Chronic Rhinosinusitis Integrative Studies Program 2 (CRISP2)

慢性鼻窦炎综合研究计划 2 (CRISP2)

• 批准号: 10225446
• 负责人: Robert P Schleimer
• 金额: $ 185.28万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10225446
• 关键词: Address; Airway Disease; Asthma; Attention; Basic Science; Biological; Biological Assay; Biological Markers; Bronchiectasis; CD8-Positive T-Lymphocytes; Case-Control Studies; Cells; Chronic; Clinical; Coagulation Process; Congestive; Data Collection; Deposition; Development; Diagnostic Procedure; Disease; Disease Outcome; Early identification; Electronic Health Record; Epidemiologist; Epidemiology; Epithelial; Evaluation; Fibrin; Fresh Tissue; Functional disorder; Goals; Grant; Headache; Hyperplasia; Immunologics; Immunologist; Inflammation; Inflammatory; Integrins; Knowledge; Laboratories; Link; Longitudinal Studies; Lung diseases; Lymphoid Cell; Macroglobulins; Mediating; Medical Research; Mesenchymal; Modeling; Molecular; Nasal Lavage Fluid; Nasal Polyps; Natural History; Natural Killer Cells; Nose; Operative Surgical Procedures; Otolaryngologist; Outcome; Outpatients; Pain; Pathogenesis; Pathogenicity; Patients; Pharmacologic Substance; Phenotype; Physicians; Play; Population; Prevalence; Prevention; Primary Health Care; Principal Investigator; Process; Quality of life; Research; Retrospective Studies; Retrospective cohort; Retrospective cohort study; Risk; Risk Factors; Role; Sampling; Severities; Sex Differences; Sinus; Smell Perception; Smooth Muscle Actin Staining Method; Study Subject; Symptoms; System; Taste Perception; Testing; Th1 Cells; Th2 Cells; Time; Tissues; Translating; Visit; Vulnerable Populations; Woman; base; chronic rhinosinusitis; clinical care; clinical phenotype; cohort; comorbidity; cost; cytokine; data management; disease heterogeneity; eosinophil; epidemiology study; experience; insight; macrophage; mast cell; men; neutrophil; novel; population based; programs; protective factors; repaired; response; sample collection; single-cell RNA sequencing; tertiary care; transcriptome sequencing

The Chronic Rhinosinusitis Integrative Studies Program 2 (CRISP2) is an integrated program of epidemiologists, otolaryngologists, allergists and immunologists with highly collaborative studies to better understand the molecular and cellular mechanisms of disease heterogeneity and how these mechanisms translate into clinical phenotypes, natural history and long term outcomes. There is a compelling need for more research in chronic rhinosinusitis (CRS). Patients with CRS experience a dramatic decrement in quality of life, CRS has a prevalence approaching 12%, nearly half a million patients per year undergo surgery and the estimated total costs of CRS in the US are $22-32 billion per year. Hypotheses and themes of CRISP2 are: 1.) Heterogeneous underlying pathogenic mechanisms yield variable clinical phenotypic manifestations; 2.) Comorbidity of sinus disease and lung disease tracks with selected molecular endotypes; 3.) There are profound differences between mechanisms and manifestations of CRS in men and women; 4.) Pathogenic mechanisms of CRSsNP, the more prevalent form of disease, have not been well studied; 5.) There is a significant need to study CRS in primary care populations; 6.) New assays are needed to evaluate molecular endotypes in an outpatient setting. This grant addresses all of these hypotheses and themes. Relating molecular endotypes to clinical manifestations, natural history, comorbidity and outcomes of disease is an overarching goal of this program. Three projects and two cores (Administrative Core A and Clinical, Laboratory and Data Management Core B) comprise the CRISP2 program. The three main project main aims are: Project 1-To study the mechanisms of epithelial barrier dysfunction and tissue hyperplasia in CRS. Project 1 will use a novel microparticle (MP) based assay of epithelial differentiation and will assay components of the coagulation and fibrinolytic systems to test the hypothesis that fibrin deposition, barrier dysfunction and epithelial mesenchymal transition (EMT) play important pathogenic roles in CRS. These responses will be related to immunological endotypes, clinical phenotypes, comorbidity and clinical outcomes. Project 2-To dissect molecular endotypes and relate them to manifestations of CRS. Project 2 will test the hypothesis that inflammation in CRS is heterogeneous and that inflammatory endotypes control clinical phenotypes of CRS. Preliminary results implicate select endotypes as inducers of certain symptom constellations and have led to hypotheses about the cells and molecules that drive the main immunological endotypes, type 1, 2 and 3. Both Project 1 and Project 2 will utilize large sample sets from patients at both Geisinger (Project 3) and NU (Core B). Project 3-To use population-based CRS epidemiology to evaluate sex differences, natural history, and long-term outcomes based on clinically-defined phenotypes and biologically- based endotypes. Large retrospective cohort and longitudinal epidemiological studies proposed include an ongoing study of nearly 8000 study subjects; an EHR-based retrospective study of 10,000 patients and 20,000 controls; a longitudinal study of 450 subjects; and case-control studies of risk factors for bronchiectasis.

慢性鼻腔炎综合研究计划2（CRISP2）是一个流行病学家的综合计划， 耳鼻喉科医生，过敏者和免疫学家进行高度协作研究，以更好地了解 疾病异质性的分子和细胞机制以及这些机制如何转化为临床 表型，自然史和长期结果。在慢性方面需要更多研究 鼻炎（CRS）。 CRS患者的生活质量急剧下降，CRS患病率很高 接近12％，每年将近一百万名患者接受手术和CRS的估计总成本 在美国，每年为22-32亿美元。 CRISP2的假设和主题是：1。）底层异质 致病机制产生可变的临床表型表现； 2.）鼻窦病的合并症和 肺部疾病轨道具有选定的分子内型； 3.）机制之间存在深刻的差异 男女CR的表现； 4.）CRSSNP的致病机制，越普遍 疾病的形式尚未得到很好的研究； 5.）重要需要在初级保健中研究CR 人口； 6.）需要新的测定方法来评估门诊环境中的分子内型。这笔赠款 解决所有这些假设和主题。将分子内型与临床表现相关，天然 历史，合并症和疾病结果是该计划的总体目标。三个项目和两个 核心（行政核心A和临床，实验室和数据管理核心b）构成CRISP2 程序。三个主要项目主要目的是：项目1到研究上皮屏障的机制 CRS中的功能障碍和组织增生。项目1将使用基于上皮的新型微粒（MP）测定 分化并将测定凝血和纤维蛋白水解系统的组成部分，以检验以下假设。 纤维蛋白沉积，屏障功能障碍和上皮间质转变（EMT）发挥重要的致病性 在CRS中的角色。这些反应将与免疫学内型，临床表型，合并症和 临床结果。项目2用于剖析分子内型，并将其与CR的表现相关联。项目 2将检验以下假设：CRS中的炎症是异质的，并且炎症性内型控制 CRS的临床表型。初步结果暗示了某些症状的诱导者选择的选择性型 星座并导致了有关驱动主要免疫学的细胞和分子的假设 内型，1、2和3型。项目1和项目2均将利用两者的患者的大量样本集 Geisinger（项目3）和NU（核心B）。项目3用于使用基于人群的CRS流行病学评估性行为 基于临床定义的表型和生物学上的差异，自然史和长期结局 基于内型。提出的大型回顾性队列和纵向流行病学研究包括 正在进行的近8000名研究对象的研究；基于EHR的回顾性研究，对10,000名患者和20,000例 控件； 450名受试者的纵向研究；以及支气管扩张危险因素的病例对照研究。