Population-based CRS epidemiology: sex differences, natural history, and long-term outcomes based on clinically-defined phenotypes and biologically-based endotypes - Geisinger

基于人群的 CRS 流行病学：基于临床定义的表型和生物学内型的性别差异、自然史和长期结果 - Geisinger

• 批准号: 10225451
• 负责人: Robert P Schleimer
• 金额: $ 55.55万
• 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/10225451
• 关键词: Address; Adrenal Cortex Hormones; Airway Disease; Antibiotics; Asthma; Biological; Biological Markers; Bronchiectasis; Case-Control Studies; Chronic; Clinical; County; Data; Data Collection; Deltastab; Deposition; Development; Diagnosis; Diagnostic; Diffuse Pattern; Disease; Electronic Health Record; Enrollment; Epidemiology; Epithelial; European; Factor Analysis; Fibrin; Follow-Up Studies; General Population; Heterogeneity; Inflammation; Link; Location; Longitudinal Studies; Measurement; Measures; Medical History; Mesenchymal; Methods; Nasal Lavage Fluid; Natural History; Operative Surgical Procedures; Outcome; Paper; Participant; Patients; Pattern; Pennsylvania; Persons; Phenotype; Population; Positioning Attribute; Prevalence; Prevention; Productivity; Quality of life; Questionnaires; Research; Respondent; Retrospective cohort study; Risk; Risk Factors; Sampling; Severities; Sex Differences; Sinus; Source; Subgroup; Symptoms; Test Result; Text; Time; Woman; Work; Workplace; X-Ray Computed Tomography; base; case finding; chest computed tomography; chronic rhinosinusitis; cohort; comorbidity; comparative; health care service utilization; improved; innovation; longitudinal analysis; novel; novel strategies; population based; programs; prospective; rhinosinusitis; sex; symptom cluster; tertiary care

ABSTRACT: The proposed studies build upon CRISP1, a five-year study of chronic rhinosinusitis (CRS) in a cohort of 7847 subjects, representative of the general population in central Pennsylvania, across the full spectrum of CRS. CRISP1 included the first U.S. longitudinal studies of chronic nasal and sinus symptoms and sinus inflammation by CT scan in the general population. We made novel observations regarding CRS symptom and CT patterns; risks associated with CRS; and sex differences. To improve CRS prevention, diagnosis, and management, studies are now needed to identify the presence of inflammation earlier in the disease than is detected by CT; identify phenotypic and endotypic patterns associated with outcomes; identify risk of longer- term outcomes; and further evaluate sex differences. We will combine CRISP1 data with longitudinal EHR data and new prospective data collection in five separate studies to address four specific aims. In Specific Aim 1 we will develop new approaches to CRS phenotyping. We hypothesize that patterns of longitudinal symptoms, medical history, and CT scan findings will identify new CRS phenotypes that are associated with natural history and long-term outcomes. This aim will be addressed across several of our studies, including by re-contacting CRISP1 participants. Specific Aim 2 will evaluate if CRS endotypes, defined with NLF biomarkers, are associated with phenotype, natural history, and outcomes. For this aim, two studies will be completed. In the first, 450 subjects will be enrolled, have a baseline sinus CT scan and NLF sampling and followed for 18 months with questionnaires, another NLF sample, and linkage to EHR data. In the second, we will conduct a study in parallel with Northwestern to measure NLF biomarkers in 50 subjects each with CRS alone, CRS with asthma, and CRS with bronchiectasis. Our data will be combined with those from a similar study at Northwestern, enabling us to evaluate the impact of setting (general population vs. tertiary care) on findings. Specific Aim 3 is to evaluate CRS as a risk factor for other diseases. We hypothesize that CRS subgroups will be differentially associated with increased risk for development of asthma and bronchiectasis. For this aim, we will conduct an EHR-based CRS retrospective cohort study of 10,000 subjects with sinus CT evidence of CRS and 20,000 persons without; and a bronchiectasis case-control study of 1000 persons with chest CT evidence of bronchiectasis and 4000 controls without. These studies will evaluate associations of CRS phenotypes and severity with risk of development of asthma and bronchiectasis. Specific Aim 4 will evaluate sex differences. We hypothesize that associations among endotypes, phenotypes, natural history, and longer-term outcomes will differ by sex. Sex differences will be evaluated in all five studies. The proposed research continues our novel collaborative work focused on measurement of CRS symptoms, inflammation, co-morbidities, and natural history, linked to longitudinal EHR data, for up to 15-20 years of total observation time, in ways that should advance understanding, diagnosis, and management of CRS across the full spectrum of disease.

摘要：拟议的研究以 CRISP1 为基础，CRISP1 是一项针对慢性鼻窦炎 (CRS) 的五年研究。 由 7847 名受试者组成的队列，代表宾夕法尼亚州中部的一般人群，涵盖整个地区 CRS 的频谱。 CRISP1 包括美国第一个针对慢性鼻腔和鼻窦症状的纵向研究 CT 扫描显示普通人群的鼻窦炎症。我们对 CRS 症状进行了新的观察 和 CT 模式；与 CRS 相关的风险；和性别差异。改善 CRS 的预防、诊断和治疗 管理，现在需要研究来确定疾病早期是否存在炎症 通过CT检测；识别与结果相关的表型和内型模式；识别长期风险 学期成果；并进一步评估性别差异。我们将把 CRISP1 数据与纵向 EHR 数据结合起来 以及五项独立研究中新的前瞻性数据收集，以实现四个具体目标。在具体目标 1 中，我们 将开发 CRS 表型分析的新方法。我们假设纵向症状的模式， 病史和 CT 扫描结果将识别与自然史相关的新 CRS 表型 和长期成果。我们的几项研究将解决这一目标，包括通过重新联系 CRISP1 参与者。具体目标 2 将评估用 NLF 生物标志物定义的 CRS 内型是否符合 与表型、自然史和结果相关。为此，将完成两项研究。在 首先，将招募 450 名受试者，进行基线鼻窦 CT 扫描和 NLF 采样，并随访 18 个月 包括问卷、另一个 NLF 样本以及与 EHR 数据的链接。第二，我们将进行一项研究 与西北大学平行测量 50 名受试者的 NLF 生物标志物，每名受试者均患有单独的 CRS、患有哮喘的 CRS、 以及伴有支气管扩张的 CRS。我们的数据将与西北大学类似研究的数据相结合， 使我们能够评估环境（普通人群与三级医疗保健）对研究结果的影响。具体目标 3 是 评估 CRS 作为其他疾病的危险因素。我们假设 CRS 亚组将有差异 与哮喘和支气管扩张的风险增加有关。为了这个目标，我们将开展 基于 EHR 的 CRS 回顾性队列研究，涉及 10,000 名具有 CRS 鼻窦 CT 证据的受试者和 20,000 名受试者 没有的人；以及一项针对 1000 名患者的支气管扩张病例对照研究，其胸部 CT 证据表明 支气管扩张，4000对照无。这些研究将评估 CRS 表型和 严重程度与发生哮喘和支气管扩张的风险有关。具体目标 4 将评估性别差异。 我们假设内型、表型、自然史和长期结果之间的关联将 因性别而异。所有五项研究都将评估性别差异。拟议的研究继续我们的小说 协作工作的重点是测量 CRS 症状、炎症、合并症和自然症状 历史记录，与纵向 EHR 数据相关联，长达 15-20 年的总观察时间，其方式应 促进对全谱疾病的 CRS 的理解、诊断和管理。