Abdominal Symptom Phenotypes: Pathways to New Biomarkers

腹部症状表型：新生物标志物的途径

• 批准号: 7852671
• 负责人: Margaret McLean Heitkemper
• 金额: $ 99.55万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-28 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7852671
• 关键词: Abdomen; Abdominal Pain; Adult; Affect; American; Analgesics; Antidepressive Agents; Antidiarrheals; Autonomic nervous system; Biological Markers; Catecholamines; Child; Clinical; Clinical Management; Collaborations; Constipation; Control Groups; Coping Skills; Data; Developed Countries; Diarrhea; Diet; Endoscopy; Ensure; Equipment; Etiology; Faculty; Fatigue; Female Adolescents; Fibromyalgia; Functional Gastrointestinal Disorders; Functional disorder; Gastrointestinal Diseases; Gastrointestinal Motility; Genetic; Genomics; Genotype; Goals; Grant; Headache; Health Personnel; Healthcare; Hydrocortisone; Hypersensitivity; Hypnosis; Industry; Inflammation; Institution; Interdisciplinary Study; Intervention Studies; Irritable Bowel Syndrome; Life Style; Link; Liquid substance; Lymphocyte Activation; Measures; Medicine; Pain; Pathway interactions; Patients; Pharmaceutical Preparations; Phenotype; Play; Population; Probiotics; Procedures; Proteins; Proteomics; Psychophysiology; Recovery; Recruitment Activity; Research Infrastructure; Research Personnel; Resources; Sampling; School Nursing; Serotonin Agents; Serum; Severities; Sleeplessness; Spasmolytics; Stress; Subgroup; Symptoms; Testing; Training; Universities; Urine; Variant; Visceral; Washington; Woman; Work; capsule; cognitive behavior therapy; college; coping; cytokine; depressive symptoms; diaries; diffuse noxious inhibitory control; drug development; effective therapy; experience; gastrointestinal; girls; heart rate variability; inflammatory marker; laxative; meetings; psychological distress; public health relevance; response; symptom management; urinary

DESCRIPTION (provided by applicant): This application Abdominal Symptom Phenotype: Pathways to New Biomarkers (ASPPNB) is in response to RFA-OD-09-004, American Recovery and Reinvestment Act for research and infrastructure. This application is responsive to NINR priorities related to discovery of biomarkers and understanding linkages between symptoms and biomarkers, the mechanisms leading to symptoms, and ultimately symptom management. Functional gastrointestinal (GI) disorders (FGIDs), in particular irritable bowel syndrome (IBS) in adults and children, are among the most common and costly health care problems in the US. In adults, IBS disproportionately affects women (10-15% of women in western nations) and adolescent girls. There are well-recognized associations between IBS and other conditions (fibromyalgia, headache) and symptoms (depression, fatigue, insomnia). Therapies are typically prescribed to relieve particular symptoms (drugs such as antispasmodics, analgesics or antidepressants for pain, laxatives, antidiarrheals) or change lifestyle features (e.g., diet, cognitive behavioral therapy, hypnosis, or comprehensive self management2, 3 to modify coping ability). We posit that by understanding better these different expressions of IBS (i.e., better defined patient subgroups) and linking them to newer biomarkers, ultimately greater progress on understanding the etiologies and defining effective treatments can be achieved. Our Specific Aims are to 1) use existing symptom diary data on 400 women with IBS from two studies to define clusters of women with differing symptoms. A similar approach will be taken using diary data from 100 girls with IBS. 2) Perform proteomic analyses of urine samples from the women and girls in Aim 1 and identify potential biomarkers, namely proteins whose levels differ between IBS and Control groups. 3) Advances in high throughput genomics and proteomics have increased the potential for new biomarkers including urine proteomics. We will recruit 20 women and 20 girls with IBS and 40 Controls (20 women, 20 girls). Collect diary data, urine samples for proteomics, serum for lymphocyte activation, cytokine expression and perform DNIC and video capsule endoscopy procedures. The goals of this application will be accomplished by developing infrastructure (equipment and collaborations), partnerships with industry and resources necessary to collect preliminary data for larger mechanistic and intervention studies. PUBLIC HEALTH RELEVANCE: Functional gastrointestinal disorders, in particular functional abdominal pain (FAP) in children and adults and irritable bowel syndrome (IBS) in adults, are among the most common and costly health care problems in the U.S. These functional pain conditions disproportionately affect women (10-15% in industrialized nations) and adolescent girls, and likely have multiple causes and symptom profiles. Until we have some way of identifying subgroups, progress on understanding etiology will be difficult to achieve. The goal of this proposed interdisciplinary study is to use existing symptom data and urine samples from 400 adults and 100 children with IBS to define clusters of patients with distinct symptom profiles and then test whether urinary proteomics can identify biomarkers which distinguish these symptom subtypes from each other and from healthy controls. New biomarkers (video capsule endoscopy, lymphocyte activation/cytokine diffuse noxious inhibitory control testing) will be used with newly recruited IBS and control subjects.

描述（由申请人提供）：本申请腹部症状表型：新生物标志物途径 (ASPPNB) 是对 RFA-OD-09-004、美国研究和基础设施复苏和再投资法案的回应。该应用程序响应与发现生物标志物和了解症状与生物标志物之间的联系、导致症状的机制以及最终症状管理相关的 NINR 优先事项。功能性胃肠道 (GI) 疾病 (FGID)，特别是成人和儿童的肠易激综合征 (IBS)，是美国最常见且成本最高的医疗保健问题之一。在成人中，肠易激综合症对女性（西方国家女性的 10-15%）和青春期女孩的影响尤为严重。肠易激综合症与其他病症（纤维肌痛、头痛）和症状（抑郁、疲劳、失眠）之间存在着众所周知的关联。治疗通常用于缓解特定症状（解痉药、镇痛药或抗抑郁药等止痛药、泻药、止泻药）或改变生活方式特征（例如饮食、认知行为疗法、催眠或综合自我管理2, 3以改变应对能力） 。我们认为，通过更好地理解IBS的这些不同表达（即更好定义的患者亚组）并将它们与更新的生物标志物联系起来，最终可以在理解病因和确定有效治疗方面取得更大进展。我们的具体目标是 1) 使用两项研究中 400 名 IBS 女性的现有症状日记数据来定义具有不同症状的女性群体。我们将使用 100 名患有 IBS 的女孩的日记数据来采取类似的方法。 2) 对目标 1 中妇女和女孩的尿液样本进行蛋白质组学分析，并确定潜在的生物标志物，即 IBS 组和对照组之间水平不同的蛋白质。 3) 高通量基因组学和蛋白质组学的进步增加了包括尿液蛋白质组学在内的新生物标志物的潜力。我们将招募 20 名患有 IBS 的女性和 20 名女孩以及 40 名对照者（20 名女性，20 名女孩）。收集日记数据、蛋白质组学尿液样本、淋巴细胞活化血清、细胞因子表达，并执行 DNIC 和视频胶囊内窥镜检查程序。该应用程序的目标将通过开发基础设施（设备和合作）、与行业的合作伙伴关系以及为更大的机械和干预研究收集初步数据所需的资源来实现。 公共健康相关性：功能性胃肠道疾病，特别是儿童和成人的功能性腹痛 (FAP) 和成人肠易激综合征 (IBS)，是美国最常见且成本最高的医疗保健问题之一。这些功能性疼痛状况对女性的影响尤为严重（工业化国家为 10-15%）和青春期女孩，并且可能有多种原因和症状。在我们找到某种方法来识别亚组之前，在理解病因学方面将很难取得进展。这项拟议的跨学科研究的目标是使用 400 名成人和 100 名 IBS 儿童的现有症状数据和尿液样本来定义具有不同症状特征的患者群，然后测试尿液蛋白质组学是否可以识别区分这些症状亚型的生物标志物以及健康对照。新的生物标志物（视频胶囊内窥镜检查、淋巴细胞活化/细胞因子弥漫性有害抑制控制测试）将用于新招募的 IBS 和对照受试者。