Advancing Clinical Science in Pediatric Gastroparesis

儿童和成人的胃轻瘫(GP)的特点是在缺乏胃排空障碍的情况下 机械障碍物。GP与严重的发病率和死亡率有关，但对其知之甚少 发病率、流行率和自然病史，特别是在儿童中。儿科全科医生的这一知识差距是 由于缺乏胃排空的标准数据和GP患者报告的结果而加剧 测量。有限的数据表明，儿童GP的临床症状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和填补知识空白 关于儿童的全科医生。这些问题(以及其他问题)强调了儿童全科医生专项研究的必要性。 策略，而不是将基于成人的全科医生知识翻译给这一非常不同的人群。 开始确定有效的诊断和治疗策略，从而改善儿童的预后 鉴于全科医生在这一领域的巨大知识差距，我们提出了以下前瞻性的具体目标， 多机构协作： 1)用~(13)C-螺旋藻呼气试验(BT)(与胃核素扫描有很好的相关性)定义正常 260名健康对照组(5-18岁)的固体食物排空值。年龄)。子目标：在 儿童(n=420，5-18岁。年龄)，推定为全科医生，正在接受胃部核素扫描以识别儿童 根据Hc中获得的正常值定义的真正患有GP的人。 2)在(Sub)目标1中接受胃部核素扫描的儿童，确定其可行性、可靠性和有效性 使用儿科生活质量对普通和胃肠道(GI)特定健康相关生活质量的影响 库存(PedsQL)通用核心量表和PedsQL GI症状量表和PedsQL GI担忧量表。子- 目标2A：使用量表来区分GP患者与年龄、性别和种族/民族相匹配的儿童 患有功能性消化不良(其症状往往与GP重叠)和HC；分目标2B：使用GI量表和 认知访谈，以创建儿科全科医生特定的健康相关生活质量测量。 3)建立国家前瞻性：(A)登记患有全科医生的儿童和青少年，包括人口统计； 临床、心理和营养特征和(B)血清、胃肠道粘膜活检的生物信息库(#年) 接受上消化道内窥镜检查的患者)，以及用于未来分析的粪便，如DNA、细胞因子、微生物组。 这种多学科的方法是创新的，因为它将第一次有望开始填补巨大的 儿童对全科医生的认识不足。这些数据将是迈向目标和儿科的重要一步- 对GP儿童的友好干预。该项目也将是发展国家儿科的第一步 调查儿童中的GP的联盟。目前的提案符合RFA-DK-16-010，以更好地实现其他目标 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，以及人类微生物群在疾病表达中的作用。

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.