Development of a Diagnostic Test for Eosinophilic Chronic Rhinosinusitis

嗜酸性粒细胞性慢性鼻窦炎诊断测试的开发

• 批准号: 10761350
• 负责人: Abigail Pulsipher
• 金额: $ 30.49万
• 依托单位: GLYCOMIRA, LLC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10761350
• 关键词: Achievement; Affect; American; Basic Science; Biological Assay; Biological Response Modifier Therapy; Biological Sciences; Biopsy; Cells; Clinical; Cytolysis; Detection; Development; Diagnosis; Diagnostic; Diagnostic Reagent Kits; Diagnostic tests; Disease; Disease Progression; Economic Burden; Engineering; Eosinophilia; Failure; Goals; Guidelines; Health Personnel; Healthcare; Human; Immunologic Markers; Infiltration; Inflammatory; Link; Marketing; Measures; Mediator; Medical; Medical center; Methods; Modeling; Monitor; Nasal Polyps; Notification; Observational Study; Operative Surgical Procedures; Pathologic; Pathology; Patient Monitoring; Patient-Focused Outcomes; Patients; Peripheral; Peroxidases; Phase; Physiological; Pilot Projects; Predictive Value; Preparation; Process; Quality of life; Resources; Sampling; Scientist; Seasons; Sinus; Slide; Specific qualifier value; Specificity; Swab; Symptoms; Testing; Therapeutic; Time; Tissues; Treatment Failure; Universities; Utah; accurate diagnosis; accurate diagnostics; assay development; candidate identification; care burden; chronic rhinosinusitis; clinical diagnosis; clinical practice; cohort; commercialization; cost; cost effective; detection assay; detection limit; enzyme activity; eosinophil; eosinophil peroxidase; eosinophilic inflammation; health care economics; improved; innovation; instrument; large scale production; manufacture; medical schools; meetings; minimally invasive; nasal swab; novel diagnostics; observational cohort study; patient response; personalized medicine; point of care; point of care testing; prognostic; prospective; standard of care; targeted treatment; tool; translational scientist; treatment response; validation studies

PROJECT SUMMARY The goal of this proposal is to optimize and clinically validate a new diagnostic test for eosinophilic chronic rhinosinusitis (eCRS) at the point-of-care, improving the efficiency, value, and accessibility of personalized medicine. eCRS affects up to 5 million Americans and is characterized by varying degrees of sinonasal and peripheral eosinophilia, linked to treatment responsiveness in CRS. This predominantly type 2 inflammatory disease leads to significant declines in patient quality of life and imposes an annual economic burden of greater than $5.7B. Patients with eCRS typically fail the standard of care and turn to costly surgical intervention and eosinophil-targeting biologic therapies to manage their disease. Moreover, these patients have significant sinonasal symptoms despite aggressive medical management and are more likely to undergo revision sinus surgery compared to other CRS cohorts. A definitive diagnosis of eCRS currently relies on meeting a sinonasal tissue eosinophil count threshold obtained through surgical biopsy and pathologic examination, limiting diagnoses to patients electing sinus surgery after medical treatment failure, with no potential to assess changes in eosinophilia over time. Given the difficulty in controlling eCRS disease and that tissue eosinophilia is correlated to treatment responsiveness, an accurate and reliable diagnosis of eCRS is critical, as it may have prognostic and therapeutic implications for patients. GlycoMira is developing a minimally invasive, cost-effective, and timely diagnostic solution based on a sinonasal swab and detection of an immunologic marker of tissue eosinophilia to improve the treatment management and outcomes for patients with eCRS. A pilot study in patients demonstrated that this test is capable of confirming a clinical diagnosis of eCRS within 25 minutes and with high sensitivity and moderate specificity, suggesting that this test has a high potential to accurately predict a diagnosis of eCRS, as well as serve as an objective tool by which to measure patient response to medical and surgical intervention. In this proposal, the tissue eosinophil detection assay will be optimized and validated in patients using sinonasal swabs that were specifically engineered to improve patient sampling precision and reliability, as well as assay specificity for accurately confirming a diagnosis of eCRS in Aim 1. A prospective observational cohort study will be performed to assess the clinical utility of this new test method to predict a diagnosis of eCRS at the point-of- care in Aim 2. Test parameters will be optimized to minimize readout time and improve test specificity and positive predictive value by comparing sinonasal swab results obtained from clinically diagnosed patients with eCRS to those from patients with non-eCRS. Milestone achievements will result in the submission of a Phase II proposal to expand test validation studies, obtain Premarket Notification 510(k) clearance, and conduct large- scale manufacturing of eCRS test kits towards the commercialization of a point-of-care test for diagnosing and monitoring eCRS.

项目总结