Clusters of Severe Eosinophilic Asthma in a Korean Asthma Cohort

Respiration ◽  
2021 ◽  
pp. 1-11
Author(s):  
Ji-Hyang Lee ◽  
Jin An ◽  
Ha-Kyeong Won ◽  
Bomi Seo ◽  
Jung-Hyun Kim ◽  
...  
Keyword(s):  
Cluster Analysis ◽  
Lung Function ◽  
Severe Asthma ◽  
Treatment Options ◽  
Clinical Importance ◽  
Forced Expiratory Volume ◽  
Blood Eosinophil ◽  
Eosinophilic Asthma ◽  
Severe Eosinophilic Asthma ◽  
Patient Subgroups

<b><i>Background:</i></b> Targeted therapies have broadened the available treatment options for patients with severe eosinophilic asthma (SEA). However, differences in the magnitude of treatment responses among patients indicate the presence of various underlying pathophysiological processes and patient subgroups. <b><i>Objectives:</i></b> We aimed to describe the characteristics of SEA and identify its patient subgroups. <b><i>Methods:</i></b> Clinical data from the Cohort for Reality and Evolution of Adult Asthma in Korea were analyzed. Cluster analysis was performed among those with SEA using 5 variables, namely, prebronchodilator forced expiratory volume in 1 s, body mass index, age at symptom onset, smoking amount, and blood eosinophil counts. <b><i>Results:</i></b> Patients with SEA showed prevalent sensitization to aeroallergens, decreased lung function, and poor asthma control status. Cluster analysis revealed 3 distinctive subgroups among patients with SEA. Cluster 1 (<i>n</i> = 177) consisted of patients reporting the lowest blood eosinophils (median, 346.8 cells/μL) and modest severe asthma with preserved lung function during the 12-month treatment period. Cluster 2 (<i>n</i> = 42) predominantly included smoking males with severe persistent airway obstruction and moderate eosinophilia (median, 451.8 cells/μL). Lastly, cluster 3 (<i>n</i> = 95) included patients with the most severe asthma, the highest eosinophil levels (median, 817.5 cells/μL), and good treatment response in terms of improved lung function and control status. <b><i>Conclusions:</i></b> Three subgroups were identified in SEA through the cluster analysis. The distinctive features of each cluster may help physicians predict patients who will respond to biologics with greater magnitude of clinical improvement. Further research regarding the underlying pathophysiology and clinical importance of each subgroup is warranted.

scholarly journals Precision medicine applications for severe asthma

2019 ◽  
Vol 6 (4) ◽  
pp. 117-135
Author(s):  
Orit Gourgy Hacohen ◽  
Shai Cohen
Keyword(s):  
Precision Medicine ◽  
Severe Asthma ◽  
Oral Corticosteroid ◽  
Treatment Options ◽  
Current Evidence ◽  
Blood Eosinophil ◽  
Eosinophilic Asthma ◽  
Severe Eosinophilic Asthma ◽  
Beneficial Effects ◽  
New Treatment

Asthma is a heterogeneous condition in which multiple pathological pathways manifest with similar symptoms. Severe asthma (SA) is challenging to manage and comprises a significant health and economic burden. Many studies have been conducted in an attempt to define different clinical phenotypes that translate into biological endotypes, with the goal of tailoring treatment based on precision medicine. This review summarizes the current evidence for the treatments of SA, and in particular, the biologic treatments that are currently available: omalizumab, mepolizumab, reslizumab, benralizumab and dupilumab. We found only limited high-quality direct evidence regarding treatment with anti-IgE (omalizumab) in SA patients. Data regarding anti-interleukin (IL)-5 (mepolizumab, reslizumab and benralizumab) showed beneficial effects in severe eosinophilic asthma (SEA) with different levels of blood eosinophils used in clinical trials. Dupilumab, anti-IL-4/IL-13, was shown to be effective in SEA and is the only agent currently FDA-approved for the indication of oral corticosteroid dependent asthma, regardless of the blood eosinophil level. This review also summarizes the existing knowledge regarding the characteristics of the patient who may respond to the different therapies. As of today, more studies are needed to better understand the diverse mechanisms that underlie SA phenotypes. We have not yet adequately reached the goal of precision medicine. Additional studies are necessary in order to find novel surrogate markers that can predict the response to a specific biologic therapy, especially in patients who are oral corticosteroid dependent. In addition, efforts must be invested into research looking for new treatment options for patients with non-type-2 inflammation SA. Statement of novelty: we review the current evidence regarding tailored treatment therapies in SA, with a particular focus on the knowledge regarding patient selection for specific biologic treatments.

scholarly journals Efficacy of mepolizumab for patients with severe asthma and eosinophilic chronic rhinosinusitis

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Takanori Numata ◽  
Katsutoshi Nakayama ◽  
Hirofumi Utsumi ◽  
Kenji Kobayashi ◽  
Haruhiko Yanagisawa ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Severe Asthma ◽  
Predictive Factors ◽  
Systemic Corticosteroid ◽  
Multivariate Logistic Regression Analysis ◽  
Patient Characteristics ◽  
Blood Eosinophil ◽  
Eosinophilic Asthma ◽  
Severe Eosinophilic Asthma ◽  
Eosinophilic Chronic Rhinosinusitis

Abstract Background Several major randomized control studies have demonstrated that mepolizumab, an anti-IL-5 monoclonal antibody, is effective for patients with severe eosinophilic asthma who show exacerbation or require systemic corticosteroid maintenance therapy. However, the predictive factors of the response to mepolizumab other than blood eosinophil count are unclear in clinical practice. Objective To elucidate the predictive factors of the response to mepolizumab for patients with severe eosinophilic asthma. Methods From July 2016 to December 2017, 28 patients with severe asthma received mepolizumab in our hospital. To determine the predictive factors, we retrospectively evaluated patient characteristics, comorbidities, biomarkers, pulmonary function, maintenance dose of systemic corticosteroids and number of exacerbations. Results The response rate to mepolizumab treatment was 70% (19/27; one pregnant woman was excluded from analysis). Compared with 11 patients without eosinophilic chronic rhinosinusitis (ECRS), 16 patients with ECRS showed significantly improved systemic corticosteroid-sparing effects [− 71.3 ± 37.0% vs − 10.7 ± 20.1%, P = 0.006], change from baseline FeNO [− 19 ± 57 (%) vs 30 ± 77 (%), P = 0.023] and symptoms [14 patients (88%) vs five patients (45%), P = 0.033]. ECRS was identified as a predictive factor of the response to mepolizumab in a multivariate logistic regression analysis [odds ratio = 22.5, 95% CI (1.5–336), P = 0.024]. Of the eight patients previously administered omalizumab, five responded to mepolizumab. Staphylococcus aureus enterotoxin B IgE results were negative in 80% of responders (P = 0.14). Conclusion Both groups showed improved symptom scores and a decreased number of exacerbations. Mepolizumab substantially improved the clinical variables of patients with eosinophilic asthma complicated with ECRS.

Diagnosis and Management of Severe Asthma

2018 ◽  
Vol 39 (01) ◽  
pp. 091-099 ◽  
Author(s):  
Kian Fan Chung
Keyword(s):  
Severe Asthma ◽  
Inhaled Corticosteroids ◽  
Immunoglobulin E ◽  
High Dose ◽  
Blood Eosinophil ◽  
Exhaled Breath ◽  
Eosinophilic Asthma ◽  
Severe Eosinophilic Asthma ◽  
Asthma Patients ◽  
Long Acting

AbstractSevere therapy-resistant asthma has been defined as “asthma which requires treatment with high dose inhaled corticosteroids (ICSs) plus a second controller (and/or systemic corticosteroids) to prevent it from becoming ‘uncontrolled’ or which remains ‘uncontrolled’ despite this therapy”. Patients who usually present with ‘difficult-to-treat asthma’ should first be assessed to determine whether he/she has asthma with the exclusion of other diagnoses and if so, whether the asthma can be classified as severe therapy-resistant. This necessitates an assessment of adherence to medications, confounding factors, and comorbidities. Increasingly, management of severe therapy-resistant asthma will be helped by the determination of phenotypes to optimize responses to existing and new therapies. Severe asthma patients are usually on a combination of high dose ICS and long-acting β-agonist (LABA) and, in addition, are often on a maintenance dose of oral corticosteroids. Phenotyping can be informed by measuring blood eosinophil counts and the level of nitric oxide in exhaled breath, and the use of sputum granulocytic counts. Severe allergic asthma and severe eosinophilic asthma are two defined phenotypes for which there are efficacious targeted biologic therapies currently available, namely anti-immunoglobulin E (IgE) and anti-interleukin (IL)-5 antibodies, respectively. Further progress will be realized with the definition of noneosinophilic or non-T2 phenotypes. It will be important for patients with severe asthma to be ultimately investigated and managed in specialized severe asthma centers.

scholarly journals Mepolizumab effectiveness and identification of super-responders in severe asthma

2020 ◽  
Vol 55 (5) ◽  
pp. 1902420 ◽  
Author(s):  
Erin S. Harvey ◽  
David Langton ◽  
Constance Katelaris ◽  
Sean Stevens ◽  
Claude S. Farah ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Real World ◽  
Rate Ratio ◽  
Disease Burden ◽  
Symptom Control ◽  
Blood Eosinophil ◽  
Eosinophilic Asthma ◽  
Asthma Control Questionnaire ◽  
Peripheral Blood Eosinophil ◽  
Severe Eosinophilic Asthma

Severe asthma is a high-burden disease. Real-world data on mepolizumab in patients with severe eosinophilic asthma is needed to assess whether the data from randomised controlled trials are applicable in a broader population.The Australian Mepolizumab Registry (AMR) was established with an aim to assess the use, effectiveness and safety of mepolizumab for severe eosinophilic asthma in Australia.Patients (n=309) with severe eosinophilic asthma (median age 60 years, 58% female) commenced mepolizumab. They had poor symptom control (median Asthma Control Questionnaire (ACQ)-5 score of 3.4), frequent exacerbations (median three courses of oral corticosteroids (OCS) in the previous 12 months), and 47% required daily OCS. Median baseline peripheral blood eosinophil level was 590 cells·µL−1. Comorbidities were common: allergic rhinitis 63%, gastro-oesophageal reflux disease 52%, obesity 46%, nasal polyps 34%.Mepolizumab treatment reduced exacerbations requiring OCS compared with the previous year (annualised rate ratio 0.34 (95% CI 0.29–0.41); p<0.001) and hospitalisations (rate ratio 0.46 (95% CI 0.33–0.63); p<0.001). Treatment improved symptom control (median ACQ-5 reduced by 2.0 at 6 months), quality of life and lung function. Higher blood eosinophil levels (p=0.003) and later age of asthma onset (p=0.028) predicted a better ACQ-5 response to mepolizumab, whilst being male (p=0.031) or having body mass index ≥30 (p=0.043) predicted a lesser response. Super-responders (upper 25% of ACQ-5 responders, n=61, 24%) had a higher T2 disease burden and fewer comorbidities at baseline.Mepolizumab therapy effectively reduces the significant and long-standing disease burden faced by patients with severe eosinophilic asthma in a real-world setting.

scholarly journals Stratification of eosinophilic asthma patients treated with reslizumab and GINA Step 4 or 5 therapy

2017 ◽  
Vol 3 (3) ◽  
pp. 00004-2017 ◽  
Author(s):  
Guy Brusselle ◽  
Janice Canvin ◽  
Sivan Weiss ◽  
Shawn X. Sun ◽  
Roland Buhl
Keyword(s):  
Lung Function ◽  
Patient Reported Outcomes ◽  
Secondary Analysis ◽  
Forced Expiratory Volume ◽  
Phase Iii ◽  
Eosinophilic Asthma ◽  
Interleukin 5 ◽  
Severe Eosinophilic Asthma ◽  
Patient Reported ◽  
Asthma Patients

Reslizumab, an anti-interleukin-5 monoclonal antibody, significantly reduces exacerbation frequency and improves lung function, asthma control and quality of life in adults with severe eosinophilic asthma, as demonstrated in Phase III studies.This secondary analysis assessed reslizumab's efficacy in patients receiving baseline treatment per Global Initiative for Asthma (GINA) Step 4 and Step 5 guidelines.Pooled data from duplicate, Phase III, reslizumab versus placebo studies in patients with severe eosinophilic asthma (blood eosinophils ≥400 cells·µL−1) were stratified by baseline therapy. Efficacy assessments were exacerbation rates and changes from baseline forced expiratory volume in 1 s (FEV1) and patient-reported outcomes.Of 953 patients, 69% (n=657) and 11% (n=106) were receiving Step 4 and Step 5 therapy, respectively. Compared with placebo, reslizumab reduced exacerbation rates by 53% (95% CI 0.36–0.62) and 72% (95% CI 0.15–0.52), in Step 4 and Step 5 groups respectively. By study end, reslizumab increased FEV1 in Step 4 and Step 5 groups by 103 mL (95% CI 52–154 mL) and 237 mL (95% CI 68–407 mL), respectively. Reslizumab also improved patient-reported outcomes compared with placebo in both groups.Reslizumab reduces exacerbation rates and improves lung function and patient-reported outcomes in patients with eosinophilic asthma receiving therapy per Steps 4 and 5 of the GINA guidelines.

scholarly journals The effectiveness of benralizumab in the treatment of the eosinophilic phenotype of severe asthma in real clinical practice

2021 ◽  
Vol 31 (5) ◽  
pp. 628-634
Author(s):  
Olga N. Titova ◽  
Natalia A. Kuzubova ◽  
Daria B. Sklyarova ◽  
Maria A. Petrova
Keyword(s):  
Clinical Practice ◽  
Asthma Control ◽  
Severe Asthma ◽  
Forced Expiratory Volume ◽  
Current Therapy ◽  
Eosinophilic Asthma ◽  
Asthma Control Questionnaire ◽  
Severe Eosinophilic Asthma ◽  
Night And Day ◽  
Real Clinical Practice

To evaluate the effectiveness of benralizumab in patients with the eosinophilic phenotype of severe asthma in real clinical practice after a year of therapy.Methods. During Benralizumab therapy, 13 patients with severe eosinophilic asthma (average age – 55.44 ± 7.18 years old) were examined twice: before the treatment and after 1 year of benralizumab therapy. The assessment included collection of complaints, medical history, current therapy, Asthma Control Questionnaire (ACQ-5) test, absolute blood count of eosinophils, spirometry.Results. All patients initially had pronounced eosinophilia of 577.5 ± 356.4 cells/μl. After 1 year of using benralizumab, the eosinophil count decreased by 96.15%. During therapy, the ACQ-5 index decreased from 1.63 ± 0.62 to 0.73 ± 0.41 in the study patients, which corresponded to the achievement of asthma control. The forced expiratory volume in 1 second (FEV1) increased by 23 %. The number of exacerbations decreased by 58.09%. 12 (92.31%) patients were on oral corticosteroids (OCS) (10 ± 2.17 mg of prednisolone daily) before benralizumab therapy. All subjects noted a decrease in night and day symptoms over time and were able to reduce the use of OCS. 5 (38.46%) patients achieved complete elimination of daily OCS use, 7 (53.84%) patients were able to reduce their daily OCS dose.Conclusion. Benralizumab therapy as an add-on maintenance treatment in patients with eosinophilic phenotype of severe asthma contributes to a significant decrease in peripheral blood eosinophils, which mediates an improvement in asthma control, an increase in FEV1, a reduction in the number of exacerbations, and a decrease in the need for the OCS usage. Careful monitoring of long-term adverse events is necessary during treatment with benralizumab.

scholarly journals Dupilumab improves lung function in patients with uncontrolled, moderate-to-severe asthma

2020 ◽  
Vol 6 (1) ◽  
pp. 00204-2019 ◽  
Author(s):  
Mario Castro ◽  
Klaus F. Rabe ◽  
Jonathan Corren ◽  
Ian D. Pavord ◽  
Constance H. Katelaris ◽  
...  
Keyword(s):  
Lung Function ◽  
Severe Asthma ◽  
Human Monoclonal Antibody ◽  
Forced Expiratory Volume ◽  
Interleukin 4 ◽  
Blood Eosinophil ◽  
Elevated Type ◽  
Forced Expiratory Flow ◽  
Type 2 Inflammation

BackgroundDupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key drivers of type 2 inflammation. In the phase 3 LIBERTY ASTHMA QUEST trial (NCT02414854) in patients with uncontrolled, moderate-to-severe asthma, add-on dupilumab 200 mg or 300 mg every 2 weeks reduced exacerbations and improved forced expiratory volume in 1 s (FEV1) and quality of life over 52 weeks. This analysis evaluates dupilimab's effect on lung function in the overall population, and subgroups with baseline elevated type 2 inflammatory biomarkers.MethodsPatients were randomised to 52 weeks of subcutaneous dupilumab 200 mg every 2 weeks, 300 mg every 2 weeks, or matched-volume placebos. Lung function outcomes were analysed in the overall population, in patients with ≥150 eosinophils·µL−1, ≥300 eosinophils·µL−1, ≥25 ppb fractional exhaled nitric oxide (FeNO), and both ≥150 eosinophils·µL−1 and ≥25 ppb FeNO, at baseline.ResultsDupilumab treatment (200 mg and 300 mg every 2 weeks) resulted in significant improvements versus placebo after 52 weeks in pre-bronchodilator FEV1 (0.20 and 0.13 L, respectively, versus placebo) and post-bronchodilator FEV1 (0.19 and 0.13 L, respectively), forced vital capacity (FVC) (0.20 and 0.14 L, respectively), forced expiratory flow (0.19 and 0.13 L·s−1, respectively) and pre-bronchodilator FEV1/FVC ratio (1.75% and 1.61%, respectively) in the overall population (p<0.001). Difference versus placebo in post-bronchodilator FEV1 slope of change (weeks 4–52) was significant (0.04 L·year−1; p<0.05). Greater improvements were achieved in patients with elevated baseline blood eosinophil and/or FeNO levels for most outcomes.ConclusionsDupilumab improves lung function outcomes, including large and small airway measurements and fixed airway obstruction, in patients with uncontrolled, moderate-to-severe asthma; particularly in patients with elevated biomarkers of type 2 inflammation.

scholarly journals Management of severe asthma: a European Respiratory Society/American Thoracic Society guideline

2019 ◽  
Vol 55 (1) ◽  
pp. 1900588 ◽  
Author(s):  
Fernando Holguin ◽  
Juan Carlos Cardet ◽  
Kian Fan Chung ◽  
Sarah Diver ◽  
Diogenes S. Ferreira ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Task Force ◽  
American Thoracic Society ◽  
Adult Patients ◽  
Blood Eosinophil ◽  
European Respiratory Society ◽  
Eosinophilic Asthma ◽  
Severe Eosinophilic Asthma ◽  
Evaluation Approach ◽  
Meta Analyses

This document provides clinical recommendations for the management of severe asthma. Comprehensive evidence syntheses, including meta-analyses, were performed to summarise all available evidence relevant to the European Respiratory Society/American Thoracic Society Task Force's questions. 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 syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of asthma experts, who made specific recommendations on six specific questions. After considering the balance of desirable and undesirable consequences, quality of evidence, feasibility, and acceptability of various interventions, the Task Force made the following recommendations: 1) suggest using anti-interleukin (IL)-5 and anti-IL-5 receptor α for severe uncontrolled adult eosinophilic asthma phenotypes; 2) suggest using a blood eosinophil cut-point ≥150 μL−1 to guide anti-IL-5 initiation in adult patients with severe asthma; 3) suggest considering specific eosinophil (≥260 μL−1) and exhaled nitric oxide fraction (≥19.5 ppb) cut-offs to identify adolescents or adults with the greatest likelihood of response to anti-IgE therapy; 4) suggest using inhaled tiotropium for adolescents and adults with severe uncontrolled asthma despite Global Initiative for Asthma (GINA) step 4–5 or National Asthma Education and Prevention Program (NAEPP) step 5 therapies; 5) suggest a trial of chronic macrolide therapy to reduce asthma exacerbations in persistently symptomatic or uncontrolled patients on GINA step 5 or NAEPP step 5 therapies, irrespective of asthma phenotype; and 6) suggest using anti-IL-4/13 for adult patients with severe eosinophilic asthma and for those with severe corticosteroid-dependent asthma regardless of blood eosinophil levels. These recommendations should be reconsidered as new evidence becomes available.

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