PATINA - Precision Administration of Treatment in Neutrophilic severe Asthma

PATINA - 中性粒细胞性严重哮喘的精准治疗

基本信息

  • 批准号:
    10454802
  • 负责人:
  • 金额:
    $ 43.43万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-09-23 至 2024-06-30
  • 项目状态:
    已结题

项目摘要

Project Summary Severe asthma accounts for a disproportionate share of the morbidity associated with asthma. Multiple biological therapies are now becoming available that target eosinophilic or Type 2- driven asthma. However, data from SARP indicate that >60% of patients have severe asthma with a neutrophilic phenotype (SANP), as defined by induced sputum differentials. These patients experience excess morbidity, and there are currently no therapies that effectively target neutrophilic inflammation. We recently completed a study wherein we showed that targeting mast cells with imatinib (an inhibitor of stem-cell factor signaling at KIT) was most effective in patients with a neutrophilic phenotype. Further, we found that reductions in serum tryptase could identify patients most likely to respond to this treatment. Additionally, we have shown that in severe asthma, despite aggressive corticosteroid therapy (which normally reduces inflammatory eicosanoids) these patients continue to elaborate pro-inflammatory eicosanoids and low-pro-resolving eicosanoids. This is indicated by our discovery of persistent elevation of LTB4 (which is a potent neutrophil chemoattractant) in exhaled breath condensate. Lastly, IL-6 has been associated with non-Type 2 asthma, insulin resistance, and TH17 skewing of CD4+ cells. IL6 receptor polymorphisms have been associated with asthma risk, and high IL6 has been associated with reduced lung function and increased exacerbations, even in a cohort of severe asthmatics. We posit the following set of primary hypotheses and in each case we list the severe asthma phenotype and its phenotype marker(s) (PM), our primary candidate response marker at 2 months (RM) (in parentheses our secondary RMs), and the targeted intervention (TI). Our hypotheses are that in subjects with : 1) SANP with high serum IL6 (PM), a fall in—C-reactive protein (TH17 cells, insulin resistance ) (RM), will identify those more likely to improve after anti-IL6 therapy (TI); 2) SANP with high exhaled LTB4 (PM), a fall in exhaled LTB4 (urinary cysteinyl leukotrienes) (RM) will identify those more likely to improve with a 5- lipoxygenase inhibitor (5-LOi) (that blocks production of pro-inflammatory eicosanoids); 3) Severe asthma with increased sputum neutrophils (PM), a fall in serum tryptase (sputum supernatant tryptase) (RM) will identify asthmatics more likely to improve after treatment with a KIT inhibitor (TI). Our adaptive study design and treatment approach will allow us to define the threshold values of our RM that identify patients with a higher likelihood of response to targeted therapy. We have a team of seasoned trialists in adult and pediatric asthma, experts in biomarker development, the mechanisms behind these biomarkers, and adaptive trial design and integrative analyses, which will add significant strength to a PRECISE network.
项目总结

项目成果

期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Elliot Israel其他文献

Elliot Israel的其他文献

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{{ truncateString('Elliot Israel', 18)}}的其他基金

Project 3: Therapeutic Control of AERD
项目3:AERD的治疗控制
  • 批准号:
    10208132
  • 财政年份:
    2020
  • 资助金额:
    $ 43.43万
  • 项目类别:
PATINA - Precision Administration of Treatment in Neutrophilic severe Asthma
PATINA - 中性粒细胞性严重哮喘的精准治疗
  • 批准号:
    9406614
  • 财政年份:
    2017
  • 资助金额:
    $ 43.43万
  • 项目类别:
PATINA - Precision Administration of Treatment in Neutrophilic severe Asthma
PATINA - 中性粒细胞性严重哮喘的精准治疗
  • 批准号:
    9751385
  • 财政年份:
    2017
  • 资助金额:
    $ 43.43万
  • 项目类别:
PATINA - Precision Administration of Treatment in Neutrophilic severe Asthma
PATINA - 中性粒细胞性严重哮喘的精准治疗
  • 批准号:
    10216322
  • 财政年份:
    2017
  • 资助金额:
    $ 43.43万
  • 项目类别:
PATINA - Precision Administration of Treatment in Neutrophilic severe Asthma
PATINA - 中性粒细胞性严重哮喘的精准治疗
  • 批准号:
    9979941
  • 财政年份:
    2017
  • 资助金额:
    $ 43.43万
  • 项目类别:
PESBART: Effects of Physical Environment and Stress in Blacks in Relation to Asth
PESBART:物理环境和压力对黑人哮喘的影响
  • 批准号:
    8692300
  • 财政年份:
    2013
  • 资助金额:
    $ 43.43万
  • 项目类别:
Lipoxins in Severe Asthma (LIPSA)
严重哮喘中的脂氧素 (LIPSA)
  • 批准号:
    8263755
  • 财政年份:
    2011
  • 资助金额:
    $ 43.43万
  • 项目类别:
AMSA: ALXR/FBR Mediated Signaling in Severe Asthma
AMSA:ALXR/FBR 介导的严重哮喘信号传导
  • 批准号:
    8496109
  • 财政年份:
    2011
  • 资助金额:
    $ 43.43万
  • 项目类别:
AMSA: ALXR/FBR Mediated Signaling in Severe Asthma
AMSA:ALXR/FBR 介导的严重哮喘信号传导
  • 批准号:
    8316388
  • 财政年份:
    2011
  • 资助金额:
    $ 43.43万
  • 项目类别:
AMSA: ALXR/FBR Mediated Signaling in Severe Asthma
AMSA:ALXR/FBR 介导的严重哮喘信号传导
  • 批准号:
    8175601
  • 财政年份:
    2011
  • 资助金额:
    $ 43.43万
  • 项目类别:

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Investigating the Social Determinant and Developmental Risk Patterns in Childhood and Adolescence Associated with Adult Asthma and Diabetes Onset
调查儿童期和青少年期与成人哮喘和糖尿病发病相关的社会决定因素和发育风险模式
  • 批准号:
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  • 批准号:
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  • 批准号:
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  • 财政年份:
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    $ 43.43万
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A Pilot Study of the DASH Diet in Not-Well-Controlled Adult Asthma
DASH 饮食治疗未得到良好控制的成人哮喘的初步研究
  • 批准号:
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Transition from childhood to adult asthma: Predicting persistent and adult-onset asthma in young adults in the Raine longitudinal birth cohort
从童年到成人哮喘的转变:预测雷恩纵向出生队列中年轻人的持续性和成人发病性哮喘
  • 批准号:
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  • 财政年份:
    2012
  • 资助金额:
    $ 43.43万
  • 项目类别:
    Project Grants
Adult Asthma: Biology, Society and Environment
成人哮喘:生物学、社会和环境
  • 批准号:
    6799506
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    2001
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    $ 43.43万
  • 项目类别:
Physical and Social Environmental Factors in Adult Asthma Outcomes
成人哮喘结果中的物理和社会环境因素
  • 批准号:
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成人哮喘:生物学、社会和环境
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    $ 43.43万
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Adult Asthma: Biology, Society and Environment
成人哮喘:生物学、社会和环境
  • 批准号:
    6914953
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    2001
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    $ 43.43万
  • 项目类别:
Physical and Social Environmental Factors in Adult Asthma Outcomes
成人哮喘结果中的物理和社会环境因素
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