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.

项目概要 该提案的目标是优化并临床验证嗜酸性粒细胞慢性病的新诊断测试 鼻窦炎 (eCRS) 护理点，提高个性化治疗的效率、价值和可及性 药品。 eCRS 影响着多达 500 万美国人，其特点是不同程度的鼻窦和鼻窦疾病。 外周血嗜酸性粒细胞增多，与 CRS 的治疗反应有关。这主要是 2 型炎症 疾病导致患者生活质量显着下降，每年造成更大的经济负担 超过 $5.7B。 eCRS 患者通常无法达到护理标准，转而寻求昂贵的手术干预和 针对嗜酸性粒细胞的生物疗法来控制其疾病。此外，这些患者还具有显着的 尽管进行了积极的医疗治疗，但仍出现鼻窦症状，并且更有可能进行鼻窦修复术 与其他 CRS 队列相比，手术。 eCRS 的明确诊断目前依赖于满足鼻窦检查 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 医疗失败后选择鼻窦手术的患者的诊断，无法评估变化 随着时间的推移，出现嗜酸性粒细胞增多。鉴于控制 eCRS 疾病的难度和组织嗜酸性粒细胞增多的相关性 对于治疗反应，准确可靠的 eCRS 诊断至关重要，因为它可能具有预后意义 以及对患者的治疗意义。 GlycoMira 正在开发一种微创、具有成本效益且及时的 基于鼻腔拭子和组织嗜酸性粒细胞免疫标记物检测的诊断解决方案 改善 eCRS 患者的治疗管理和结果。一项针对患者的试点研究表明 该测试能够在 25 分钟内确认 eCRS 的临床诊断，并且具有高灵敏度和 中等特异性，表明该测试很有可能准确预测 eCRS 的诊断，因为 并作为衡量患者对医疗和手术干预反应的客观工具。在 根据该提案，组织嗜酸性粒细胞检测分析将在使用鼻窦的患者中进行优化和验证 专为提高患者采样精度和可靠性以及检测而设计的拭子 目标 1 中准确确认 eCRS 诊断的特异性。前瞻性观察队列研究将 进行评估这种新测试方法的临床效用，以预测 eCRS 的诊断 目标 2 中的护理。将优化测试参数，以最大限度地缩短读出时间并提高测试特异性和 通过比较临床诊断患者的鼻腔拭子结果得出阳性预测值 eCRS 至非 eCRS 患者。里程碑式的成就将导致提交第二阶段 建议扩大测试验证研究，获得上市前通知 510(k) 许可，并进行大规模 大规模生产 eCRS 测试套件，以实现用于诊断和治疗的现场护理测试的商业化 监控 eCRS。