Chronic Rhinosinusitis Integrative Studies Program 2 (CRISP2)

慢性鼻窦炎综合研究计划 2 (CRISP2)

• 批准号: 10671609
• 负责人: Robert P Schleimer
• 金额: $ 181.05万
• 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/10671609
• 关键词: Actins; Address; Airway Disease; Asthma; Attention; Basic Science; Biological Assay; Biological Markers; Bronchiectasis; CD8-Positive T-Lymphocytes; Case/Control Studies; Cells; Chronic; Clinical; Coagulation Process; Data Collection; Deposition; Development; Diagnostic Procedure; Disease; Disease Outcome; Early identification; Electronic Health Record; Epidemiologist; Epidemiology; Epithelium; 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; Macrophage; Mediating; Medical; 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 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; Study Subject; Symptoms; System; Taste Perception; Testing; Th1 Cells; Th2 Cells; Time; Tissues; Translating; Visit; Vulnerable Populations; Woman; chronic rhinosinusitis; clinical care; clinical phenotype; cohort; comorbidity; cost; cytokine; data management; disease heterogeneity; eosinophil; epidemiology study; experience; insight; mast cell; men; neutrophil; novel; particle; 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.

慢性鼻窦炎综合研究计划2（CRISP 2）是流行病学家的综合计划， 耳鼻喉科医生、过敏症专家和免疫学家进行高度合作的研究，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。迫切需要更多的研究慢性 鼻窦炎（CRS）。CRS患者的生活质量急剧下降，CRS的患病率 接近12%，每年有近50万患者接受手术，CRS的估计总成本 在美国每年是220 - 320亿美元。CRISP 2的假设和主题是：1。异质底层 致病机制产生可变的临床表型表现; 2.）鼻窦疾病合并症， 肺部疾病追踪所选择的分子内型; 3.）机制之间存在着深刻的差异 和CRS在男性和女性中的表现; 4.）CRSsNP的致病机制越普遍， 疾病的形式，没有得到很好的研究; 5。有一个显着的需要研究CRS在初级保健 人口; 6.）需要新的检测方法来评估门诊患者的分子内型。这笔赠款 解决了所有这些假设和主题。分子内型与临床表现、自然 疾病的历史、合并症和结果是该计划的首要目标。三个项目和两个 核心（管理核心A和临床、实验室和数据管理核心B）组成CRISP 2 程序.项目1-研究上皮屏障的机制 功能障碍和组织增生。项目1将使用一种新的基于微粒（MP）的上皮细胞检测方法， 分化，并将测定凝血和纤溶系统的组分，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化（EMT）是重要的致病因素 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-解剖分子内型并将其与CRS的表现联系起来。项目 2将检验CRS中炎症是异质性的并且炎症内型控制炎症的假设。 CRS的临床表型。初步结果暗示选择内型作为某些症状的诱导物 星座，并导致有关细胞和分子的假设，驱动主要的免疫 内型，1、2和3型。项目1和项目2都将使用来自两个研究中心患者的大样本集。 Geisinger（项目3）和NU（核心B）。项目3-使用基于人群的CRS流行病学评估性别 基于临床定义的表型和生物学的差异、自然史和长期结局- 基于endotypes拟议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名研究受试者的研究;一项基于EHR的回顾性研究，包括10,000名患者和20000名 对照组; 450例受试者的纵向研究;支气管扩张危险因素的病例对照研究。

项目成果

The Management of Chronic Rhinosinusitis With Nasal Polyps (CRSwNP) With Biologics.

用生物制剂治疗慢性鼻窦炎伴鼻息肉 (CRSwNP)。

• DOI: 10.1016/j.jaip.2023.04.054
• 发表时间: 2023
• 期刊: The journal of allergy and clinical immunology. In practice
• 作者: Wautlet,A;Bachert,C;Desrosiers,M;Hellings,PeterW;Peters,AnjuT
• 通讯作者: Peters,AnjuT

Mast Cell and Eosinophil Activation Are Associated With COVID-19 and TLR-Mediated Viral Inflammation: Implications for an Anti-Siglec-8 Antibody.

• DOI: 10.3389/fimmu.2021.650331
• 发表时间: 2021
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Gebremeskel S;Schanin J;Coyle KM;Butuci M;Luu T;Brock EC;Xu A;Wong A;Leung J;Korver W;Morin RD;Schleimer RP;Bochner BS;Youngblood BA
• 通讯作者: Youngblood BA

Two-stage genome-wide association study of chronic rhinosinusitis and disease subphenotypes highlights mucosal immunity contributing to risk.

• DOI: 10.1002/alr.22731
• 发表时间: 2021-04
• 期刊: International forum of allergy & rhinology
• 影响因子: 6.4
• 作者: Soliai M;Sundaresan AS;Morin A;Hirsch AG;Stanhope C;Kuiper J;Schwartz BS;Ober C;Pinto JM
• 通讯作者: Pinto JM