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.

项目摘要 该提案的目的是优化和临床验证嗜酸性慢性的新诊断测试 鼻塞炎（ECRS）在护理点上，提高了个性化的效率，价值和可及性 药品。 ECR会影响多达500万美国人，其特征是不同程度的Sinonasal和 周围嗜酸性粒细胞，与CR中的治疗反应性有关。这主要是2型炎症 疾病导致患者生活质量的显着下降，并施加更大的年度经济负担 超过$ 5.7B。 ECRS患者通常会失败护理标准，并转向昂贵的手术干预和 嗜酸性粒细胞靶向生物疗法以控制其疾病。此外，这些患者的意义很大 尽管有积极的医疗管理，鼻窦症状，并且更有可能接受修订 与其他CRS队列相比，手术。 ECRS的确切诊断目前依赖于遇到鼻窦 通过手术活检和病理检查获得的组织嗜酸性粒细胞计数阈值，限制 诊断出治疗后选择鼻窦手术的患者，没有评估变化的潜力 随着时间的流逝，嗜酸性粒细胞。鉴于难以控制ECRS疾病，并且组织嗜酸性粒细胞相关 对于治疗反应能力，准确可靠的ECR诊断至关重要，因为它可能具有预后 和对患者的治疗意义。 Glycomira正在开发一种微创，成本效益和及时的 基于鼻窦拭子和组织嗜酸性粒细胞的免疫标记的诊断解决方案 改善ECRS患者的治疗管理和结果。对患者的试点研究证明 该测试能够在25分钟内确认ECR的临床诊断，并且具有高灵敏度和 中等特异性，表明该测试具有准确预测ECRS诊断的高潜力，因为 并用作衡量患者对医学和手术干预反应的客观工具。在 该提案，将在使用硝酸盐的患者中优化和验证组织嗜酸性粒细胞检测测定法 专门设计以提高患者采样精度和可靠性的拭子以及测定 准确确认AIM 1中ECRS诊断的特异性。前瞻性观察队列研究将 进行以评估这种新测试方法的临床实用性，以预测ECRS的诊断 AIM 2的护理。测试参数将被优化以最大程度地减少读数时间并提高测试特异性和 通过比较临床诊断患者获得的鼻窦拭子结果，从而阳性预测值 来自非ECRS患者的ECR。里程碑成就将导致II阶段的提交 提议扩展测试验证研究，获得前通知510（k）清除率，并进行大量 ECRS测试套件的规模制造，以进行诊断和护理测试的商业化。 监视ECRS。