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.

抽象的哮喘是一种异质性疾病，吸入皮质类固醇 (ICS) 是治疗哮喘的基石然而，高达 45% 的患者对 ICS 治疗没有反应。更有效地对抗 2 型免疫反应驱动的气道炎症，此外，约 50% 成人哮喘患者没有表现出明显的 2 型空气炎症的证据。 “2 型低度”哮喘包括一个疾病病因知之甚少的大亚组，此外，2 型低度患者慢性 ICS 治疗的后果也有限。最近的支气管镜检查研究表明，2 型低。哮喘，即使是未接受过 ICS 的患者，也与气道微生物群的显着改变相关（“气道失调”），气道失调的模式与哮喘控制的差异有关。研究结果很大程度上依赖于使用支气管镜检查的侵入性研究，相反，诱导分析。痰液可以对更多的患者进行纵向研究，以便研究之间的关系可以更好地了解气道生态失调、气道免疫反应模式和哮喘控制。此外，基于痰的哮喘表型或结果的微生物生物标志物将允许在目标 1 中，我们将识别特定患者以进行针对微生物组的定制干预措施。进行横断面分析以确定差异富集的诱导痰微生物群在 2 型低个体中，根据 ICS 使用情况进行分层，其哮喘得到或未得到良好控制。在目标 2 中，a 每组中的哮喘受试者子集将被跟踪 12 个月，跨越季节变化哮喘控制、气道微生物组组成和 ICS 治疗中需要考虑的重要因素。我们将进行宏基因组测序研究，以全面了解所有微生物群目前，它们贡献的功能以及气道微生物组之间的关系，并发我们期望确定 2 型低水平患者的气道免疫反应模式和临床结果。基于痰的新型 2 型哮喘微生物生物标志物以及该人群中的哮喘结果这将为这一重要亚组带来新的治疗途径。