Validation and further insight into the International Severe Asthma Registry (ISAR) eosinophil gradient algorithm in the Wessex AsThma CoHort of difficult asthma (WATCH) using historical blood eosinophil counts and induced sputum (original) (raw)
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Value of peripheral blood eosinophil markers to predict severity of asthma
BMC pulmonary medicine, 2016
Asthma represents a significant clinical and economic burden to the US healthcare system. Along with other clinical manifestations of the disease, elevated sputum and blood eosinophil levels are observed in patients experiencing asthma exacerbations. The aim of this study was to evaluate the association between blood eosinophil levels and asthma severity defined using Expert Panel Report 3 guidelines. Patients with asthma diagnosis between 2004 and 2011 were extracted from the EMRClaims+ database (eMAX Health, White Plains, NY) containing electronic medical records linked to insurance claims for over 675,000 patients. The date of first asthma diagnosis was defined as the 'index date'. Patients were required to have at least 1 peripheral eosinophil test (elevated defined as ≥ 400 cells/μL) in the 12 month 'assessment' period following the index date. We classified patients as those with mild asthma and moderate-to-severe asthma based on the pattern of medication use, ...
Respiratory medicine, 2018
Identifying asthma patients suitable for biologic therapy includes the assessment of blood biomarkers (IgE and eosinophils (EOS)). How they relate to each other is unclear. This retrospective, database study used routinely collected clinical data to identify and evaluate an asthma cohort (classification code for asthma; ≥ 18 years; ≥1 prescription for asthma; ≥1 estimation of serum IgE, in 2 years prior to index date). Distribution into high and low IgE and EOS groups (IgE cut-point: > or ≤75 kU/L; EOS cut point: >or ≤400 μ/L), and characteristics by group are described. In patients with severe asthma (British Thoracic Society Step (BTS) ≥4; N = 884), using maximum recorded IgE/EOS, 33% had high IgE/high EOS, 28% low IgE/low EOS and approximately a fifth each had high IgE/low EOS or low IgE/high EOS. Proportions were similar when EOS values measured 2 or 4 weeks before an exacerbation were excluded. Using EOS/IgE 'same day' measurements (N = 578) only identified half o...
Comparison between eosinophilic markers in induced sputum and blood in asthmatic patients
Clinical <html_ent glyph="@amp;" ascii="&"/> Experimental Allergy, 1998
Background The usefulness and safety of the analysis of blood inflammatory markers in asthma are widely recognized. Recently, the analysis of induced sputum has been proposed as a safe, non-invasive tool in the study of airway inflammation in asthma. Objective Our aim was to test whether sputum analysis is more useful than blood analysis in the evaluation of airway inflammation in untreated and treated asthmatic patients. Methods Twelve untreated patients with mild to moderate asthma underwent a methacholine challenge test, sputum induction and blood sampling. A group of 14 normal subjects was also evaluated for baseline comparison. The same evaluation was repeated after 3 months of budesonide treatment. Before and after treatment, we tested the relationship of eosinophilic markers in induced sputum and blood with clinical and functional data. We also compared eosinophilic markers in induced sputum with the same markers in blood. Results Untreated patients showed a significant relationship between sputum eosinophils and symptom score, and between sputum eosinophilic cationic protein and symptom score, FEV 1 and PD 20 FEV 1. No relationship between blood eosinophilic markers and clinical or functional data was observed. In budesonide-treated patients, both sputum and blood eosinophils were significantly lower than in untreated patients, but eosinophil decrease was greater in sputum than in blood. Sputum eosinophilic proteins were also significantly lower in treated patients, whereas serum eosinophilic proteins were low at baseline and remained unchanged after treatment. Sputum eosinophilic markers were lower in normal subjects than in both untreated and treated patients, while blood eosinophils, but not serum eosinophilic cationic protein, were lower in normals than in untreated patients. Conclusions The analysis of induced sputum is more useful than the analysis of blood in the evaluation of asthma severity and of the effect of glucocorticoid treatment in patients with mild to moderate asthma.
Clinical & Experimental Allergy, 2014
Background Sputum eosinophil counts and eosinophil cationic protein (ECP) levels are usually increased in asthmatic patients. The correlation between sputum eosinophils or ECP and clinical findings of asthma has been previously investigated but many of these studies have been performed on small samples of asthmatic patients, considering only few clinical indices and often including patients on oral or inhaled corticosteroids, which might be confounding when interpreting the relationship between disease activity and airway inflammation. Objective To assess whether sputum eosinophils and ECP were differently related to functional and clinical parameters of asthma in a large number of steroid-na€ ıve asthmatic patients, taking into account several potential determinants of activity and chronicity of asthma. Methods One hundred and twenty-nine patients with mild-moderate asthma were studied. Sputum was induced by hypertonic saline inhalation and processed using the whole sample method. Results Sputum eosinophils and ECP significantly correlated with each other (r = 0.41, P < 0.001). When patients were grouped on the basis of high/low sputum eosinophils and high/low sputum ECP levels, significant differences were observed among groups, with patients with high sputum eosinophils and ECP showing the greatest asthma severity. In the overall sample, disease duration inversely correlated with sputum eosinophils, whereas FEV 1 and peak expiratory flow (PEF) inversely correlated with sputum ECP. Rescue b 2-agonist use and total symptom score positively correlated with both eosinophil counts and sputum ECP. Stepwise regression analysis showed that symptom score and disease duration accounted for 17.6% of sputum eosinophil variance, whereas symptom score and FEV 1 accounted for 14.7% of sputum ECP variance. Conclusions and Clinical Relevance Both sputum eosinophils and ECP are weakly related to clinical markers of asthma severity. However, ECP was more closely related to lung function parameters than eosinophil counts.
Respiratory Research
The concept of asthma inflammatory phenotypes has proved to be important in predicting response to inhaled corticosteroids. Induced sputum, which has been pivotal in the development of the concept of inflammatory phenotypes, is however not widely available. Several studies have proposed to use surrogate exhaled or blood biomarkers, like fractional exhaled nitric oxide (FENO), blood eosinophils and total serum immunoglobulin E (IgE). However, taken alone, each of these biomarkers has moderate accuracy to identify sputum eosinophilia. Here, we propose a new approach based on the likelihood ratio to study which thresholds of these biomarkers, taken alone or in combination, were able to rule in or rule out sputum eosinophils ≥3%. We showed in a large population of 869 asthmatics that combining FENO, blood eosinophils and total serum IgE could accurately predict sputum eosinophils ≥ or <3% in 58% of our population.
Variability of blood eosinophils in patients in a clinic for severe asthma
Clinical & Experimental Allergy, 2018
Background: Blood eosinophils are used to determine eligibility for agents targeting IL-5 in patients with uncontrolled asthma. However, little is known about the variability of blood eosinophil measures in these patients before treatment initiation. Objective: To characterize variability and patterns of variability of blood eosinophil levels in a real-world clinic for severe asthmatics. Methods: Retrospective review of blood eosinophils measured over a 5-year period in patients enrolled in an urban clinic. Repeated measures of blood eosinophil levels in individuals were evaluated, and cluster analysis was performed to characterize patients by eosinophil patterns. Clinical characteristics associated with eosinophil levels and patterns of variability were analysed. Results: Patients treated in the Bellevue Hospital Asthma Clinic within a 3-month period were identified (n = 219). Blood eosinophil measures were obtained over the previous 5 years. Only 6% (n = 13) of patients had levels that were consistently above 300 cells/μL. Nearly 50% (n = 104) had eosinophil levels that traversed the threshold of 300 cells/μL. In contrast, 102 (46%) had levels that never reached the threshold of 300 cells/μL. Cluster analyses revealed three clusters with differing patterns of levels and variability. There was a suggestion of decreased clinical control and increased atopy in the cluster with the greatest variability in blood eosinophil measures. Conclusion: In an urban clinic for patients referred for uncontrolled asthma, blood measures of eosinophils were variable and showed differing patterns of variability. These data reinforce the need to perform repeated eosinophil blood measures for appropriate designation for therapeutic intervention. 1 | INTRODUCTION Asthma affects over 25 million people in the United States. 1 Severe asthma, including difficult-to-treat asthma, accounts for approximately 4%-10% of the overall adult asthma population and is responsible for significant morbidity and cost. 2-5 The development of new therapeutics and the underlying heterogeneity of asthma make it imperative that we identify patients who will respond to these new agents to promote their appropriate use. 5,6 This identification requires understanding phenotypes and biologic markers that reflect the underlying pathophysiology of asthma. Patients with "eosinophilic asthma" often have severe asthma with poor symptom control, frequent exacerbations as well as fixed airflow limitation. 7-10 Indeed, eosinophilia has been considered a "treatable trait." 10 Interleukin 5 (IL-5) participates in the formation of eosinophils in the bone marrow, as well as their recruitment to the
Applied Sciences
Asthma and eosinophilia are two closely related pathologies whose interaction is key in the era of precision medicine. However, this relationship is rarely taken into account without the influence of therapeutic prescriptions. In this study involving 1296 subjects, the relationship between eosinophilia and asthma was analyzed without taking into account other biases. We observed that rhinitis only appears in non-asthmatic patients with elevated blood eosinophil levels, while atopy was elevated in parallel to eosinophilia regardless of whether the patients were asthmatic or not. In terms of lung function, a decrease was observed for higher blood eosinophil levels, which is especially relevant in the FEV1/FVC ratio. FENO is elevated in relation to higher eosinophilia, but total IgE is only elevated in patients with high peripheral blood eosinophil levels and asthma. Finally, the only feature of asthma that is altered by increased peripheral eosinophilia is persistent asthma, with all ...