sneezing. Significant decline in pre-treatment AEC and serum IgE levels was observed.The findings of the study indicates that treatment response had an association with AEC and Serum IgE levels.

Genetic relations between type 1 diabetes, coronary artery disease and leukocyte counts.

Type 1 diabetes is associated with excess coronary artery disease (CAD) risk even when known cardiovascular risk factors are accounted for. Genetic perturbation of haematopoiesis that alters leukocyte production is a novel independent modifier of CAD risk. We examined whether there are shared genetic determinants and causal relationships between type 1 diabetes, CAD and leukocyte counts. Genome-wide association study summary statistics were used to perform pairwise linkage disequilibrium score regression and heritability estimation from summary statistics (ρ-HESS) to respectively estimate the genome-wide and local genetic correlations, and two-sample Mendelian randomisation to estimate the causal relationships between leukocyte counts (335,855 healthy individuals), type 1 diabetes (18,942 cases, 501,638 control individuals) and CAD (122,733 cases, 424,528 control individuals). A latent causal variable (LCV) model was performed to estimate the genetic causality proportion of the genetic correlation between type 1 diabetes and CAD. There was significant genome-wide genetic correlation (rg) between type 1 diabetes and CAD (rg=0.088, p=8.60 × 10-3) and both diseases shared significant genome-wide genetic determinants with eosinophil count (rg for type 1 diabetes [rg(T1D)]=0.093, p=7.20 × 10-3, rg for CAD [rg(CAD)]=0.092, p=3.68 × 10-6) and lymphocyte count (rg(T1D)=-0.052, p=2.76 × 10-2, rg(CAD)=0.176, p=1.82 × 10-15). Sixteen independent loci showed stringent Bonferroni significant local genetic correlations between leukocyte counts, type 1 diabetes and/or CAD. Cis-genetic regulation of the expression levels of genes within shared loci between type 1 diabetes and CAD was associated with both diseases as well as leukocyte counts, including SH2B3, CTSH, MORF4L1, CTRB1, CTRB2, CFDP1 and IFIH1. Genetically predicted lymphocyte, neutrophil and eosinophil counts were associated with type 1 diabetes and CAD (lymphocyte OR for type 1 diabetes [ORT1D]=0.67, p=2.02-19, ORCAD=1.09, p=2.67 × 10-6; neutrophil ORT1D=0.82, p=5.63 × 10-5, ORCAD=1.17, p=5.02 × 10-14; and eosinophil ORT1D=1.67, p=5.45 × 10-25, ORCAD=1.07, p=2.03 × 10-4. The genetic causality proportion between type 1 diabetes and CAD was 0.36 ± 0.16 (pLCV=1.30 × 10-2), suggesting a possible intermediary causal variable. This study sheds light on shared genetic mechanisms underlying type 1 diabetes and CAD, which may contribute to their co-occurrence through regulation of gene expression and leukocyte counts and identifies cellular and molecular targets for further investigation for disease prediction and potential drug discovery.

Assessing the Impact of the Updated 2021 European Respiratory Society/American Thoracic Society Criteria on Bronchodilator Responsiveness in Asthma.

Introduction The European Respiratory Society/American Thoracic Society (ERS/ATS) Task Force released new technical standards on spirometry interpretation in 2021. Our study compares bronchodilator responsiveness (BDR) in asthma, evaluating the impact of the 2005 and 2021 ERS/ATS criteria and the influence of predictive equations. Methods A retrospective cohort study of adult patients with asthma was referred to spirometry with a BDR test at the Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica, Serbia. The study included adult patients with asthma who underwent BDR testing in the Department of Respiratory Pathophysiology at the institute and had available data on height, gender, age, race, and eosinophil count. Results Among 197 patients, 69 were men (35.0%), the median age was 47 years (interquartile range (IQR) 38-60), and a positive BDR test occurred in 50 (25.38%)according to the 2005 criteria and 42 (21.32%) according to 2021 criteria when using the Global Lung Initiative (GLI) reference equations. Strong agreement was observed between the ERS/ATS 2005 and 2021 criteria (Cohen's kappa index: 0.887, 95%, CI 0.810 to 0.963). Similar results were found with the Third National Health and Nutrition Examination Survey (NHANES III) and the European Community of Coal and Steel (ECCS) predictive equations. Positive BDR tests were common in patients with moderately severe and severe forced expiratory volume in one second (FEV1) impairment and were not associated with eosinophil count or total serum immunoglobulin E (IgE) levels. Conclusion The introduction of the 2021 ERS/ATS criteriadid not significantly alter the classification of BDR in the majority of asthma patients, ensuring diagnostic stability. Whichever criterion was used, positive BDR correlated with the extent of FEV1 impairment, but not asthma biomarkers.

Differences in immunological profile in atopic dermatitis patients with and without dupilumab therapy

Our aim is to determine the number of leukocytes, T lymphocytes and B lymphocytes and the expression of activation markers CD200 and CD23 on B lymphocytes in atopic dermatitis (AD) patients (treated and not treated with dupilumab) during the pollen season. We examined 29 patients not treated with dupilumab, 24 patients treated with dupilumab and 40 healthy subjects as a control group. The count of T and B lymphocytes and their subsets were assessed by flow cytometry. The non-parametric Kruskal–Wallis one-factor analysis of variance with post hoc by Dunn’s test with Bonferroni’s modification was used for statistical processing. Although there was a significant improvement in skin findings in patients treated with dupilumab, the changes in immunological profile show a persistent altered immune response characterized by dysregulation and overactivation of B lymphocytes. Dupilumab therapy leads to normalization of relative T regulatory lymphocytes and total memory B lymphocytes and to decreased count of absolute CD8+ T lymphocytes. Why carry out this study?Studies investigating the immunological profile of atopic dermatitis (AD) patients during the pollen season are rare. There are no studies investigating the count of B lymphocytes (CD5+, CD22+ and CD73+ B lymphocytes) and the expression of activation markers CD23 and CD200 on B lymphocytes and on their subsets during pollen season in AD patients treated and non-treated with dupilumab therapy. What was learned from the study?In atopic dermatitis (AD) patients with and without dupilumab therapy, we confirmed the significantly higher count of absolute neutrophils, absolute monocytes, absolute eosinophils, absolute basophils, non-switched B lymphocytes, transitional B lymphocytes, CD23 memory, naive, non-switched, switched and total CD23 B lymphocytes, the relative count of CD200 memory and CD200 switched B lymphocytes. In dupilumab treated patients, we confirmed the significantly higher count of relative eosinophils, relative CD16+ eosinophils, relative CD200 non-switched B lymphocytes and lower count of absolute CD8+ T lymphocytes. Further studies should focus on investigating the effect of dupilumab on CD8+ T lymphocytes and their subpopulations. In patients without dupilumab therapy, we confirmed the significantly higher count of relative neutrophils, relative T regulatory lymphocytes and total memory B lymphocytes. The changes in the count of CD5+, CD22+ and CD73+ B lymphocytes were not observed during pollen season in both groups of AD patients.

Amiodarone-Induced Anaphylaxis.

Background: Amiodarone-induced anaphylaxis is seldom reported. The mechanism of this anaphylaxis is unknown. Methods: A literature search was carried out with keywords "Amiodarone" and "Anaphylaxis" and "polysorbate 80" or "hypotension." A search using "amiodarone" in the FDA Adverse Event Reporting System (FAERS) from 1969 to 2024 was also conducted. Results: There are a total of 10 cases of amiodarone-induced anaphylaxis in the literature. Six patients were male. Ages ranged from 15 to 86years old. Nine cases were triggered by intravenous injection (IV) and one by oral administration. Eight patients did not have previous exposure to amiodarone. The trigger times for IV amiodarone were immediate to 90 minutes. All nine cases of IV amiodarone resulted in hypotension (90%), with an immeasurable blood pressure (70%). Presentations included bronchospasm or a skin rash (60%), angioedema (40%), and unconsciousness (20%). Only one patient had a history of allergy to penicillin and sulfonamide. An amiodarone skin test was positive on one patient. Increased blood tryptase (4 cases), positive basophil activation test to amiodarone (2 cases), increased eosinophil count (1 case), and increased serum IgE (1 case) were reported. Amiodarone was terminated in 80% of the patients. Epinephrine, norepinephrine, antihistamine-1, or steroids were used to rescue patients. Four patients were intubated. All patients fully recovered. In the FAERS database, 89 cases of amiodarone-associated anaphylaxis were reported, resulting in 14 deaths. Conclusions: Solvent polysorbate 80, amiodarone, and iodide may contribute to amiodarone-induced anaphylaxis. Prompt treatment is the key to saving patients.

Relationship between parasitism with milk yield and body weight of Mafriwal cattle

Mafriwal cattle have good characteristics, but parasitism effects on their production have never been explored. This study aimed to determine the relationship between phenotypic markers of parasitism, namely packed cell volume (PCV), peripheral eosinophils count (PEC), nematode eggs (EPG), and coccidia oocyst (OPG) with the milk yield and body weight of Mafriwal cattle. Fecal and blood samples were collected from 242 cattle between 2021 and 2022. PCV and PEC were obtained from blood samples, while EPG and OPG were obtained from fecal samples. PCR was conducted to identify haemoparasite species. Milk yield data and the body weight of calves were also recorded. Spearman’s rank correlation showed that body weight has a negative correlation with PCV (r=-0.4; P<0.01) and a positive correlation with PEC (r=0.39; P<0.01) in 2022. Multiple linear regression models were used to determine the effect of phenotypic markers and year of sampling on milk yield and body weight. The best models were selected based on the lowest Akaike Information Criterion. Milk yield decreased significantly (P<0.001) from 2021 to 2022. An increase in PEC led to a significant reduction (P<0.001) in milk yield. Conversely, body weight increased significantly (P<0.001) from 2021 to 2022 and an increase in PCV caused a significant (P<0.001) reduction in body weight. Elevated EPG and OPG led to significant (P<0.01) reductions in body weight but the interaction between EPG and OPG has a significant positive (P<0.001) impact on body weight. Overall, the findings suggest that milk yield and body weight of Mafriwal cattle were significantly affected by parasitism thus necessitating the implementation of parasite control approaches.

THE RELATIONSHIP BETWEEN TOCILIZUMAB USE AND EOSINOPHIL COUNT IN PATIENTS WITH RHEUMATOID ARTHRITIS: A RETROSPECTIVE STUDY

Objective: This study aimed to determine the relationship between tosilizumab use and eosinophil counts in patients with rheumatoid arthritis. Material and Methods: Thirty five patients diagnosed with rheumatoid arthritis (RA) receiving either synthetic disease-modifying antirheumatic drugs (DMARDs) or tocilizumab treatment were included in this study. Patient age and disease duration, disease activity parameters and eosinophil values were recorded. Results: Comparing the eosinophil counts and percentages of the DMARD group with the Tocilizumab group, any statistically significant differences were found. There was no significant difference in eosinophil counts and percentages in the DMARD group in repeated measurements. However, in the Tocilizumab group, there was a significant difference in both parameters. Conclusion: A significant increase in eosinophil counts was observed in the group receiving tocilizumab therapy at the 1st month. Therefore, during treatment monitoring, especially in the early stages, attention should also be paid to eosinophil values.

Benefits of budesonide/glycopyrronium/formoterol fumarate dihydrate on lung function and exacerbations of COPD: a post-hoc analysis of the KRONOS study by blood eosinophil level and exacerbation history

BackgroundJapanese guidelines recommend triple inhaled corticosteroid (ICS)/long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) therapy in patients with chronic obstructive pulmonary disease (COPD) and no concurrent asthma diagnosis who experience frequent exacerbations and have blood eosinophil (EOS) count ≥ 300 cells/mm3, and in patients with COPD and asthma with continuing/worsening symptoms despite receiving dual ICS/LABA therapy. These post-hoc analyses of the KRONOS study in patients with COPD and without an asthma diagnosis, examine the effects of fixed-dose triple therapy with budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) versus dual therapies on lung function and exacerbations based on blood EOS count – focusing on blood EOS count 100 to < 300 cells/mm3 – as a function of exacerbation history and COPD severity.MethodsIn KRONOS, patients were randomized to receive treatments that included BGF 320/14.4/10 µg, glycopyrronium/formoterol fumarate dihydrate (GFF) 14.4/10 µg, or budesonide/formoterol fumarate dihydrate (BFF) 320/10 µg via metered dose inhaler (two inhalations twice-daily for 24 weeks). These post-hoc analyses assessed changes from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV1) over 12–24 weeks and moderate or severe COPD exacerbations rates over 24 weeks. The KRONOS study was not prospectively powered for these subgroup analyses.ResultsAmong patients with blood EOS count 100 to < 300 cells/mm3, least squares mean treatment differences for lung function improvement favored BGF over BFF in patients without an exacerbation history in the past year and in patients with moderate and severe COPD, with observed differences ranging from 62 ml to 73 ml across populations. In this same blood EOS population, moderate or severe exacerbation rates were reduced for BGF relative to GFF by 56% in patients without an exacerbation history in the past year, by 47% in patients with moderate COPD, and by 50% in patients with severe COPD.ConclusionsThese post-hoc analyses of patients with moderate-to-very severe COPD from the KRONOS study seem to indicate clinicians may want to consider a step-up to triple therapy in patients with persistent/worsening symptoms with blood EOS count > 100 cells/mm3, even if disease severity is moderate and there is no recent history of exacerbations.Trial registrationClinicalTrials.gov registry number NCT02497001 (registration date, 13 July 2015).

Relationship between circulating white blood cell count and inflammatory skin disease: a bidirectional mendelian randomization study.

Observational studies have shown a strong association between circulating white blood cell counts (WBC) and inflammatory skin diseases such as acne and psoriasis. However, the causal nature of this relationship is unclear. We performed a two-way two-sample Mendelian randomization (MR) analysis to investigate potential causal relationships between leukocytes and inflammatory skin diseases. The circulating white blood cell count, basophil cell count, leukocyte cell count, lymphocyte cell count, eosinophil cell count, and neutrophil cell count data were obtained from the Blood Cell Consortium (BCX). The data for inflammatory skin disorders, including acne, atopic dermatitis (AD), hidradenitis suppurativa (HS), psoriasis, and seborrheic dermatitis (SD), were obtained from the FinnGen Consortium R10. The primary analysis utilized inverse variance weighting (IVW) along with additional methods such as MR-Egger, weighted mode, and weighted median estimator. To assess heterogeneity among instrument variables, Cochran's Q test was employed, while MR-Egger intercept and MR-PRESSO were used to test for horizontal pleiotropy. IVW demonstrated that an elevated monocyte count was significantly associated with a decreased risk of psoriasis (OR = 0.897, 95% CI: 0.841-0.957, P = 0.001, FDR = 0.016). Additionally, an increased eosinophil count was causally associated with a higher risk of AD (OR = 1.188, 95% CI: 1.093-1.293, P = 0.000, FDR = 0.002). No inverse causal relationship between inflammatory skin disease and circulating white blood cell count was found. In conclusion, this study provides evidence that increased monocyte count is associated with a reduced risk of psoriasis and that there is a causal relationship between increased eosinophil counts and an increased risk of AD. These findings help us understand the potential causal role of specific white blood cell counts in the development of inflammatory skin diseases.

Proton pump inhibitor effect on esophageal protein signature of eosinophilic esophagitis, prediction, and evaluation of treatment response.

Recently, we have identified a dysregulated protein signature in the esophageal epithelium of eosinophilic esophagitis (EoE) patients including proteins associated with inflammation and epithelial barrier function; however, the effect of proton pump inhibitor (PPI) treatment on this signature is unknown. Herein, we used a proteomic approach to investigate: (1) whether PPI treatment alters the esophageal epithelium protein profile observed in EoE patients and (2) whether the protein signature at baseline predicts PPI response. We evaluated the protein signature of esophageal biopsies using a cohort of adult EoE (n = 25) patients and healthy controls (C) (n = 10). In EoE patients, esophageal biopsies were taken before (pre) and after (post) an 8-week PPI treatment, determining the histologic response. Eosinophil count PostPPI was used to classify the patients: ≥15 eosinophils/hpf as non-responders (non-responder) and < 15 eosinophils/hpf as responders (R). Protein signature was determined and differentially accumulated proteins were characterized to identify altered biological processes and signaling pathways. Comparative analysis of differentially accumulated proteins between groups revealed common signatures between three groups of patients with inflammation (responder-PrePPI, non-responder-PrePPI, and non-responder-PostPPI) and without inflammation (controls and responder-PostPPI). PPI therapy almost reversed the EoE specific esophageal protein signature, which is enriched in pathways associated with inflammation and epithelial barrier function, in responder-PostPPI. Furthermore, we identified a set of candidate proteins to differentiate responder-PrePPI and non-responder-PrePPI EoE patients before treatment. These findings provide evidence that PPI therapy reverses the alterations in esophageal inflammatory and epithelial proteins characterizing EoE, thereby providing new insights into the mechanism of PPI clinical response. Interestingly, our results also suggest that PPI response could be predicted at baseline in EoE.

Allergen Sensitivity Patterns and Their Correlation With Total Serum IgE Levels and Absolute Eosinophil Counts Among Patients With Allergic Rhinitis and Asthma in North Karnataka.

Introduction Respiratory allergies are prevalent across all populations and age groups, with the specific types of allergens varying according to geographic area, climate, location, economic status, and ethnic identity. While skin prick testing is considered the gold standard for assessing specific IgE against particular allergens, several factors can make the test less preferred. Consequently, total serum IgE levels and eosinophil counts are often used instead. Objectives The study aimed to determine allergen sensitivity patterns among patients with allergic rhinitis and/or asthma and to correlate skin prick test (SPT) reactivity with total serum IgE levels and absolute eosinophil count (AECs). This was done to assess the potential use of these measures as screening tests. Materials and methods A cross-sectional study was conducted on 44 patients diagnosed with allergic rhinitis and/or asthma. Each patient underwent an allergen SPT, and measurements were taken for total serum IgE levels and eosinophil counts. The study identified the most common allergens resulting in positive SPTs. Pearson correlation test was used for continuous variables, and a p-value of <0.05 was considered statistically significant. Results The study found that the majority of patients had only allergic rhinitis (17, 38.6%), followed by those with only asthma (12, 27.3%), and those with both allergic rhinitis and asthma (15, 34.1%). The most common allergen was Blomia (house dust mite), affecting 22 (50%) patients, while the least common were honey bee and lemon, each affecting 1 (2.3%) patient. There was a significant correlation between total serum IgE levels and AECs (p < 0.05). Additionally, a statistically significant correlation was found between total serum IgE levels, eosinophil counts, and the number of allergens to which patients were sensitized. Conclusion Blomia (house dust mite) is the most common allergen among patients with respiratory allergies in North Karnataka. While total serum IgE levels and AECs may help identify the extent of allergen sensitivity, the SPT remains the gold standard.

Interactions between eosinophils and IL-5Rα–positive mast cells in nonadvanced systemic mastocytosis

Bidirectional interactions between eosinophils and mast cells (MCs) have been reported in various allergic diseases. Bone marrow (BM) eosinophilia, and to a lesser extent blood eosinophilia, is common in systemic mastocytosis (SM), but its significance remains unknown. To describe blood and BM eosinophil characteristics in SM. A large collection of BM biopsies was analyzed using immunohistochemical staining and whole-slide imaging. Eosinophil and extracellular granules were detected by eosinophil peroxidase (EPX) staining, and MCs by KIT staining. Complementary analyses were conducted using flow cytometry and immunofluorescence. Eosinophil infiltrates and large areas of eosinophil degranulation were observed within or around BM MC infiltrates in SM. EPX staining surface, highlighting intact eosinophils and eosinophil degranulation, was higher in non-advanced-SM (n=37 BM biopsies) compared to both controls (n=8, p=0.0003) and to advanced SM (n=24, p=0.014). In non-advanced SM, positive correlations were observed between serum tryptase levels and percentages of eosinophil counts in BM aspirations (Spearman r coefficient r=0.38, p=0.038), eosinophils count in BM biopsies (r=0.45, p=0.007), EPX staining (r=0.37, p=0.035) and eosinophil degranulation (r=0.39, p=0.023). Eosinophil counts in BM biopsies also correlated with MC counts (r=0.47, p=0.006) and KIT staining surface (r=0.49, p=0.003). BM MCs expressed interleukin-5 receptor and other usual eosinophil cytokine/chemokine receptors, and blood eosinophils display several increased surface markers compared to controls, suggesting an activated state. Our data suggest a possible crosstalk between MCs and eosinophils, supporting MC tryptase release and MC activation-related symptoms. This suggests a rationale for targeting eosinophils in non-advanced-SM not fully controlled by other therapies.

Severe Eosinophilic Asthma or Eosinophilic Granulomatosis With Polyangiitis: Potential Biomarkers for Novel Diagnostic Strategies

BackgroundSevere Eosinophilic Asthma (SEA) may be the prodromal phase of Eosinophilic Granulomatosis with Polyangiitis (EGPA). Nevertheless, few studies have tried to recognize EGPA in the early stages of the disease. ObjectivesTo identify a panel of clinical and biological markers to detect which severe asthmatic patient might be considered in a prodromal phase of EGPA and crafting a strategy for diagnostic decision-making. Methods30 patients with EGPA and 49 with SEA were enrolled. A complete pulmonary, ear, nose and Throat (ENT) and rheumatologic assessment were made. Blood (eosinophil count, eosinophilic cationic protein-ECP, IL5, IL4, total-IgE, IgG4, anti-neutrophil cytoplasmic antibody (ANCA), sputum (eosinophils count, periostin, IL8 and GMCSF) and nasal smear (eosinophilia) biomarkers were assessed. Asthma Control Test, Short Form-36, SinoNasalOutcome Test-22, and Asthma Quality of Life Questionnaire were also used. ResultsSEA patients had poorer asthma control (p<0.001) and higher level of sputum eosinophils (p<0.002) while EGPA patients reported higher levels of blood eosinophils in the past. Sputum GMCSF was the only biomarker significantly increased in EGPA patients compared with SEA (p<0.0001). Among SEA patients, those with some suggestive but not diagnostic criteria of EGPA, particularly tissue eosinophilic infiltrates, presented higher levels of sputum GMCSF (p<0.0005), blood and sputum eosinophils (p<0.0006, p<0.011) in comparison with the other patients. ConclusionSputum GMCSF and eosinophils might be useful biomarkers to support early diagnosis and treatment choices in SEA patients, suspected of having EGPA

Dual Phosphodiesterase 3 and 4 Inhibitor Ensifentrine Reduces Exacerbation Rate and Risk in Patients With Moderate to Severe COPD

IntroductionExacerbations in chronic obstructive pulmonary disease (COPD) can be life-threatening and lead to irreversible declines in lung function and quality of life. Medications that reduce exacerbation burden are an unmet need, as exacerbations put patients at risk for more exacerbations and decrease quality of life. Ensifentrine is a novel, first-in-class, selective, dual inhibitor of phosphodiesterase 3/4 with demonstrated nonsteroidal anti-inflammatory activity and bronchodilatory effects. Research QuestionDoes ensifentrine reduce the rate and/or risk of COPD exacerbations? Study Design and MethodsA prespecified, pooled analysis of the phase 3 clinical trials ENHANCE-1 (NCT04535986) and ENHANCE-2 (NCT04542057) was conducted to assess the effect of ensifentrine on exacerbation rate and risk (time to first exacerbation). The trials included symptomatic patients aged 40-80 years with moderate-to-severe COPD who received 3 mg twice-daily ensifentrine over 24 weeks or placebo. Subgroup analyses and frequent exacerbator transition risk were conducted post-hoc. ResultsIn total, 975 ensifentrine-treated and 574 placebo-treated patients were included in the pooled analysis, including 62% on concomitant LAMA or LABA therapy and 18% on concomitant inhaled corticosteroid therapy. Ensifentrine was associated with significant reductions in the rate (rate ratio, 0.59; 95% CI, 0.43-0.80; P < 0.001) and risk (hazard ratio, 0.59; 95% CI, 0.44-0.81; P < 0.001) of moderate/severe exacerbations compared with placebo. Reductions in the rate and risk of exacerbations were generally consistent across patient subgroups, including age, sex, race, background maintenance medication use, chronic bronchitis, eosinophil count, COPD severity, and exacerbation history. Ensifentrine was associated with a numerical delay in transitioning from an infrequent exacerbator (GOLD B) to a frequent exacerbator (GOLD E) compared with placebo. ConclusionEnsifentrine reduced the rate of exacerbations and increased the time to first exacerbation among patients with COPD across a broad range of clinically relevant subgroups.

The storage mite Tyrophagus putrescentiae induces greater lung inflammation than house dust mites in mice.

Exposure to storage mite (SM) and house dust mite (HDM) allergens is a risk factor for sensitization and asthma development; however, the related immune responses and their pathology have not been fully investigated. The HDMs Dermatophagoides farinae and Dermatophagoides pteronyssinus and SM Tyrophagus putrescentiae are potent allergens that induce asthma. Most SM-related studies have focused on the allergic reactions of individuals by measuring their immunoglobulin (Ig)E expression. Considering the limited research on this topic, the present study aims to investigate the differences in the immune responses induced by HDMs and SMs and histologically analyze lung tissues in a mouse asthma model to understand the differential effects of HDM and SM. The results revealed that all mite species induced airway inflammation. Mice challenged with T. putrescentiae had the highest airway resistance and total cell, eosinophil, and neutrophil counts in the bronchoalveolar lavage fluid (BALF). The SM-sensitized groups showed more severe lesions and mucus hypersecretions than the HDM-sensitized groups. Although the degree of HDM and SM exposure was the same, the damage to the respiratory lung tissue was more severe in SM-exposed mice, which resulted in excessive mucin secretion and increased fibrosis. Furthermore, these findings suggest that SM sensitization induces a more significant hypersensitivity response in mucosal immunity than HDM sensitization in asthma models.

Inflammatory Profile of Chronic Rhinosinusitis With Nasal Polyp Patients in Brazil: Multicenter Study.

To determine the inflammatory profile of CRSwNP in Brazil and characterize the subgroups of CRSwNP patients in this population through cluster analysis. Multicenter cross-sectional study involving 15 centers representing different regions of Brazil. Clinical data of 166 patients and 80 controls, aged 18 to 70 years old, number of surgeries for CRS, history of asthma and aspirin sensitivity, and Lund-Mackay scores on CT scans. During nasal endoscopy, we obtained the Lund-Kennedy scores and collected 2 samples of nasal polyps: one for eosinophil and neutrophil tissue counts and one to quantify different cytokines. 79.6% of our patients had 10 or more eosinophils/HPF. CRSwNP groups exhibited significantly lower concentrations of TNF-alpha and significantly higher concentrations of IFN-gamma, CCL11/Eotaxin, CCL24/Eotaxin-2/MPIF-2, and CCL26/Eotaxin-3 versus the control group (Kruskal-Wallis test). Comparison between CRSwNP groups (≥10 vs <10 eosinophils/HPF) showed no difference in cytokine concentration (Mann-Whitney test). Hierarchical clustering and PCA according to cytokine concentrations revealed 2 main Clusters, with a significantly higher concentration of all cytokines in Cluster 1 (n = 35) than in Cluster 2 (n = 121), except IL-6 and IL-33 (Mann-Whitney test). According to ROC curve analysis the best cut-off to differentiate the 2 clusters was 43 eosinophils/HPF. The group with ≥43 presented a higher prevalence of men and a higher Lund-Mackay score (Mann-Whitney test). CRSwNP patients in Brazil present mixed inflammation, with 2 distinct groups (high and low inflammatory pattern) that can be distinguished by tissue eosinophilia of ≥43 eosinophils/HPF cut-off in nasal polyps.

Association of blood inflammatory phenotypes and asthma burden in children with moderate-to-severe asthma

BackgroundUnderlying immunological mechanisms in children with moderate-to-severe asthma are complex and unclear. We aimed to investigate the association between blood inflammatory parameters and asthma burden in children with moderate-to-severe asthma.MethodsBlood inflammatory parameters (eosinophil(E) and neutrophil(N) counts and inflammatory mediators using multiplex immunoassay technology) were measured in children (6–17 years) with moderate-to-severe asthma from SysPharmPediA cohort across four European countries. Based upon low(L)/high(H) blood(B) eosinophil (LBE/HBE: &lt;/≥0.3×109/L, respectively) and neutrophil counts (LBN/HBN: &lt;/≥4×109/L, respectively), mixed(HBE-HBN), eosinophilic(HBE-LBN), neutrophilic(LBE-HBN), and paucigranulocytic(LBE-LBN) phenotypes were defined. Inflammatory mediator profiles and burden of disease (asthma control status, exacerbations and school days missed in the past year) were compared between phenotypes using adjusted logistic regression models.ResultsAmong 126 included children (41% girls and mean(sd) age of 11.94(2.76)), 22%, 44%, 11%, and 23% were classified as mixed, eosinophilic, neutrophilic, and paucigranulocytic phenotypes respectively. Neutrophilic children had lowest lung function (FEV1%predicted pre-salbutamol) compared to other groups. Children with mixed asthma were most often uncontrolled and had highest asthma-related school absence in the past year. Interleukin-6(IL-6) and matrix metalloproteinase-9(MMP-9) levels were significantly higher in patients with mixed or neutrophilic asthma, while tissue inhibitor of metalloproteinase-2(TIMP-2) was lower in patients with neutrophilic asthma compared to eosinophilic or paucigranulocytic asthma. Interleukin-5(IL-5) was increased in eosinophilic group compared to neutrophilic and paucigranulocytic groups, irrespective of the chosen cut-off for eosinophilia.ConclusionDifferences in asthma burden-related clinical expression and distinct blood inflammatory mediator profiles were found between phenotypes, highlighting implications for optimizing personalized treatment and management strategies in children with moderate-to-severe asthma.

Therapeutic relevance of eosinophilic inflammation and airway viral interactions in severe asthma.

The role of eosinophils in airway inflammation and asthma pathogenesis is well established, with raised eosinophil counts in blood and sputum associated with increased disease severity and risk of asthma exacerbation. Conversely, there is also preliminary evidence suggesting antiviral properties of eosinophils in the airways. These dual roles for eosinophils are particularly pertinent as respiratory virus infections contribute to asthma exacerbations. Biologic therapies targeting key molecules implicated in eosinophil-associated pathologies have been approved in patients with severe asthma and, therefore, the effects of depleting eosinophils in a clinical setting are of considerable interest. This review discusses the pathological and antiviral roles of eosinophils in asthma and exacerbations. We also highlight the significant reduction in asthma exacerbations seen with biologic therapies, even at the height of the respiratory virus season. Furthermore, we discuss the implications of these findings in relation to the role of eosinophils in inflammation and antiviral responses to respiratory virus infection in asthma.

Suplatast tosilate reduces peripheral blood eosinophil levels in patients with eosinophilia: A real-world retrospective study

IntroductionEosinophilia is a rare disease characterized by an increase in eosinophils. Suplatast tosilate is a selective Th2 cytokine inhibitor that can reduce eosinophils. There is currently a lack of clinical studies of suplatast tosilate in the treatment of eosinophilia. Research objectiveTo explore whether suplatast tosilate can reduce blood eosinophil levels in eosinophilia and the factors that might influence the improvement. MethodsA real-world retrospective study of 20 patients with eosinophilia was conducted using electronic medical record information. The main outcome measure was the difference in peripheral blood absolute eosinophil count (AEC) and percentage (EOS%) before suplatast tosilate (baseline) and the lowest AEC during the 1-year period of suplatast tosilate treatment (post-treatment). Data on age, gender, disease duration, involved organs, and concomitant medication were collected, and subgroup analysis and linear regression analysis were performed. ResultsSubjects were predominantly male, with a mean age of 33 years and a disease duration of approximately 30 months. After treatment with suplatast tosilate, the patient's AEC (p ​= ​0.029) and EOS% (p ​= ​0.016) significantly decreased. The decline in eosinophils was more pronounced in patients who were male, age <33 years, disease duration <30 months and gastrointestinal system involvement. In addition, the shorter the course of the disease, the greater the relative decrease in eosinophils after suplatast tosilate treatment (β ​= ​−0.018, p ​< ​0.001). ConclusionsSuplatast tosilate is effective in reducing peripheral blood eosinophil levels in patients with eosinophilia. Large-scale prospective cohort studies are needed for further confirmation.