Abdominal Symptom Phenotypes: Pathways to New Biomarkers

Summary

Principal Investigator: Margaret McLean Heitkemper
Abstract: 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.
Funding Period: ----------------2009 - ---------------2011-
more information: NIH RePORT

Top Publications

  1. pmc Endogenous inhibition of somatic pain is impaired in girls with irritable bowel syndrome compared with healthy girls
    Amy E Williams
    Department of Psychiatry and Behavioral Neurosciences, Loyola University Medical Center, Maywood, Illinois
    J Pain 14:921-30. 2013
  2. pmc Interprovider variation of celiac disease testing in childhood chronic abdominal pain
    Bruno Pedro Chumpitazi
    Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA
    BMC Gastroenterol 13:150. 2013
  3. ncbi Conditioned pain modulation in women with irritable bowel syndrome
    Monica E Jarrett
    Department of Biobehavioral Nursing and Health Systems, University of Washington, Seattle, WA, USA
    Biol Res Nurs 16:368-77. 2014
  4. pmc Creation and initial evaluation of a Stool Form Scale for children
    Bruno P Chumpitazi
    Department of Pediatrics, Baylor College of Medicine, Texas Children s Hospital, University of Texas Health Science Center Houston, Houston, TX 77030, USA
    J Pediatr 157:594-7. 2010
  5. pmc Subtypes of irritable bowel syndrome based on abdominal pain/discomfort severity and bowel pattern
    Margaret Heitkemper
    Department of Biobehavioral Nursing and Health Systems, University of Washington, Box 357266, Seattle, WA 98195, USA
    Dig Dis Sci 56:2050-8. 2011
  6. pmc Reliability and validity of a modified Bristol Stool Form Scale for children
    Mariella M Lane
    Baylor College of Medicine, Menninger Department of Psychiatry and Behavioral Sciences, Houston, TX, USA
    J Pediatr 159:437-441.e1. 2011
  7. pmc Searching for the noninvasive biomarker holy grail: are urine proteomics the answer?
    Joachim Voss
    Department of Biobehavioral Nursing and Health Systems, University of Washington, Seattle, WA, USA
    Biol Res Nurs 13:235-42. 2011

Scientific Experts

  • Margaret McLean Heitkemper
  • Bruno P Chumpitazi
  • Mariella M Lane
  • Monica E Jarrett
  • Robert J Shulman
  • Amy E Williams
  • Joachim Voss
  • Margaret Eugenio
  • Kevin C Cain
  • Philippe Richebe
  • Lynne T Smith
  • Wimon Deechakawan
  • Mariella M Self
  • Danita I Czyzewski
  • Lynne Smith
  • Kevin Cain
  • Monica Jarrett
  • Robert Shulman
  • Nancy Woods
  • Young Ah Goo

Detail Information

Publications7

  1. pmc Endogenous inhibition of somatic pain is impaired in girls with irritable bowel syndrome compared with healthy girls
    Amy E Williams
    Department of Psychiatry and Behavioral Neurosciences, Loyola University Medical Center, Maywood, Illinois
    J Pain 14:921-30. 2013
    ..Findings have implications for better understanding of onset and maintenance of IBS and other chronic pain conditions...
  2. pmc Interprovider variation of celiac disease testing in childhood chronic abdominal pain
    Bruno Pedro Chumpitazi
    Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA
    BMC Gastroenterol 13:150. 2013
    ....
  3. ncbi Conditioned pain modulation in women with irritable bowel syndrome
    Monica E Jarrett
    Department of Biobehavioral Nursing and Health Systems, University of Washington, Seattle, WA, USA
    Biol Res Nurs 16:368-77. 2014
    ..Overall, women with IBS exhibited an increased sensitivity to thermal stimuli. Impaired CPM was present in a subset of women with IBS. ..
  4. pmc Creation and initial evaluation of a Stool Form Scale for children
    Bruno P Chumpitazi
    Department of Pediatrics, Baylor College of Medicine, Texas Children s Hospital, University of Texas Health Science Center Houston, Houston, TX 77030, USA
    J Pediatr 157:594-7. 2010
    ..To develop a pediatric stool form rating scale and determine its interrater reliability, intrarater reliability, and agreement among pediatric gastroenterologists...
  5. pmc Subtypes of irritable bowel syndrome based on abdominal pain/discomfort severity and bowel pattern
    Margaret Heitkemper
    Department of Biobehavioral Nursing and Health Systems, University of Washington, Box 357266, Seattle, WA 98195, USA
    Dig Dis Sci 56:2050-8. 2011
    ..However, other patterns of symptoms have long been recognized, e.g., pain severity. Our objective was to examine the utility of subtyping women with IBS based on pain/discomfort severity as well as predominant bowel pattern...
  6. pmc Reliability and validity of a modified Bristol Stool Form Scale for children
    Mariella M Lane
    Baylor College of Medicine, Menninger Department of Psychiatry and Behavioral Sciences, Houston, TX, USA
    J Pediatr 159:437-441.e1. 2011
    ..This study sought to: evaluate the ability of children to reliably use a modified Bristol Stool Form Scale for Children (mBSFS-C), evaluate criterion-related validity of the mBSFS-C, and identify the lower age limit for mBSFS-C use...
  7. pmc Searching for the noninvasive biomarker holy grail: are urine proteomics the answer?
    Joachim Voss
    Department of Biobehavioral Nursing and Health Systems, University of Washington, Seattle, WA, USA
    Biol Res Nurs 13:235-42. 2011
    ..This article provides a review of proteomics and a rationale for utilizing urine proteomics in biobehavioral research. It addresses as well some of the challenges involved in data collection and sample preparation...