INSPPIRE to Study Pediatric Chronic Pancreatitis

 描述(申请人提供)：急性胰腺炎(AP)在儿童中得到越来越多的认识，发病率接近成人。大多数患有胰腺炎的儿童只有一个轻微的急性发作，没有并发症地消失。然而，AP儿童的一部分会出现反复发作(定义为急性复发性胰腺炎或ARP)和一些进展为慢性胰腺炎(CP)。很少有研究对儿童ARP和CP进行特征描述。我们认识到，缺乏良好表型的儿科队列是理解CP及其后遗症的主要障碍。为了解决这一知识差距，我们成立了INSPPIRE(儿童胰腺炎国际研究小组：寻找治疗方法)，由18个参与站点组成。纳入我们研究的301名儿科患者的研究结果显示，在慢性胰腺炎儿童中，胰腺炎相关基因突变的频率很高，并且有大量的疾病负担。这项应用的目的是确定儿童CP的自然病史，确定其发病和后遗症的危险因素和遗传修饰物，并开发改善临床结果的方法。这一建议的总体假设是，儿科CP具有决定疾病发病和后遗症的独特特征。我们的具体目标是：1)确定儿童CP的特征，确定疾病严重程度和从ARP到CP的进展的预测因素；2)确定基因突变在早发性CP中的作用，并确定疾病修饰物；3)确定通过认知行为干预对儿童CP进行早期疼痛治疗的有效性。我们的长期目标是开发儿童ARP和CP的诊断模式、预后因素和创新的治疗方法。

 DESCRIPTION (provided by applicant): 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). Few studies have been performed to characterize ARP and CP in children. We recognized that the lack of a well-phenotyped pediatric cohort presented a major obstacle in understanding the pathophysiology of CP and its sequelae. To address this knowledge gap, we have formed INSPPIRE (INternational Study Group of Pediatric Pancreatitis: In search for a cuRE), composed of 18 participating sites. Results from 301 pediatric patients enrolled into our study revealed a high frequency of pancreatitis-associated gene mutations and substantial disease burden in children with CP. The objective of this application is to determine the natural history of pediatric CP, identify risk factors and genetic modifiers for its onset and sequelae and develop approaches to improve clinical outcomes. The overall hypothesis of this proposal is that pediatric CP has unique characteristics that determine disease onset and sequelae. Our specific aims are: 1) Characterize pediatric CP, determine predictors of disease severity and progression from ARP to CP; 2) Define the role of genetic mutations in early onset CP and identify disease modifiers; 3) Determine the efficacy of early pain management using cognitive-behavioral intervention on pediatric CP. Our long-term goal is to develop diagnostic modalities, prognostic factors and innovative treatment approaches for pediatric ARP and CP.