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Show 63 6.1.2 Protein biomarkers in esophageal secretions are feasible for noninvasive diagnosis of EoE Esophageal endoscopic biopsies are necessary to diagnose EoE but are very invasive and incur significant costs for patients [9]. In surveys, 67% of patients avoid adequate management of their disease due to financial burden and quality-of-life [10]. The average cost of upper endoscopy with biopsy is estimated to be $1775 [9]. EoE has an estimated $1.4 billion direct annual healthcare cost, which is largely attributable to repeat endoscopies [9]. Noncompliance with upper endoscopy is substantial and can be attributed to increased financial burden, inconvenience, reduced quality-of-life, or lack of healthcare literacy, issues that disproportionately affect underserved populations in healthcare [11, 12]. Previous attempts to create diagnostic modalities that are less invasive than endoscopic biopsy have shown limited success. Diagnostic devices designed to collect esophageal secretions have been proposed, which include the Cytosponge [13, 14], the esophageal string test [15], and esophageal brushings [16]. Diagnoses are based on eosinophil counts [17] or the concentration of eosinophil granule proteins [16] in esophageal secretions. These markers show only moderate diagnostic accuracy for EoE. There is still a need for accurate biomarkers that can be detected noninvasively for diagnosing EoE. In Chapter 4, we identify biomarkers for EoE that can be detected noninvasively in esophageal secretions obtained by brushing rather than biopsy. We reanalyzed the RNAseq data generated in Chapter 3 using decision trees to find biomarkers for active EoE. In a small validation study, we used quantitative protein assays to show that these protein biomarkers could be detected in esophageal secretions and were feasible for noninvasive diagnosis of eosinophilic esophagitis. This study directly addresses the need for noninvasive biomarkers for EoE, and presents a method for biomarker discovery and validation may be used in other diseases. 6.1.3 Food-specific antibodies greatly expedite the identification of antigen triggers for EoE Diet elimination trials are the only established method to identify food antigens that trigger EoE [18, 19, 20, 21]. However, diet elimination trials often span years, and they consist of endoscopic biopsies that must be repeated on a periodic basis, often monthly, to assess clinical response [18, 19, 20, 21]. These trials compound the financial burden and |
