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The varied treatment response to inhaled corticosteroids (ICS) in patients with COPD and the associated increased risk of pneumonia necessitate a personalized ICS therapeutic approach. This is informed by blood eosinophil count (BEC), which predicts ICS treatment response. However, BEC appears to change in response to ICS treatment. Does (1) BEC measured on ICS treatment (2) BEC measured off ICS treatment, or (3) the change in BEC during ICS treatment best predict treatment response to ICS in COPD? The Fluticasone Salmeterol on COPD Exacerbations Trial (FLAME), a 52-week, double-blind randomized controlled trial compared long-acting beta-2 agonists (LABAs)/long-acting muscarinic antagonists (LAMAs) with LABA/ICS. Corticosteroids were prohibited during a 4-week run-in period. We chose patients previously on ICS, thereby allowing BEC before and after the run-in period to represent BEC on and off ICS, respectively. In this post hoc analysis, we revisited outcome data, exploring how the three BEC biomarkers interacted with treatment response to the ICS-containing regimen. Our study showed that LABA/LAMA combination was superior, or at least noninferior, to LABA/ICS in curbing exacerbations for most FLAME participants. However, higher BEC off ICS, higher BEC on ICS, and significant BEC suppression during ICS treatment corresponded to superior response to LABA/ICS in terms of exacerbation rate, time to first exacerbation, and time to first pneumonia. In a subgroup, including 9% of participants, BEC changed significantly during ICS treatment (≥ 200 cells/μL), and higher BEC on ICS did not predict ICS treatment response. For these patients, BEC off ICS and BEC change proved more predictive. Excess pneumonia risk associated with ICS appeared to be confined to patients who do not benefit from this treatment. BEC was not predictive of treatment effects on lung function and health status. This exploratory analysis advocates preferentially using BEC off ICS or BEC change during ICS treatment for guiding ICS treatment decisions. BEC measured on ICS is less predictive of treatment response. ClinicalTrials.gov; No.: NCT01782326 ; URL: www.clinicaltrials.gov [ABSTRACT FROM AUTHOR]

Abstract Background Although blood eosinophil count is recognized as a useful biomarker for the management of chronic obstructive pulmonary disease (COPD), the impact of eosinophils in COPD has not been fully elucidated. Here we aimed to investigate the relationships between the blood eosinophil count and various clinical parameters including lung structural changes. Methods Ninety-three COPD patients without concomitant asthma were prospectively enrolled in this study. Blood eosinophil count, serum IgE level, serum periostin level, and chest computed tomography (CT) scans were evaluated. Eosinophilic COPD was defined as COPD with a blood eosinophil count ≧ 300/µL. We examined the correlation between the blood eosinophil count and structural changes graded by chest CT, focusing specifically on thin airway wall (WT thin) and thick airway wall (WT thick) groups. In a separate cohort, the number of eosinophils in the peripheral lungs of COPD patients with low attenuation area (LAA) on chest CT was assessed using lung resection specimens. Results The mean blood eosinophil count was 212.1/µL, and 18 patients (19.3%) were categorized as having eosinophilic COPD. In the whole group analysis, the blood eosinophil count correlated only with blood white blood cells, blood basophils, C-reactive protein level, and sputum eosinophils. However, the blood eosinophil count positively correlated with the percentage of LAA and negatively correlated with the diffusing capacity for carbon monoxide in the WT thin group. Lung specimen data showed an increased number of eosinophils in the peripheral lungs of COPD patients with LAA on chest CT scans compared to normal controls. Conclusions Some COPD patients without concomitant asthma showed a phenotype of high blood eosinophils. Alveolar damage may be related to eosinophilic inflammation in patients with COPD without asthma and thickening of the central airway wall.

Background: Evidence on how decisions regarding escalation to triple therapy and de- or re-escalation are taken and the rationale on which these decisions are based is currently limited in Germany. Objectives: The TETRIS study aims to elucidate influences on treatment decisions surrounding triple therapy in a real-world practice setting in Germany. Design: TETRIS is an ongoing, multicenter, prospective, observational cohort study recruiting patients with chronic obstructive pulmonary disease (COPD) with or without asthma who have already been treated with triple therapy for 2–48 weeks. Methods: For better representation of the treatment reality in Germany, patients are recruited from general practitioners and pulmonologists. Data are collected in two parts. Part 1 involves cross-sectional phenotyping of patients at enrollment. Part 2 involves a 2-year longitudinal follow-up period to monitor/document all visits by the patients during the 24-month observation period per routine clinical practice. Here, we report the demographic and baseline characteristics of 1213 eligible patients recruited to part 1 of the study. Results: The mean patient age was 66.4 years overall, and 29.3% (356/1213) of patients had no comorbidities. The mean CAT score was 19.4; the number of exacerbations and hospitalizations due to exacerbations in the past 3 years before starting triple therapy was 0.6 and 0.1, respectively. Dual bronchodilation with a long-acting muscarinic antagonist (LAMA) plus a long-acting β-2 agonist (LABA) was the most common therapy for COPD before initiation of triple therapy in 58.3% of patients. Conclusion: In this real-world setting in Germany, patients with COPD have a relatively low reported exacerbation rate but high symptom burden, and over 70% are multimorbid. Triple therapy is initiated in patients who are primarily highly symptomatic despite being on LAMA + LABA. Future prospective studies in patients with multimorbidity are warranted to better understand the treatment landscape across the disease spectrum. Trial registration: https://clinicaltrials.gov/study/NCT04657211 [ABSTRACT FROM AUTHOR]

Background: Although blood eosinophil count is recognized as a useful biomarker for the management of chronic obstructive pulmonary disease (COPD), the impact of eosinophils in COPD has not been fully elucidated. Here we aimed to investigate the relationships between the blood eosinophil count and various clinical parameters including lung structural changes. Methods: Ninety-three COPD patients without concomitant asthma were prospectively enrolled in this study. Blood eosinophil count, serum IgE level, serum periostin level, and chest computed tomography (CT) scans were evaluated. Eosinophilic COPD was defined as COPD with a blood eosinophil count ≧ 300/µL. We examined the correlation between the blood eosinophil count and structural changes graded by chest CT, focusing specifically on thin airway wall (WT thin) and thick airway wall (WT thick) groups. In a separate cohort, the number of eosinophils in the peripheral lungs of COPD patients with low attenuation area (LAA) on chest CT was assessed using lung resection specimens. Results: The mean blood eosinophil count was 212.1/µL, and 18 patients (19.3%) were categorized as having eosinophilic COPD. In the whole group analysis, the blood eosinophil count correlated only with blood white blood cells, blood basophils, C-reactive protein level, and sputum eosinophils. However, the blood eosinophil count positively correlated with the percentage of LAA and negatively correlated with the diffusing capacity for carbon monoxide in the WT thin group. Lung specimen data showed an increased number of eosinophils in the peripheral lungs of COPD patients with LAA on chest CT scans compared to normal controls. Conclusions: Some COPD patients without concomitant asthma showed a phenotype of high blood eosinophils. Alveolar damage may be related to eosinophilic inflammation in patients with COPD without asthma and thickening of the central airway wall. [ABSTRACT FROM AUTHOR]

Purpose: Bronchiectasis is predominantly marked by neutrophilic inflammation. The relevance of type 2 biomarkers in disease severity and exacerbation risk is poorly understood. This study explores the clinical significance of these biomarkers in bronchiectasis patients. Methods: In a cross-sectional cohort study, bronchiectasis patients, excluding those with asthma or allergic bronchopulmonary aspergillosis, underwent clinical and radiological evaluations. Bronchoalveolar lavage samples were analyzed for cytokines and microbiology. Blood eosinophil count (BEC), serum total immunoglobulin E (IgE), and fractional exhaled nitric oxide (FeNO) were measured during stable disease states. Positive type 2 biomarkers were defined by established thresholds for BEC, total IgE, and FeNO. Results: Among 130 patients, 15.3% demonstrated BEC ≥ 300 cells/μL, 26.1% showed elevated FeNO ≥ 25 ppb, and 36.9% had high serum total IgE ≥ 75 kU/L. Approximately 60% had at least one positive type 2 biomarker. The impact on clinical characteristics and disease severity was variable, highlighting BEC and FeNO as reflective of different facets of disease severity and exacerbation risk. The combination of low BEC with high FeNO appeared to indicate a lower risk of exacerbation. However, Pseudomonas aeruginosa colonization and a high neutrophil-to-lymphocyte ratio (NLR ≥ 3.0) were identified as more significant predictors of exacerbation frequency, independent of type 2 biomarker presence. Conclusions: Our study underscores the distinct roles of type 2 biomarkers, highlighting BEC and FeNO, in bronchiectasis for assessing disease severity and predicting exacerbation risk. It advocates for a multi-biomarker strategy, incorporating these with microbiological and clinical assessments, for comprehensive patient management. [ABSTRACT FROM AUTHOR]

Introduction: Chronic Obstructive Pulmonary Disorder (COPD) was estimated to be the sixth leading cause of death in 2019, and second most common cause of non-communicable disease-related deaths in India. Systemic or inhaled corticosteroid use must be assessed against any known toxicities risk to determine potential benefits. Thus, there should be a system to streamline the utilization of corticosteroids in COPD patients. Objective: To highlight the potential of clinical markers in promoting steroid stewardship. Additionally this study also emphasizes the need to identify more clinical markers that could determine steroid efficacy and help in tailoring the therapy for patients with COPD. Methodology: Two independent researchers conducted a systematic review to recognize the markers affecting COPD therapy. A literature search was conducted using a thorough search strategy, including search terms “COPD,” “corticosteroids,” “biomarkers,” and related MeSH terms to recruit all relevant literature between 2007 and 2023. In total, 919 PubMed, Embase, and Scopus articles were screened, and 16 were finalized. Results: After thoroughly screening articles, two biomarkers were identified from the review. The majority (n = 13) stated that blood eosinophil count (BEC) could impact steroid therapy in COPD patients, further strengthened by the latest Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. Fractional Exhaled Nitric Oxide (FeNO) is another component captured from (n = 3) studies presenting its benefit in directing corticosteroid therapy in COPD patients. Conclusion: This study showed that with an understanding of patient history, using BEC and FENO to determine steroid therapy in COPD could benefit. Although more studies are required, it is believed these markers can individualize steroid therapy, leading to better patient care and shaping the core of the steroid stewardship program.

Background and Objectives This retrospective study, conducted at a single tertiary medical center, aimed to investigate the correlation between the severity of allergic rhinitis (AR) based on subjective symptoms and the severity assessed through laboratory data. Methods In total, 584 patients who were diagnosed with AR by a multiple-allergen simultaneous test were included. Patients were classified into four groups according to the Allergic Rhinitis and its Impact on Asthma (ARIA) classification guideline. The visual analog scale (VAS) score for overall discomfort and laboratory parameters, including the serum total immunoglobulin E (IgE) level and peripheral blood eosinophil count, were evaluated in all patients. An analysis was conducted to examine the differences in VAS scores and laboratory findings among the four groups. Additionally, the correlations between the laboratory findings and VAS score were analyzed. Results The serum total IgE level and the percentage and count of peripheral blood eosinophils showed no significant differences among the groups. However, the VAS score for overall discomfort exhibited notable between-group differences. The average VAS score was 6.14 (95% confidence interval 5.94–6.34) in the overall group. The mean scores of each group showed a noticeable increasing trend from the mild intermittent group to the mild persistent, moderate to severe intermittent, and moderate to severe persistent groups (p

Abstract Background The concept of eosinophilic bronchiectasis has received clinical attention recently, but the association between blood eosinophil count (BEC) and hospital characteristics has rarely been reported yet. We aim to investigate the clinical impact of BEC on patients with acute bronchiectasis exacerbation. Methods A total of 1332 adult patients diagnosed with acute exacerbation of bronchiectasis from January 2012 to December 2020 were included in this retrospective study. A propensity-matched analysis was performed by matching age, sex and comorbidities in patients with high eosinophil count (≥ 300 cell/µL) and low eosinophil count (

Genetic relationships between blood eosinophil count (BEC), asthma susceptibility, and severity are unclear. We sought to identify the genetic difference between type 2 (T2) and nontype 2 (non-T2) asthma (defined by BEC) and investigate genetic relationships between high BEC, asthma susceptibility, and severity. Genome-wide association studies (GWASs) were performed for T2 (n = 9,064; BEC ≥ 300 cells/μL) versus non-T2 asthma (n = 14,379; BEC < 150 cells/μL) and asthma susceptibility (37,227 asthmatics vs. 124,132 nonasthma controls) in the UK Biobank and asthma severity (moderate-to-severe asthma [n = 2,153] vs. mild asthma [n = 5165]) in the All of Us Research Program (AoURP). Genetic causality between BEC, asthma susceptibility, and severity were dissected using Mendelian randomization (MR). High BEC was associated with asthma and decreased pulmonary function. GWASs revealed four sets of genetic variants (p < 5 × 10−8): genes associated with only BEC or asthma and genes associated with high BEC and asthma in the same or opposite direction. The C allele of rs653178 in ATXN2 was associated with high BEC, risk for autoimmune diseases, and protection for asthma. Genetic variants associated with BEC or asthma were not associated with asthma severity. MR indicated high BEC and asthma were in bidirectional causal relationship (p <.001); however, they were not causal for asthma severity. Genetic variants associated with asthma or BEC and asthma severity are distinctive. High BEC is a risk factor for asthma; however, it is neither necessary nor sufficient for asthma susceptibility and severity. [ABSTRACT FROM AUTHOR]

Forest Day de Larrañaga,1,2 Alexandre Joubert,3 Isabelle Drouin,3 Isabelle Ouellet,3 Pei Zhi Li,1 Bryan A Ross,1– 3 Carolyn J Baglole,1,2 Jean Bourbeau1– 3 1Research Institute of McGill University Health Centre, Montreal, Quebec, Canada; 2Department of Medicine, Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada; 3COPD Clinic, McGill University Health Centre, Montreal, Quebec, CanadaCorrespondence: Jean Bourbeau, Respiratory Epidemiology and Clinical Research Unit, Research Institute of the McGill University Health Centre, 5252 De Maisonneuve, room 3D.62, Montreal, QC, H4A 3S5, Canada, Email jean.bourbeau@mcgill.caIntroduction: We describe the use of anti-IL-5 monoclonal antibodies from a COPD clinic, a source other than traditional clinical trials. The objectives were to characterize the patient subgroup prescribed anti-IL-5 monoclonal antibodies and to report potential benefits.Methods: This is a retrospective case series study of 17 patients treated in a COPD subspecialty clinic. All patients had a diagnosis of COPD (post-bronchodilator FEV1/FVC < 0.7) and had been prescribed an anti-IL-5 biologic for at least 8 months. Acute exacerbations of COPD (AECOPDs) were collected as reported in electronic medical records.Results: All patients (17) enrolled were treated with biologics for ≥ 8 months, and 13 (76%) for ≥ 1 year. Patients were characterized by severe disease traits, FEV1 < 50% predicted, recurrent exacerbations (3.5 moderate-to-severe AECOPDs in the year before treatment), high peripheral blood eosinophil counts (≥ 250 cells/μL in the previous year), all on inhaled triple therapy, and only 1 patient with a diagnosis of asthma prior to smoking. There was a statistically significant decrease in the exacerbation rate compared with baseline after 8 and 12 months of anti-IL-5 treatment, respectively, yielding the equivalent of a 2– 3x reduction in exacerbation rate. Absolute FEV1 decreased, and the decline in FEV1 % of predicted reached statistical significance (p< 0.05); CAT score improved (p< 0.05).Discussion: This real-world evidence data aligns with existing studies suggesting the potential benefit of anti-IL-5 treatment for specific patients with COPD and therefore advocates for further investigation of RCTs on the use of anti-IL-5 biologics for well-characterized patients with COPD.Keywords: COPD, biologics, anti-IL5 therapy, blood eosinophil count, RWE, RWD

Objective: Accurate biomarkers for evaluating mortality rates in patients with chronic obstructive pulmonary disease (COPD) remain scarce. This study aimed to explore the relationships between mortality rates in patients with COPD and blood eosinophil counts, neutrophil counts, and lymphocyte counts, along with the neutrophil--to--lymphocyte ratio (NLR). Additionally, we sought to identify the optimal response values for these biomarkers when utilizing inhaled corticosteroids (ICS). Methods: Utilizing a nationally representative, multistage cross--sectional design and mortality correlation study, we analyzed data from the National Health and Nutrition Examination Survey (NHANES) 1999--2018 involving US adults aged 40 years or older with COPD. The primary endpoint was all--cause mortality, with Kaplan--Meier survival curves and restricted cubic splines applied to illustrate the relationship between leukocyte--based inflammatory markers and mortality. The analysis was conducted in 2023. Results: Our analysis included 1,715 COPD participants, representing 6,976,232 non--institutionalized US residents [weighted mean age (SE), 62.09 (0.28) years; range, 40--85 years]. Among the participants, men constituted 50.8% of the population, and the weighted mean follow--up duration was 84.9 months. In the ICS use group, the weighted proportion of participants over 70 years old was significantly higher compared with the non--ICS use group (31.39% vs 25.52%, p < 0.0001). The adjusted hazard ratios for all--cause mortality related to neutrophil counts, lymphocyte counts, and NLR were 1.10 [95% confidence interval (CI), 1.04--1.16, p < 0.001], 0.83 (95% CI, 0.71--0.98; p = 0.03), and 1.10 (95% CI, 1.05-- 1.15; p < 0.0001), respectively. Optimal ICS response was linked with higher levels of eosinophil count (≥240 cells/mL), neutrophil count (≥3,800 cells/mL), NLR (≥4.79), and lower levels of lymphocyte count (<2,400 cells/mL). Conclusion: Adjusted baseline neutrophil, lymphocyte counts, and NLR serve as independent risk factors for all--cause mortality in patients with COPD. Further, ICS application appears to mitigate mortality risk, particularly when NLR levels reach 4.79 or higher, underlining the importance of ICS in COPD management. [ABSTRACT FROM AUTHOR]

Background: Fraction of exhaled nitric oxide (FeNO) is used for diagnosing and monitoring asthma in children, but the influence of allergic sensitization is still poorly understood. Here, we investigate how asthma and allergic sensitization influence FeNO levels during childhood. Methods: We investigated the associations between asthma, aeroallergen sensitization, and FeNO measured from age 5–18 years in the COPSAC2000 birth cohort of 411 children using repeated measurement mixed models adjusted for gestational age, sex, concurrent airway infection, inhaled corticosteroids, and tobacco exposure. Replication was sought in the similarly designed COPSAC2010 cohort of 700 children. Results: In the COPSAC2000 cohort, 133 had asthma between age 5 and 18 years, and in the COPSAC2010 cohort, 112 had asthma between age 5 and 10 years. In the COPSAC2000 cohort, asthma and aeroallergen sensitization were both associated with higher FeNO from age 5 to 18 years: adjusted geometric mean ratio (aGMR), 1.22 (1.08–1.35), p <.01, and 1.41 (1.21–1.65), p < 0.001, respectively. However, asthma was associated with increased FeNO among children with aeroallergen sensitization: 1.44 (1.23–1.69), p <.0001, whereas asthma was associated with decreased FeNO among nonsensitized children: 0.80 (0.65–0.99), p =.05 (p‐interaction<.0001 for asthma x sensitization). Replication in the COPSAC2010 cohort showed similar results (p‐interaction <.01). Further, blood eosinophil count, total‐IgE, bronchodilator response, and bronchial hyperreactivity were all associated with increased FeNO among children sensitized to aeroallergens, but not among nonsensitized children. Conclusion: Fraction of exhaled nitric oxide is elevated through childhood in children with asthma and is correlated with asthma‐associated traits depending on the presence of aeroallergen sensitization. These findings indicate that FeNO is only a valid asthma biomarker in children with concurrent aeroallergen sensitization, which is important for guideline recommendations on the clinical use of FeNO. [ABSTRACT FROM AUTHOR]

Objective: Recently, a type 2 inflammation (T2) high endotype in bronchiectasis was identified. The fraction of exhaled nitric oxide (FeNO) and blood eosinophil count (BEC) are recognized as representative biomarkers of T2 inflammation. Herein, we investigate the clinical characteristics of T2-high endotype in non-cystic fibrosis bronchiectasis patients classified by FeNO and BEC. Methods: This retrospective study included 164 bronchiectasis patients treated in the First Affiliated Hospital of Sun Yat- sen University from December 2017 to July 2022. Clinical characteristics were analyzed after classifying patients into four groups according to T2 inflammation biomarkers (FeNO >25 ppb; BEC >200/p.L). Results: Among the 164 bronchiectasis patients, 35.3% (58/164) presented with high FeNO, 30.5% (50/164) presented with high BEC, and 10.4% (17/164) had high FeNO and BEC. Patients with high FeNO and low BEC presented with better lung function, fewer affected lobes, and lower dyspnea prevalence compared with the three other groups. Moreover, decreased FeNO, instead of decreased BEC, is revealed to be an independent predictor for disease severity and airflow obstruction in bronchiectasis. Conclusions: Simultaneous evaluation of FeNO and BEC proposed different endotypes of bronchiectasis established that patients with low BEC and high FeNO had better lung function, fewer affected lobes, lower dyspnea prevalence, and less disease severity. This result will contribute to a more comprehensive assessment of the disease severity and lead to more precise treatment of T2 inflammation in bronchiectasis patients. [ABSTRACT FROM AUTHOR]

Gianenrico Senna,1,2 Maria Aliani,3 Elena Altieri,4 Pietro Bracciale,5 Luisa Brussino,6 Maria Filomena Caiaffa,7 Paolo Cameli,8 Giorgio Walter Canonica,9,10 Cristiano Caruso,11 Maria D’Amato,12 Fausto De Michele,13 Stefano Del Giacco,14 Fabiano Di Marco,15 Francesco Menzella,16 Girolamo Pelaia,17 Paola Rogliani,18,19 Micaela Romagnoli,20 Pietro Schino,21 Jan Walter Schroeder,22 Alessandra Vultaggio,23 Sara Rizzoli,24 Alessandro Zullo,24 Silvia Boarino,25 Marilena Palmisano,26 Alessandra Rossi,26 Gianfranco Vitiello,26 Stefano Centanni27 1Department of Medicine, University of Verona, Verona, Italy; 2Allergy Unit and Asthma Center, Verona University Hospital, Verona, Italy; 3UO Pneumologia e Pneumologia Riabilitativa, ICS Maugeri, IRCCS Bari, Bari, Italy; 4Reparto di Pneumologia, P.O., Garbagnate Milanese, Italy; 5Reparto di Pneumologia, Ospedale Ostuni, Ostuni, BR, Italy; 6Dipartimento di Scienze Mediche, SSDDU Allergologia e Immunologia Clinica, Università degli Studi di Torino, AO Ordine Mauriziano Umberto I, Torino, Italy; 7Cattedra e Scuola di Allergologia e Immunologia Clinica, Dipartimento di Scienze Mediche, Università di Foggia, Foggia, Italy; 8Respiratory Diseases and Lung Transplantation, Department of Medical and Surgical Sciences & Neurosciences, Siena University Hospital, Siena, Italy; 9Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, MI, Italy; 10Personalized Medicine Center: Asthma and Allergology, Humanitas Research Hospital, Rozzano, MI, Italy; 11Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico A. Gemelli, IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy; 12UOSD Malattie Respiratorie “Federico II”, Ospedale Monaldi, AO Dei Colli, Napoli, Italy; 13UOC Pneumologia e Fisiopatologia Respiratoria, AORN A. Cardarelli, Napoli, Italy; 14Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy; 15Department of Health Sciences, Università Degli Studi Di Milano, Pneumologia, ASST Papa Giovanni XXIII, Bergamo, Italy; 16UOC Pneumologia, Ospedale “S. Valentino”, AULSS 2 Marca Trevigiana, Montebelluna, TV, Italy; 17Dipartimento di Scienze della Salute, Università Magna Graecia, Catanzaro, Italy; 18Division of Respiratory Medicine, University Hospital “Tor Vergata”, Roma, Italy; 19Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome “Tor Vergata”, Roma, Italy; 20UOC Pneumologia, ULSS 2 Marca Trevigiana, Treviso, Italy; 21Fisiopatologia Respiratoria, Ospedale Generale Regionale, Ente Ecclesiastico “F. Miulli”, Acquaviva delle Fonti, BA, Italy; 22Allergy and Clinical Immunology, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy; 23Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, Firenze, Italy; 24Medineos Observational Research - An IQVIA Company, Modena, Italy; 25Medical Evidence R&I, AstraZeneca, Milano, Italy; 26Medical Affairs R&I, AstraZeneca, Milano, Italy; 27Respiratory Unit, ASST Santi Paolo e Carlo, Department of Health Sciences, Università degli Studi di Milano, Milano, ItalyCorrespondence: Marilena Palmisano, Medical Affairs R&I, AstraZeneca, Milano, Italy, Email marilena.palmisano@astrazeneca.comPurpose: Benralizumab effectively reduces severe eosinophilic asthma (SEA) exacerbations in patients with a wide range of baseline blood eosinophil count (BEC). Patients included in real-world studies are often characterized by high mean/median BEC, while patients with BEC close to 300 cells/mm3 are poorly represented. This post hoc analysis from the Italian study ANANKE aims to define the clinical features and corroborate the efficacy of benralizumab in real world in the BEC 300– 450 cells/mm3 subset of patients.Patients and Methods: Post hoc analysis of the Italian, multicenter, observational, retrospective real-life study ANANKE (NCT04272463). Baseline clinical and laboratory characteristics were collected in the 12 months prior to benralizumab treatment and presented for a BEC 300– 450 cells/mm3 subgroup of patients. Change over time of BEC, annualized exacerbation rate (AER), asthma control (ACT), lung function and oral corticosteroid (OCS) use at 16, 24 and 48 weeks after benralizumab introduction were collected.Results: A total of 164 patients were analyzed, 34 of whom with a BEC of 300– 450 cells/mm3. This subgroup was more likely to be female (64.7%), with lower rates of severe exacerbations at baseline when compared to the total population (0.69 vs 1.01). After 48 weeks of benralizumab treatment, the BEC 300– 450 subset showed similar reductions in AER (− 94.8% vs − 92.2%) and OCS use (median dose reduction of 100% in both groups), as well as improvement in ACT score (median scores 22.5 vs 22) and lung function (pre-BD FEV1: +200 mL vs +300 mL) when compared to the total population. No discontinuations for safety reasons were registered.Conclusion: At baseline, apart from lower severe exacerbation rate, the BEC 300– 450 cells/mm3 subset of patients is comparable to the total population prescribed with benralizumab. In this real-life study, benralizumab is as effective in BEC 300– 450 patients as in the total population.Keywords: severe eosinophilic asthma, blood eosinophil count, benralizumab, observational, real-world evidence, real-life

Chronic obstructive pulmonary disease (COPD) is a common chronic airway inflammatory disease. With its heterogeneity in clinical manifestations, treatment responses and prognosis, biomarkers that can predict treatment benefits and risk stratification of deterioration are very important. In recent years, many studies have reported that eosinophils are highly involved in the development of airway inflammation in COPD. The baseline blood eosinophil count(EOS) is related to the therapeutic effect of inhaled corticosteroids(ICS) and the risk of acute exacerbation in patients. The level of EOS may be affected by many factors such as geography, race, etc. In domestic clinical work, the actual reference data of EOS may not be consistent with the recommended reference threshold value in GOLD. Since there is no uniform and accurate epidemiological data on EOS in COPD patients in China, this review focuses on the research progress and controversy in the areas of EOS and COPD airway inflammation, development as biomarkers, and the role of guiding the clinical application of ICS, to discuss the setting of the critical value of EOS of Chinese COPD patients. [ABSTRACT FROM AUTHOR]

Abstract Background Data on changes in lung function in eosinophilic chronic obstructive pulmonary disease (COPD) are limited. We investigated the longitudinal changes in forced expiratory volume in 1 s (FEV1) and effects of inhaled corticosteroid (ICS) in Korean COPD patients. Methods Stable COPD patients in the Korean COPD subgroup study (KOCOSS) cohort, aged 40 years or older, were included and classified as eosinophilic and non-eosinophilic COPD based on blood counts of eosinophils (greater or lesser than 300 cells/μL). FEV1 changes were analyzed over a 3-year follow-up period. Results Of 627 patients who underwent spirometry at least twice during the follow up, 150 and 477 patients were classified as eosinophilic and non-eosinophilic, respectively. ICS-containing inhalers were prescribed to 40% of the patients in each group. Exacerbations were more frequent in the eosinophilic group (adjusted odds ratio: 1.49; 95% confidence interval: 1.10–2.03). An accelerated FEV1 decline was observed in the non-eosinophilic group (adjusted annual rate of FEV1 change: − 12.2 mL/y and − 19.4 mL/y for eosinophilic and non-eosinophilic groups, respectively). In eosinophilic COPD, the adjusted rate of annual FEV1 decline was not significant regardless of ICS therapy, but the decline rate was greater in ICS users (− 19.2 mL/y and − 4.5 mL/y, with and without ICS therapy, respectively). Conclusions The annual rate of decline in FEV1 was favorable in eosinophilic COPD compared to non-eosinophilic COPD, and ICS therapy had no beneficial effects on changes in FEV1.

Objective: Recently, a type 2 inflammation (T2) high endotype in bronchiectasis was identified. The fraction of exhaled nitric oxide (FeNO) and blood eosinophil count (BEC) are recognized as representative biomarkers of T2 inflammation. Herein, we investigate the clinical characteristics of T2-high endotype in non-cystic fibrosis bronchiectasis patients classified by FeNO and BEC. Methods: This retrospective study included 164 bronchiectasis patients treated in the First Affiliated Hospital of Sun Yatsen University from December 2017 to July 2022. Clinical characteristics were analyzed after classifying patients into four groups according to T2 inflammation biomarkers (FeNO ≥25 ppb; BEC ≥200/µL). Results: Among the 164 bronchiectasis patients, 35.3% (58/164) presented with high FeNO, 30.5% (50/164) presented with high BEC, and 10.4% (17/164) had high FeNO and BEC. Patients with high FeNO and low BEC presented with better lung function, fewer affected lobes, and lower dyspnea prevalence compared with the three other groups. Moreover, decreased FeNO, instead of decreased BEC, is revealed to be an independent predictor for disease severity and airflow obstruction in bronchiectasis. Conclusions: Simultaneous evaluation of FeNO and BEC proposed different endotypes of bronchiectasis established that patients with low BEC and high FeNO had better lung function, fewer affected lobes, lower dyspnea prevalence, and less disease severity. This result will contribute to a more comprehensive assessment of the disease severity and lead to more precise treatment of T2 inflammation in bronchiectasis patients. [ABSTRACT FROM AUTHOR]

Purpose: Benralizumab effectively reduces severe eosinophilic asthma (SEA) exacerbations in patients with a wide range of baseline blood eosinophil count (BEC). Patients included in real-world studies are often characterized by high mean/median BEC, while patients with BEC close to 300 cells/mm3 are poorly represented. This post hoc analysis from the Italian study ANANKE aims to define the clinical features and corroborate the efficacy of benralizumab in real world in the BEC 300– 450 cells/mm3 subset of patients. Patients and Methods: Post hoc analysis of the Italian, multicenter, observational, retrospective real-life study ANANKE (NCT04272463). Baseline clinical and laboratory characteristics were collected in the 12 months prior to benralizumab treatment and presented for a BEC 300– 450 cells/mm3 subgroup of patients. Change over time of BEC, annualized exacerbation rate (AER), asthma control (ACT), lung function and oral corticosteroid (OCS) use at 16, 24 and 48 weeks after benralizumab introduction were collected. Results: A total of 164 patients were analyzed, 34 of whom with a BEC of 300– 450 cells/mm3. This subgroup was more likely to be female (64.7%), with lower rates of severe exacerbations at baseline when compared to the total population (0.69 vs 1.01). After 48 weeks of benralizumab treatment, the BEC 300– 450 subset showed similar reductions in AER (− 94.8% vs − 92.2%) and OCS use (median dose reduction of 100% in both groups), as well as improvement in ACT score (median scores 22.5 vs 22) and lung function (pre-BD FEV1: +200 mL vs +300 mL) when compared to the total population. No discontinuations for safety reasons were registered. Conclusion: At baseline, apart from lower severe exacerbation rate, the BEC 300– 450 cells/mm3 subset of patients is comparable to the total population prescribed with benralizumab. In this real-life study, benralizumab is as effective in BEC 300– 450 patients as in the total population. [ABSTRACT FROM AUTHOR]

Introduction: The ACO Registry Study was a multicenter, prospective, observational cohort study aiming to clarify the situation of asthma–chronic obstructive pulmonary disease (COPD) overlap (ACO) within the COPD population using the Japanese Respiratory Society (JRS) criteria. We reported the proportion of patients who met the ACO criteria among the COPD population at study registration. Methods: Using data collected at registration, we investigated the implementation of each diagnostic examination/test required for ACO diagnosis in the full analysis set. Among patients with data necessary for ACO diagnosis, ACO/non-ACO patients with/without asthma diagnosed by a physician and proportions of inhaled corticosteroid (ICS) treatments for COPD were calculated. Results: Of 708 patients analyzed, 396 (55.9%) had the data necessary for ACO diagnosis, and 312 (44.1%) did not. The proportions of patients who underwent laboratory and respiratory function tests (peripheral blood eosinophil count [79.8%], fractional exhaled nitric oxide [63.7%], airway reversibility [46.8%], and total immunoglobulin [Ig] E/specific IgE [33.3%]) were lower than those who underwent subjective examinations (perennial allergic rhinitis [100%], asthma before age 40 years [97.2%], and variable/paroxysmal respiratory symptoms [94.5%]). Among patients with the data necessary for ACO diagnosis and without asthma complications according to the physician's diagnosis, 15.1% (33/219) met the ACO criteria. Of patients who met the ACO criteria, 74.3% (75/101) received ICS, and 25.7% (26/101) did not. By comparison, among patients who did not meet the ACO criteria, 35.6% (105/295) were receiving ICS, and 64.4% (190/295) were not. Conclusions: The proportion of objective laboratory and physiological tests was lower than expected, despite study sites having the clinical resources for objective tests. Most ACO patients were being treated with ICS as recommended in the JRS treatment guidelines. Attempts should be made to further increase the proper use of ICS among these patients in Japan. Trial Registration: ClinicalTrials.gov, NCT03577795. [ABSTRACT FROM AUTHOR]

Abstract Background Tests to identify reversible airflow limitation are important in asthma diagnosis, but they are time-consuming and it may be difficult for patients to cooperate. We aimed to evaluate whether the combination of fractional exhaled nitric oxide (FeNO) and blood eosinophil (B-Eos) can be used to distinguish some asthma patients who could avoid objective tests. Methods We conducted a retrospective cohort study on 7463 suspected asthma cases between January 2014 and December 2019 in Chongqing, China, and identified 2349 patients with complete FeNO, B-Eos count, and spirometry data. Asthma was diagnosed by clinicians by the criteria of recurrent respiratory symptoms and a positive bronchial-provocation or bronchodilation test (BPT, BPD). We evaluated the diagnostic accuracy of FeNO or B-Eos alone or both in combination for asthma using receiver operating characteristic (ROC) curve analysis. Results In this study, 824 patients were diagnosed with asthma. When FeNO and B-Eos counts were used in combination, the area under the ROC curve (AUC) for diagnosing asthma increased slightly (0.768 vs. 0.745 [FeNO] or 0.728 [B-Eos]; both P 40 ppb and B-Eos > 300 cells/μl) support a diagnosis of asthma because diagnostic specificity was > 95% and the positive likelihood ratio (PLR) was > 10. This conclusion was verified when selecting the 2017–2019 data as the internal validation dataset. Conclusion FeNO or B-Eos count alone is insufficient to accurately diagnose asthma. Patients with moderately elevated biomarkers (FeNO > 40 ppb and B-Eos > 300 cells/μl) could be diagnosed with asthma and avoid objective tests when such tests are not feasible.

Mei Yang,&ast; Ting Yang,&ast; Xiaoou Li,&ast; Diandian Li, Zenglin Liao, Yongchun Shen, Dan Xu, Lei Chen, Fuqiang Wen Department of Respiratory and Critical Care Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Chen; Fuqiang WenDepartment of Respiratory and Critical Care Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of ChinaEmail lchens@126.com; wenfuqiang@scu.edu.cnPurpose: Elevated blood eosinophils have been implicated in chronic obstructive pulmonary disease (COPD) progression and exacerbation. We aim to investigate clinical predictors of high blood eosinophils in a Chinese COPD cohort.Patients and Methods: We conducted a retrospective cohort study in Sichuan province, a Southwest province with high prevalence of COPD in China. All patients in this cohort were extracted from the Chinese Pulmonary Health study, a large cross-sectional study on COPD epidemiology in China. Demographics, personal and family history, living condition, spirometry and blood eosinophil counts were obtained. Univariate and multiple linear regression analyses were performed to determine predictors of high blood eosinophils.Results: A total of 375 COPD patients were included in this cohort. The median absolute blood eosinophil count was 138.8 cells/μL, and the prevalence of COPD with high blood eosinophils was 66.7% and 14.7% when using the thresholds of 100 cells/μL and 300 cells/μL, respectively. Univariate analyses indicated that male gender, lower body mass index, high-density lipoprotein (HDL), lower family income, raising pets and biomass use were significantly associated with high blood eosinophils (p < 0.05). Multiple linear regression model further revealed male gender (unstandardized coefficient (B)=66.125, 95% confidence intervals (CI) 16.350 to 115.900, p=0.009), age (B=2.819, 95% CI 0.639 to 5.000, p=0.012) predicted high blood eosinophil level, whereas HDL (B=− 64.682, 95% CI − 123.451 to − 5.914, p=0.031) was a negative predictor for high blood eosinophils.Conclusion: This retrospective cohort study suggests male gender, oldness and lower HDL could be clinical predictors of high blood eosinophils in Chinese COPD patients.Keywords: chronic obstructive pulmonary disease, blood eosinophil count, high-density lipoprotein, predictor, retrospective study

Background: Eosinophilic cationic protein (ECP) is associated with airway inflammation and asthma. However, the clinical value of measuring ECP in childhood asthma is not fully known. We aimed to study the diagnostic performance of serum ECP and other common asthma biomarkers, individually and in combinations. Methods: In a cross-sectional study, 5–16-year-old children with current asthma (CA) (n = 37), transient asthma (TA) (n = 43), (previous history of wheezing/asthma), and healthy children (HC) (n = 86) were investigated for ECP, blood eosinophil count (B-Eos), fractional exhaled nitric oxide (FeNO), and lung function, i.e., spirometry (forced expiratory volume during the first second [FEV1]/forced vital capacity [FVC] ratio). Results: Both ECP and B-Eos were higher in CA compared to TA (p < 0.01) and HC (p < 0.0001). ECP and B-Eos were also higher in TA compared to HC (p < 0.05 and p < 0.001, respectively). FeNO was higher in CA (p < 0.0001) and TA (p < 0.01) compared to HC but similar between the asthma groups. The FEV1/FVC ratio was lower in CA compared to TA and HC (both p < 0.01) but similar between TA and HC. The best diagnostic performance regarding CA was found for ECP and B-Eos with receiver operating characteristics area under curve (AUC) of 0.801 and 0.810, respectively. The optimal cutoff for ECP (29 μg/L) yielded a sensitivity and specificity of 70.3% and 81.4%. The corresponding AUCs for FeNO and FEV1/FVC were 0.732 and 0.670, respectively. ECP and B-Eos showed the highest AUCs (0.669 and 0.673) for differentiation between CA and TA. Combining ECP with FeNO and FEV1/FVC increased the odds ratio (OR) for having CA from OR 3.97–10.3 for the single biomarkers to OR 20.2 (95% confidence interval: 5.76–68.6). Conclusion: Our results show that serum ECP is a reliable biomarker in the diagnosis of childhood asthma, with additional value in combination with FeNO and FEV1/FVC, and that ECP can be an alternative to B-Eos. [ABSTRACT FROM AUTHOR]

Abstract Objective Asthma is one of the most common diseases amongst children. Blood eosinophil count and neutrophil–lymphocyte ratio (NLR) are known as markers for phenotyping asthma. This study was performed to investigate blood eosinophil count and NLR as predictors of hospitalization in pediatric asthma exacerbations. Data sources and study selections In this cross-sectional study, children admitted to hospital ward for more severe asthma exacerbation were compared with non-hospitalized children with moderate to severe asthma exacerbation whose asthma exacerbation was managed in emergency department or outpatient clinic. We investigated patients’ characteristic and factors associated with hospitalization. Results A total of 211 children with moderate to severe asthma exacerbation (mean age $$5.76 \pm 3.28$$ 5.76 ± 3.28 years old) were enrolled in the study including 91 hospitalized patients and 120 non-hospitalized patients. For the prediction of hospitalization, an ROC Curve analysis was performed and revealed a cut-off of 298 cells/µL and 2.52 of blood eosinophil count and NLR, respectively. In multivariate analysis, not using an asthma action plan (OR 2.22, 95% CI 1.09–4.49; P = 0.027), a blood eosinophil count $$\ge$$ ≥ 298 (OR 8.79, 95% CI 4.44–17.4; P

Background: Combining a fraction of exhaled nitric oxide (FeNO) and blood eosinophil count (B-EOS) may be a useful strategy for administration of biologics such as anti-IgE or anti-IL-5 to patients with type 2 inflammatory-predominant severe asthma and is important to be elucidated considering the increasing use of biologics. Methods: This cross-sectional study analyzed the clinical data from 114 adult patients with severe asthma, who were treated at Saitama Medical University Hospital. The eligible patients were stratified into four subgroups defined by thresholds of FeNO and blood eosinophil (B-EOS) counts to detect sputum eosinophilia, using the receiver operating characteristic curve analysis. A total of 75 patients with optimal samples were stratified into four subtypes defined by thresholds of sputum eosinophilia and neutrophilia. Clinical characteristics, pattern of biologics, and distribution of sputum subtypes were analyzed in the stratified subclasses according to the FeNO and B-EOS thresholds. The asthma exacerbation (AE)-free time of the FeNO/B-EOS subgroups and any biologics treatment including anti-IgE or anti-IL-5 use were examined using the Kaplan–Meier method. The hazard ratios (HRs) for AE-free time were examined using the Cox proportional hazard model. Results: The optimal cutoff values for prediction of sputum eosinophilia were defined as ≥2.7% wherein for FeNO as ≥27 ppb and B-EOS as ≥265/µL were considered. The high-FeNO subgroups showed significant high total IgE, compared with the low FeNO. The high-FeNO/high-B-EOS and the high-FeNO/low-B-EOS subgroups showed the largest prevalence of mepolizumab and benralizumab use among the other FeNO/B-EOS, respectively. The high-FeNO/low-B-EOS showed the largest frequency of AEs, high HR, and the shortest AE-free time, among the other FeNO/B-EOS. The sputum eosinophil-predominant subtype was the great majority in the high FeNO/high B-EOS. A diverse distribution of sputum leukocyte-predominant subtype was observed in the other FeNO/B-EOS. The subsequent AE-free time and its HR were comparable among the biologics use groups. Conclusion: The strategy of classifying severe asthma based on the combination of FeNO and B-EOS proposes particular refractory type 2 severe asthma and underlying airway inflammation as a feasible trait for optimal biologics use. [ABSTRACT FROM AUTHOR]

Background: Data on changes in lung function in eosinophilic chronic obstructive pulmonary disease (COPD) are limited. We investigated the longitudinal changes in forced expiratory volume in 1 s (FEV1) and effects of inhaled corticosteroid (ICS) in Korean COPD patients.Methods: Stable COPD patients in the Korean COPD subgroup study (KOCOSS) cohort, aged 40 years or older, were included and classified as eosinophilic and non-eosinophilic COPD based on blood counts of eosinophils (greater or lesser than 300 cells/μL). FEV1 changes were analyzed over a 3-year follow-up period.Results: Of 627 patients who underwent spirometry at least twice during the follow up, 150 and 477 patients were classified as eosinophilic and non-eosinophilic, respectively. ICS-containing inhalers were prescribed to 40% of the patients in each group. Exacerbations were more frequent in the eosinophilic group (adjusted odds ratio: 1.49; 95% confidence interval: 1.10-2.03). An accelerated FEV1 decline was observed in the non-eosinophilic group (adjusted annual rate of FEV1 change: - 12.2 mL/y and - 19.4 mL/y for eosinophilic and non-eosinophilic groups, respectively). In eosinophilic COPD, the adjusted rate of annual FEV1 decline was not significant regardless of ICS therapy, but the decline rate was greater in ICS users (- 19.2 mL/y and - 4.5 mL/y, with and without ICS therapy, respectively).Conclusions: The annual rate of decline in FEV1 was favorable in eosinophilic COPD compared to non-eosinophilic COPD, and ICS therapy had no beneficial effects on changes in FEV1. [ABSTRACT FROM AUTHOR]

Thus, using SEC, a very high proportion of patients with severe asthma of up to 76.8% would have severe eosinophilic asthma, which is higher than in other severe asthma cohorts7-9 of Caucasian populations. Keywords: blood eosinophil count; cigarette smoking; exacerbations; fractional exhaled nitric oxide; severe asthma EN blood eosinophil count cigarette smoking exacerbations fractional exhaled nitric oxide severe asthma 1 7 7 03/03/22 20220201 NES 220201 Dear Editor, In China, asthma affects 45.7 million adults with a prevalence of 4.2%,1 while that of severe asthma ranges from 3.4% to 8.3% among asthmatic patients.2-4 There is scarce information on the characteristics and biomarker expression, and the different phenotypes of severe asthma. Therefore, severe asthma patients have more symptoms, more exacerbations, more airflow obstruction, and more nasal polyps even if they are on high-dose asthma medication regimens, including oral corticosteroids. [Extracted from the article]

Background: Combining a fraction of exhaled nitric oxide (FeNO) and blood eosinophil count (B-EOS) may be a useful strategy for administration of biologics such as anti-IgE or anti-IL-5 to patients with type 2 inflammatory-predominant severe asthma and is important to be elucidated considering the increasing use of biologics.Methods: This cross-sectional study analyzed the clinical data from 114 adult patients with severe asthma, who were treated at Saitama Medical University Hospital. The eligible patients were stratified into four subgroups defined by thresholds of FeNO and blood eosinophil (B-EOS) counts to detect sputum eosinophilia, using the receiver operating characteristic curve analysis. A total of 75 patients with optimal samples were stratified into four subtypes defined by thresholds of sputum eosinophilia and neutrophilia. Clinical characteristics, pattern of biologics, and distribution of sputum subtypes were analyzed in the stratified subclasses according to the FeNO and B-EOS thresholds. The asthma exacerbation (AE)-free time of the FeNO/B-EOS subgroups and any biologics treatment including anti-IgE or anti-IL-5 use were examined using the Kaplan–Meier method. The hazard ratios (HRs) for AE-free time were examined using the Cox proportional hazard model.Results: The optimal cutoff values for prediction of sputum eosinophilia were defined as ≥2.7% wherein for FeNO as ≥27 ppb and B-EOS as ≥265/µL were considered. The high-FeNO subgroups showed significant high total IgE, compared with the low FeNO. The high-FeNO/high-B-EOS and the high-FeNO/low-B-EOS subgroups showed the largest prevalence of mepolizumab and benralizumab use among the other FeNO/B-EOS, respectively. The high-FeNO/low-B-EOS showed the largest frequency of AEs, high HR, and the shortest AE-free time, among the other FeNO/B-EOS. The sputum eosinophil-predominant subtype was the great majority in the high FeNO/high B-EOS. A diverse distribution of sputum leukocyte-predominant subtype was observed in the other FeNO/B-EOS. The subsequent AE-free time and its HR were comparable among the biologics use groups.Conclusion: The strategy of classifying severe asthma based on the combination of FeNO and B-EOS proposes particular refractory type 2 severe asthma and underlying airway inflammation as a feasible trait for optimal biologics use.

Background: Tests to identify reversible airflow limitation are important in asthma diagnosis, but they are time-consuming and it may be difficult for patients to cooperate. We aimed to evaluate whether the combination of fractional exhaled nitric oxide (FeNO) and blood eosinophil (B-Eos) can be used to distinguish some asthma patients who could avoid objective tests.Methods: We conducted a retrospective cohort study on 7463 suspected asthma cases between January 2014 and December 2019 in Chongqing, China, and identified 2349 patients with complete FeNO, B-Eos count, and spirometry data. Asthma was diagnosed by clinicians by the criteria of recurrent respiratory symptoms and a positive bronchial-provocation or bronchodilation test (BPT, BPD). We evaluated the diagnostic accuracy of FeNO or B-Eos alone or both in combination for asthma using receiver operating characteristic (ROC) curve analysis.Results: In this study, 824 patients were diagnosed with asthma. When FeNO and B-Eos counts were used in combination, the area under the ROC curve (AUC) for diagnosing asthma increased slightly (0.768 vs. 0.745 [FeNO] or 0.728 [B-Eos]; both P < 0.001). The odds ratio for having asthma increased progressively with a gradual increase in FeNO or B-Eos count (both P < 0.001; assessed using the Cochran-Armitage trend test). Further analysis of in-series combinations of different threshold values for these biomarkers indicated that moderately elevated biomarker levels (FeNO > 40 ppb and B-Eos > 300 cells/μl) support a diagnosis of asthma because diagnostic specificity was > 95% and the positive likelihood ratio (PLR) was > 10. This conclusion was verified when selecting the 2017-2019 data as the internal validation dataset.Conclusion: FeNO or B-Eos count alone is insufficient to accurately diagnose asthma. Patients with moderately elevated biomarkers (FeNO > 40 ppb and B-Eos > 300 cells/μl) could be diagnosed with asthma and avoid objective tests when such tests are not feasible. [ABSTRACT FROM AUTHOR]

Objective: Asthma is one of the most common diseases amongst children. Blood eosinophil count and neutrophil–lymphocyte ratio (NLR) are known as markers for phenotyping asthma. This study was performed to investigate blood eosinophil count and NLR as predictors of hospitalization in pediatric asthma exacerbations. Data sources and study selections: In this cross-sectional study, children admitted to hospital ward for more severe asthma exacerbation were compared with non-hospitalized children with moderate to severe asthma exacerbation whose asthma exacerbation was managed in emergency department or outpatient clinic. We investigated patients' characteristic and factors associated with hospitalization. Results: A total of 211 children with moderate to severe asthma exacerbation (mean age 5.76 ± 3.28 years old) were enrolled in the study including 91 hospitalized patients and 120 non-hospitalized patients. For the prediction of hospitalization, an ROC Curve analysis was performed and revealed a cut-off of 298 cells/µL and 2.52 of blood eosinophil count and NLR, respectively. In multivariate analysis, not using an asthma action plan (OR 2.22, 95% CI 1.09–4.49; P = 0.027), a blood eosinophil count ≥ 298 (OR 8.79, 95% CI 4.44–17.4; P < 0.001) and an NLR ≥ 2.52 (OR 2.13, 95% CI 1.09–4.14; P = 0.027) were associated with hospitalization. Conclusion: Blood eosinophil count and NLR were found to be higher in hospitalized children with more severe asthma exacerbation compared to non-hospitalized patients. These markers can be indicators for asthma exacerbation severity. [ABSTRACT FROM AUTHOR]

Background: High blood eosinophil count (BEC) is a useful biomarker for guiding inhaled corticosteroid therapy in patients with chronic obstructive pulmonary disease (COPD), yet its implications in a community setting remain underexplored. This study aimed to elucidate the clinical characteristics and outcomes of COPD patients with high BEC within the Chinese community., Methods: We obtained baseline and 2-year follow-up data from COPD patients (post-bronchodilator forced expiratory volume in 1 second/forced vital capacity <0.70) in the early COPD study. Patients with a BEC ≥300cells/μL were classified as the high BEC group. We assessed differences in the clinical characteristics and outcomes between high and low BEC patients. Subgroup analyses were conducted on COPD patients without a history of corticosteroid use or asthma., Results: Of the 897 COPD patients, 205 (22.9%) had high BEC. At baseline, high BEC patients exhibited a higher proportion of chronic respiratory symptoms, lower lung function, and more severe small airway dysfunction than low BEC patients. Over the 2-year period, high BEC patients experienced a significantly higher risk of acute exacerbations (relative risk: 1.28, 95% confidence interval: 1.09-1.49; P=0.002), even after adjusting for confounders. No significant difference was observed in lung function decline rates. The subgroup analysis yielded consistent results., Conclusions: COPD patients with high BEC in a Chinese community exhibited poorer health status, more severe small airway dysfunction, and a higher risk of exacerbations. Future research should explore the pathological mechanisms underlying the poorer prognosis in patients with high BEC., (Copyright © 2024 The Authors. Published by Elsevier España, S.L.U. All rights reserved.)

Neil Barnes,1,2 Takeo Ishii,3,4 Nobuyuki Hizawa,5 Dawn Midwinter,6 Mark James,3 Emma Hilton,1 Paul Jones1,71Respiratory Medicine Franchise, GlaxoSmithKline, Brentford, UK; 2William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, London, UK; 3Medical Affairs, GlaxoSmithKline K.K., Tokyo, Japan; 4Graduate School of Medicine, Nippon Medical School, Tokyo, Japan; 5Department of Pulmonary Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan; 6Global Respiratory Department, GlaxoSmithKline, Stockley Park, UK; 7Institute of Infection and Immunity, St George’s University of London, London, UK Background: Blood eosinophil measurements may help to guide physicians on the use of inhaled corticosteroids (ICS) for patients with chronic obstructive pulmonary disease (COPD). Emerging data suggest that COPD patients with higher blood eosinophil counts may be at higher risk of exacerbations and more likely to benefit from combined ICS/long-acting beta2-agonist (LABA) treatment than therapy with a LABA alone. This analysis describes the distribution of blood eosinophil count at baseline in Japanese COPD patients in comparison with non-Japanese COPD patients.Methods: A post hoc analysis of eosinophil distribution by percentage and absolute cell count was performed across 12 Phase II–IV COPD clinical studies (seven Japanese studies [N=848 available absolute eosinophil counts] and five global studies [N=5,397 available eosinophil counts] that included 246 Japanese patients resident in Japan with available counts). Blood eosinophil distributions were assessed at baseline, before blinded treatment assignment.Findings: Among Japanese patients, the median (interquartile range) absolute eosinophil count was 170 cells/mm3 (100–280 cells/mm3). Overall, 612/1,094 Japanese patients (56%) had an absolute eosinophil count ≥150 cells/mm3 and 902/1,304 Japanese patients (69%) had a percentage eosinophil ≥2%. Among non-Japanese patients, these values were 160 (100–250) cells/mm3, 2,842/5,151 patients (55%), and 2,937/5,155 patients (57%), respectively. The eosinophil distribution among Japanese patients was similar to that among non-Japanese patients. Within multi-country studies with similar inclusion criteria, the eosinophil count was numerically lower in Japanese compared with non-Japanese patients (median 120 vs 160 cells/mm3).Interpretation: The eosinophil distribution in Japanese patients seems comparable to that of non-Japanese patients; although within multi-country studies, there was a slightly lower median eosinophil count for Japanese patients compared with non-Japanese patients. These findings suggest that blood eosinophil data from global studies are of relevance in Japan.Keywords: COPD, blood eosinophil count, percentage blood eosinophil, Japan

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common heterogenous disease in the patients with chronic airway diseases. This study investigated the role of blood eosinophil count (BEC) in the classification of CRSwNP and its recurrence in eosinophilic CRSwNP. Methods: Sixty‐five patients who underwent nasal endoscopic resection of CRSwNP were recruited and divided into eosinophilic CRSwNP and non‐eosinophilic CRSwNP groups based on the levels (10% cutoff) of eosinophil infiltration as indicated by hematoxylin and eosin (H&E) staining. Results: We recruited 30 patients in the eosinophilic CRSwNP group and 35 patients in the non‐eosinophilic CRSwNP group. The outcome of preoperative visual analogue scale (VAS) score, preoperative Lund‐Mackay score, and preoperative Lund‐Kennedy score between the 2 groups were comparable. The level of BEC in the eosinophilic CRSwNP group was significantly higher than that of non‐eosinophilic CRSwNP group (0.79 ± 0.27 × 109/L vs 0.30 ± 0.22 × 109/L; p < 0.001). We observed a statistical significance in the number of H&E eosinophils (29.11 ± 2.93 vs 3.17 ± 0.51; p < 0.001) and CRSwNP phenotypes (eosinophilic/non‐eosinophilic, 28/3 vs 2/32; p < 0.001) when the cutoff value of BEC was set at 0.39 × 109/L. The disease‐free recurrence (DFR) was found to be statistically significant when the cutoff value of BEC was 0.73 × 109/L in eosinophilic CRSwNP (p = 0.009). Conclusion: Results indicate that BEC may be capable of distinguishing CRSwNP phenotypes as well as predicting polyp recurrence in eosinophilic CRSwNP. Given the relatively small sample size, further studies will be necessary to confirm a role for BEC as a systemic biomarker in CRSwNP. [ABSTRACT FROM AUTHOR]

Objective: To evaluate usability of mepolizumab as a liquid drug product self-administered via a single-use prefilled autoinjector (AI) by patients with severe eosinophilic asthma (SEA), or their caregivers, in-clinic and at home. Methods: This open-label, single-arm, Phase IIIa study (NCT03099096; GSK ID: 204959) included patients aged ≥12 years with SEA who were either receiving mepolizumab (100 mg subcutaneously [SC]) every 4 weeks (Q4W) for ≥12 weeks before screening or not receiving mepolizumab but met criteria indicative of SEA. Patients/caregivers self-administered mepolizumab (100 mg SC) via an AI Q4W for 12 weeks. The first (Week 0) and third (Week 8) doses were observed in-clinic; the second dose (Week 4) was administered unobserved at home. Primary and secondary endpoints were the proportion of patients who successfully self-administered their third and second doses, respectively (determined by investigator/site staff). Patient experience, mepolizumab trough concentrations, blood eosinophil count (BEC), and safety were also assessed. Results: Of 159 patients/caregivers who self-administered ≥1 dose of mepolizumab, 157 completed the study. Nearly all patients successfully self-administered their third mepolizumab dose in-clinic and second dose at home (≥98% and ≥96%, respectively); this was further confirmed by mepolizumab trough concentrations/BEC. At study end, ≥88% of patients were "very" or "extremely" confident about using the AI correctly. Incidence of on-treatment drug-related adverse events (AEs) was low (3%); no fatal AEs occurred. Conclusions: Patients/caregivers successfully self-administered mepolizumab via the AI both in-clinic and at home; no new safety concerns were identified. [ABSTRACT FROM AUTHOR]

Objective: A liquid mepolizumab formulation in a single-use prefilled syringe (PFS) is under development. We evaluated the usability of mepolizumab self-injected via PFS by patients with severe eosinophilic asthma (SEA), or their caregivers, in clinic and at home. Methods: This open-label, single-arm, Phase IIIa study included patients with SEA, aged ≥12 years, and receiving mepolizumab (100 mg subcutaneously) every 4 weeks for ≥12 weeks prior to screening. Patients with SEA not receiving mepolizumab at screening who met additional criteria were also included. Patients/caregivers self-administered mepolizumab (100 mg subcutaneously) via PFS every 4 weeks for 12 weeks. The first (Week 0) and third (Week 8) dose were observed in clinic; the second dose (Week 4) was unobserved at home. Primary and secondary endpoints were the proportion of patients who successfully self-administered their third and second doses, respectively. Injection success was determined by investigator/site staff. Patient experience, mepolizumab trough concentrations, blood eosinophil counts, and safety were also assessed. Results: Of the 56 patients/caregivers who self-administered ≥1 dose of mepolizumab, 55 completed the study. All patients were reported to have successfully self-administered their third mepolizumab dose in clinic (N = 55, 100%); this was further evidenced by trough concentrations/blood eosinophil counts. Most patients/caregivers found the PFS easy and convenient to use with 75% (n = 42) expressing little/no anxiety about using the device at home. Incidence of on-treatment drug-related adverse events was low (4%); none were fatal. Conclusions: Patients/caregivers successfully self-administered mepolizumab via the PFS both in clinic and at home, with no new safety concerns identified. [ABSTRACT FROM AUTHOR]

Objective: Human brucellosis is a systemic disease that mimics many diseases, and its diagnosis is extremely difficult in children. Childhood brucellosis may present with serious clinical pictures and cause complications. This study aimed to investigate the characteristics of childhood brucellosis and the diagnostic role of laboratory markers for hospitalization. Material and Methods: Sixty children aged between 0 and 18 years who were diagnosed with brucellosis between January 1, 2018 and December 31, 2019 were evaluated retrospectively. The demographic characteristics and clinical, microbiological, and other laboratory findings of brucellosis patients who were followed up as outpatient and inpatient were examined. Results: The median age of the patients was 9.3±4.3 years; 41.7% were girls and 58.3% were boys. Joint involvement was 83.3% of the patients. Total 33.3% patients were hospitalized. The median value of blood serum eosinophil counts was 60/µL (10-90/µL) in hospitalized patients and 110/µL (55-205/µL) in outpatients (p=0.022). For blood eosinophil count cutoff level ≤ 90/µL (confidence interval [Cl] 95%, 54.4-93.9), sensitivity was 78.95% (Cl 95%, 54.4-93.9) and specificity was 60%, (Cl 95%, 43.3-75.1). Conclusion: Childhood brucellosis remains an important public health problem for our country. Blood eosinophil levels may have a role in indicating the degree of disease and deciding hospitalization in childhood brucellosis. New studies with more patients are needed to understand this relationship better and to evaluate its specificity and sensitivity. [ABSTRACT FROM AUTHOR]

Background and Objectives: This retrospective study, conducted at a single tertiary medical center, aimed to investigate the correlation between the severity of allergic rhinitis (AR) based on subjective symptoms and the severity assessed through laboratory data., Methods: In total, 584 patients who were diagnosed with AR by a multiple-allergen simultaneous test were included. Patients were classified into four groups according to the Allergic Rhinitis and its Impact on Asthma (ARIA) classification guideline. The visual analog scale (VAS) score for overall discomfort and laboratory parameters, including the serum total immunoglobulin E (IgE) level and peripheral blood eosinophil count, were evaluated in all patients. An analysis was conducted to examine the differences in VAS scores and laboratory findings among the four groups. Additionally, the correlations between the laboratory findings and VAS score were analyzed., Results: The serum total IgE level and the percentage and count of peripheral blood eosinophils showed no significant differences among the groups. However, the VAS score for overall discomfort exhibited notable between-group differences. The average VAS score was 6.14 (95% confidence interval 5.94-6.34) in the overall group. The mean scores of each group showed a noticeable increasing trend from the mild intermittent group to the mild persistent, moderate to severe intermittent, and moderate to severe persistent groups (p<0.001), although there was no clear correlation between the increase in VAS scores and laboratory parameters., Conclusion: Neither the symptom-based ARIA guideline nor the VAS score correlated with the AR laboratory test measurements. The current laboratory data alone may not be sufficient to reflect the severity of AR based on subjective symptoms., Competing Interests: Conflicts of Interest The authors have no potential conflicts of interest to disclose., (Copyright © 2024 by The Korean Rhinologic Society.)

Treating patients hospitalised with acute exacerbations of chronic obstructive pulmonary disease (COPD) usually involves administering systemic corticosteroids. The many unwanted side effects associated with this treatment have led to increased interest in minimising the accumulated corticosteroid dose necessary to treat exacerbations. Studies have shown that short-term treatment with corticosteroids is preferred, and recent trials have shown that biomarkers can be used to further reduce exposure to corticosteroids. Interestingly, high eosinophil counts in patients with acute exacerbations of COPD are indicative of an eosinophilic phenotype with a distinct response to treatment with corticosteroids. In addition, post-hoc analysis of randomised control trials have shown that higher blood eosinophil counts at the start of the study predict a greater response to inhaled corticosteroids in stable COPD. In this review, we examine the studies on this topic, describe how blood eosinophil cell count may be used as a biomarker to guide treatment with corticosteroids, and identify some relevant challenges.

Objective: Accurate biomarkers for evaluating mortality rates in patients with chronic obstructive pulmonary disease (COPD) remain scarce. This study aimed to explore the relationships between mortality rates in patients with COPD and blood eosinophil counts, neutrophil counts, and lymphocyte counts, along with the neutrophil-to-lymphocyte ratio (NLR). Additionally, we sought to identify the optimal response values for these biomarkers when utilizing inhaled corticosteroids (ICS)., Methods: Utilizing a nationally representative, multistage cross-sectional design and mortality correlation study, we analyzed data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 involving US adults aged 40 years or older with COPD. The primary endpoint was all-cause mortality, with Kaplan-Meier survival curves and restricted cubic splines applied to illustrate the relationship between leukocyte-based inflammatory markers and mortality. The analysis was conducted in 2023., Results: Our analysis included 1,715 COPD participants, representing 6,976,232 non-institutionalized US residents [weighted mean age (SE), 62.09 (0.28) years; range, 40-85 years]. Among the participants, men constituted 50.8% of the population, and the weighted mean follow-up duration was 84.9 months. In the ICS use group, the weighted proportion of participants over 70 years old was significantly higher compared with the non-ICS use group (31.39% vs 25.52%, p < 0.0001). The adjusted hazard ratios for all-cause mortality related to neutrophil counts, lymphocyte counts, and NLR were 1.10 [95% confidence interval (CI), 1.04-1.16, p < 0.001], 0.83 (95% CI, 0.71-0.98; p = 0.03), and 1.10 (95% CI, 1.05-1.15; p < 0.0001), respectively. Optimal ICS response was linked with higher levels of eosinophil count (≥240 cells/μL), neutrophil count (≥3,800 cells/μL), NLR (≥4.79), and lower levels of lymphocyte count (<2,400 cells/μL)., Conclusion: Adjusted baseline neutrophil, lymphocyte counts, and NLR serve as independent risk factors for all-cause mortality in patients with COPD. Further, ICS application appears to mitigate mortality risk, particularly when NLR levels reach 4.79 or higher, underlining the importance of ICS in COPD management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hu, Wang, Jian, Zhao and Liu.)

Introduction:  Differentiating between bacterial and viral gastroenteritis is crucial in pediatric enteritis practice. Our objective was to use machine learning (ML) to identify acute gastroenteritis (AG) caused by bacteria based on blood cell counts and interview findings., Methods:  ML was performed using a decision tree classifier based on data from previously published papers. We included 164 children between one and 108 months diagnosed with gastroenteritis, with 112 having bacterial AG and 52 having viral AG as subjects and controls. Feature selection was performed using least absolute shrinkage and selection operator (LASSO), and the classifier's performance was evaluated by five-fold cross-validation. Additionally, we presented a tree diagram of the decision tree classifier as a flowchart for practical applications., Results:  The area under curve (AUC) was 0.80, indicating a moderate model. Three important features in this model were platelet-lymphocyte ratio, eosinophil count, and leukocyte count., Conclusions:  In conclusion, this study demonstrates that bacterial AG can be estimated from blood cell counts with moderate accuracy. These findings may be valuable in narrowing down bacterial AG in children with gastrointestinal symptoms., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Miyagi et al.)

Background: The stability and variability of blood eosinophil counts (BECs) to phenotype patients with severe asthma is not fully understood., Objective: This post hoc, longitudinal, pooled analysis of placebo-arm patients from 2 phase 3 studies evaluated the clinical implications of BEC stability and variability in moderate-to-severe asthma., Methods: This analysis included patients from SIROCCO and CALIMA who received maintenance medium- to high-dosage inhaled corticosteroids plus long-acting β 2 -agonists; 2:1 patients with BECs of 300 cells/μL or higher and less than 300 cells/μL were enrolled. The BECs were measured 6 times over 1 year in a centralized laboratory. Exacerbations, lung function, and Asthma Control Questionnaire 6 scores were documented across patients grouped by BEC (<300 cells/μL or ≥300 cells/μL) and variability (<80% or ≥80% BECs less than or greater than 300 cells/μL)., Results: Among 718 patients, 42.2% (n = 303) had predominantly high, 30.9% (n = 222) had predominantly low, and 26.9% (n = 193) had variable BECs. Prospective exacerbation rates (mean ± SD) were significantly greater in patients with predominantly high (1.39 ± 2.20) and variable (1.41 ± 2.09) BECs versus predominantly low (1.05 ± 1.66) BECs. Similar results were observed for the number of exacerbations while on placebo., Conclusions: Although patients with variable BECs had intermittently high and low BECs, they experienced similar exacerbation rates to the predominantly high group, which were greater than those in the predominantly low group. A high BEC supports an eosinophilic phenotype in clinical settings without additional measurements, whereas a low BEC requires repeated measurements because it could reflect intermittently high or predominantly low BECs., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background The fractional exhaled nitric oxide ( FENO) and the blood eosinophil count (B-eos) are markers of eosinophilic inflammation used in the diagnosis and management of asthma. The relationships between smoking cigarette and both FENO and B-eos are complex and raise questions about the association between these markers and asthma in smokers. Objective To determine the relationships between both FENO and B-eos on one hand and asthma and atopy on the other, according to smoking status. Methods FENO and B-eos were measured in, respectively, 1579 and 1496 of the 1607 middle-aged adults randomly selected from the general population in the cross-sectional ELISABET survey. Allergic asthma was defined as asthma (a self-report of physician-diagnosed asthma, and wheezing in the previous 12 months or the use of asthma medications) with atopy (allergic rhinitis or hayfever in the previous 12 months, or a previous positive prick test or allergen desensitization therapy). Non-allergic asthma was defined as asthma without atopy. Results The analysis included 812 (51.4%) never, 473 (30%) former and 294 (18.6%) current smokers. A total of 490 (32%) participants were atopic, 80 (5.1%) had allergic asthma, and 31 (2%) had non-allergic asthma. Only 16.2% (18/111) of asthmatics were treated with glucocorticoid inhalants, suggesting that among them a majority of participants had mild asthma. A positive interaction between smoking status and allergic asthma was observed in multivariate models explaining FENO ( P = 0.003) and B-eos ( P = 0.001). Thus, compared to those without allergic asthma, participants with allergic asthma had higher FENO values (+ 63.4%, 95% CI = [39; 92]) and higher B-eos (+ 63.2% [38.2; 92.7]) in never and former smokers, but not in current smokers. Lastly, an analysis of receiver-operating characteristic curves showed that each of the two markers was able to discriminate moderately allergic asthma but only in non-smokers. Conclusions & Clinical Relevance FENO and B-eos were associated with the presence of mild allergic asthma only in non-smokers, not in current smokers. These findings raise questions about the clinical value of FENO and B-eos in smokers. [ABSTRACT FROM AUTHOR]