scholarly journals Defining type 2 asthma and patients eligible for dupilumab in Italy: a biomarker-based analysis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Giorgio Walter Canonica ◽  
Francesco Blasi ◽  
Nunzio Crimi ◽  
Pierluigi Paggiaro ◽  
Alberto Papi ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Immunoglobulin E ◽  
Cost Effective ◽  
Mucus Production ◽  
Clinical Indicators ◽  
Asthmatic Patients ◽  
Eligible Population ◽  
Asthma Patients ◽  
Severe Type

Abstract Background Asthma is a chronic disease characterized by airway hyperresponsiveness, inflammation and mucus production. In Type 2 asthma, two phenotypic components are often co-expressed (eosinophilic and allergic). Elevated biomarker levels, such as eosinophils (EOS), fraction of exhaled nitric oxide (FeNO) and immunoglobulin E (IgE), are key clinical indicators of Type 2 inflammation. Dupilumab has been recently approved for the treatment of uncontrolled severe Type 2 asthma. Type 2 asthma includes allergic and/or eosinophilic phenotypes. The aim of this analysis was to estimate the dupilumab-eligible population in Italy and characterize it by expected biomarker status. Methods A 4-step approach was carried out to calculate dupilumab-eligible population. The approach consisted in: (1) estimating the total number of asthma patients in Italy (using 2016–2017 Italian-adapted Global Initiative for Asthma -GINA- guidelines); (2) estimating the number of severe asthma patients with poorly controlled or uncontrolled disease (using the findings of two recent administrative claim analyses conducted in Italy); (3) stratifying the severe uncontrolled population by biomarker levels (EOS, FeNO and IgE) according to the outcomes of the QUEST trial (a clinical study assessing the efficacy of dupilumab in patients with uncontrolled moderate-to-severe asthma; NCT02414854); (4) identifying the sub-populations of severe uncontrolled asthma patients characterised by raised blood EOS and/or FeNO level (thus indicated to receive dupilumab). Results According to these estimates, about 3.3 million asthmatic patients live in Italy (6.10% of the population). Of them, almost 20 thousand (N = 19,960) have uncontrolled severe asthma. Dupilumab-eligible patients would be N = 15,988, corresponding to 80.1% of the total uncontrolled severe population. Most of these patients (89.3%; N = 14,271) have at least an increase of EOS level, while slightly more than half (51.9%; N = 8,303) have raised levels of both biomarkers. Increased FeNO levels without increased EOS are observed less frequently (N = 1,717; 10.7% of the eligible population). Conclusions There is a strong rationale for testing all asthma biomarkers during diagnosis and disease follow-up. Given the large availability and the limited costs, these tests are cost-effective tools to detect severe Type 2 asthma, stratify patients by phenotype, and drive appropriate treatment decisions.

scholarly journals Defining Type 2 asthma and patients eligible for dupilumab in Italy: a biomarker-based analysis

2020 ◽  
Author(s):  
Giorgio Walter Canonica ◽  
Francesco Blasi ◽  
Nunzio Crimi ◽  
Pierluigi Paggiaro ◽  
Alberto Papi ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Immunoglobulin E ◽  
Cost Effective ◽  
Mucus Production ◽  
Clinical Indicators ◽  
Asthmatic Patients ◽  
Eligible Population ◽  
Asthma Patients ◽  
Severe Type

Abstract Background Asthma is a chronic disease characterized by airway hyperresponsiveness, inflammation and mucus production. In Type 2 asthma, two phenotypic components are often co-expressed (eosinophilic and allergic). Elevated biomarker levels, such as eosinophils (EOS), fraction of exhaled nitric oxide (FeNO) and immunoglobulin E (IgE), are key clinical indicators of Type 2 inflammation. Dupilumab has been recently approved for the treatment of uncontrolled severe Type 2 asthma. Type 2 asthma includes allergic and/or eosinophilic phenotypes. The aim of this analysis was to estimate the dupilumab-eligible population in Italy and characterize it by expected biomarker status.Methods A 4-step approach was carried out to calculate dupilumab-eligible population. The approach consisted in: 1) estimating the total number of asthma patients in Italy (using 2016–2017 Italian-adapted Global Initiative for Asthma -GINA- guidelines); 2) estimating the number of severe asthma patients with poorly controlled or uncontrolled disease (using the findings of two recent administrative claim analyses conducted in Italy); 3) stratifying the severe uncontrolled population by biomarker levels (EOS, FeNO and IgE) according to the outcomes of the QUEST trial (a clinical study assessing the efficacy of dupilumab in patients with uncontrolled moderate-to-severe asthma; NCT02414854); 4) identifying the sub-populations of severe uncontrolled asthma patients characterised by raised blood EOS and/or FeNO level (thus indicated to receive dupilumab).Results According to these estimates, about 3.3 million asthmatic patients live in Italy (6.10% of the population). Of them, almost 20 thousand (N = 19,960) have uncontrolled severe asthma. Dupilumab-eligible patients would be N = 15,988, corresponding to 80.1% of the total uncontrolled severe population. Most of these patients (89.3%; N = 14,271) have at least an increase of EOS level, while slightly more than half (51.9%; N = 8,303) have raised levels of both biomarkers. Increased FeNO levels without increased EOS are observed less frequently (N = 1,717; 10.7% of the eligible population).Conclusions There is a strong rationale for testing all asthma biomarkers during diagnosis and disease follow-up. Given the large availability and the limited costs, these tests are cost-effective tools to detect severe Type 2 asthma, stratify patients by phenotype, and drive appropriate treatment decisions.

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 Prevalence of specific immunoglobulin E and G against Aspergillus fumigatus in patients with asthma

2019 ◽  
Author(s):  
Newsha Hedayati ◽  
Vida Mortezaee ◽  
Seyed Alireza Mahdaviani ◽  
Maryam Sadat Mirenayat ◽  
Maryam Hassanzad ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Severe Asthma ◽  
Immunoglobulin E ◽  
Clinical Symptoms ◽  
Specific Ige ◽  
Total Ige ◽  
Asthmatic Patients ◽  
Specific Immunoglobulin E ◽  
Specific Immunoglobulin ◽  
The Mean

Background and Purpose: Aspergillus fumigatus as a ubiquitous fungus can be found in the respiratory tract of the asthmatic and healthy people. The inhalation of Aspergillus spores leads to an immune response in individuals with asthma and results in the aggravation of the clinical symptoms. The present study aimed to investigate the prevalence of specific immunoglobulin E and G (IgE and IgG) against A.fumigatus in asthmatic patients.Materials and Methods: This study was conducted on 200 consecutive patients with moderate to severe asthma referring to Masih Daneshvari hospital Tehran, Iran, from January 2016 to February 2018. Skin prick test (SPT) was performed in all subjects with Aspergillus allergens. Moreover, all patients underwent specific IgE testing for Aspergillus using Hycor method. Enzyme immune assay was applied to measure total IgE and Aspergillus-specific IgG.Results: According to the results, the mean age of the patients was 45.8 years (age range: 18-78 years). The mean levels of total IgE and Aspergillus specific IgE in asthmatic patients were obtained as 316.3 (range: 6-1300 IU/ml) and 1.5 (range: 0.1-61.3 IU/ml), respectively. Out of 200 patients, 27 (13.5%), 65 (32.5%), 22 (11.0%), and 86 (43.0%) cases had positive Aspergillus SPT, total IgE of > 417 IU/ml, Aspergillus-specific IgE, and IgG, respectively. The level of these variables in patients with severe asthma were 16 (16.5%), 36 (37.1%), 15 (15.5%), and 46 (47.4%), respectively.Conclusion: As the findings indicated, reactivity to Aspergillus is a remarkable phenomenon in asthmatic patients. It is also emphasised that the climatic condition may affect the positive rate of hypersensitivity to Aspergillus.

scholarly journals Ruxolitinib Ameliorates Airway Hyperresponsiveness and Lung Inflammation in a Corticosteroid-Resistant Murine Model of Severe Asthma

2021 ◽  
Vol 12 ◽  
Author(s):  
Hariharan Subramanian ◽  
Tanwir Hashem ◽  
Devika Bahal ◽  
Ananth K. Kammala ◽  
Kanedra Thaxton ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Murine Model ◽  
Airway Hyperresponsiveness ◽  
Lung Inflammation ◽  
Janus Kinase ◽  
Asthma Prevalence ◽  
Asthma Patients ◽  
Antibody Titers ◽  
Model Treatment

Asthma prevalence has increased considerably over the decades and it is now considered as one of the most common chronic disorders in the world. While the current anti-asthmatic therapies are effective for most asthma patients, there are 5-10% subjects whose disease is not controlled by such agents and they account for about 50% of the asthma-associated healthcare costs. Such patients develop severe asthma (SA), a condition characterized by a dominant Th1/Th17 cytokine response that is accompanied by Type 2 (T2)-low endotype. As JAK (Janus Kinase) signaling is very important for the activation of several cytokine pathways, we examined whether inhibition of JAKs might lessen the clinical and laboratory manifestations of SA. To that end, we employed a recently described murine model that recapitulates the complex immune response identified in the airways of human SA patients. To induce SA, mice were sensitized with house dust mite extract (HDME) and cyclic (c)-di-GMP and then subsequently challenged with HDME and a lower dose of c-di-GMP. In this model, treatment with the JAK inhibitor, Ruxolitinib, significantly ameliorated all the features of SA, including airway hyperresponsiveness and lung inflammation as well as total IgE antibody titers. Thus, these studies highlight JAKs as critical targets for mitigating the hyper-inflammation that occurs in SA and provide the framework for their incorporation into future clinical trials for patients that have severe or difficult-to manage asthma.

scholarly journals Small RNA Species and microRNA Profiles are Altered in Severe Asthma Nanovesicles from Broncho Alveolar Lavage and Associate with Impaired Lung Function and Inflammation

2019 ◽  
Vol 5 (4) ◽  
pp. 51 ◽  
Author(s):  
Ana S. Francisco-Garcia ◽  
Eva M. Garrido-Martín ◽  
Hitasha Rupani ◽  
Laurie C. K. Lau ◽  
Rocio T. Martinez-Nunez ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Small Rna ◽  
Small Rna Sequencing ◽  
Filtration Method ◽  
Asthmatic Patients ◽  
Expression Of Genes ◽  
Severe Asthmatic ◽  
Asthma Patients ◽  
Impaired Lung Function ◽  
The Impact

MicroRNAs are known to regulate important pathways in asthma pathology including the IL-6 and IFN pathways. MicroRNAs have been found not only within cells but also within extracellular vesicles such as exosomes. In this study, we particularly focused on microRNA cargo of nanovesicles in bronchoalveolar lavage of severe asthmatic patients. We extracted nanovesicle RNA using a serial filtration method. RNA content was analyzed with small RNA sequencing and mapped to pathways affected using WebGestalt 2017 Software. We report that severe asthma patients have deficient loading of microRNAs into their airway luminal nanovesicles and an altered profile of small RNA nanovesicle content (i.e., ribosomal RNA and broken transcripts, etc.). This decrease in microRNA cargo is predicted to increase the expression of genes by promoting inflammation and remodeling. Consistently, a network of microRNAs was associated with decreased FEV1 and increased eosinophilic and neutrophilic inflammation in severe asthma. MicroRNAs in airway nanovesicles may, thus, be valid biomarkers to define abnormal biological disease processes in severe asthma and monitor the impact of interventional therapies.

Comparison of exacerbation phenotypes among patients with severe asthma

2020 ◽  
Vol 41 (4) ◽  
pp. e67-e79
Author(s):  
Karina Ruth Soenjoyo ◽  
Nivedita Nadkarni ◽  
Mariko Siyue Koh
Keyword(s):  
Severe Asthma ◽  
Immunoglobulin E ◽  
Laboratory Data ◽  
Therapeutic Strategies ◽  
Demographic Differences ◽  
Asthma Exacerbations ◽  
Singapore General Hospital ◽  
Asthma Patients ◽  
Hospital Stays

Background: Exacerbation phenotypes among patients with severe asthma have been largely characterized during stable periods. Little is known about severe asthma patients during exacerbation periods. Objective: To compare persistently frequent exacerbators (PFE), non‐persistently frequent exacerbators (NPFE), and infrequent exacerbators (IFE) among patients with severe asthma during stable and exacerbation periods. Methods: Patients with severe asthma who were admitted for asthma exacerbations from 2011 to 2017 and on follow up at Singapore General Hospital were recruited and categorized as PFEs (two or more exacerbations per year over 2 consecutive years), NPFEs (two or more exacerbations in 1 year only), or IFEs (fewer than two exacerbations per year over 2 consecutive years). Demographic, clinical, and laboratory data were collected at baseline and during exacerbation periods. Results: The participants were categorized as the following: 20 PFEs, 36 NPFEs, and 57 IFEs, with no significant demographic differences. The participants as PFEs (versus NPFEs and IFEs) were characterized by having a higher prevalence of psychiatric disorders (25% versus 8% versus 5%; p = 0.046), more comorbidities (7 versus 4 versus 2; p < 0.001), and a higher steroid burden per year (1150 versus 456 versus 350 mg; p < 0.001). The participants who were PFEs (versus IFEs) had a higher total immunoglobulin E (IgE) level (625 versus 232 IU/mL; p = 0.046) and longer duration of admission stay (3 versus 2 days; p = 0.009). All three groups had higher blood neutrophil counts during exacerbation periods than during stable periods (p = 0.008 versus p < 0.001 versus p = 0.004). Conclusion: The participants categorized as PFEs were characterized by comorbidities, higher steroid burden, IgE levels, and longer hospital stays. Exacerbations in the participants with severe asthma, regardless of exacerbation phenotype, were characterized by neutrophilia. These findings provided insights into potential therapeutic strategies to reduce exacerbations in patients with severe asthma.

scholarly journals Dual vaccination against IL-4 and IL-13 protects against chronic allergic asthma in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Eva Conde ◽  
Romain Bertrand ◽  
Bianca Balbino ◽  
Jonathan Bonnefoy ◽  
Julien Stackowicz ◽  
...  
Keyword(s):  
Allergic Asthma ◽  
Mouse Models ◽  
Cost Effective ◽  
Interleukin 4 ◽  
Mucus Production ◽  
Post Vaccination ◽  
Type 2 Cytokines ◽  
Therapeutic Monoclonal Antibodies

AbstractAllergic asthma is characterized by elevated levels of IgE antibodies, type 2 cytokines such as interleukin-4 (IL-4) and IL-13, airway hyperresponsiveness (AHR), mucus hypersecretion and eosinophilia. Approved therapeutic monoclonal antibodies targeting IgE or IL-4/IL-13 reduce asthma symptoms but require costly lifelong administrations. Here, we develop conjugate vaccines against mouse IL-4 and IL-13, and demonstrate their prophylactic and therapeutic efficacy in reducing IgE levels, AHR, eosinophilia and mucus production in mouse models of asthma analyzed up to 15 weeks after initial vaccination. More importantly, we also test similar vaccines specific for human IL-4/IL-13 in mice expressing human IL-4/IL-13 and the related receptor, IL-4Rα, to find efficient neutralization of both cytokines and reduced IgE levels for at least 11 weeks post-vaccination. Our results imply that dual IL-4/IL-13 vaccination may represent a cost-effective, long-term therapeutic strategy for the treatment of allergic asthma as demonstrated in mouse models, although additional studies are warranted to assess its safety and feasibility.

scholarly journals FACTORS ASSOCIATED WITH A SEVERE ASTHMA IN ASTHMATIC ADOLESCENT PATIENTS

2020 ◽  
Vol 4 (12) ◽  
Author(s):  
Khaled Hassan
Keyword(s):  
Severe Asthma ◽  
Well Being ◽  
Asthma Patient ◽  
Cross Sectional ◽  
Significance Level ◽  
Factors Associated ◽  
Individual Interviews ◽  
Asthmatic Patients ◽  
Asthma Patients ◽  
History Of

Introduction: The present study aims to determine the frequency of severe asthma in asthma patients followed at the National Hospital of Pneumo-Phtisiology (CNHPP) of Cotonou and to identify the risk factors associated with it Methods: The cross-sectional, descriptive and analytical study focused on 213 asthmatic patients in the 2013 active file of the CNHPP. The data were collected through the use of files and individual interviews with patients. They were processed and analyzed using EPIINFO7 and STATA11 software. Pearson's Chi 2 test, unvaried and multivariate logistic regression were used at the significance level of 0.05 Results: A total of 154 asthmatic patients, ie 72.7%, answered the questionnaire. Among them 20.8% (95% CI: (14.67; 28.05)) suffered from severe asthma. Patient ages ranged from 10 to 76 years with a median of 41 years; 51.3% were female, 79.9% had a history of allergy, 61.7% started their asthma after the age of 12, and only 11% had used or consumed tobacco. The factors associated with the onset of severe asthma were: age 46 to 55 years (p = 0.04); the third and fourth quintiles of economic well-being (p = 0.01) and the onset of asthma after the age of 12 (p <0.001) Conclusion: The study showed a high frequency of severe asthma in Benin and will improve its management at the CNHPP. Keywords: Severe asthma, patients, associated factors, Benin

scholarly journals Biological therapy for severe asthma

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Silvano Dragonieri ◽  
Giovanna Elisiana Carpagnano
Keyword(s):  
Severe Asthma ◽  
Biological Therapy ◽  
Immunoglobulin E ◽  
New Drugs ◽  
Biologic Agent ◽  
Uncontrolled Asthma ◽  
Asthmatic Patients ◽  
Health Care Burden ◽  
Clinical Benefits

AbstractAround 5–10% of the total asthmatic population suffer from severe or uncontrolled asthma, which is associated with increased mortality and hospitalization, increased health care burden and worse quality of life. In the last few years, new drugs have been launched and several asthma phenotypes according to definite biomarkers have been identified. In particular, therapy with biologics has revolutionized the management and the treatment of severe asthma, showing high therapeutic efficacy associated with significant clinical benefits. To date, four types of biologics are licensed for severe asthma, i.e. omalizumab (anti-immunoglobulin E) antibody, mepolizumab and reslizumab (anti-interleukin [IL]-5antibody), benralizumab (anti-IL-5 receptor a antibody) and dupilumab (anti-IL-4 receptor alpha antibody). The aim of this article was to review the biologic therapies currently available for the treatment of severe asthma, in order to help physicians to choose the most suitable biologic agent for their asthmatic patients.

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