The Natural History of Pediatric Crohn's Disease

描述（由申请人提供）： 该奖项将为候选人提供获得临床研究培训，教育工具，科学技术和指导的机会，这将有助于她成功地成为儿科IBD研究的独立研究者以及IBD领域的重要贡献者。职业发展计划将包括通过K30计划进行的教学式学习、当地GCRC培训和研究伦理行为培训以及研究计划中提出的研究活动。工作环境：在K23奖和机构承诺提供的保护时间内，候选人将能够将75%的时间用于教学部分（K30计划）并完成以下所述的科学建议。Cedars-Sinai的常见疾病遗传学主任将提供培训和资源，以获得对遗传研究的深入了解，Cedars-Sinai的免疫生物学研究所所长将提供将免疫学领域新发现的知识纳入拟议研究的机会，并将指导该项目中的免疫工作。此外，GCRC将提供进行所有基因检测所需的资源和设施。调研：儿童期发作的克罗恩病通常被描述为具有侵袭性临床过程，使得患者在疾病过程的早期发展疾病并发症，通常需要侵袭性的医学和/或手术管理。该项目提出，有可识别的风险因素，确定或预测更积极的疾病过程中克罗恩病的儿童。目的是进行一项前瞻性纵向队列研究，以确定儿童期发病的克罗恩病的自然史，并分析人口统计学，遗传，免疫和环境对侵袭性疾病表型和疾病进展的影响。该项目的具体目的是1）建立一个来自北美西部地区的临床特征良好的患者队列，以研究新发克罗恩病儿童的疾病进展或自然史，2）确定是否存在可识别的人口统计学、遗传学、免疫学和/或环境危险因素影响新冠肺炎患儿侵袭性疾病表型和疾病进展，克罗恩病的发病将入组来自北美西部地区的共计400例患者。主要程序将包括临床和环境史数据收集以及用于基因分型和检测免疫反应的血液采样。收集的数据将存储在安全的儿科IBD相关数据库中。主要结果指标包括并发疾病行为发生的频率和时间，以及风险标志物与定义的患者结果之间的相关性。定义儿童期发病克罗恩病的自然史和描述侵袭性疾病进展的潜在决定因素将导致长期努力来定义疾病的临床前自然史，并开发干预研究以防止临床疾病进展为临床并发症。

DESCRIPTION (provided by applicant): This award will afford the candidate an opportunity to acquire the clinical research training, educational tools, scientific techniques and mentorship that will be instrumental for her to succeed as an independent investigator in Pediatric IBD research as well as an important contributor to the field of IBD. The career development plan will include didactic learning through the K30 program, local GCRC training and training in the ethical conduct of research as well as the research activities proposed in the research plan. Environment: With the protected time afforded by the K23 award and the institutional commitment, the candidate will be able to devote 75% of her time to the didactic component (K30 program) and to completing the scientific proposal described below The mentors for this award bring with an expertise critical to the success of the career and research plan. The Director of Common Diseases Genetics at Cedars-Sinai will provide the training and resources to acquire a solid understanding of genetic research and the Director of the Immunobiology Institute at Cedars-Sinai, will provide the opportunities to incorporate newfound knowledge in the field of immunology into the proposed research and will direct the immune work to be done in this project. Additionally the GCRC will provide the resources and facilities that will be necessary to conduct all genetic testing. Research: Childhood-onset Crohn's disease is often described as having an aggressive clinical course such that patients develop disease complications early in the disease course, often necessitating aggressive medical and/or surgical management. This project proposes that there are identifiable risk factors that determine or predict a more aggressive disease course of Crohn's disease in children. The objective is to conduct a prospective longitudinal cohort study to define the natural history of childhood-onset Crohn's disease and to analyze the demographic, genetic, immune and environmental influences on aggressive disease phenotypes and disease progression. The specific aims of this project are 1) to establish a clinically well characterized patient cohort from the Western Region of North America to study disease progression or natural history of children with new-onset Crohn's disease and 2) To determine if there are identifiable demographic, genetic, immunologic and/or environmental risk factors that influence aggressive disease phenotypes and disease progression in children with new-onset Crohn's disease. A total of 400 patients from the Western Region of North America will be enrolled. Principal procedures will include data collection on clinical and environmental history as well as blood sampling for genotyping and testing immune response. Collected data will be stored in a secured relational pediatric IBD database. Primary outcome measures include frequency and time to occurrence of complicating disease behaviors and the associations between markers of risk and defined patient outcome. Defining the natural history of childhood-onset Crohn's disease and delineating the potential determinants of aggressive disease progression will lead to long term efforts to define the preclinical natural history of the disease, and to develop intervention studies to prevent progression of clinical disease to clinical complications.