Active clinical trials for "Asthma"

This study is being undertaken in order to enhance our understanding how human airways are being constricted in healthy people and in individuals with asthma. There is an unmet need for identification of new pathways (mediators) related to enhanced constriction of the asthmatic airways that would reveal new targets for therapy. Sphingosine-1-phosphate (S1P) is a naturally occurring bioactive lipid molecule that has been suggested to play an important role in asthma. Physiologically, S1P can be detected in human blood but local tissue concentrations (for example in the lung) are very low. Upon activation many cells can secrete S1P. Increased concentrations of S1P have been detected in airways of asthmatic subjects after allergen inhalation. When studied in animal models, S1P did not cause contraction of airways in healthy animals but contracted airways in animal with pulmonary inflammation. In laboratory experiments S1P has been shown to be a potent constrictor of cells responsible for contraction of human airways. As yet, however, we lack evidence that S1P actually causes constriction of airways in real life. Establishing S1P as a molecule capable of causing airway constriction in humans and perhaps specifically in asthmatics will have important implications for our understanding of physiological and pathophysiological responses in human airways and could open new windows for therapeutic strategies in diseases like asthma.

Rationale Although the majority of asthma patients can be effectively treated with currently available medications, a substantial subset remains severe, causing a considerable proportion of resource expenditure. Severe asthma is now widely accepted to be a heterogeneous syndrome consisting of multiple phenotypes identified by specific biomarkers and targeted by tailored biological therapies. However, much remains unclear regarding the best approaches to manage these patients, or concerning the pathophysiological mechanisms underlying the disease. Small airways (SA) are defined as those airways with an internal diameter <2 mm. In patients affected by asthma, it has been reported that SA are the predominant site of airflow resistance. Peripheral airways are thickened in asthma due to chronic inflammation in the epithelium, submucosa and muscle area. It has been suggested that the outer wall is more inflamed than the inner wall, with a higher number of lymphocytes, eosinophils, and neutrophils associated to an increased mRNA expression of interleukin-4 (IL-4), IL-5 and eotaxin. Moreover, it is well documented that SA inflammation and dysfunction contributes significantly to the clinical impact of asthma and that 50-60% of asthmatics have a SA involvement across all disease severities. An important question is whether SA disease in asthma is variable among distinct asthma phenotypes and whether it occurs in all patients. Cluster analyses have been recently used to identify specific asthma phenotypes, but markers of SA function have not been investigated. However, evidence is accumulating to support the concept that SA dysfunction and inflammation may contribute to distinct asthma phenotypes. Recent findings indicate that SA are significantly affected in severe asthma and that their involvement is associated with worse disease outcomes. It has been reported that patients with asthma and a history of frequent exacerbations per year had a significant SA involvement Furthermore, peripheral airways significantly contribute not only to the level of asthma control, but also to patients' quality of life and perception of symptoms. At last more thickened SA and higher numbers of eosinophils are detectable in subjects with fatal asthma. The assessment of SA represents a big challenge and requires qualified expertise and sophisticated techniques including body plethysmography, single and multiple breath nitrogen washout, impulse oscillometry (IOS), fraction exhaled NO at multiflow, sputum induction and high-resolution chest CT (HRCT). Such procedures can either provide functional information on the degree/extent of ventilation heterogeneity and air trapping or facilitate the understanding of the inflammatory and remodeling processes. These measures are not usually part of the evaluation of asthmatic patients and in the monitoring of the effects of drugs recommended for severe asthma. Mepolizumab represents an innovative weapon for the treatment of severe eosinophilic asthma. In most of these patients the drug controls inflammation, improves lung function, ameliorates clinical symptoms, reduces exacerbations and has a marked steroid-sparing effect. However, there is still a significant proportion of non-responders and a lack of validated predictive biomarkers in such subpopulation. In regard to this, very limited findings are available about the effect of mepolizumab on SA. At the best of our knowledge, the only paper available in literature, addressing the topic, is the study of Farah and co-workers. The authors found that an early improvement in SA function was associated with better asthma control and represented a significant contributor to the therapeutic response. However, the study was conducted in a limited cohort of patients, assessing SA only through multi breath nitrogen washout, and not considering the relationship between SA disease and levels of peripheral/sputum eosinophils. Also, a study was recently initiated at the Hopitaux de Paris to evaluate airway remodelling during mepolizumab treatment (REMOMEPO, NCT03797404). A better definition of severe asthma phenotypes and endotypes, as well as the identification of novel disease targets and biomarkers to predict treatment response and monitor efficacy and safety of biological drugs over time, would favor a Precision Medicine approach translating in both improved disease management and reduced healthcare costs and social burdens. This is considered a crucial unmet need and further research in the field is strongly recommended by international guidelines, respiratory scientific societies, healthcare systems and regulatory boards.

The purpose of this research is to develop and evaluate an mHealth communication intervention designed to improve asthma medication adherence amongst rural Latino children in South Carolina.

(i) To validate the inversed occlusion technique by comparing the results of resistance obtained on the relaxed expiratory occlusion monitor (REOM) with the resistance obtained with respiratory oscillometry (OSC) measurements on the tremoflo® C-100 and (ii) explore (within-test and day-to-day) repeatability and responsiveness to change of this technique when used as home monitoring device in children with asthma.

This study will recruit patients who are being prescribed Mepolizumab as part of their standard clinical care for the treatment of severe eosinophilic asthma. Over the course of their treatment, research data (questionnaires) and research samples (blood, breath and urine) will be collected in parallel to standard clinical measurements. The data and samples will be investigated to help better understand how Mepolizumab works, why it doesn't work in certain patients and why it works very well in others. This will help prescribers better identify patients that will benefit from Mepolizumab.

The purpose of this study is to evaluate clinical and histological response to bronchial thermoplasty in severe asthma patients.

Asthma is the most common chronic respiratory disorder in children. Despite significant advances in understanding of asthma, available therapies fail to alter the natural history and progression of the disease. Airway epithelial cells are continuously exposed to and injured by environmental irritants, such as viruses and pollutants, and as such are ideally situated to orchestrate airway function in response to these stimuli. Severe or difficult-to-treat asthma in children is a complicated disorder characterized by ongoing symptoms and persistent airway inflammation and oxidant stress despite corticosteroid treatment. Although severe asthma is likely a heterogeneous disorder, affected children similar clinical features, including gas trapping, bronchial hyperresponsiveness, and aeroallergen sensitization. However, the molecular and cellular pattern of inflammation in children with severe asthma are not uniform : some investigators have found increased eosinophils and TH2 derived cytokines, others have noted noneosinophilic patterns with neutrophil activation. Given the heterogeneity of the inflammatory response in children with severe asthma, additional methods to distinguish severe asthma are needed.

Background Ambient airborne particulate material (PM) is defined according the aerodynamic diameter into coarse, fine, and ultrafine or "nano" sized particles ranging between 2.5-10 µm (coarse), <2.5 µm (fine), and <0.1 µm (nano(. Many studies have examined particle effect on respiratory health in children, mainly by environmental monitoring of coarse and fine particles. Biological assessment of individual exposure to nano sized particles in correlation to adverse health effect was not previously studied. Hypothesis individual exposure to nano sized particles in children is associated with reduction in forced expiratory volume at one second.

The goal of the project is to define the prevalence and inflammatory background of exercise-induced bronchoconstriction (EIB) in school children and determine individual and environmental risk factors for EIB. The obtained results will provide objective measures on biological processes leading to bronchoconstriction during exercise, as might be experienced naturally during the school life. The results could be applied in the management of EIB patients with or without asthma. The results of planned research will be published in journals with national and international impact, and presented during symposia and conferences.

The purpose of this study is to learn the pediatric asthma control status under community management model. To learn the differences of pediatric asthma control status when subjects assigned to community hospitals or Shanghai Childrens Medical Centre. To learn the treatment adherence and the frequency of asthma attack under community management model.