Elevated Blood Eosinophil Research Articles

Distinct phenotype and risk factor analysis of persistent airflow limitation among asthmatic children: a case-control study

BackgroundPersistent airflow limitation (PAL) in childhood asthma is associated with a poor prognosis. The aim of this study was to categorize asthmatic children with PAL into distinct phenotypes and investigate the risk factors associated with each phenotype.MethodsWe conducted a case-control study with a total of 119 PAL patients and 120 non-PAL (NPAL) individuals. To classify the patients into appropriate clusters, unsupervised cluster analysis using K-means clustering was employed. The clusters were then compared to explore different PAL phenotypes. Univariate and multivariate logistic regression analyses were performed to identify risk factors for PAL and calculate odds ratios (ORs) with 95% confidence intervals (95%CIs).ResultsK-means clustering divided patients into three clusters: Cluster 0 included 120 NPAL patients, Cluster 1 characterized by elevated blood neutrophils included 66 PAL patients, and Cluster 2 exhibited elevated blood eosinophils and FeNO levels, containing 53 PAL patients. Independent risk factors for PAL included older age in both Cluster 1 (9∼\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\sim$$\\end{document}11y: OR 12.67, 95%CI 3.30-55.74; ≥\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\ge$$\\end{document}11y: OR 5.42, 95%CI 1.26-25.69) and Cluster 2 (9∼\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\sim$$\\end{document}11y: OR 7.25, 95%CI 1.70-33.35; ≥\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\ge$$\\end{document}11y: OR 11.28, 95%CI 2.79-51.89), as well as pneumonia history, with an OR of 6.41(95%CI 1.34-33.41) in Cluster 1 and an OR of 7.92(95%CI 1.83-37.44) in Cluster 2. Furthermore, specific factors associated with Cluster 1 included BMI above 22 kg/m2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$m^2$$\\end{document}(OR 12.28, 95%CI 2.68-70.45), asthma duration exceeding three years (OR 4.77, 95%CI 1.60-15.94), and a blood neutrophil percentage between 0.4 and 0.5 (OR 4.13, 95%CI 1.17-16.6). In Cluster 2, independent risk factors included a blood eosinophil percentage greater than 0.07 (OR 4.36, 95%CI 1.16-19.73) and a high FeNO level (OR 3.94, 95%CI 1.35-11.97).ConclusionOur study identified two phenotypes of PAL in asthmatic children: non-eosinophilic and eosinophilic inflammation. Older age and a history of pneumonia were independent risk factors for both phenotypes. For non-eosinophilic inflammation PAL, specific contributing factors included higher BMI, long duration of asthma, and a blood neutrophil percentage between 0.4 and 0.5. Elevated FeNO levels and blood eosinophilic percentage were independently associated with eosinophilic inflammation PAL.

Dupilumab Efficacy and Safety in Children With Moderate-to-Severe Asthma and High Blood Eosinophils: A Post Hoc Analysis of VOYAGE

Elevated blood or tissue eosinophils are considered to characterize type 2 inflammation in children with asthma and are associated with increased exacerbation rates and worse asthma control. Dupilumab, a human monoclonal antibody that blocks type 2 inflammatory drivers IL-4 and IL-13, reduced severe exacerbation rates and improved lung function vs placebo in children aged 6-11 years with uncontrolled moderate-to-severe asthma in the phase 3 LIBERTY ASTHMA VOYAGE study (NCT02948959). This post hoc analysis assessed dupilumab efficacy and safety in children from VOYAGE with moderate-to-severe asthma and ≥500 and <1500 blood eosinophils/μL at baseline. Children received add-on dupilumab (100/200 mg by body weight) or matched placebo every 2 weeks for 52 weeks. We assessed annualized severe exacerbation rates, least squares mean (LSM) change from baseline in pre-bronchodilator percent predicted forced expiratory volume in 1 second (ppFEV1), and incidence of treatment-emergent adverse events. In children with elevated baseline eosinophils (N = 174), dupilumab vs placebo significantly reduced annualized exacerbation rates by 67% (95% CI: 38-82%; P < .001) and improved pre-bronchodilator ppFEV1 from baseline at Weeks 24 and 52 (LSM difference [95% CI] 7.58 percentage points [2.85-12.31]; P = .002; 7.98 percentage points [2.17-13.78]; P = .007, respectively). The incidence of treatment emergent adverse events was similar with dupilumab and placebo. Dupilumab significantly reduced severe exacerbations and improved lung function in children with moderate-to-severe asthma and baseline blood eosinophil counts ≥500 and <1500 cells/μL, with a safety profile comparable with the overall study population.

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

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

Inflammatory profile of eosinophils in asthma-COPD overlap and eosinophilic COPD: a multi-omics study.

Elevated blood eosinophil levels in patients with chronic obstructive pulmonary disease (COPD) with or without asthma are linked to increased exacerbations and the effectiveness of inhaled corticosteroid treatment. This study aimed to delineate the inflammatory cellular properties of eosinophils in patients with asthma-COPD overlap (ACO) and eosinophilic COPD (eCOPD). Eosinophils were isolated from the peripheral blood of healthy volunteers, patients with non-eCOPD, and those with ACO/eCOPD. Multi-omics analysis involving transcriptomics, proteomics, and lipidomics was performed, followed by bioinformatic data analyses. In vitro experiments using eosinophils from healthy volunteers were conducted to investigate the molecular mechanisms underlying cellular alterations in eosinophils. Proteomics and transcriptomics analyses revealed cellular characteristics in overall COPD patients represented by viral infection (elevated expression of sterol regulatory element-binding protein-1) and inflammatory responses (elevated levels of IL1 receptor-like 1, Fc epsilon receptor Ig, and transmembrane protein 176B). Cholesterol metabolism enzymes were identified as ACO/eCOPD-related factors. Gene Ontology and pathway enrichment analyses demonstrated the key roles of antiviral responses, cholesterol metabolism, and inflammatory molecules-related signaling pathways in ACO/eCOPD. Lipidomics showed the impaired synthesis of cyclooxygenase-derived mediators including prostaglandin E2 (PGE2) in ACO/eCOPD. In vitro assessment confirmed that IL-33 or TNF-α stimulation combined with IL-5 and IFN-γ stimulation induced cellular signatures in eosinophils in ACO/eCOPD. Atorvastatin, dexamethasone, and PGE2 differentially modulated these inflammatory changes. ACO/eCOPD is associated with viral infection and an inflammatory milieu. Therapeutic strategies using statins and inhaled corticosteroids are recommended to control these pathogenic changes.

Real-world phenotyping and risk assessment of childhood asthma burden using national registries

BackgroundPhenotype classification contributes to risk assessment of asthma. Previous studies have applied this concept primarily to adult populations and in the setting of research protocol assessments which may not be applicable to clinical settings. ObjectiveExploring the value of routinely collected clinical data for phenotype classification and risk assessment of childhood asthma. MethodsUsing hospital and laboratory data, 29,851 children in a Danish nationwide database aged 2–17 years with ICS-treated asthma in 2015 followed for two years (730 days) were classified to have T2 (elevated blood eosinophils (>300 cells/μL) and/or elevated total- or specific-IgE), and/or non-T2 risk factors (in utero tobacco exposure and/or severe viral infections). Logistic regression was applied to quantify associations of risk factors with asthma severity, control, and exacerbation risk. ResultsIn a complete case analysis, 85.8 % children had at least one T2 risk factor and 29.3 % had mixed T2/non-T2 risk factors. Elevated blood eosinophils and total/specific IgE were associated with exacerbations (ORs 1.55 (1.38–1.73) and 1.41 (1.20–1.66) and higher asthma severity (1.42 (1.24–1.63) and 1.31 (1.08–1.60)), respectively.Dose-dependency was observed between blood eosinophil counts, total IgE levels, and risk of adverse outcomes. Furthermore, accumulation of risk factors demonstrated an increasing risk, with children with all four risk factors having a high risk of any adverse asthma-related outcome (OR 3.13 (2.03–4.82) ConclusionAsthma phenotypic markers defined in research protocols can be reliably applied in real-world settings by utilizing data collected during routine clinical care and enable better classification of risk of adverse asthma outcomes.

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

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

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

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

Dupilumab for COPD with Blood Eosinophil Evidence of Type 2 Inflammation

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

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

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

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

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

Aspergillus Sinusitis: Risk Factors and Phenotyping.

Background: Aspergillus can cause fungal rhinosinusitis (FRS). We aimed to identify risk factors for sinonasal Aspergillus disease. Methods: Patients with a positive sinonasal mycological culture for Aspergillus species diagnosed in our hospital located in a continental climate were included in the 9-year retrospective study. Results: Of the 86 patients, 3 had invasive FRS (IFRS), 51 had fungal ball (FB) disease, and 32 had chronic rhinosinusitis with fungus (CFRS). In the IFRS group, all patients had a malignancy and were immunocompromised. Allergies, allergic rhinitis, asthma, nasal polyps, and the use of inhaled and nasal steroids were more common in the CFRS group, and IgE levels were greater than those in the FB and IRFS groups (p < 0.05). Conclusion: FB disease is a relatively symptom-free single-sinus disease among elderly individuals, and IFRS is dominant among immunocompromised patients. We discovered a third patient group, predominantly with nasal polyps, atopy, asthma, and elevated blood IgE and eosinophils, that did not fulfill the allergic FRS (AFRS) criteria. It is possible that a less fulminant category of underdiagnosed AFRS exists in cold climates. Treatment with local debridement is usually sufficient for FRS, apart from IFRS, and relapses are not common in cold climates.

Association of blood eosinophils with corticosteroid treatment failure stratified by smoking status among inpatients with AECOPD

BackgroundRecent studies have suggested elevated blood eosinophils are independent predictors of response to corticosteroid therapy in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Smoking status has been...

The role of matrix metalloproteinase-2 and miR-196a2 in bronchial asthma pathogenesis and diagnosis

BackgroundBronchial asthma is a persistent inflammatory respiratory condition that restricts the passage of air and causes hyperresponsiveness. Chronic asthma can be classified into three categories: mild, moderate, and severe. Remodeling took place as the extracellular matrix accumulated in the walls of the airways. Inflammation occurs as a result of the damage caused by matrix metalloproteinase-2 (MMP-2) to basement membrane type IV collagen. The severity of asthma may be associated with miR-196a2. The objective of our study was to investigate the underlying mechanisms and clinical relevance of miR-196a2 and MMP-2 serum levels in relation to the severity of asthma. MethodsThis study recruited 85 controls and 95 asthmatics classified as mild, moderate, or severe. Expression of miR-196a2 was measured by quantitative reverse transcriptase PCR. Using the enzyme-linked immunosorbent assay (ELISA), MMP-2, IL-6, and total immunoglobulin E (IgE) levels in the serum of asthmatics of various grades were compared to a control group. MMP-2's diagnostic and prognostic potential was determined using ROC curve analysis. This study also measured blood Eosinophils and PFTs. We examined MMP-2's connections with IgE, blood Eosinophils, and PFTs. ResultsThe current investigation found that miR-196a2 expression was significantly higher in the control group than in asthmatic patients as a whole. The study found that severe asthmatics had higher MMP-2, IL-6, and IgE serum levels than healthy controls. We identified the MMP-2 serum concentration cutoff with great sensitivity and specificity. Significant relationships between MMP-2 serum level and miR-196a2 expression in the patient group with severe asthmatics were found. The MMP-2, IL-6, and IgE serum levels were considerably higher in mild, moderate, and severe asthmatics than controls. The miR-196a2 expression and MMP-2 serum concentration correlated positively with IgE and blood eosinophils % and negatively with all lung function tests in the asthmatic patient group.Conclusion: the study revealed that the elevated miR-196a2 expression and serum concentration of MMP-2, IL-6, and IgE associated with elevated blood eosinophils % is associated with pathophysiology and degree of asthma severity. The miR-196a2 expression and MMP-2 serum concentration have a promising diagnostic and prognostic ability in bronchial asthma.

Lebrikizumab in Uncontrolled Asthma: Reanalysis in a Well-Defined Type 2 Population

LAVOLTA (L)I, LII, and ACOUSTICS were randomized, placebo-controlled, Phase 3 trials of lebrikizumab, a monoclonal antibody targeting IL-13 in patients with uncontrolled asthma. Failure to demonstrate efficacy may have been related to patient selection in those trials. To assess the efficacy in a well-defined subpopulation of patients with elevated blood eosinophil counts and a minimum number of prior asthma exacerbations. We performed an additional analysis in a subpopulation of patients with elevated FeNO and prior exacerbations. Adult (LI and LII) and adolescent patients (aged 12-17 years weighing ≥40 kg, ACOUSTICS) with uncontrolled asthma received lebrikizumab (125 mg, n= 832; or 37.5 mg, n= 829) or placebo (n= 833) subcutaneously every 4 weeks. Post hoc analysis of the annualized adjusted exacerbation rate (AER) was performed in a subpopulation of patients with baseline blood eosinophils of 300 cells/μL or greater and history of one or more exacerbations. In this subpopulation, there were 227 patients in the placebo group, 222 in the lebrikizumab 37.5-mg group, and 217 in the lebrikizumab 125-mg group. We summarized safety in patients who received at least one dose of lebrikizumab using adverse events. Lebrikizumab significantly reduced AER compared with placebo in adults (AER reduction: 125 mg [38%]; and 37.5 mg [41%]) and adolescents (AER reduction:125 mg [59%]; 37.5 mg [64%]) with baseline blood eosinophils of 300 cells/μL or greater and one or more exacerbations. Most adverse events were mild or moderate in severity and did not lead to treatment discontinuation. Lebrikizumab significantly reduced asthma exacerbations in a subpopulation of patients with elevated blood eosinophils, elevated FeNO, and a history of asthma exacerbation.

Low Serum IL-18 Levels May Predict the Effectiveness of Dupilumab in Severe Asthma.

Objective Dupilumab, a monoclonal antibody specific for the human interleukin (IL)-4 receptor α, is used to treat severe asthma, especially in patients with elevated blood eosinophil counts and fractional exhaled nitric oxide (FeNO). The therapeutic response to dupilumab is highly variable. In this study, we explored new serum biomarkers to accurately predict the effect of dupilumab and examine the effect of dupilumab based on changes in the clinical parameters and cytokine levels. Methods Seventeen patients with severe asthma treated with dupilumab were enrolled. Responders, defined as those with a >0.5-point decrease in the Asthma Control Questionnaire (ACQ) score after 6 months of treatment, were included. Results There were 10 responders and 7 non-responders. Serum type 2 cytokines were equivalent between responders and non-responders; the baseline serum IL-18 level was significantly lower in responders than in non-responders (responders, 194.9±51.0 pg/mL; non-responders, 323.4±122.7 pg/mL, p=0.013). The cut-off value of IL-18 at 230.5 pg/mL could be used to distinguish non-responders from responders (sensitivity 71.4, specificity 80.0, p=0.032). Conclusion A low baseline serum IL-18 level may be a useful predictor of an unfavorable response to dupilumab in terms of the ACQ-6.

Type-2 inflammation and lung function decline in chronic airway disease in the general population

BackgroundIt is unclear if type-2 inflammation is associated with accelerated lung function decline in individuals with asthma and chronic obstructive pulmonary disease (COPD). We tested the hypothesis that type-2 inflammation...

Triple Therapy with Budesonide/Glycopyrronium/Formoterol Fumarate Dihydrate versus Dual Therapies for Patients with COPD and Phenotypic Features of Asthma: A Pooled Post Hoc Analysis of KRONOS and ETHOS.

We evaluated the inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β2-agonist (ICS/LAMA/LABA) triple therapy with budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) versus dual LAMA/LABA and ICS/LABA therapies in patients with chronic obstructive pulmonary disease (COPD) and phenotypic features of asthma (bronchodilator reversibility and elevated blood eosinophils), but no asthma diagnosis, for whom treatment guidelines are limited. KRONOS (NCT02497001) and ETHOS (NCT02465567) enrolled patients with moderate-to-very-severe COPD, no current asthma diagnosis, and either ≥0 (KRONOS) or ≥1 (ETHOS) moderate/severe exacerbations in the prior year. This pooled post hoc analysis evaluated trough forced expiratory volume in 1 second (FEV1) and FEV1 area under the curve from hours 0 to 4 (AUC0-4) change from baseline over 12-24weeks, moderate/severe exacerbation rates, and St George's Respiratory Questionnaire (SGRQ) total score over 24weeks with ICS/LAMA/LABA (BGF 320/14.4/10µg), LAMA/LABA (glycopyrronium/formoterol fumarate dihydrate [GFF] 14.4/10µg), and ICS/LABA (budesonide/formoterol fumarate dihydrate [BFF] 320/10µg) in patients with phenotypic features of asthma defined as reversibility to salbutamol and blood eosinophils ≥300 cells/mm3. Analyses were not adjusted for multiplicity. BGF improved trough FEV1 and FEV1 AUC0-4 versus GFF (least squares mean [LSM] difference [95% confidence interval (CI)] 125 [39-211] and 153 [59-247] mL) and BFF (LSM difference [95% CI] 118 [30-207] and 146 [49-243] mL). Exacerbation rates were estimated to be lower with BGF versus GFF and BFF (respective rate ratios [95% CI] 0.28 [0.19-0.43] and 0.69 [0.45-1.05]) and SGRQ total score was estimated to be improved with BGF versus GFF and BFF (respective LSM differences [95% CI] -5.18 [-8.11 to -2.24] and -1.09 [-4.08 to 1.91]). BGF was estimated to have benefits on lung function, exacerbations, and health-related quality of life versus dual therapies in patients with COPD and phenotypic features of asthma. ClinicalTrials.gov NCT02497001 and NCT02465567.

An Observational Study of Early Treatment Response and Predictors of Dupilumab in the Treatment of Moderate‐to‐Severe Atopic Dermatitis

Background. Dupilumab has shown good effectiveness and safety in patients with moderate‐to‐severe atopic dermatitis. However, there is a lack of clinical data that focuses solely on the treatment response for the endpoint to observe the short‐term goal (12 weeks) in the treatment‐to‐target (T2T) concept. Study on predictors of early treatment response is also limited. Objective. To evaluate the early effectiveness and safety of dupilumab in the treatment of moderate‐to‐severe atopic dermatitis and to identify possible predictors of response. Methods. Using a retrospective study method, patients with moderate‐to‐severe atopic dermatitis who received dupilumab for ≥12 weeks at the Southwest Hospital between September 2019 and April 2022 were included. Results. Totally 16.25% of patients achieved EASI75 after 4 weeks and 53.75% achieved EASI75 after 12 weeks. SCORAD, EASI, and NRS were 50.17 ± 17.35, 13.51 ± 12.33 and 7.10 ± 1.82 in turn at baseline, and decreased to 29.94 ± 15.01, 6.97 ± 7.92, 3.64 ± 1.39 and 14.96 ± 10.31, 3.05 ± 4.16, 2.19 ± 1.09 after 4 and 12 weeks, respectively, with statistically significant differences (p &lt; 0.01). After 12 weeks, the changes in peripheral blood eosinophil count (decreased from (0.60 ± 0.43) ∗ 10^9/L to (0.30 ± 0.21) ∗ 10^9/L), total IgE level (decreased from 547.00 (179.00, 2167.50) IU/ml to 216.50 (106.00, 825.00) IU/ml), and LDH (decreased from (166.11 ± 171.59) IU/L to (67.54 ± 70.68) IU/L) from baseline were significant (p &lt; 0.01). Elevated peripheral blood eosinophil counts might be associated with an inadequate response to dupilumab (SCORAD12w: p = 0.007; EASI12w: p = 0.003; NRS12w: p = 0.030). The most common adverse events were reactions at the injection site (6/80) and conjunctivitis (4/80). Conclusion. Dupilumab showed good early effectiveness and safety in real‐world practice in Chinese patients with moderate‐to‐severe atopic dermatitis.

The association between blood eosinophils and clinical outcome of acute exacerbations of chronic obstructive pulmonary disease: A systematic review and meta-analysis

ObjectivesStudies have shown an association between eosinophilia and clinical outcomes in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, contradictory findings exist. Our study aims to systematically evaluate the association between elevated peripheral blood eosinophils and clinical outcome of patients with AECOPD. MethodsAn electronic search was conducted for relevant studies published from database inception to February 28, 2023, on PubMed, EMBASE, Cochrane Library, and Web of Science. The analysis covered studies on the correlation between EOS AECOPD and mortality, hospital stay duration, readmission and hospitalization rates, and invasive mechanical ventilation. Where applicable, relative risk (RR) and weighted mean difference (WMD) were extracted, pooled, and assessed using meta-analysis. Sensitivity analysis was performed to explore the source of heterogeneity. ResultsFifteen high-quality studies including 14 cohort studies and one case-control study were included in the meta-analysis. Compared with non-eosinophilic AECOPD patients, those with eosinophilic AECOPD had a lower risk of mortality (RR = 0.65, 95 % confidence interval [CI] 0.54, 0.77, P < 0.001), shorter length of hospital stay (WMD = −1.56, 95%CI -2.16, −0.96, P < 0.001), and higher readmission rate (RR = 1.07, 95%CI 1.01,1.13, P = 0.029). No difference was found concerning the rate of hospitalization and invasive mechanical ventilation between the two groups. ConclusionIndividuals diagnosed with eosinophilic AECOPD had a reduced mortality rate, a truncated period of hospitalization, and an insubstantial increase in the probability of readmission relative to their non-eosinophilic AECOPD counterparts. The level of eosinophils in blood has been shown to serve as a potential predictive biomarker for AECOPD patients.

Bacterial colonisation of the airway in neonates and risk of asthma and allergy until age 18 years.

We previously showed an association between neonatal bacterial airway colonisation and increased risk of persistent wheeze/asthma until age 5 years. Here, we study the association with persistent wheeze/asthma and allergy-related traits until age 18 years. We investigated the association between airway colonisation with Streptococcus pneumoniae, Moraxella catarrhalis and/or Haemophilus influenzae in 1-month-old neonates from the COPSAC2000 mother-child cohort and the development of persistent wheeze/asthma and allergy-related traits longitudinally until age 18 years using generalised estimating equations. Replication was sought in the similarly designed COPSAC2010 cohort of 700 children. Neonatal airway colonisation was present in 66 (21%) out of 319 children and was associated with a 4-fold increased risk of persistent wheeze/asthma (adjusted OR 4.01 (95% CI 1.76-9.12); p<0.001) until age 7 years, but not from age 7 to 18 years. Replication in the COPSAC2010 cohort showed similar results using 16S data. Colonisation was associated with an increased number of exacerbations (adjusted incidence rate ratio 3.20 (95% CI 1.38-7.44); p<0.01) until age 7 years, but not from age 7 to 18 years. Colonisation was associated with increased levels of blood eosinophils (adjusted geometric mean ratio 1.24 (95% CI 1.06-1.44); p<0.01) and tumour necrosis factor (TNF)-α (adjusted geometric mean ratio 1.09 (95% CI 1.02-1.16); p=0.01) until age 12 years. There were no associations with lung function, bronchial reactivity, fractional exhaled nitric oxide, allergic sensitisation, total IgE or atopic dermatitis up to age 18 years. Neonatal airway colonisation was associated with early-onset persistent wheeze/asthma, exacerbations, elevated blood eosinophils and elevated TNF-α in blood, most prominent in early childhood, thereafter diminishing and no longer evident by age 18 years.