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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 $$\ge$$ ≥ 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.

RATIONALE: Blood eosinophil count predicts response to inhaled corticosteroids and specific biologic therapies in selected asthma patients. Despite this important role, fundamental aspects of eosinophil behavior in asthma have not been studied. Objectives To investigate the behavior of blood eosinophils in a population comparing their distribution with the general population and studying their intra-individual variability over time in relation to hospital episodes (emergency department visits and hospitalizations) in clinical practice.METHODS: The distribution and variability of 35,703 eosinophil determinations in 10,059 stable asthma patients were investigated in the Majorca Real-Life Investigation in COPD and Asthma cohort (MAJORICA). Eosinophil distribution in the asthma population was compared with a control sample from the general population of 8,557 individuals. Eosinophil variability and hospital episodes were analyzed using correlations, ROC curves and multiple regression analysis. We defined the Eosinophil Variability Index (EVI) as (Eosmax-Eosmin/Eosmax) x 100%. The findings of the asthma population were re-tested in an external well-characterized asthma cohort.RESULTS: The eosinophil count values and variability were higher in the asthma population than in the general population (p-valueCONCLUSION: The eosinophil variability in asthma patients better identifies the risk of any hospital episode than the absolute counting values currently used to target specific treatments.

BackgroundGreater precision in asthma exacerbation risk prediction may improve outcomes. We sought to identify clinical characteristics and biomarkers associated with elevated exacerbation risk in patients with severe, uncontrolled asthma.MethodsData were pooled from seven similarly designed phase II and III randomised controlled clinical trials of biologic therapies for the treatment of severe, uncontrolled asthma that enrolled comparable patient populations. Annualised asthma exacerbation rates (AAERs) for patients randomised to placebo were assessed by baseline clinical characteristics, and by biomarker concentrations at baseline and over the study duration.ResultsThe AAER for the 2016 patients in the combined placebo group was 0.91 (95% CI 0.84‒0.98). Baseline characteristics associated with greater AAER were frequent or severe exacerbations within the prior 12 months, nasal polyposis, maintenance oral corticosteroid use, Asian race and Asian or Western European region. AAER increased with baseline blood eosinophil counts and exhaled nitric oxide fraction (FENO) concentration, with the greatest AAER occurring for patients with eosinophils ≥300 cells·μL−1 and FENO ≥50 ppb. No relationship was observed between baseline serum IgE concentration and AAER. Combining type 2 inflammation criteria for eosinophils and FENO had greater prognostic value than either biomarker alone. Persistent eosinophil and FENO elevations throughout the study period were associated with greater AAER.ConclusionsExacerbation history, maintenance corticosteroid use, nasal polyposis, Asian race, geographic region, and elevations in blood eosinophil counts and FENO concentrations (particularly when combined and/or persistently achieving type 2 inflammation criteria) were associated with increased exacerbation risk in patients with severe, uncontrolled asthma.

Randomised controlled trials (RCTs) are the gold standard for evaluating treatment efficacy in patients with obstructive lung disease. However, due to strict inclusion criteria and the conditions required for ascertaining statistical significance, the patients included typically represent as little as 5% of the general obstructive lung disease population. Thus, studies in broader patient populations are becoming increasingly important. These can be randomised effectiveness trials or observational studies providing data on real-world treatment effectiveness and safety data that complement efficacy RCTs. In this review we describe the features associated with the diagnosis of asthma and chronic obstructive pulmonary disease (COPD) in the real-world clinical practice setting. We also discuss how RCTs and observational studies have reported opposing outcomes with several treatments and inhaler devices due to differences in study design and the variations in patients recruited by different study types. Whilst observational studies are not without weaknesses, we outline recently developed tools for defining markers of quality of observational studies. We also examine how observational studies are capable of providing valuable insights into disease mechanisms and management and how they are a vital component of research into obstructive lung disease. As we move into an era of personalised medicine, recent observational studies, such as the NOVEL observational longiTudinal studY (NOVELTY), have the capacity to provide a greater understanding of the value of a personalised healthcare approach in patients in clinical practice by focussing on standardised outcome measures of patient-reported outcomes, physician assessments, airway physiology, and blood and airway biomarkers across both primary and specialist care., Observational studies can support RCTs in influencing clinical practice in the field of obstructive lung disease https://bit.ly/36YWu0W

Inhaled corticosteroids (ICS) combined with bronchodilators can reduce the frequency of exacerbations in some patients with chronic obstructive pulmonary disease (COPD). There is evidence, however, that ICS are frequently used in patients where their benefit has not been established. Therefore, there is a need for a personalised approach to the use of ICS in COPD and to consider withdrawal of ICS in patients without a clear indication. This document reports European Respiratory Society recommendations regarding ICS withdrawal in patients with COPD.Comprehensive evidence synthesis was performed to summarise all available evidence relevant to the question: should ICS be withdrawn in patients with COPD? The evidence was appraised using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and the results were summarised in evidence profiles. The evidence synthesis was discussed and recommendations formulated by a committee with expertise in COPD and guideline methodology.After considering the balance of desirable and undesirable consequences, quality of evidence, and feasibility and acceptability of interventions, the guideline panel made: 1) conditional recommendation for the withdrawal of ICS in patients with COPD without a history of frequent exacerbations, 2) strong recommendation not to withdraw ICS in patients with blood eosinophil counts ≥300 eosinophils·µL−1 and 3) strong recommendation to treat with one or two long-acting bronchodilators if ICS are withdrawn.A conditional recommendation indicates that there was uncertainty about the balance of desirable and undesirable consequences of the intervention, and that well-informed patients may make different choices regarding whether to have or not have the specific intervention.

In asthmatic adults, monoclonals directed against Type 2 airway inflammation have led to major improvements in quality of life, reductions in asthma attacks and less need for oral corticosteroids. The paediatric evidence base has lagged behind. All monoclonals currently available for children are anti-eosinophilic, directed against the T helper (TH2) pathway. However, in children and in low and middle income settings, eosinophils may have important beneficial immunological actions. Furthermore, there is evidence that paediatric severe asthma may not be TH2 driven, phenotypes may be less stable than in adults, and adult biomarkers may be less useful. Children being evaluated for biologicals should undergo a protocolised assessment, because most paediatric asthma can be controlled with low dose inhaled corticosteroid if taken properly and regularly. For those with severe therapy resistant asthma, and refractory asthma which cannot be addressed, the two options if they have TH2 inflammation are omalizumab and mepolizumab. There is good evidence of efficacy for omalizumab, particularly in those with multiple asthma attacks, but only paediatric safety, not efficacy, data for mepolizumab. There is an urgent need for efficacy data in children, as well as data on biomarkers to guide therapy, if the right children are to be treated with these powerful new therapies.

Chronic obstructive pulmonary disease (COPD) describes a predominantly smoking-induced small airway and/or emphysematous disease associated with airflow limitation. Considered progressive, irreversible, and responsible for substantial morbidity and mortality worldwide, COPD remains the subject of vigorous study, and advances made during 2016 are already reflected in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 guidelines (1). Researchers continue to explore strategies, pharmacological or otherwise, to improve the lives of those who have developed this condition; and it is hoped, by improving phenotyping of this heterogeneous disease, that we might ultimately deliver personalized medicine. Debate remains over how to identify undiagnosed COPD in individuals who would benefit from intervention, while avoiding overdiagnosis, and these controversies perhaps highlight shortcomings in accepted disease definitions. Not unrelatedly, renewed interest has emerged in explaining why some individuals develop COPD and identifying the formative stages of COPD development.

Introduction XC8 (histamine glutarimide) is a novel agent which targets eosinophilic migration and mast cell degranulation and has shown anti-asthmatic effects in animal studies. Objective The objective of this placebo-controlled phase 1 study was to assess the safety of oral XC8 and to evaluate its pharmacokinetic and pharmacodynamic properties. Methods 32 healthy volunteers in three dose-escalation treatment groups (10 mg [n = 8], 50 mg [n = 8] and 200 mg [n = 16]) were randomized in a 3:1 ratio to XC8 or placebo respectively. The subjects received a single dose of the drug at Day 1 and then once-daily for 14 days (Days 8–21). Results No severe adverse events occurred. The number of adverse events was similar in the treatment arms compared to placebo and all subjects completed the study as planned. No clinically significant changes occurred in hematologic and biochemical blood tests in subjects receiving XC8. The pharmacokinetic data showed similar dose and time dependent mean plasma XC8 concentrations after single (Day 1) and multiple (Day 21) dosing. The mean maximum concentrations were 114–1993 ng/mL after single and 115–2089 ng/mL after multiple dosing. The mean times to maximum concentration were 0.68–1.01 and 0.67–0.98 h, respectively. There was no evidence for accumulation of XC8 after multiple dosing. Conclusion XC8 was safe and well tolerated. A phase 2 study is being performed to further evaluate the potential role of XC8 in asthma treatment. Trial registration ClinicalTrials.gov, NCT02882217.

Precision medicine is a patient-specific approach that integrates all relevant clinical, genetic and biological information in order to optimise the therapeutic benefit relative to the possibility of side-effects for each individual. Recent clinical trials have shown that higher blood eosinophil counts are associated with a greater efficacy of inhaled corticosteroids (ICSs) in chronic obstructive pulmonary disease (COPD) patients. Blood eosinophil counts are a biomarker with potential to be used in clinical practice, to help target ICS treatment with more precision in COPD patients with a history of exacerbations despite appropriate bronchodilator treatment.The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 pharmacological treatment algorithms, based on the ABCD assessment, can be applied relatively easily to treatment-naive individuals at initial presentation. However, their use is more problematic during follow-up in patients who are already on maintenance treatment. There is a need for a different system to guide COPD pharmacological management during follow-up.Recent large randomised controlled trials have provided important new information concerning the therapeutic effects of ICSs and long-acting bronchodilators on exacerbations. The new evidence regarding blood eosinophils and inhaled treatments, and the need to distinguish between initial and follow-up pharmacological management, led to changes in the GOLD pharmacological treatment recommendations. This article explains the evidence and rationale for the GOLD 2019 pharmacological treatment recommendations.

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.

Zuzana Diamant,1–3 Guy Brusselle,4 Richard E Russell5,6 1Department of Respiratory Medicine and Allergology, Lund University, Lund, Sweden; 2Department of Clinical Pharmacy & Pharmacology University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands; 3QPS-Netherlands, University Medical Centre Groningen, Groningen, the Netherlands; 4Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium; 5Respiratory Medicine Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK; 6Lymington New Forest Hospital, Southern Health National Health Service Foundation Trust, Lymington, Hampshire, UKThe airway diseases asthma and COPD affect millions of individuals worldwide.1 These diseases are major determinants of chronic morbidity and mortality, and represent a substantial public health burden.2–4 Despite differences in etiology, clinical characteristics, and pathophysiology, both conditions share important features, such as airway obstruction and chronic airway inflammation. As a result of modern lifestyle, the incidence of both diseases is steadily increasing worldwide and effective preventive and treatment strategies are unmet needs.5

The efficacy, safety and positioning of inhaled corticosteroids (ICS) in the treatment of patients with chronic obstructive pulmonary disease (COPD) is much debated, since it can result in clear clinical benefits in some patients (“friend”) but can be ineffective or even associated with undesired side effects,e.g.pneumonia, in others (“foe”). After critically reviewing the evidence for and against ICS treatment in patients with COPD, we propose that: 1) ICS should not be used as a single, stand-alone therapy in COPD; 2) patients most likely to benefit from the addition of ICS to long-acting bronchodilators include those with history of multiple or severe exacerbations despite appropriate maintenance bronchodilator use, particularly if blood eosinophils are >300 cells·µL−1, and those with a history of and/or concomitant asthma; and 3) the risk of pneumonia in COPD patients using ICS is higher in those with older age, lower body mass index (BMI), greater overall fragility, receiving higher ICS doses and those with blood eosinophils −1. All these factors must be carefully considered and balanced in any individual COPD patient before adding ICS to her/his maintenance bronchodilator treatment. Further research is needed to clarify some of these issues and firmly establish these recommendations.

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 ≥150cells/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\ud \ud Asthma attacks are common, serious, and costly. Individual factors associated with attacks, such as poor symptom control, are not robust predictors.\ud \ud Objective\ud \ud We investigated whether the rich data available in UK electronic medical records could identify patients at risk of recurrent attacks.\ud \ud Methods\ud \ud We analyzed anonymized, longitudinal medical records of 118,981 patients with actively treated asthma (ages 12-80 years) and 3 or more years of data. Potential risk factors during 1 baseline year were evaluated using univariable (simple) logistic regression for outcomes of 2 or more and 4 or more attacks during the following 2-year period. Predictors with significant univariable association (P < .05) were entered into multiple logistic regression analysis with backward stepwise selection of the model including all significant independent predictors. The predictive accuracy of the multivariable models was assessed.\ud \ud Results\ud \ud Independent predictors associated with future attacks included baseline-year markers of attacks (acute oral corticosteroid courses, emergency visits), more frequent reliever use and health care utilization, worse lung function, current smoking, blood eosinophilia, rhinitis, nasal polyps, eczema, gastroesophageal reflux disease, obesity, older age, and being female. The number of oral corticosteroid courses had the strongest association. The final cross-validated models incorporated 19 and 16 risk factors for 2 or more and 4 or more attacks over 2 years, respectively, with areas under the curve of 0.785 (95% CI, 0.780-0.789) and 0.867 (95% CI, 0.860-0.873), respectively.\ud \ud Conclusions\ud \ud Routinely collected data could be used proactively via automated searches to identify individuals at risk of recurrent asthma attacks. Further research is needed to assess the impact of such knowledge on clinical prognosis.

Introduction: Patients with chronic airway disease may present features of both asthma and COPD, commonly referred to as asthma–COPD overlap syndrome (ACOS). Recommendations on their diagnosis are diffuse and inconsistent. This survey aimed to identify consensus on criteria for diagnosing ACOS. Methods: A Belgian expert panel developed a survey on ACOS diagnosis, which was completed by 87 pulmonologists. Answers chosen by ≥70% of survey respondents were considered as useful criteria for ACOS diagnosis. The two most frequently selected answers were considered as major criteria, others as minor criteria. The expert panel proposed a minimal requirement of two major criteria and one minor criterion for ACOS diagnosis. Respondents were also asked which criteria are important for considering inhaled corticosteroids prescription in a COPD patient. Results: To diagnose ACOS in COPD patients, major criteria were “high degree of variability in airway obstruction over time (change in forced expiratory volume in 1 second ≥400 mL)” and “high degree of response to bronchodilators (>200 mL and ≥12% predicted above baseline)”. Minor criteria were “personal/family history of atopy and/or IgE sensitivity to ≥1 airborne allergen”, “elevated blood/sputum eosinophil levels and/or increased fractional exhaled nitric oxide”, “diagnosis of asthma 40 years”; “emphysema on chest computed tomography scan”. Conclusion: Specific criteria were identified that may guide physicians to a more uniform diagnostic approach for ACOS in COPD or asthma patients. These criteria are largely similar to those used to prescribe inhaled corticosteroids in COPD., SCOPUS: ar.j, info:eu-repo/semantics/published