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一种新的诊断嗜酸性粒细胞慢性炎症的检测方法。 鼻窦炎（eCRS）在护理点，提高个性化的效率，价值和可及性 药eCRS影响多达500万美国人，其特征在于不同程度的鼻窦和鼻窦炎。 外周嗜酸性粒细胞增多症，与CRS的治疗反应有关。这主要是2型炎性 疾病导致患者生活质量显著下降，并造成每年更大的经济负担。 超过5.7亿美元。患有eCRS的患者通常无法达到标准护理，并转向昂贵的手术干预， 嗜酸性粒细胞靶向生物疗法来控制他们的疾病。此外，这些患者具有显著的 尽管进行了积极的药物治疗，但仍有鼻窦症状，更有可能接受鼻窦翻修术 与其他CRS队列相比。目前，eCRS的明确诊断依赖于满足鼻窦炎。 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， 对在医疗失败后选择鼻窦手术的患者进行诊断，没有可能评估变化 嗜酸性粒细胞增多症考虑到控制eCRS疾病的难度以及组织嗜酸性粒细胞增多与 对于治疗反应性，准确和可靠的eCRS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、经济、及时的 基于鼻窦拭子和组织嗜酸性粒细胞增多的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局。一项针对患者的初步研究表明， 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， 中度特异性，表明该测试具有准确预测eCRS诊断的高潜力， 并用作测量患者对内科和外科干预的反应的客观工具。在 根据这项建议，组织嗜酸性粒细胞检测试验将在使用鼻窦炎的患者中进行优化和验证。 专门设计用于提高患者采样精度和可靠性的拭子， 准确确认目标1中eCRS诊断的特异性。一项前瞻性观察性队列研究将 进行评估这种新测试方法预测eCRS诊断的临床实用性 关注目标2。将优化检测参数，以最大限度地减少读出时间并提高检测特异性， 通过比较临床诊断患者的鼻窦拭子结果得出阳性预测值， eCRS与非eCRS患者相比。里程碑式的成就将导致提交第二阶段 建议扩大试验验证研究，获得上市前通知510（k）许可，并进行大型- eCRS检测试剂盒的规模化生产，以实现用于诊断和 监测eCRS。