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In asthmatics with airway hyperresponsiveness and a "T2 immune signature" (type 2), Dupilumab will suppress airway hyperresponsiveness (assessed by methacholine PC20 ≤ 4 mg/mL (PC20: provocative concentration causing a 20% fall in FEV1) OR ≥15% decreased in forced expired volume in 1 second (FEV1) during saline inhalation for sputum induction OR ≥25% improvement in FEV1 after bronchodilator) and airway eosinophilia (assessed by sputum eosinophils) and this will be associated with greater asthma control and improved ventilation heterogeneity.
Along with these features of eosinophil recruitment, degranulation and autoantibody generation, that are partly dependent on (interleukin-4) IL-4 and (interleukin-13) IL-13 signalling, two additional characteristic features of asthma ie airway hyperresponsiveness and mucus hypersecretion are also determined by IL-13 biology. Neither of these important features have been investigated in any clinical trials of anti-IL-13 molecules. Accurate endotyping to identify patients in whom IL-13 mediated biology is the dominant pathobiology of asthma (selecting patients with significant airway hyperresponsiveness and mucus secretion) may elicit greater clinical effect. Taken together, we propose to investigate the effects of Dupilumab on airway hyperresponsiveness, on airway eosinophilia and mucus biology and their relation to airway structure and function (ventilation heterogeneity), and airway autoimmune responses.
To satisfy the proposed objective we will evaluate well-established outcome measures of airway hyperresponsiveness (provocation concentration of methacholine causing a 20% fall in FEV1 (PC20), type 2 inflammation (sputum eosinophils, blood eosinophils and exhaled nitric oxide (eNO)) and mucus biology.
Firestone Institute for Respiratory Health, St. Joseph's Healthcare
Not yet recruiting
Published on BioPortfolio: 2019-03-27T08:10:42-0400
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A long-term observational registry in patients with atopic dermatitis initiating treatment with DUPIXENT® (dupilumab)
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Interleukin (IL)-4 and IL-13, signature type 2 cytokines, exert their actions by binding to two types of receptors sharing the IL-4R α chain (IL-4Rα). Since IL-4 and IL-13 play important and redunda...
Dupilumab blocks the shared receptor component for interleukin-4 and interleukin-13, key drivers of type 2 inflammation, including immunoglobulin E (IgE)-mediated allergic inflammation in asthma. In t...
The objective of this article was to conduct a systematic review of the treatment of moderate-to-severe asthma by administrating Dupilumab.
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Misunderstanding among individuals, frequently research subjects, of scientific methods such as randomization and placebo controls.
Asthma attacks caused, triggered, or exacerbated by OCCUPATIONAL EXPOSURE.
An effect usually, but not necessarily, beneficial that is attributable to an expectation that the regimen will have an effect, i.e., the effect is due to the power of suggestion.
Asthma attacks following a period of exercise. Usually the induced attack is short-lived and regresses spontaneously. The magnitude of postexertional airway obstruction is strongly influenced by the environment in which exercise is performed (i.e. inhalation of cold air during physical exertion markedly augments the severity of the airway obstruction; conversely, warm humid air blunts or abolishes it).
Drugs that are used to treat asthma.
Asthma is caused by inflammation of small tubes, called bronchi, which carry air in and out of the lungs. If you have asthma, the bronchi will be inflamed and more sensitive than normal. When you come into contact with something that irritates your...
The term allergy is used to describe a response, within the body, to a substance, which is not necessarily harmful in itself, but results in an immune response and a reaction that causes symptoms and disease in a predisposed person, which in turn can cau...