Sputum Microbial Markers of Type 2-Low Asthma

2 型低度哮喘的痰微生物标志物

基本信息

批准号：
10474069
负责人：
Yvonne Jean Huang
金额：
$ 7.97万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
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：
2017-06-07 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10474069
关键词：
Accounting Actinobacteria class Adrenal Cortex Hormones Adult Anti-Inflammatory Agents Asthma Bacteria Biological Markers Bronchoscopy Caring Chronic Clinical Clinical Research Cross-Sectional Studies Development Disease Epithelial Etiology Exhibits Gammaproteobacteria Genes Goals Guidelines Health Immune response Individual Inflammation Inhalation Intervention Link Longitudinal Studies Lower respiratory tract structure Outcome Pathogenesis Patients Pattern Phenotype Population Proteobacteria Research Respiratory Tract Infections Role Sampling Seasonal Variations Shapes Sputum Steroids Subgroup Testing Therapeutic airway inflammation antimicrobial asthmatic asthmatic patient bacterial community base cost effective cytokine disorder control dysbiosis eosinophil improved insight member metagenomic sequencing microbial microbiome microbiome composition microbiota novel novel diagnostics novel therapeutics prognostic prospective randomized trial respiratory microbiome respiratory pathogen tool treatment strategy

项目摘要

ABSTRACT Asthma is a heterogeneous disease for which inhaled corticosteroids (ICS) are a cornerstone of treatment by current guidelines. However, up to 45% of patients do not respond to ICS therapy, which is more effective against airway inflammation driven by type 2 immune responses. Moreover, ~50% of asthmatic adults do not demonstrate evidence of significant type 2 airway inflammation. Thus, patients with “Type 2-low” asthma comprise a large subgroup with poorly understood disease etiologies and limited treatment options. Moreover, the consequences of chronic ICS treatment in Type 2-low patients are uncertain and potentially even harmful. Recent bronchoscopy studies have revealed that Type 2-low asthma, even in ICS-naïve patients, is associated with significant alterations in the airway microbiome (“airway dysbiosis”), and patterns of airway dysbiosis are linked to differences in asthma control. These findings have largely relied on invasive studies using bronchoscopy. In contrast, analysis of induced sputum allows for larger numbers of patients to be studied longitudinally, so that relationships between airway dysbiosis, airway immune response patterns, and asthma control can be better understood. In addition, a sputum-based microbial biomarker(s) of asthma phenotype or outcome would allow for identification of particular patients for tailored interventions targeting the microbiome. In Aim 1 we will conduct cross-sectional analyses to identify induced sputum microbiota that are differentially enriched among Type 2-low individuals, stratified by ICS use, whose asthma is or is not well controlled. In Aim 2, a subset of asthmatic subjects in each group will be followed for 12 months, spanning seasonal variations in asthma control, airway microbiome composition, and ICS treatments that are important to consider. We will perform metagenomic sequencing studies to gain comprehensive insights into all microbiota present, the functions they contribute, and relationships between the airway microbiome, concurrent airway immune response patterns and clinical outcomes in Type 2-low patients. We expect to identify novel sputum-based microbial biomarkers of Type 2-low asthma and asthma outcomes in this population that will lead to new therapeutic avenues for this important subgroup.

抽象的哮喘是一种遗传性皮质类固醇（IC）的异质疾病通过当前准则进行处理。但是，多达45％的患者对ICS疗法没有反应，即更有效地抵抗由2型免疫反应驱动的气道炎症。此外，约有50％哮喘成年人没有证明2型气道炎症的证据。那，病人用“ 2型 - 低”哮喘完成一个大型亚组，疾病病因和有限的治疗选择。此外，慢性ICS治疗在2型低患者中的后果不确定，甚至有害。最近的支气管镜检查研究表明，2型低。哮喘，即使在没有ICS的患者中，哮喘与气道微生物组的显着改变有关（“气道营养不良”），气道营养不良的模式与哮喘控制的差异有关。这些发现很大程度上依赖于使用支气管镜检查的侵入性研究。相反，对诱导的分析痰液允许大量患者纵向研究，以便可以更好地理解气道营养不良，气道免疫响应模式和哮喘控制。在此外，哮喘表型或结果的基于痰液的微生物生物标志物将允许鉴定特定患者针对微生物组的量身定制干预措施。在目标1中，我们将进行横截面分析以鉴定诱导的痰液菌群不同的富集在2型低个体中，通过ICS使用分层，其哮喘是或无法很好地控制的。在AIM 2中每个组中哮喘受试者的子集将遵循12个月，跨越季节性变化在哮喘控制中，气道微生物组组成和重要的考虑。我们将进行核元素测序研究，以获得对所有微生物群的全面见解现在，它们贡献的功能以及气道微生物组之间的关系 2型低患者的气道免疫响应模式和临床结果。我们希望确定新型基于痰液的微生物生物标志物在该人群中的2-高哮喘和哮喘结果这将为这一重要子组带来新的治疗途径。