View clinical trials related to Severe Asthma.
Filter by:Asthma is a heterogeneous disease, characterized by reversible airflow obstruction, airway hyperresponsiveness, and airway inflammation, in which 40% of patients exhibit eosinophil-driven pathobiology.The main treatment of asthma is the use of corticosteroid, whose use induces a reduction in eosinophils that is considered a strong predictor of response to treatment. Corticosteroids have remained the mainstay treatment of asthma and reduction in eosinophils has remained the unequivocal predictor of steroid response. The prevalence of asthma, which is expected to increase, it is about 300 million people worldwide. About 5-10% of asthma patients have severe disease, which is defined as asthma that requires high-dose inhaled corticosteroids (ICSs) plus a second controller to prevent it from becoming "uncontrolled" or which remains "uncontrolled" despite this therapy. Patients with severe disease have worse quality of life, and disproportionately high morbidity, mortality, and use of health care resources when compared with their peers with well-controlled disease.The pathophysiology of asthma is complex and heterogeneous between patients, as the disease itself; however, on the basis of immune system involvement, it is possible to define 2 subtypes - or endotypes- of asthma. These endotypes are named T2 (for type 2 cells) high or low, and are defined by the levels of expression of the T2 cytokines, IL-4, IL-5, and IL-13 produced by T helper 2 lymphocytes, and innate lymphoid cell-2.T2 high endotype patients display an increase in the number of blood and sputum eosinophils, and have a better response to the current available biological therapies , such as the administration of mepolizumab (anti IL-5 antibody). Eosinophilic asthma is associated to a more severe clinical phenotype,but patients with a T2 endotype respond better to biological therapies. The hypothesis of the present proposal is that the activation status of these cells, analyzed by the expression of activation markers, can be used to define a new, different, endotype, in which eosinophils, although quantitatively low or normal, are qualitatively more active and aggressive, and could therefore act as an indicator of the progression toward a T2 high endotype.Moreover, the investigators will verify whether a different expression of these molecules on eosinophil's surface might be associated with different clinical response to biologic medications.
There are many symptoms associated with severe asthma, not all of them related to the lung. These are referred to as extra-pulmonary symptoms and their relationship with quality of life is complex. Body reprogramming (BR) is a non-drug intervention originally developed for fibromyalgia patients with the aim of improving health and wellbeing in a personalised way, with evidence-based lifestyle changes. The frequency and severity of multiple symptoms in severe asthma is similar to fibromyalgia and the investigators propose that BR may be a suitable non-drug intervention for severe asthma patients who are about to step up drug treatment. Our study aims are therefore to assess how BR may be suitable for people with severe asthma, and to adapt and optimise the programme for these people. In two phases, severe asthma patients will be recruited via a regional severe asthma clinic at the Royal Devon & Exeter NHS Trust and invited to take part in a short course of BR. In phase one, patients will be asked to attend four weekly researcher-led sessions of BR via video call and be given practice tasks to report on at the subsequent session. Questionnaires will be completed for the first and last session. At the end of BR, patients will also be invited to take part in a focus group. The data collected will inform development of the programme for phase two, which will involve recruitment of severe asthma patient who are about to start biologic drug treatment for their severe asthma
This is a hypothesis-generating project to investigate a) infective etiology and b) inflammatory profile of the exacerbations of asthma in severe asthmatic patients treated with the humanized monoclonal antibody against interleukin-5 Mepolizumab. Under these treatment conditions the study will inform on the relationship between these two axes: infection & innate immunity Vs inflammatory profile changes occurring during exacerbation events. In addition, the study will also explore the effect of Mepolizumab treatment on airway microbial composition and on airway/systemic immune response both at stable state and at the exacerbation.
Asthma currently affects 358 million individuals worldwide, posing a substantial burden on health care systems. In particular patients with severe asthma have higher morbidity, mortality and asthma-related costs than non-severe patients. The management of severe asthma is still an unmet need and improving the disease-related knowledge is important to optimize care pathways. Registries provide an opportunity to phenotypically describe a cohort of patients in real-world settings. We hypothesize whether patient profiling based on data in the Portuguese Severe Asthma Registry (RAG - Registo de Asma Grave) may contribute to identify predictors of disease control and therapeutic response. This study aims to (Coprimary Objectives): 1) Identify multidimensional phenotypes associated with health outcomes and therapeutic responses, based on demographic characteristics, clinical features and biomarkers; 2) Explore novel composite endpoint measures of disease control and evaluate its association with the different severe asthma profiles. This is a cross-sectional, observational, multicenter, real-world study. The study population are the patients of all ages with severe asthma included in the RAG, until Dec 2021. It is estimated that 150 patients will be enrolled, in approximately 12 sites throughout Portugal, which is expected to be a representative sample of Portuguese patients with severe asthma. Eligible patients will be invited to integrate RAG by clinicians at scheduled clinic appointments. The criteria for patients' inclusion in the RAG is based on the definition of Severe Asthma by GINA guidelines, based on step of treatment, adherence and comorbidities management. An additional inclusion criterion is the patient's signed consent to have his/her data included in the registry. The main data source of this project is the data collected by RAG, an electronic Case Report Form. Descriptive and inferential statistics will be used to characterize and compare the characteristics across different sub-groups. Advanced data-driven statistical methods, such clustering analysis and latent class analysis, will be used for phenotype classification. Multivariate logistic regression modelling and Classification and Regression Tree analysis will be considered. To address the potential limitations, the RAG has database specifications concerning data definitions and parameters and data validation rules enabling collection of data in the same manner for every patient, with specific and consistent data definitions. To minimize errors related to data completeness and consistency, several validation rules have been implemented and periodic data audits are planned. To avoid unnecessary burden within the clinical workflow, data will be collected at the time of routine medical appointments by the clinician and data entry personnel will assist on this task.
The primary objective of this project is to extensively characterize the endotypes of pre-schoolers (0 to 6 years) and school-age children (6 to 12 years) with SA using an integrated approach, combining a description of their phenotype (asthma symptoms, atopy, and lung function) associated with histological (airway inflammation and remodelling), immune (innate and adaptive immunity), metabolomics, and microbiota analyses. This goal shall be achieved by an unsupervised in-depth analysis of patients requiring bronchial endoscopy, with bronchial alveolar lavage (BAL) and bronchial biopsy, as part of their clinical assessment.
Primary Objectives: 1. To describe the demographic and baseline characteristics in patients with severe eosinophilic asthma in Spain who received at least one dose of Benralizumab, after its marketing authorization 2. To describe background treatment patterns of severe eosinophilic asthma patients at baseline and after the index date (benralizumab initiation) This is a descriptive, observational, multi-centre, longitudinal, retrospective cohort study in adults patients (≥18 years) with severe asthma (maintenance treatment with high dose inhaled corticosteroids combined with long-acting agonist β2) and eosinophilic phenotype, who, at the discretion of the physician, received benralizumab accordingly to the clinical practice, in the period after the marketing authorization of benralizumab in Spain, on January 1st 2019.
Interleukin (IL)-5 is the main cytokine responsible for the activation of eosinophils, hence therapeutic strategies have been investigated and developed for clinical use. Biologics targeting IL-5 and its receptor (first mepolizumab and subsequently, reslizumab and benralizumab), have been recently approved and used as add-on therapy for severe eosinophilic asthma resulting in a reduction in the circulating eosinophil count, improvement in lung function and exacerbation reduction in patients with severe asthma. Response to biologic therapies in severe asthma is variable, with patients being either non-responders, responders or super-responders. There is currently no explanation for this broad variation in response. It is important to examine whether these patients have distinct characteristics that could help the treating physician in making the correct diagnosis in clinical practice. Aim of this clinical study is to evaluate the efficacy of mepolizumab, a humanized IL-5 antagonist monoclonal antibody in patients with late-onset severe eosinophilic asthma with fixed obstruction and to identify the characteristics of non-responders and super-responders under mepolizumab treatment. This study is considered as non-interventional and every procedure included is happening in a clinical routine for the diagnosis and phenotyping of the asthmatic patients. Hypothesis includes the efficacy of mepolizumab treatment in late-onset severe eosinophilic asthmatic patients with fixed obstruction and relation to clinical and inflammatory biomarkers. Patients will be collected from the outpatient clinics of bronchial asthma from each site included (8 in number) which cover the whole population of Greece. Overall, this is a prospective multicenter study including eight Pulmonary Clinics. Five Pulmonary University Clinics, two of National Health System and one Army General Hospital in Thessaloniki. The study will include a screening period of up to 2 weeks to assess eligibility and obtain written informed consent, a mepolizumab treatment period of 52 weeks, once every 4 weeks, including follow up visits every 3 months during treatment. The study population will consist of 45 patients with late-onset severe eosinophilic asthma and fixed obstruction receiving mepolizumab, aged 20 and above.
The objective of the study is to establish the predictive value of early blood gene expression signature of Benralizumab response associated with a significant reduction of the number of exacerbations in treated severe asthmatic patients. This trial is a French, multicenter and no-randomized trial. Patients enrolled will be clinically followed for 16 months (the treatment period: 12 months and 1 month follow-up; 6 clinical visit on site and in phone call at 13 months)
The investigators will measure different cytokines in the sputum (IL3, GM-CSF, IL5, IL-13, IL-33, IL-4…) and in the blood to evaluate their ability to predict the response after 6 months and 1 year of treatment with a biologic treatment (anti-IgE, anti-IL5, anti-IL5R) in terms of reduction in exacerbations and corticosteroid use, improvement in FEV1 (+200ml), in asthma control (ACQ decrease >0.5, ACT increase >3), in asthma quality of life (increase in AQLQ score > 0.5) and the effect on sputum and blood inflammation.
Title: Phenotyping circulating and lung resident eosinophils in severe asthma (3 years). Background: Asthma is a long-term condition that affects the airways. When a person with asthma comes into contact with something that irritates their sensitive airways, the lungs respond with contracting the muscles around the airway tubes, an inflammation process and mucus production. The airway will become narrower and inflamed making it hard to breathe and results in symptoms such as wheezing and coughing. The treatment of asthma consists of using inhalers that work to widen the airway to relief these symptoms. Often severe asthmatics have difficulty in controlling their disease, despite good medical care and taking asthma medicines. At the moment there is no cure for asthma. A new medicine called Mepolizumab (anti-Interleukin(IL)-5 therapy) has now shown to improve the symptoms of asthma particularly patients with severe asthma in whom the normal medicines prescribed for asthma are not highly effective in controlling their disease. You have been chosen receive this new medicine as we believe it will improve the control of your disease. The aim for this study is to understand the effect of Mepolizumab on a particular type of cell, called an eosinophil, which in present lungs and blood of all people but is increased in asthma patients. Rationale: The relationship between subsets of circulating and lung resident eosinophils in severe asthma and Mepolizumab (anti-IL-5 therapy) efficacy has not been explored. Objectives: To determine the gene expression and release of inflammatory proteins (mediator profiles) of eosinophils from the circulation and the lung, specifically blood and tissue resident, in patients with severe asthma at baseline and on Mepolizumab therapy. Study 1: Phenotype subsets of circulating eosinophils in patients with severe asthma at one time-point Recruit: 15 biologic naïve SA and 15 SA currently on Mepo therapy. Blood eosinophils will be isolated by negative selection. Single-cell RNA-seq 10xGenomics and bulk-RNA-seq to be used to simultaneously measure gene and cell surface protein expression in the same cell to understand cellular heterogeneity in asthmatic eosinophils and identify novel targets and biomarkers for non-responsiveness Study 2: Phenotype subsets of circulating and lung eosinophils in patients with severe asthma on Mepolizumab therapy over one year. Treat 30 appropriately characterised severe asthmatics (Eos>300/ul) with Mepolizumab Blood eosinophils will be isolated by negative selection. Single-cell RNA-seq 10xGenomics and bulk -RNA -seq to be used to understand cellular heterogeneity in asthmatic eosinophils post Mepo Therapy. Sampling at baseline, 3 and 12 months post Mepo Therapy. Bronchoscopy performed on 30 patients, sampling endobronchial lung biopsy at baseline and 1 yr post Mepo Therapy. Single-cell RNA-seq 10xGenomics on lung resident eosinophils at baseline and 1yr post Mepolizumab therapy. Immunohistochemistry will also be performed to characterise cellular content and structure.