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(CRISP2)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、自然历史和长期结果。迫切需要对慢性病进行更多的研究 鼻窦炎(CRS)。CRS患者的生活质量显著下降，CRS的患病率 接近12%，每年有近50万患者接受手术，估计CRS的总成本 在美国，每年有220亿至320亿美元。CRISP2的假设和主题如下：1)异质底层 致病机制产生不同的临床表型表现；鼻窦疾病与鼻窦疾病的共病 肺部疾病与选定的分子内型有关；两种机制之间存在着深刻的差异 以及CRS在男性和女性中的表现；CRSsNP的致病机制越普遍 疾病的形式，还没有得到很好的研究；很有必要研究初级保健中的CRS 种群；6.)需要新的分析方法来评估门诊环境中的分子内型。这笔赠款 阐述了所有这些假设和主题。分子内型与临床表现的关系，自然 疾病的病史、合并症和结局是这项计划的首要目标。三个项目和两个项目 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。该项目的三个主要目标是：项目1-研究上皮屏障的机制 CRS的功能障碍和组织增生。项目1将使用一种新的基于微粒(MP)的上皮细胞分析方法 分化和Will分析凝血和纤溶系统的成分来检验这一假设 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 CRS中的角色。这些反应将与免疫内型、临床表型、共病和 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的炎症是异质性的和炎症内型控制的假设 CRS的临床表型。初步结果表明，选择的内型是某些症状的诱因 并导致了关于驱动主要免疫学的细胞和分子的假说 内型，类型1、2和3型。项目1和项目2都将使用来自患者的大样本集 盖辛格(项目3)和NU(核心B)。项目3--使用以人口为基础的CRS流行病学来评估性 基于临床定义的表型和生物学上的差异、自然病史和长期结果- 基于内型。建议的大型回溯性队列和纵向流行病学研究包括 对近8000名研究对象进行的持续研究；对10,000名患者和20,000名患者进行的基于电子病历的回顾性研究 对照组；对450名受试者的纵向研究；以及对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