Multi-omics of the Frequent Exacerbator Asthmatic

频繁加重哮喘的多组学

基本信息

项目摘要

ABSTRACT Asthma is a common, complex and costly pediatric chronic condition in the U.S., resulting in nearly 2 million acute-care visits and $82 billion in overall costs each year. Children of low-income families in urban communities have the highest prevalence of asthma and the greatest disparities in asthma morbidity and mortality. In Hamilton County, OH, over 36,000 children have asthma, >14,000 of whom are Medicaid- insured with a 10-fold higher rate of hospitalization. Asthma exacerbations, acute episodes of increased asthma symptoms and deteriorations in lung function, are a major cause of stress for patients and families. While exacerbations are a prominent feature of poorly controlled and severe asthma, exacerbation rates can be high even in patients with mild asthma and asthma exacerbation frequency can remain unchanged despite intensive controller therapy. Indeed, pediatric studies have revealed that exacerbations continue to occur despite good baseline symptom control. A frequent exacerbator phenotype of asthma (defined by 2 or more exacerbations/year), has been described, but little is known about this asthma subgroup, which disproportionately affects urban populations and is responsible for considerable asthma morbidity and healthcare costs. No specific clinical characteristics can reliably discriminate between frequent and nonfrequent exacerbators highlighting the need for systems level approaches. Our center-specific project will fill this gap in understanding. Our preliminary data reveal differentially expressed and differentially methylated genes in the nasal epithelial of children who are frequent exacerbators and highlight biologic pathways that implicate distinct mechanisms that underlie the frequent exacerbator phenotype. We will test the hypothesis: the frequent exacerbator is a distinct endotype of asthma that is characterized by host nasal epithelial transcriptomic and/or DNA methylomic patterns that distinguish the frequent exacerbator from asthmatic children who are not frequent exacerbators, and that these patterns are, in part, triggered by distinct nasal microbial patterns. We propose an innovative strategy utilizing multiple systems-based approaches that layer host nasal biome and methylome patterns with nasal epithelial transcriptomics taken during an acute exacerbation (before administration of steroids). We are uniquely poised to conduct this study due to the tremendous infrastructure that we have established as part of the Ohio Pediatric Asthma Repository, and our multidisciplinary team. The overall objective of our studies is to improve the lives of children with asthma from low-income families who live in urban communities. We propose to 2 aims: (1) To contribute to the overall CAUSE goals by conducting network-wide CAUSE clinical research projects and participating in the CAUSE Steering Committee and other network functions; (2) To conduct a center- specific project aligned with CAUSE goals focused on the frequent exacerbator asthma phenotype.
摘要

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
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Gurjit K. Khurana Hershey其他文献

Frequent exacerbator—a novel endotype of pediatric asthma
  • DOI:
    10.1016/j.jaci.2025.05.006
  • 发表时间:
    2025-07-01
  • 期刊:
  • 影响因子:
    11.200
  • 作者:
    Kieran J. Phelan;Gurjit K. Khurana Hershey
  • 通讯作者:
    Gurjit K. Khurana Hershey
Biomarker-driven drug development for allergic diseases and asthma: An FDA public workshop
针对过敏性疾病和哮喘的生物标志物驱动的药物开发:FDA 公共研讨会
  • DOI:
    10.1016/j.jaci.2025.03.014
  • 发表时间:
    2025-06-01
  • 期刊:
  • 影响因子:
    11.200
  • 作者:
    Ronald L. Rabin;Matthew C. Altman;S. Hasan Arshad;Richard D. Beger;Pamela A. Frischmeyer-Guerrerio;Elena Goleva;Robert G. Hamilton;Gurjit K. Khurana Hershey;Mohamed H. Shamji;Hugh A. Sampson;Alexandra F. Santos;Wayne G. Shreffler;Alkis Togias;Stefan Vieths;Erik Wambre;Sally E. Wenzel;Kathleen Hise;Joohee Lee;Anubha Tripathi;Jay E. Slater
  • 通讯作者:
    Jay E. Slater
Rhinoconjunctivitis symptoms in children and adolescents with asthma: Longitudinal clustering analysis
哮喘儿童和青少年的鼻结膜炎症状:纵向聚类分析
  • DOI:
    10.1016/j.jaci.2024.12.1084
  • 发表时间:
    2025-05-01
  • 期刊:
  • 影响因子:
    11.200
  • 作者:
    Alkis Togias;Peter J. Gergen;Andrew H. Liu;Haejin Kim;Robert A. Wood;George T. O’Connor;Melanie Makhija;Gurjit K. Khurana Hershey;Carolyn M. Kercsmar;Rebecca S. Gruchalla;Carin Lamm;Leonard B. Bacharier;Shilpa J. Patel;James E. Gern;Daniel J. Jackson;Cynthia M. Visness;Agustin Calatroni;William W. Busse
  • 通讯作者:
    William W. Busse
emTSLP/em disease-associated genetic variants combined with airway TSLP expression influence asthma risk
  • DOI:
    10.1016/j.jaci.2021.05.033
  • 发表时间:
    2022-01-01
  • 期刊:
  • 影响因子:
    11.200
  • 作者:
    Liza Bronner Murrison;Xiaomeng Ren;Kristina Preusse;Hua He;John Kroner;Xiaoting Chen;Seth Jenkins;Elisabet Johansson;Jocelyn M. Biagini;Matthew T. Weirauch;Raphael Kopan;Lisa J. Martin;Gurjit K. Khurana Hershey
  • 通讯作者:
    Gurjit K. Khurana Hershey
High number of early respiratory infections in association with allergic sensitization to mold promotes childhood asthma
  • DOI:
    10.1016/j.jaci.2017.11.058
  • 发表时间:
    2018-05-01
  • 期刊:
  • 影响因子:
  • 作者:
    Leilanie Perez Ramirez;Heepke Wendroth;Lisa J. Martin;Valentina V. Pilipenko;Hua He;John Kroner;Patrick H. Ryan;Grace K. LeMasters;James E. Lockey;David I. Bernstein;Gurjit K. Khurana Hershey;Jocelyn M. Biagini Myers
  • 通讯作者:
    Jocelyn M. Biagini Myers

Gurjit K. Khurana Hershey的其他文献

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{{ truncateString('Gurjit K. Khurana Hershey', 18)}}的其他基金

Medical Scientist Training Program
医学科学家培训计划
  • 批准号:
    10620999
  • 财政年份:
    2023
  • 资助金额:
    $ 45.2万
  • 项目类别:
Multi-omics of the Frequent Exacerbator Asthmatic
频繁加重哮喘的多组学
  • 批准号:
    10197294
  • 财政年份:
    2021
  • 资助金额:
    $ 45.2万
  • 项目类别:
Multi-omics of the Frequent Exacerbator Asthmatic
频繁加重哮喘的多组学
  • 批准号:
    10390405
  • 财政年份:
    2021
  • 资助金额:
    $ 45.2万
  • 项目类别:
Atopic dermatitis: mechanisms of disease progression
特应性皮炎:疾病进展的机制
  • 批准号:
    10379962
  • 财政年份:
    2020
  • 资助金额:
    $ 45.2万
  • 项目类别:
Atopic dermatitis: mechanisms of disease progression
特应性皮炎:疾病进展的机制
  • 批准号:
    10596577
  • 财政年份:
    2020
  • 资助金额:
    $ 45.2万
  • 项目类别:
Atopic dermatitis: mechanisms of disease progression
特应性皮炎:疾病进展的机制
  • 批准号:
    9974832
  • 财政年份:
    2020
  • 资助金额:
    $ 45.2万
  • 项目类别:
Role and Regulation of TSLP in Childhood Allergic Disease
TSLP在儿童过敏性疾病中的作用和调节
  • 批准号:
    10307538
  • 财政年份:
    2017
  • 资助金额:
    $ 45.2万
  • 项目类别:
Role and Regulation of TSLP in Childhood Allergic Disease
TSLP在儿童过敏性疾病中的作用和调节
  • 批准号:
    10063471
  • 财政年份:
    2017
  • 资助金额:
    $ 45.2万
  • 项目类别:
Infrastructure and Opportunity Fund Management
基础设施和机会基金管理
  • 批准号:
    8329216
  • 财政年份:
    2011
  • 资助金额:
    $ 45.2万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    8196249
  • 财政年份:
    2011
  • 资助金额:
    $ 45.2万
  • 项目类别:

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Positive Affect and Pediatric Asthma: An Innovative Positive Psychology Model to Improve Asthma Management and Health
积极情绪与小儿哮喘:改善哮喘管理和健康的创新积极心理学模型
  • 批准号:
    10712703
  • 财政年份:
    2023
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How the immune response can affect influenza virus and asthma
免疫反应如何影响流感病毒和哮喘
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    nhmrc : GNT1054081
  • 财政年份:
    2013
  • 资助金额:
    $ 45.2万
  • 项目类别:
    Early Career Fellowships
How do thick airway walls affect airway hyperresponsiveness in asthma?
气道壁厚如何影响哮喘气道高反应性?
  • 批准号:
    nhmrc : 512387
  • 财政年份:
    2008
  • 资助金额:
    $ 45.2万
  • 项目类别:
    NHMRC Project Grants
WHAT FAMILY PROCESSES AFFECT CHILDHOOD ASTHMA OUTCOME?
哪些家庭过程会影响儿童哮喘的结局?
  • 批准号:
    6566335
  • 财政年份:
    2000
  • 资助金额:
    $ 45.2万
  • 项目类别:
WHAT FAMILY PROCESSES AFFECT CHILDHOOD ASTHMA OUTCOME?
哪些家庭过程会影响儿童哮喘的结局?
  • 批准号:
    6504483
  • 财政年份:
    2000
  • 资助金额:
    $ 45.2万
  • 项目类别:
WHAT FAMILY PROCESSES AFFECT CHILDHOOD ASTHMA OUTCOME?
哪些家庭过程会影响儿童哮喘的结局?
  • 批准号:
    6304309
  • 财政年份:
    1999
  • 资助金额:
    $ 45.2万
  • 项目类别:
WHAT FAMILY PROCESSES AFFECT CHILDHOOD ASTHMA OUTCOME?
哪些家庭过程会影响儿童哮喘的结局?
  • 批准号:
    6114202
  • 财政年份:
    1998
  • 资助金额:
    $ 45.2万
  • 项目类别:
The way in which newly discovered protein messengers in the lung affect asthma
肺部新发现的蛋白质信使影响哮喘的方式
  • 批准号:
    nhmrc : 970947
  • 财政年份:
    1997
  • 资助金额:
    $ 45.2万
  • 项目类别:
    NHMRC Project Grants
WHAT FAMILY PROCESSES AFFECT CHILDHOOD ASTHMA OUTCOME?
哪些家庭过程会影响儿童哮喘的结局?
  • 批准号:
    6275437
  • 财政年份:
    1997
  • 资助金额:
    $ 45.2万
  • 项目类别:
WHAT FAMILY PROCESSES AFFECT CHILDHOOD ASTHMA OUTCOME
哪些家庭过程会影响儿童哮喘的结局
  • 批准号:
    6245226
  • 财政年份:
    1997
  • 资助金额:
    $ 45.2万
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