INSPPIRE: A Longitudinal Cohort Study of Pediatric Chronic Pancreatitis to Predict Clinical Course and Identify Disease Modifiers

INSPPIRE：儿科慢性胰腺炎的纵向队列研究，用于预测临床病程并确定疾病调节因子

• 批准号: 10657692
• 负责人: MARK E. LOWE
• 金额: $ 46.3万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-28 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10657692
• 关键词: Acute; Adult; Age; Aggressive course; Ancillary Study; Autoantibodies; Autoimmunity; Beta Cell; C-Peptide; Characteristics; Child; Childhood; Clinical; Cognitive Therapy; Cohort Analysis; Cystic Fibrosis Transmembrane Conductance Regulator; Defect; Development; Diabetes Mellitus; Diagnosis; Diagnostic; Disease; Disease Progression; Endocrine; Environmental Risk Factor; Exocrine pancreatic insufficiency; Fibrosis; Functional disorder; Funding; Genes; Genetic; Genetic Risk; Genetic Screening; Glucagon; Glucose; Goals; Health Care Costs; Hyperlipidemia; Hypertriglyceridemia; Image; Impaired health; Incidence; Insulin; Interdisciplinary Study; International; Islet Cell; Longitudinal cohort study; Modality; Natural History; Onset of illness; Outcome; Pain; Pancreatic Polypeptide; Pancreatitis; Pathogenicity; Patient Outcomes Assessments; Pediatric cohort; Peptides; Physiologic calcification; Predisposing Factor; Prevalence; Prognostic Factor; Quality of life; Recurrence; Research Personnel; Risk; Risk Factors; Risk Marker; SPINK1 gene; Susceptibility Gene; Testing; Therapeutic; United States National Institutes of Health; Variant; Work; acute pancreatitis; blood glucose regulation; burden of illness; chronic pancreatitis; clinical predictors; cohort; demographics; early onset; genetic risk factor; genetic variant; genomic locus; glucagon-like peptide 1; glucose tolerance; health related quality of life; innovation; insight; islet; longitudinal analysis; pain-related disability; premature; prospective; response; risk variant; virulence gene

PROJECT SUMMARY Acute pancreatitis (AP) is increasingly recognized in children, with an incidence approaching that of adults. Most children with pancreatitis have a single, mild, acute episode that resolves without complications. However, a subset of children with AP develops recurrent episodes (defined as acute recurrent pancreatitis or ARP) and some progress to chronic pancreatitis (CP). Pediatric ARP and CP significantly impact quality of life and carry high healthcare costs. Few studies have been performed to characterize the natural history pediatric ARP and CP, to identify its risk factors and to determine predictors of disease course. As INSPPIRE (INternational Study Group of Pediatric Pancreatitis: In search for a cuRE), the first multicenter, multidisciplinary collaboration in pediatric pancreatitis, we determined that children with ARP harbor multiple genetic risk variants and rapidly transition to CP, exocrine pancreatic insufficiency (EPI) and diabetes mellitus (DM). The risk factors that predispose children to early onset pancreatitis, rapid progression to CP and premature loss of exocrine and endocrine function are not well-known. The objective of this application is to delineate the natural history of pediatric CP through careful prospective analysis of INSPPIRE-2 cohort, to define the impact of genetic modifiers on disease course and to determine the mechanisms involved in pancreatogenic diabetes mellitus (T3cDM). The overall hypothesis is that genetic factors predispose children to early onset CP, EPI, and DM. Our specific aims are: 1) Characterize pediatric CP, determine predictors of disease onset and progression; 2) Determine the impact of genetic variants on disease onset and progression; 3) Identify mechanisms underlying disturbed glucose regulation in pediatric ARP and CP. This project will provide insight into the pathophysiology of pediatric pancreatitis, investigate the impact of genetic variants on disease course and explore the mechanisms of early islet cell dysfunction in pediatric ARP and CP. Our long-term goal is to develop diagnostic modalities, prognostic factors and innovative treatment approaches for pediatric ARP and CP.

项目概要 儿童急性胰腺炎 (AP) 的发病率接近 成人的。大多数患有胰腺炎的儿童都会有一次轻微的急性发作，但可以自行缓解 无并发症。然而，一部分患有 AP 的儿童会反复发作 （定义为急性复发性胰腺炎或 ARP）以及慢性胰腺炎的一些进展 （CP）。儿科 ARP 和 CP 严重影响生活质量并带来高昂的医疗费用。 很少有研究来描述儿科 ARP 和 CP 的自然史特征， 确定其危险因素并确定病程的预测因子。作为灵感 （小儿胰腺炎国际研究组：寻找 cuRE），第一个多中心、 多学科合作治疗小儿胰腺炎，我们确定患有 ARP 的儿童 携带多种遗传风险变异并迅速转变为 CP、外分泌胰腺 功能不全（EPI）和糖尿病（DM）。导致儿童易患此病的危险因素 早发性胰腺炎、快速进展为 CP 以及外分泌和功能过早丧失 内分泌功能尚不清楚。该应用程序的目的是描绘 通过对 INSPPIRE-2 队列进行仔细的前瞻性分析，了解儿科 CP 的自然史， 定义遗传修饰剂对病程的影响并确定其机制 参与胰源性糖尿病（T3cDM）。总体假设是遗传 儿童易患早发 CP、EPI 和 DM 的因素。我们的具体目标是：1） 描述儿科 CP 的特征，确定疾病发作和进展的预测因素； 2）确定 遗传变异对疾病发生和进展的影响； 3）确定机制 儿科 ARP 和 CP 中潜在的葡萄糖调节紊乱。该项目将提供 深入了解小儿胰腺炎的病理生理学，研究遗传因素的影响 病程变异并探讨早期胰岛细胞功能障碍的机制 儿科 ARP 和 CP。我们的长期目标是开发诊断方式、预后因素 儿科 ARP 和 CP 的创新治疗方法。