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Annual Report


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Gastrointestinal Eosinophilic Diseases Program: Annual Report 2015

The Gastrointestinal Eosinophilic Diseases Program (GEDP) had a remarkable 2015! Highlighting the year was the receipt of an endowment for the Program, The La Cache Chair for Gastrointestinal Allergic and Immunological Diseases. The first chair holder is Glenn T. Furuta, MD.

Clinical

Our clinical program provided care to over 200 patients and families in 2015. Here we seek to improve the lives of children by providing diagnostic testing and implementing individualized care plans. Our engagement with parents and children gives us invaluable insights into areas of need and how we can improve future patient care experiences.

Highlights

  • Transition into new multidisciplinary space at CHCO. This new state-of-the-art clinical space provides an outstanding area for our patients and providers to engage.
  • Development of videos to improve patient care. Instructional videos were created to improve adherence to treatments and provide information about transnasal endoscopy.
  • Introduction of transnasal endoscopy for monitoring disease activity. This new approach provides a cost-effective alternative to traditional endoscopy in order to avoid sedation and reduce time spent in the hospital.
  • Alignment with new Section of Allergy at CHCO. Under the direction of Dan Atkins, MD, the Allergy and Immunology section at CHCO has blossomed to now include 11 faculty members, 3 nurse practitioners and 15 nurses. The GEDP continues to enjoy a rich relationship with our allergy/immunology colleagues.
  • JoAnne Newton, RN, BSN, CGRN: Promoted to Clinical Nurse IV, exemplifying her patient care, leadership, and advocacy contributions as the program coordinator

Research

Our research program seeks to perform novel studies that will have immediate and long-term impact on the care of patients with eosinophilic gastrointestinal diseases (EGIDs). Research is performed through collaborative work with our local investigators and with colleagues across the world. The research is supported by grants from the National Institutes of Health (NIH), Food and Drug Administration (FDA), Children’s Hospital Colorado Research Institute, the University of Colorado School of Medicine, academic societies, industry and philanthropy. Results from our research led to 18 publications in 2015.

Highlights

  • Global effort to identify how best to measure disease activity – In order to better understand what happens to patients over time, natural history studies are urgently needed. Knowledge gained will improve advice given to patients and families and provide new insights for treatment studies. In addition, studies were performed that were lead by our Swiss colleagues in Bern that developed novel ways to measure symptoms. Natural history studies are supported by an NIH Rare Diseases Clinical Research Network grant titled “Consortium of Eosinophilic Gastrointestinal Disease Researchers”.
  • Developing of novel ways to monitor disease activity – Although endoscopy is an important tool to obtain biopsies and visualize the intestine, we are always seeking new ways to improve the patient experience. To that end, we reported use of the transnasal endoscopy, esophageal string test and the EndoFLIP to reduce anesthesia use, risks and costs for patient care. These studies are supported by NIH, FDA and North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) grants.
  • Improving awareness of eosinophilic esophagitis (EoE) – Several studies were published to help educate other care providers about symptoms that may indicate the presence of EoE. These included radiologic findings, tissue characteristics and other symptoms. In an effort to reach a broad audience of providers, a review article on EoE was published in the New England Journal of Medicine. To date, this has been viewed by over 36,000 people from across the world.
  • Defining mechanisms of inflammation – In order to develop new treatments, studies were performed to understand what makes EGIDs occur. Studies performed locally and in collaboration with colleagues at Northwestern University, University of Illinois, Cincinnati Children’s Hospital and University of Pennsylvania helped understand the eosinophil’s roles in inflammation and barrier function, the role of the microbiome, as well as associated genes.
  • Academic Highlights
  • Sophie Fillon, PhD: received NIH U54 Pilot Project and Cystic Fibrosis Foundation Therapeutics grants, and received the International Eosinophil Society Poster Award
    • Joanne Masterson, PhD: promoted to Assistant Professor, received K01 NIH grant, completed a pilot grant from American Partnership for Eosinophilic Disorders (APFED)
    • David Fleischer, MD. Promoted to Associate Medical Director within the Children’s Clinical Research Organization (CCRO)
    • Calies Menard-Katcher, MD: received NASPGHAN Young Investigators Award and CHCO Research Institute Research Scholar Award
  • Grants/Funding Active in 2015: Sophie Fillon, PhD (Cystic Fibrosis Foundation), David Fleischer, MD (industry grants), Glenn Furuta, MD (K24 NIH/NIDDK; FDA R01; Local PI of U54 NIH/NIAID/NIDDK), Matthew Greenhawt, MD, MBA (NIH K23) Joanne Masterson, PhD (K01 NIH/NIDDK), Pooja Mehta, MD and Nathalie Nguyen, MD (T32), Calies Menard-Katcher, MD (Young Investigator’s Award, NASPGHAN; Research Scholar Award, CHCO Research Institute)

Publications

  • Furuta GTKatzka DA. Eosinophilic Esophagitis. N Engl J Med. 2015 Oct 22;373(17):1640-8. PMID:26488694
  • Capocelli, K, Fernando S, Menard-Katcher, C, Furuta GT, Masterson J, Wartchow E. Ultrastructural features of Eosinophilic Esophagitis: impact of treatment on desmosomes. J Clin Pathol 2015;68(1):51-6. PMID 25359789
  • Masterson JC, Capocelli K, Hosford L, Biette K, de Zoeten E, Harris R, Fernando S, Jedlicka P, Protheroe C, Lee JJ, Furuta GT. Eosinophils and IL-33 perpetuate chronic inflammation and fibrosis in a pediatric population with stricturing Crohn’s ileitis. Inflamm Bowel Dis. Oct;21(10):2429-40. PMID:26218140
  • Harris JK, Fang R, Wagner BD, Choe HN, Kelly CJ, Schroeder S, Moore W, Stevens MJ, Yeckes A, Amsden K, Kagalwalla AF, Zalewski AA, Hirano I, Gonsalves N, Henry LN, Masterson JC, Robertson CE, Leung DY, Pace NR, Ackerman SA, Furuta GT, Fillon SA. Microbiome in Eosinophilic Esophagitis. PlosOne. May 2015. PMID:26020633
  • Menard-Katcher C, Zwerdlow MP, Mehta P, Furuta GT, Fenton LZ. Contribution of the esophagram to the evaluation of complicated pediatric eosinophilic esophagitis. J Pediatr Gastroenterol Nutr. May 2015. PMID: 25988559
  • Friedlander JA, DeBoer EM Soden JS, Furuta GT, Menard-Katcher CD, Atkins D, Fleischer DM,  Kramer RE, Deterding RR, Capocelli, KE, Prager, JD. Unsedated transnasal esophagoscopy for monitoring therapy in pediatric eosinophilic esophagitis. Gastrointest Endoscop, 2015: Jul 2. PMID: 26142551
  • Rassbach W, Rubenstein J, Elkins M, Dematos V, Greenson J, Greenhawt M. Age-based disparities in the care of eosinophilic esophagitis. J Allergy Clin Immunolol Pract: 2015; 3: 80-87.e1
  • Aherne CM, Saeedi B, Collins CB, Masterson JC, McNamee E, Perrenoud K, Rapp C, Curtis V, Bayless A, Fletcher A, Glover L, Evans CM, Jedlicka P, Furuta GT, de Zoeten EF, Colgan SP, Eltzschig HE. Epithelial specific A2B adenosine receptor signaling protects the colonic epithelial barrier during acute colitis. Mucosal Immunol 2015. PMID: 25850656
  • Wen T, Dellon, E, Moawad FJ, Furuta GT, Aceves SS, Rothenberg, ME. Reversibility and overlap of proton pump inhibitor-responsive esophageal eosinophilia transcriptome with that of eosinophilic esophagitis. J Allerg Clin Immunol. 2015;135(1):187-97. PMID 25441638           
  • Alexander ES, Martin LJ, Collins MH, Kottyan LD, Sucharew HJ, He H. Mukkada VA,
  • Succop PA, Abonia JA, Foote H, Eby MD, Grotjan TM, Greenler AJ, Dellon E, Demain JG, Furuta GT, Gurian LE, Harley JB, Hopp, RJ, Kaul A, Nadeau KC, Noel RJ, Putnam PE, von Tiehl KF, Rothenberg ME, Twin and Family Studies Reveal Strong Environmental and Weaker Genetic Cues That Explain High Heritability of Eosinophilic Esophagitis. J Allerg Clin Immunol 2014;134(5):1084-1092.e1. PMID 25258143.
  • Sleiman PMA, Wang ML, Cianferoni A, Aceves S, Gonsalves N, Nadeau K, Bredenoord AJ, Furuta GT, Spergel JM, Hakonarson H. GWAS identifies four novel eosinophilic esophagitis loci. Nat Comm 2014. PMID 25407941.
  • Schoepfer AM, Panczak R, Zwahlen M, Kuehni CE, Coslovsky M, Maurer E, Haas NA, Alexander JA, Dellon ES, Gonsalves N, Hirano I, Leung J, Bussmann C, Collins MH, Newbury RO, De Petris G, Smyrk TC, Woosley JT, Yan P, Yang GY, Romero Y, Katzka DA, Furuta GT, Gupta SK, Aceves SS, Chehade M, Blanchard C, Straumann A, Safroneeva E; International EEsAI Study Group. How Do Gastroenterologists Assess Overall Activity of Eosinophilic Esophagitis in Adult Patients? Am J Gastroenterol. 2015;110(3):402-14. PMID: 25732414
  • Saeedi BJ, Kao DJ, Kitzenberg DA, Dobrinskikh E, Schwisow KD, Masterson JC, Kendrick AA, Kelly CJ, Bayless AJ, Kominsky DJ, Campbell EL, Kuhn KA, Furuta GT, Colgan SP, Glover LE. HIF-dependent regulation of claudin-1 is central to intestinal epithelial tight junction integrity. Mol Biol Cell. 2015.E14-07-1194. PMID: 25904334
  • Safroneeva E, Coslovsky M, Kuehni CE, Zwahlen M, Haas NA, Panczak R, Taft TH, Hirano I, Dellon ES, Gonsalves N, Leung J, Bussmann C, Woosley JT, Yan P, Romero Y, Furuta GT, Gupta SK, Aceves SS, Chehade M, Straumann A, Schoepfer AM; Eosinophilic oesophagitis: relationship of quality of life with clinical, endoscopic and histological activity.. Aliment Pharmacol Ther. 2015 Oct;42(8):PMID: 26271642
  • Safroneeva E, Straumann A, Coslovsky M, Zwahlen M, Kuehni CE, Panczak R, Haas NA, Alexander JA, Dellon ES, Gonsalves N, Hirano I, Leung J, Bussmann C, Collins MH, Newbury RO, De Petris G, Smyrk TC, Woosley JT, Yan P, Yang GY, Romero Y, Katzka DA, Furuta GT, Gupta SK, Aceves SS, Chehade M, Spergel JM, Schoepfer AM; International EEsAI Study Group, Achem SR, Arora AS, Alpan O, Armstrong D, Attwood SE, Butterfield JH, Crowell MD, DeVault KR, Drouin E, Enav B, Enders FT, Fleischer DE, Foxx-Orenstein A, Francis DL, Guyatt GH, Harris LA, Kagalwalla AF, Kita H, Krishna M, Lee JJ, Lewis JC, Lim K, Locke GR 3rd, Murray JA, Nguyen CC, Orbelo DM, Pasha SF, Ramirez FC, Sheikh J, Umar SB, Weiler CR, Wo JM, Wu TT, Yost KJ. Symptoms Have Modest Accuracy in Detecting Endoscopic and Histologic Remission in Adults with Eosinophilic Esophagitis. Gastroenterology, 2015. PMID:26584601
  • Molina-Infante J, Brednoord AJ, Cheng E, Dellon ES, Furuta GT, Gupta S, Hirano I, Katzka DA, Moawad FJ, Rothenberg ME, Schoepfer A, Spechler SJ, Wen T, Strauman A, Lucendo AJ. Proton pump inhibitor-responsive oesophageal eosinophilia: an entity challenging current diagnostic criteria for eosinophilic oesophagitis. GUT. 2015 PMID:26685124
  • Kliewer KL, Venter C, Cassin AM, Abonia JP, Aceves SS, Bonis PA, Dellon ES, Falk GW, Furuta GT, Gonsalves N, Gupta SK, Hirano I, Kagalwalla A, Leung J, Mukkada VA, Spergel JM, Rothenberg ME Should wheat, barley, rye, and/or gluten be avoided in a 6-food elimination diet? J Allergy Clin Immunol. 2015 Dec 24. PMID:26725190

Presentations

  • Sophie Fillon, PhD Oral presentation “Role of the microbiome in Eosinophilic Esophagitis, Gastritis and Colitis”, Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) meeting
  • Sophie Fillon, PhD. Oral presentation “Impact of Treatment on the Esophageal Microbiota and Bacterial Receptor Expression in Eosinophilic Esophagitis”, NASPGHAN annual meeting
  • Sophie Fillon, PhD: Oral presentation to the Microbiome Research in Progress (RIP), Microbiology RIP, Mucosal Inflammation Program (MIP) RIP, via teleconference with University of Pennsylvania and Dallas Southwestern and Pediatrics poster session
  • Sophie Fillon, PhD: Lecture, March 2015, “Microbiome and Host interactions” for course Advance Genome Analysis and Lecture, April 2015, “Microbiome” for course Immunology
  • Joanne Masterson, PhD: Oral presentation “Claudin-7 Dysregulation in Pediatric EoE: A role for TGF-b1 in Esophageal Epithelial Barrier Function”, NASPGHAN National meeting
  • Joanne Masterson, PhD: Oral presentation “Claudin-1 Dysregulation in Eosinophilic Esophagitis: A role for HIF-1a in Esophageal Epithelial Barrier Dysfunction”, International Eosinophil Society Meeting
  • Joanne Masterson, PhD: poster on “Claudin-1 Dysregulation in Eosinophilic Esophagitis: A role for HIF-1a” at the international Keystone Hypoxia Meeting
  • Joanne Masterson, PhD: poster on “Claudin-7 Dysregulation in Pediatric EoE: A role for TGF-b1 in Esophageal Epithelial Barrier Function”, the International Eosinophil Society Meeting.
  • Joanne Masterson, PhD: poster on “Claudin-1 Dysregulation in Eosinophilic Esophagitis: A role for HIF-1a” at the national FASEB meeting.
  • Dan Atkins, MD: Kauai, Hawaii, Western Society of Allergy, Asthma & Immunology 53rd Annual Scientific Session: Lecture: The Role of the Allergist in Managing EoE
  • Dan Atkins, MD: Kauai, Hawaii, Western Society of Allergy, Asthma & Immunology 53rd Annual Scientific Session: Workshop: EoE, The Allergist and GI Approach
  • Dan Atkins, MD: Houston, Texas, Annual Meeting of the American Academy of Allergy Asthma & Immunology, Moderator, Pro/Con Session: PPI-Responsive Esophageal Eosinophilia is a Distinct Entity
  • Dan Atkins, MD: Houston, Texas, Annual Meeting of the American Academy of Allergy Asthma & Immunology, Workshop Lecture: Allergy Testing and Elimination Diets in EGIDs
  • Dan Atkins, MD: Washington, D.C., Greater Washington Asthma, Allergy & Immunology Society, Lecture: The Role of the Allergist in Managing EoE
  • Dan Atkins, MD: Miami, Florida, World Allergy Organization Symposium on Food Allergy & the Microbiome, Lecture: Shining a Light on Eosinophils Beyond the Esophagus
  • Drs. Atkins & Furuta have continued to present their research to relate their clinical experiences and research findings at numerous venues locally, nationally and internationally

Advocacy, Community Involvement, Leadership, Awards

  • Advocacy work
    • Drs. Atkins and Furuta serve on the Medical Advisory Board for APFED.org
    • Both participated in speaking at APFED and CURED patient conferences
  • The GEDP continues to serve meals at the Ronald McDonald House
  • Sophie Fillon, PhD: Served as Co-chair, Session on Eosinophils as Therapeutic Targets (Part 1), International Eosinophil Society Symposium and ad hoc reviewer for Journal of Allergy and Clinical Immunology, Journal of Immunology, PLos One, Microbiome, Frontiers in Microbiology
  • Sophie Fillon, PhD: International Eosinophil Society Poster Award, July 2015, “Impact of Treatment on the Esophageal Microbiota and Bacterial Receptor Expression in Eosinophilic Esophagitis”
  • Joanne Masterson, PhD: Selected as a member of the North American Society for Pediatric Gastroenterology, Hepatology & Nutrition (NASPGHAN) Research Committee and was accepted to attend the University of Colorado Academy of Medical Educators’ School of Medicine Faculty “Women’s Leadership Training” course over the academic year.

Mentorship

  • Drs. Furuta and Menard-Katcher participated in the NIH Clinical Translational Science Award (CTSA) mentorship program.
  • Dr. Furuta has been awarded an NIH K24 Mentoring Award to support efforts in mentoring younger investigators in the field of patient oriented research in eosinophilic GI diseases.

Team Membership Changes

  • Wendy Moore departed to engage in research with the Hematology Department
  • Shahan Fernando, MD graduated his fellowship, having published 4 manuscripts and 3 reviews, presented his work orally both at local fellows’ conferences and at the national Digestive Diseases Week meeting. Dr. Fernando is now a faculty member at the Phoenix Children’s Hospital in Arizona.
  • Katie Kemery departed to pursue opportunities in another healthcare group.
  • Nathalie Nguyen, MD joined us and is making great strides in her research skills at the bench as well as publications. Nathalie has published 1 review.
  • Juliet Hammer, a recent graduate of University of Virginia, joined the lab as a Professional Research Assistant
  • Linda Perez joined as GEDP Program Assistant. She brings a wealth of expertise from her previous position as scheduler in the Digestive Health Institute.
  • Stephanie Skirka joined as a GEDP nurse. Stephanie brings a wide range of clinical expertise and knowledge from her previous work as both a general GI and surgical nurse.
  • Matthew Greenhawt, MD, MBA from the University of Michigan, joined Drs. Fleischer and Atkins as the third allergist with the GEDP. In Michigan, he co-directed the Pediatric Eosinophilic Esophagitis Clinic and served as Research Director for the University of Michigan Food Allergy Center. Dr. Greenhawt brings a rich research and clinical expertise in food allergic diseases, EoE, and pediatric healthcare policy.
  • Susanna Kantor joined the GEDP to provide oversight for all of our clinical research studies. Her past experiences with the Children’s Clinical Research Organization (CCRO) and industry make her a perfect fit for our group.
  • Faria Ahmed joined the clinical research group after performing outreach research in diabetes. She brings great enthusiasm to enrolling patients in our industry, Esophageal String Test (EST), and EndoFLIP studies.
  • Leslie Young joined the clinical research group from the Pharmacology Section at CHCO. She brings great enthusiasm to enrolling patients in our Consortium studies and has already traveled to two meetings to increase her knowledge.