title: Pediatric Eosinophilic Esophagitis Symptom Scores (PEESS v2.0) identify histologic and molecular correlates of the key clinical features of disease.
abstract: BACKGROUND
  The Pediatric Eosinophilic Esophagitis Symptom Score (PEESS v2.0) measures patient-relevant outcomes. However, whether patient-identified domains (dysphagia, gastroesophageal reflux disease [GERD], nausea/vomiting, and pain) align with clinical symptomology and histopathologic and molecular features of eosinophilic esophagitis (EoE) is unclear.
  
  
  OBJECTIVE
  The purpose of this study was to determine whether clinical features of EoE, measured through PEESS v2.0, associate with histopathologic and molecular features of EoE. This represents a novel approach for analysis of allergic diseases, given the availability of allergic tissue biopsy specimens.
  
  
  METHODS
  We systematically recruited treated and untreated pediatric patients with EoE (aged 2-18 years) and examined parent proxy-reported symptoms using the PEESS v2.0. Clinical symptomology was collected by questionnaire. Esophageal biopsy samples were quantified for levels of eosinophils, eosinophil peroxidase (EPX) immunohistochemical staining, and mast cells. Molecular features were assessed by using the EoE Diagnostic Panel (94 EoE-related gene transcripts). Associations between domain scores and clinical symptoms and biological features were analyzed with Wilcoxon rank sum and Spearman correlation.
  
  
  RESULTS
  The PEESS v2.0 domains correlated to specific parent-reported symptoms: dysphagia (P = .0012), GERD (P = .0001), and nausea/vomiting (P < .0001). Pain correlated with multiple symptoms (P < .0005). Dysphagia correlated most strongly with overall histopathology, particularly in the proximal esophagus (P ≤ .0049). Markers of esophageal activity (EPX) were significantly associated with dysphagia (strongest r = 0.37, P = .02). Eosinophil levels were more associated with pain (r = 0.27, P = .06) than dysphagia (r = 0.24, P = .13). The dysphagia domain correlated most with esophageal gene transcript levels, predominantly with mast cell-specific genes.
  
  
  CONCLUSIONS
  We have (1) established a validated, parent proxy-reported measure for pediatric EoE, the PEESS v2.0; (2) verified that the parent proxy effectively captures symptoms; (3) determined that the dysphagia domain most closely aligns with symptoms and tissue-based molecular biomarkers; (4) established that symptoms correlate with EPX staining; and (5) observed association between mast cells and dysphagia.
authors.affiliation: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, Ohio.
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Martin
authors.affiliation: Division of Gastroenterology, Department of Pediatrics, Nemours Children's Health System, Orlando, Fla.
authors.forename: James P
authors.initials: JP
authors.lastname: Franciosi
authors.affiliation: Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, Ohio; Division of Pathology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Margaret H
authors.initials: MH
authors.lastname: Collins
authors.affiliation: Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, Ohio; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: J Pablo
authors.initials: JP
authors.lastname: Abonia
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic in Arizona, Scottsdale, Ariz.
authors.forename: James J
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, Ohio; Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Hommel
authors.affiliation: Department of Pediatrics, College of Medicine, Department of Landscape Architecture and Urban Planning, College of Architecture, Texas A&M University, College Station, Tex.
authors.forename: James W
authors.initials: JW
authors.lastname: Varni
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: J Tommie
authors.initials: JT
authors.lastname: Grotjan
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Michael
authors.initials: M
authors.lastname: Eby
authors.affiliation: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Hua
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, Ohio; Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Keith
authors.initials: K
authors.lastname: Marsolo
authors.affiliation: Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, Ohio; Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Philip E
authors.initials: PE
authors.lastname: Putnam
authors.affiliation: Children's Center for Digestive Health Care, Atlanta, Ga.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Garza
authors.affiliation: Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, Ohio; Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Ajay
authors.initials: A
authors.lastname: Kaul
authors.affiliation: Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, Ohio; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Ting
authors.initials: T
authors.lastname: Wen
authors.affiliation: Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, Ohio; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. Electronic address: Marc.Rothenberg@cchmc.org.
authors.forename: Marc E
authors.initials: ME
authors.lastname: Rothenberg
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003680:Deglutition Disorders / Q000503:physiopathology; D047209:Eosinophil Peroxidase / Q000378:metabolism; D057765:Eosinophilic Esophagitis / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D004804:Eosinophils / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005764:Gastroesophageal Reflux / Q000503:physiopathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008407:Mast Cells / Q000378:metabolism / Q000473:pathology; D009325:Nausea / Q000503:physiopathology; D010146:Pain / Q000503:physiopathology; D010290:Parents; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D059467:Transcriptome; D014839:Vomiting / Q000503:physiopathology
chemical_list: D047209:Eosinophil Peroxidase
keywords: Allergy; mast cells; microarray; molecular genetics; patient-reported outcomes; pediatrics; quality of life; reflux; surveys