Advancing Clinical Science in Pediatric Gastroparesis

儿童和成人的胃轻瘫（GP）的特征是在缺乏胃排空的情况下胃排空延迟。 机械性梗阻GP与显著的发病率和死亡率相关，但对其 发病率、患病率和自然史，尤其是儿童。儿科全科医生的这一知识缺口是 由于缺乏胃排空的规范性数据和GP特定患者报告的结局而加重 measure.有限的数据表明GP的临床症状在儿童与成人之间存在显著差异。 因此，即使是关于成人GP的有限数据也不太可能提供洞察力并填补知识空白 关于儿童GP这些问题（除其他外）强调了对儿童GP特定研究的必要性 战略，而不是翻译成人为基础的GP知识，这个非常不同的人群。 开始确定有效的诊断和治疗策略，以改善儿童的结局 由于GP在该领域存在巨大的知识缺口，我们提出了以下前瞻性的具体目标， 多机构合作： 1)使用13 C-螺旋藻呼吸试验（BT）（与胃肠道造影相关性良好）定义正常 （n=260）健康对照（HC）（5-18岁）的固体餐排空值。子目标：在以下方面开展BT 疑似GP的儿童（n=420，5-18岁），正在接受胃肠道造影以识别儿童 根据HC中获得的正常值定义，真正患有GP的患者。 2)在（子）目标1中接受胃肠道造影的儿童中，确定可行性、可靠性和有效性 使用儿科生活质量量表评估一般和胃肠道（GI）特异性健康相关生活质量 量表（PedsQL）通用核心量表、PedsQL GI症状量表和PedsQL GI担忧量表。次 目的2A：使用量表区分GP患者与年龄、性别和人种/种族匹配的儿童 功能性消化不良（其症状通常与GP重叠）和HC;子目标2B：使用GI量表， 认知访谈以创建儿科GP特异性健康相关生活质量测量。 3)创建一个国家的前景：（a）登记儿童和青少年与家庭医生，包括人口， 临床、心理和营养特征，和（B）血清、GI粘膜活组织检查的生物储库（in 进行上消化道内窥镜检查的患者），以及用于未来分析的粪便，例如DNA、细胞因子、微生物组。 这种多学科的方法是创新的，因为它将首次前瞻性地开始填补广阔的 儿童对GP缺乏了解。这些数据将是实现有针对性和儿科的重要一步- 对GP患儿进行友好干预。该项目也将是发展国家儿科的第一步。 财团调查GP在儿童。除其他目标外，当前提案更适合RFA-DK-16-010， 了解GP的流行病学，定义GP/FD谱，探索和设计新的患者报告 结果，以及人类微生物组对疾病表达的作用。

Gastroparesis (GP) in children and adults is characterized by delayed gastric emptying in the absence of mechanical obstruction. GP is associated with significant morbidity and mortality yet little is known regarding its incidence, prevalence, and natural history, particularly in children. This knowledge gap in pediatric GP is exacerbated by lack of both normative data for gastric emptying and a GP specific patient reported outcome measure. The limited data suggest significant differences between clinical symptoms of GP in children vs adults. Thus, even the limited data regarding GP in adults are unlikely to provide insight and fill the knowledge gaps regarding GP in children. These issues (among others) underscore the need for childhood GP specific research strategies rather than translation of adult based GP knowledge to this very different population. To begin to identify effective diagnostic and therapeutic strategies leading to improved outcomes for children with GP given the vast knowledge gaps in the field, we propose the following Specific Aims within a prospective, multiinstitutional collaboration: 1) Using the 13C-Spirulina breath test (BT) (which correlates well with gastric scintigraphy) define normal values for solid meal emptying in (n=260) healthy controls (HC) (5-18 yrs. of age). Sub-Aim: carry out the BT in children (n=420, 5-18 yrs. of age) with presumed GP who are undergoing gastric scintigraphy to identify children who truly have GP as defined by the normal values obtained in HC. 2) In children undergoing gastric scintigraphy in (Sub) Aim 1, determine the feasibility, reliability, and validity of generic and gastrointestinal (GI)-specific health-related quality of life using the Pediatric Quality of Life Inventory (PedsQL) Generic Core Scales and PedsQL GI Symptoms Scales and PedsQL GI Worry Scales. Sub- Aim 2A: Use the scales to differentiate patients with GP vs. age, gender, and race/ethnicity matched children with functional dyspepsia (whose symptoms often overlap with GP) and HC; Sub-Aim 2B: Use the GI scales and cognitive interviews to create a pediatric GP-specific health-related quality of life measure. 3) Create a national prospective: (a) Registry of children and adolescents with GP to include demographic, clinical, psychological, and nutritional characteristics and (b) Biorepository of serum, GI mucosal biopsies (in those undergoing upper GI endoscopy), and stool for future analyses such as DNA, cytokines, microbiome. This multidisciplinary approach is innovative as it will, for the first time, prospectively begin to fill the vast knowledge void regarding GP in children. These data will be an important step toward targeted and pediatric- friendly interventions for children with GP. This project also will be a first step to developing a national pediatric consortium to investigate GP in children. The current proposal fits RFA-DK-16-010 to, among other goals, better understand the epidemiology of GP, define the GP/FD spectrum, explore and design new patient reported outcomes, and the role of the human microbiome on disease expression.