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: 10897483
• 负责人: Robert P Schleimer
• 金额: $ 49.66万
• 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/10897483
• 关键词: Population; based; CRS; epidemiology; sex

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：拟议的研究基于CRISP1，这是一项五年的慢性鼻鼻炎（CRS）的研究 宾夕法尼亚州中部一般人口的7847名受试者的队列遍布 CRS频谱。 CRISP1包括美国第一次关于慢性鼻和鼻窦症状的纵向研究 普通人群中CT扫描的鼻窦炎症。我们对CRS症状进行了新的观察 和CT模式；与CR相关的风险；和性别差异。改善CRS预防，诊断和 现在需要研究，需要研究以确定疾病早期炎症的存在，而不是 由CT检测；确定与结果相关的表型和内型模式；确定长期结局的风险；并进一步评估性别差异。我们将将CRISP1数据与纵向EHR数据相结合 并在五项单独的研究中收集了新的前瞻性数据，以解决四个具体目标。在特定的目标1中我们 将开发新的CRS表型方法。我们假设纵向症状的模式， 病史和CT扫描发现将确定与自然史相关的新CRS表型 和长期结果。这个目标将在我们的几项研究中解决，包括通过重新连接 CRISP1参与者。具体目标2将评估是否使用NLF生物标志物定义的CRS内型是 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，具有基线窦CT扫描和NLF采样，然后进行18个月 与问卷，另一个NLF样本以及与EHR数据的联系。在第二个中，我们将进行一项研究 与西北的平行，可以在50名受试者中测量NLF生物标志物，每个受试者单独使用CRS，哮喘，CRS， 和CRS带有支气管扩张。我们的数据将与西北部类似研究的数据相结合， 使我们能够评估设置（一般人群与三级护理）对发现的影响。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子组将是差异的 与增加哮喘和支气管扩张的风险增加有关。为此，我们将进行 基于EHR的CRS回顾性队列研究对10,000名具有CRS和20,000的Sinus CT证据的受试者 没有的人；以及1000人胸部CT证据的支气管扩张病例对照研究 支气管扩张和4000个对照没有。这些研究将评估CRS表型和 严重程度有哮喘和支气管扩张的风险。特定目标4将评估性别差异。 我们假设内型，表型，自然历史和长期结局之间的关联将会 与性别不同。在所有五项研究中，都将评估性别差异。拟议的研究继续我们的小说 协作工作重点是测量CR症状，炎症，合并症和自然 与纵向EHR数据相关的历史记录，最多15 - 20年的总观察时间，以应有的方式 在整个疾病中的CRS进行预先理解，诊断和管理。