View clinical trials related to Pulmonary Eosinophilia.
Filter by:Severe eosinophilic asthma (SEA) is associated with poor disease control and compromised health-related quality of life (HRQoL), leading to a substantial psychosocial and economic disease burden. Benralizumab (Fasenra®), an interleukin (IL)-5-alpha receptor monoclonal antibody, is approved as an add-on maintenance treatment for SEA. This study aims at collecting real-world data that extend beyond the clinical effectiveness of benralizumab to the participant-reported impact of treatment on their HRQoL, sleep quality, depression, anxiety, work productivity and activity impairment, but also on treatment effectiveness. Recent technological advances in portable spirometers and wearable activity trackers (WAT) to increase physical activity for participants with asthma, even for older participants, allow this study to collect data on lung function parameters and physical activity from such devices for the first time at a country level in Greece. Using a multi-aspect approach, this study will generate real-world evidence on a broad range of both well-established clinical and novel patient-centered outcomes which are critical to the assessment of the therapeutic benefit both from the physician's and the participant's perspective. All main study outcomes will be examined at various timepoints throughout the course of the 48-week observation period, starting as early as 4 weeks after treatment initiation, thus enabling the identification of 'early' treatment responders with a closer focus on patients' physical and psychological well-being and HRQoL in addition to asthma control and lung function metrics
Severe asthma is a debilitating condition associated with frequent symptoms, life-threatening exacerbations and corticosteroid side-effects. Exercise limitation due to exercise-induced bronchoconstriction, dynamic lung hyperinflation and comorbidity may be a strong determinant of the disease burden. Mepolizumab is a monoclonal anti-interleukin-5 (IL-5) antibody that reduces the rate of severe exacerbations, asthma symptoms and oral glucocorticoid requirement, and improves quality of life and work productivity in severe eosinophilic asthma. However, its impact on physical activity and exercise tolerance is unknown. We hypothesize that a 6-month treatment with mepolizumab is associated with an improvement in daily life physical activity and exercise tolerance in relation with enhanced ventilatory mechanics.
Around 1/3 of patients with COPD have elevated eosinophil levels. However, the role of eosinophils in COPD has not been yet understood and is probably different in COPD and in asthma. The aim of this study was to assess the expression of selected surface markers on eosinophils and to assess the gene expression in eosinophils in COPD and asthma patients. We are planning to enrol 12 COPD, 12 asthma and 12 control subjects. Patients will undergo routine clinical assessment, spirometry, blood sampling and sputum induction. Eosinophils will be isolated from blood and sputum. Surface markers on eosinophils will be assessed in flow cytometry, gene expression will be assessed by RNAseq.
Advances in understanding the pathophysiology of asthma development and severity have pointed towards a prominent role of the bronchial epithelium, especially in more chronic and severe disease. Studies suggest that airway eosinophilic inflammation in asthma is linked to epithelial injury and structural changes of the airways, co called airway wall remodeling. Together the chronic airway inflammation and remodeling are associated with bronchial hyperresponsiveness, fixed airflow obstruction or progressive loss of lung function and clinical severity of asthma. Chronic rhinosinusitis with nasal polyps (CRSwNP), is another respiratory inflammatory disease often co-existing with severe asthma, sharing similar pathophysiology. The investigators hypothesize that epithelial barrier integrity may play a role in the pathophysiology of severe eosinophilic asthma and nasal polyposis and in response to anti-IL5 therapy of severe asthmatics, and that shedding of epithelial barrier proteins may be used as biomarker in the management of severe asthma. In order to study that, the investigators will conduct a prospective cohort study of adult severe asthmatics with/out CRSwNP, who live on the island of Crete, Greece and who meet the criteria for entering anti-IL5 treatment, as assessed by pulmonologist. The participants will be recruited with a convenience sampling in a period of 2 years, under real life conditions, and will be followed up for 1 year after treatment initiation. A control group of subjects diagnosed with nasal polyposis without severe asthma will be used. Eligible subjects will undergo clinical assessment with radiological (CT) and endoscopic investigations. Samples of serum, sputum, nasal secretions, as well as nasal and bronchial biopsies will be obtain for assessing clinicopathological differences among the 3 groups but also response to anti-IL5 therapy in SEA w/o CRSwNP.
Asthma is a chronic respiratory disorder characterized by bronchial inflammation and reversible bronchial obstruction. Severe asthma is an extremely heterogeneous disease, often associated with several comorbidities and risk factors. Severe uncontrolled asthma associated with bronchiectasis is an emerging phenotype. Several studies have attempted to establish an association between asthma and bronchiectasis. Mepolizumab, an Interleukin-5 (IL-5) antagonist, reduces exacerbations, eosinophils, and improves pulmonary function and asthma control. IL-5 is pivotal to eosinophils maturation and release from bone marrow, their subsequent accumulation, activation and persistence in the tissues. IL-5 therefore represents an attractive target to prevent or blunt eosinophils-mediated inflammation. The investigators hypothesize that eosinophils, stimulated by IL-5, play a crucial role in severe asthma and BE pathogenesis.
Retrospective, multicenter, routine clinical practice study with consecutive inclusion of adult patients with severe eosinophilic asthma receiving benralizumab treatment.
Patients with severe or difficult-to-treat asthma represent a small amount of total asthmatic patients, but weight on the national health system for the costs of disease management. Chronic rhinosinusitis with nasal polyposis, which the Italian severe/uncontrolled asthma registry reported with a prevalence of 30%, represents a comorbidity that significantly impact lung function and asthma control in severe asthma. Recent evidence indicates that there is a consistent heterogeneity regarding mucosal alterations present in subjects with nasal polyposis involving different pathways: inflammatory cells, remodeling, T cell activation, local IgE production, alteration induced by interactions between microorganisms and epithelial cells.
This is a real-life pragmatic non-randomised study to explore the impact of mepolizumab on the emotional and affective outcomes of patients with severe eosinophilic asthma and their partners. It will be conducted in two quantitative stages (Phases 1 and 2) with an additional third qualitative component (Phase 3).
In this project the investigators will look for auto-antibodies to relevant proteins both in native form and importantly in post-translationally modified forms. Potential modified auto-antigens are eosinophil proteins (analogous to the cytoplasmic neutrophil proteins identified in vasculitides such as Granulomatosis with Polyangiitis (formerly known as Wegener's granulomatosis) and alternatively structural proteins such as collagen V. As well as advancing the understanding of asthma pathology, identifying a serum auto-antibody that could then be used as a clinical blood test, analogous to anti-cyclic citrullinated peptide (CCP) antibodies in rheumatoid arthritis, may revolutionise diagnosis of severe eosinophilic asthma and Eosinophilic Granulomatosis with Polyangiitis (EGPA). There is a considerable burden of undiagnosed severe eosinophilic asthma in part due to difficulties in definitive diagnosis and a diagnostic blood test would help diagnose these patients, allowing them to receive necessary treatment.
Two parts: A:Case-control study including 15 healthy adult donors and 15 severe adult eosinophilic asthmatics selected for treatment with mepolizumab. B: A longitudinal cohort study,where the same patients once on mepolizumab treatment are followed over time (0, 4, 16 and 32 weeks). SCOPE: response to mepolizumab in severe adult eosinophilic asthma. INCLUSION CRITERIA: Male or female, 18-75 years-old, with severe eosinophilic asthma. EXCLUSION CRITERIA: Smoking history, recent exacerbations, other pulmonary or systemic disease with eosinophilia, malignancy, pregnancy, obesity (BMI >35). OBJECTIVES: General objective: Discovery of predictive/prognostic biomarkers of response to mepolizumab using flow cytometry, transcriptomic, and proteomic technologies. OTHER OBJECTIVES: 1.-To identify changes in surface markers of eosinophils and eosinophil subpopulations in response to treatment with mepolizumab using flow cytometry techniques. 2.-Transcriptomic analysis to identify mRNAs within the eosinophil transcriptome displaying enhanced or reduced levels in response to treatment with mepolizumab.3.-Proteomic profiling to identify proteins with differential abundance within the eosinophils in response to treatment with mepolizumab.4.-Check whether late-onset severe eosinophilic asthmatics display elevated levels of IGF-1, IGF-BP3, IGF-ALS in serum samples, if the response of mepolizumab depends on the levels of this markers, and if treatment with this biological reduces the concentration in serum of these IGF-family members. 5.-Identify proteins with differential abundance within the deep serum proteome of patients with SEA in response to treatment with mepolizumab by means of non-targeted proteomic analysis. MEASUREMENTS: Flow cytometry assays with multimarker panels 1 (regulatory), 2 (activation), and 3 eosinophil subsets. Clinical, hematological, biochemical and flow cytometry data generated at times T4, T16 and T32. Total RNA extraction from eosinophil lysates, assay of quality and quantity of RNA, and storage at -80ºC. Evaluation of the levels of 770 human protein-coding mRNAs linked to the recruitment, activation, and effector functions of myeloid cells by means of a direct multiplexed molecular measurement platform named nCounter® NanoString) in combination with a pre-made "nCounter® Human Myeloid Innate Immunity Panel (v2)". Perform retrotranscription and qPCR analyses of those mRNAs in eosinophils displaying the greatest abundance changes in response to mepolizumab treatment according to the nCounter® study. In addition, some additional mRNAs not included in the "nanoString Myeloid Innate Immunity" panel, such as FOXP3 (regulatory function), CRLF2, ST2, or IL-7R (cytokine receptors; activation), will be analysed. HPRT1 gene will be used as a house-keeping gene in this set of RTqPCR experiments. Perform SWATH-MS analysis in samples from 15 healthy donors and 15 patients (T0, T4, T16, T32) ("information-dependent acquisition" method or IDA; "Targeted label-free proteomics") in eosinophil homogenates. High abundant serum protein depletion using two protocols (P1: affinity chromatography, and P2: DTT precipitation) and SWATH-MS analysis of medium-low abundant serum proteome in samples from 15 healthy donors and 15 patients (T0, T4, T16, T32) ("information-dependent acquisition" method or IDA; "Targeted label-free proteomics").