View clinical trials related to Severe Asthma.
Filter by:Study of the clinical evolution at 10 years of children from the SAMP cohort (severe asthma, eosinophilic or not, allergic or not) in order to understand the different possible evolutions of these phenotypes at different ages.
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.
In the study of a population of severe asthmatics, not controlled despite the treatment conducted, it was possible to evidence 5 phenotypic groups of patients. According to the refractoriness of the response to treatment, severe asthma may be phenotype in some distinct groups.Other prospective study found a large proportion of severe asthmatics with persistent airway obstruction, despite optimized treatment and systematic follow-up. Small airway involvement and remodelling, characterized by bronchial muscle thickening, appear to be the main culprits for asthma severity and persistent obstruction in this population.A point of interest in the severe asthmatics cohort was the vast majority were female and there were a considerable number of obese. Recent reviews show that the more consistent division of phenotypes in patients with severe asthma is still based on 3 previously described criteria (presence of atopy, eosinophilia and age of onset of asthma) and a more recent criterion for the presence of multi-comorbidities. Heterogeneity is the rule, the presumption of a natural evolution of gravity is not confirmed and the overlap of clusters is frequent. The stability and natural history of the phenotypes is poorly understood, postulating that the inflammatory activation of the severe asma is multifactorial and may resemble that described in the oncology literature.To date, there are no markers that allow prediction of lung evolution of most patients with severe asthma, and which patients are at greater risk of developing persistent or accelerated loss airflow or lung function, factors determining the severity of asthma. It is also unclear whether and how much phenotype-based treatment impact on disease control and prognosis. Future studies will be instrumental in defining how and why. These phenotypes are evolving, leading to the disabling characteristics of severe asthma and what may be the more effective therapeutic approaches for these patients. Since the initiated research group from 2006 has an extensive clinical, functional, inflammatory, tomographic and morphological evaluation of a cohort of patients with severe asthma, the ideal scenario exists to advance the understanding and investigation of the evolution of this rare disease through standardized follow-up.
SEVERE ASTHMA IN THE COMMUNITY- BACKGROUND Severe asthma is a common problem. In the world approximately 300 million people have asthma but it is estimated that only 5% of these patients have severe asthma. Although "severe asthma" comprises a small fraction of the entire asthmatic population its share in the total economic burden of asthma is 80 percent. In Israel the prevalence of asthma among adult patients is about 5-6% but the prevalence of severe asthma is unknown. The definition of severe asthma has been changed during the years. Most recently in 2009 the WHO agreed on a unified definition of "severe asthma" that would fit countries of different socioeconomic development [1]. Severe asthma includes now 3 different groups: group one "untreated severe asthma", group two "difficult to treat severe asthma" and group three "treatment-resistant severe asthma". As all asthmatic patients in Israel have easy access to medical care, the current study will deal with the last two groups ("difficult to treat asthma" and "treatment resistant asthma"). AIMS Primary endpoints: 1. To identify the prevalence of severe asthma in the community according to the WHO definition of group two & three. 2. To assess whether anti-IgE therapy (Omalizumab), was considered in these groups of severe asthma. Secondary endpoints: 1. To assess factors involved in "difficult to treat asthma" according to the WHO definition. Factors as patient compliance, presence of co-morbidities, symptoms of untreated potential asthma triggers including GE reflux, post nasal drip/atopic rhino-sinusitis, and intervening medications including NSAID and beta-blockers. 2. To asses the level of asthma control, level of patient follow-up care including asthma specialist visits, periodic PFT's and asthma education. 3. To assess the fraction of patients with severe asthma that is eligible to anti-IgE therapy according to the indications of the Israeli Ministry of Health (proven asthma, uncontrolled by high dose of combined ICS+LABA inhaler therapy + at least 2 courses of systemic corticosteroids in the last year + proven atopy to at least one perennial aeroallergen + IgE level of 30-1,500 IU/ml) DESIGN A prospective non-blinded non-randomized observation study among the population insured by Clalit Medical Services (CMS) in the Sharon- Shomron Medical District in Israel.