Development and Validation of a Prognostic Transcriptomic Signature for Chronic Hypersensitivity Pneumonitis

慢性过敏性肺炎预后转录组特征的开发和验证

基本信息

批准号：
9973969
负责人：
Evans Fernandez
金额：
$ 86.22万
依托单位：
NATIONAL JEWISH HEALTH
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9973969
关键词：
Acute Address Antigens Area Biological Bronchoscopy California Cause of Death Cessation of life Characteristics Chicago Chronic Chronic Disease Classification Clinic Clinical Clinical Data Clinical Management Clinical Trials Clinical assessments Complement Complex Computers Counseling Data Development Diagnosis Diagnostic radiologic examination Disease Disease Outcome Disease Progression Early Diagnosis Exposure to Extrinsic allergic alveolitis Foundations Gene Expression Gene Expression Profile Genes Goals Health Immunologics Inhalation Exposure Knowledge Lead Lung diseases Measures Mediating Modeling Molecular Molecular Profiling Molecular Target Outcome Patients Peripheral Blood Mononuclear Cell Persons Phenotype Physiological Prevention approach Procedures Prospective cohort Public Health Pulmonary Fibrosis Research Respiratory physiology Risk Risk stratification Sampling Severity of illness Shotgun Sequencing Subgroup Testing Texas Time Transcript United States Universities Validation Visual X-Ray Computed Tomography base chest computed tomography clinical phenotype clinical risk cohort deep sequencing differential expression disease heterogeneity disorder risk experience follower of religion Jewish high risk improved innovation interstitial molecular phenotype molecular targeted therapies novel outcome forecast outcome prediction patient subsets peripheral blood personalized therapeutic predict clinical outcome predictive marker predictive signature prognostic prospective recruit research clinical testing transcriptome transcriptome sequencing transcriptomics

项目摘要

PROJECT SUMMARY/ABSTRACT: Hypersensitivity pneumonitis (HP) is an immunologically mediated form of lung disease, resulting from inhalational exposure to a large variety of antigens. For unknown reasons, a subgroup of patients with HP without a known inciting antigen exposure develops chronic disease with progressive pulmonary fibrosis (the leading cause of death). Accurately identifying patients at risk of disease progression is necessary for prognosis and therapy. The objective of this proposal is to refine our current clinical risk stratification by identifying and validating a transcriptomic signature from peripheral blood mononuclear cells in patients with chronic HP that is predictive of disease progression. We hypothesize that the clinical course of chronic HP is associated with a peripheral blood gene expression signature of risk that can be used to refine the prognosis and predict the clinical outcome. Guided by strong preliminary data, this hypothesis will be tested by two specific aims: i) Establish transcriptomic signatures at time of initial presentation in peripheral blood mononuclear cells from patients with chronic HP in a Discovery cohort and then validate the signature in an independent chronic HP replication cohort; and ii) Establish a time-course transcriptomic profile predictive of disease progression in the Discovery cohort and validate the signature profile in the independent chronic HP replication cohort. pursuing The proposed research is significant because it will provide the knowledge that will enhance our ability to predict disease progression, a level of prognostication which is not possible with current clinical measures alone. Relevance to Public Health: This is an important and under-investigated area that has the potential to fundamentally advance our understanding of the pathobiology of disease progression and provide the groundwork to define molecular targets relevant to chronic HP disease progression.

项目摘要/摘要：过敏性肺炎 (HP) 是一种免疫介导的肺炎形式由于吸入多种抗原而导致的肺部疾病。由于未知的原因，一个未暴露于已知刺激抗原的 HP 患者亚组会发展为慢性疾病进行性肺纤维化（死亡的主要原因）。准确识别有疾病风险的患者进展对于预后和治疗是必要的。该提案的目的是完善我们当前的临床通过识别和验证外周血单核细胞的转录组特征进行风险分层慢性 HP 患者可预测疾病进展。我们假设临床过程慢性 HP 与外周血基因表达风险特征相关，可用于改善慢性 HP 风险。预后并预测临床结果。在强有力的初步数据的指导下，这一假设将得到检验两个具体目标： i) 在外周血中首次出现时建立转录组特征来自 Discovery 队列中慢性 HP 患者的单核细胞，然后在独立的慢性HP复制队列； ii) 建立预测的时间进程转录组图谱 Discovery 队列中的疾病进展并验证独立慢性 HP 中的特征概况复制队列。追求拟议的研究意义重大，因为它将提供增强知识我们预测疾病进展的能力，这是目前临床不可能达到的预测水平单独采取措施。与公共卫生的相关性：这是一个重要且研究不足的领域，有潜力从根本上增进我们对疾病进展病理学的理解，并提供定义与慢性 HP 疾病进展相关的分子靶标的基础。