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，

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