Controlling and preventing Asthma progression and Severity in Kids (CASK)

控制和预防儿童哮喘进展和严重程度 (CASK)

基本信息

  • 批准号:
    9318449
  • 负责人:
  • 金额:
    $ 342.1万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-07-20 至 2023-06-30
  • 项目状态:
    已结题

项目摘要

Project Summary/Abstract Asthma remains one of the most important challenges to pediatric public health in the US, affecting millions of children, causing significant morbidity, mortality, and source of tremendous financial burden. Prevention of asthma is a pressing, unmet need of utmost priority. The vast majority of children with persistent and chronic asthma demonstrate aeroallergen sensitization (IgE antibody production), which remains the pivotal risk factor for developing persistent, progressive asthma throughout life. It has recently been shown that aeroallergen sensitization precedes viral wheezing and is the pivotal causal pathway and essential susceptibility factor in the persistence and progression of the disease. Most aeroallergen sensitization begins around the age of 2-3 years and escalates during school age. The progression appears to be dependent on exposures to offending allergens-- the greatest increase in development and impairment from asthma is seen in those with a tendency toward Type 2 inflammation who are sensitized and exposed to high levels of offending allergens. In addition to its role in mediating allergen-induced responses, IgE signals impair innate anti-viral immune responses which could lead to increased viral infections and thus potentially further enhance the cascade of progression to asthma. Omalizumab (anti-IgE) markedly reduces asthma exacerbations during the viral season and anti- IgE treated children have demonstrated restored IFN-α response to rhinovirus. This suggests that anti-IgE prevents IgE driven responses to offending allergen exposure in those with a Type 2 phenotype AND attenuates viral infections in this Type 2 phenotype. Thus, utilizing anti-IgE in young children has the potential to prevent the development of established asthma in susceptible children by blocking all IgE allergen-antibody interactions (including responses to subclinical exposures) AND by reducing the response to viral exposure which may lead to asthma. We hypothesize that blockade of IgE in young children (age 2-3) at high risk for development of asthma will prevent progression to established asthma. We will test this hypothesis by examining the effect of anti-IgE on the development of asthma in a double-blind, randomized, placebo- controlled parallel trial of anti-IgE vs placebo in 250 children aged 2-3 years old at high risk of developing asthma, who will be followed for 2 years after 2 years of therapy is discontinued. Primary outcome will be the proportion of participants with current, active asthma as defined in the NIAID URECA birth cohort, between the two treatment groups at the end of Year 4, the final 12 months of the trial off study medication. Secondary outcomes will include occurrence of wheezing episodes, exacerbations requiring steroids, and new and persistent allergen-specific IgE sensitizations after IgE therapy. If confirmed, anti-IgE therapy would be the first intervention to change the natural history of childhood asthma. This trial will not only allow us to expand our understanding of asthma immunopathogenesis, but will also create opportunities to identify IgE mediated and other novel approaches impacting our understanding towards preventing the disease.
项目摘要/摘要 哮喘仍然是美国儿科公共卫生面临的最重要挑战之一,影响着数百万人 儿童问题,造成严重的发病率、死亡率和巨大的经济负担。预防 哮喘是一种迫切的、最优先的、尚未得到满足的需求。绝大多数患有顽固性和慢性病的儿童 哮喘表现为空气变应原致敏(IgE抗体产生),这仍然是关键的危险因素 用于在一生中发展为持续性、进行性哮喘。最近有研究表明,空气过敏原 致敏先于病毒性喘息,是致病的关键途径和基本的易感因素。 疾病的持续性和进行性。大多数空气过敏原过敏始于2-3岁左右。 数年,并在学龄期上升。这一进展似乎依赖于接触到违规行为。 过敏原--哮喘的发展和损害的增加最多的是那些有过敏倾向的人 对于2型炎症,他们是致敏的,并暴露在高水平的令人讨厌的过敏原中。此外 由于其在介导过敏原诱导的反应中的作用,IgE信号削弱了先天的抗病毒免疫反应 这可能会导致病毒感染增加,从而有可能进一步加强级联发展 为了哮喘。奥马珠单抗(抗IgE)在病毒季节显著减少哮喘恶化,并抗 免疫球蛋白E治疗的儿童表现出对鼻病毒的干扰素-α反应恢复。这表明抗-IgE 预防2型患者对过敏原暴露的IgE驱动的反应 减轻这种2型的病毒感染。因此,在幼儿中使用抗IgE具有潜在的作用。 通过阻断所有IgE变应原抗体预防易感儿童确诊哮喘的发展 相互作用(包括对亚临床暴露的反应)和减少对病毒暴露的反应 这可能会导致哮喘。我们假设,阻断免疫球蛋白E在幼儿(2-3岁)中是高危的 哮喘的发展将防止发展为已确诊的哮喘。我们将通过以下方式验证这一假设 在双盲、随机、安慰剂中检测抗IgE在哮喘发生中的作用 250例2~3岁高危儿童抗-IgE与安慰剂对照平行试验 哮喘,在治疗2年后停止治疗,随访2年。主要结果将是 NIAID URECA出生队列中定义的患有当前活动性哮喘的参与者的比例 两组治疗均在第4年末,试验的最后12个月停药研究。次要的 结果将包括发生喘息发作,病情恶化需要类固醇,以及新的和 IgE治疗后持续的过敏原特异性IgE敏化。如果得到证实,抗IgE疗法将是第一个 干预改变儿童哮喘的自然病史。这一试验不仅将使我们能够扩大我们的 了解哮喘的免疫发病机制,但也将创造机会,以确定IgE介导的和 其他新的方法影响了我们对预防疾病的理解。

项目成果

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WANDA PHIPATANAKUL其他文献

WANDA PHIPATANAKUL的其他文献

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{{ truncateString('WANDA PHIPATANAKUL', 18)}}的其他基金

School Inner-City Asthma Intervention Study : Human Epidemiology and Response to SARS-COV-2 (HEROS) Supplement
学校内城区哮喘干预研究:人类流行病学和对 SARS-COV-2 (HEROS) 补充剂的反应
  • 批准号:
    10162929
  • 财政年份:
    2020
  • 资助金额:
    $ 342.1万
  • 项目类别:
Controlling and preventing Asthma progression and Severity in Kids (CASK)
控制和预防儿童哮喘进展和严重程度 (CASK)
  • 批准号:
    10431970
  • 财政年份:
    2016
  • 资助金额:
    $ 342.1万
  • 项目类别:
Controlling and preventing Asthma progression and Severity in Kids (CASK)
控制和预防儿童哮喘进展和严重程度 (CASK)
  • 批准号:
    10215240
  • 财政年份:
    2016
  • 资助金额:
    $ 342.1万
  • 项目类别:
Controlling and preventing Asthma progression and Severity in Kids (CASK)
控制和预防儿童哮喘进展和严重程度 (CASK)
  • 批准号:
    10074697
  • 财政年份:
    2016
  • 资助金额:
    $ 342.1万
  • 项目类别:
Controlling and preventing Asthma progression and Severity in Kids (CASK)
控制和预防儿童哮喘进展和严重程度 (CASK)
  • 批准号:
    9189905
  • 财政年份:
    2016
  • 资助金额:
    $ 342.1万
  • 项目类别:
School Inner-City Asthma Intervention Study
学校内城区哮喘干预研究
  • 批准号:
    8992349
  • 财政年份:
    2015
  • 资助金额:
    $ 342.1万
  • 项目类别:
SICAS- Diversity Supplement
SICAS-多样性补充
  • 批准号:
    9154829
  • 财政年份:
    2015
  • 资助金额:
    $ 342.1万
  • 项目类别:
Midcareer Investigator Award: Urban School Allergen Exposures and Childhood Asthm
职业生涯中期调查员奖:城市学校过敏原暴露和儿童哮喘
  • 批准号:
    9064061
  • 财政年份:
    2013
  • 资助金额:
    $ 342.1万
  • 项目类别:
K24: Midcareer Investigator Award: Urban School Allergen Exposure and Childhood Asthma
K24:职业生涯中期研究员奖:城市学校过敏原暴露和儿童哮喘
  • 批准号:
    9920076
  • 财政年份:
    2013
  • 资助金额:
    $ 342.1万
  • 项目类别:
Midcareer Investigator Award: Urban School Allergen Exposures and Childhood Asthm
职业生涯中期调查员奖:城市学校过敏原暴露和儿童哮喘
  • 批准号:
    8667990
  • 财政年份:
    2013
  • 资助金额:
    $ 342.1万
  • 项目类别:

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