Point of Care Breath Test for Biomarkers of COPD

COPD 生物标志物的护理点呼吸测试

基本信息

批准号：
8757326
负责人：
Michael Phillips
金额：
$ 22.3万
依托单位：
MENSSANA RESEARCH, INC.
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-06 至 2016-08-05
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8757326
关键词：
Acoustics Affect Algorithms Alveolar Attention Biological Assay Biological Markers Biopsy Blood Breath Tests Breathing Cause of Death Chemicals Chest Chronic Chronic Obstructive Airway Disease Clinical Clinical Research Diffuse Disease Early Diagnosis Electronics Ethanol Exhalation Gas Chromatography Goals Heart Transplantation Hospitalization Human Laboratories Learning Lung Lung diseases Malignant neoplasm of lung Marketing Mass Spectrum Analysis Membrane Methods Monitor Nose Obstruction Outcomes Research Painless Pathway interactions Patients Phase Point-of-Care Systems Radiation Reporting Research Research Design Route Sensitivity and Specificity Societies Solutions Spirometry Staging Surface System Technology Testing Time United States Food and Drug Administration Validation Vendor Viral Walking World Health Organization base commercial application cost effective detector human subject instrument malignant breast neoplasm point of care public health relevance pulmonary function response success tool user-friendly volatile organic compound

项目摘要

DESCRIPTION (provided by applicant): The clinical problem: Chronic obstructive pulmonary disease (COPD) affects an estimated 16 million people in the USA, and it is projected to increase from the sixth to the third most common cause of death worldwide by 2020. COPD imposes a burden on patients by restricting their everyday activities (e.g. walking up stairs), as well as a financial burden on society because hospitalizations for treatment of exacerbations are increasing. However, COPD is frequently underdiagnosed and more sensitive and specific biomarkers of the disease could potentially reduce its burden on patients and society, facilitate earlier diagnosis, monitor response to treatment, and identify subtypes of patients who will benefit from tailored treatments. A new solution the problem: Recent studies have shown that human breath contains many volatile organic compounds in low concentrations, and some of them are biomarkers of diseases including COPD. More than 70 studies of breath VOC biomarkers of pulmonary diseases have been reported, and biomarkers of COPD have been tentatively identified with mass spectrometry (MS) and electronic noses. A rapid new point-of-care breath test for volatile biomarkers, the BreathLink system, may offer an accurate, painless, and completely safe test for COPD. The goal of the research is to develop and validate a rapid and accurate onsite breath test for COPD. Phase 1 research: In months 1-12 (biomarker discovery phase) we will analyze breath VOCs with GCxGC TOF MS in three groups of human subjects (n=50 in each group): a. COPD; b. controls with no pulmonary disease (as shown by a negative chest CT), and c. controls with another pulmonary disease (biopsy-proven lung cancer). We will identify statistically significant breath VOC biomarkers of COPD, develop multivariate predictive algorithms for the disease, and determine their sensitivity and specificity. Phase 2 researches: In months 12-24 (onsite system optimization) we will: 1. Obtain pure biomarker VOCs identified in Phase 1 either from commercial vendors or from a consultant chemist who will synthesize those employing known synthetic routes. 2. Evaluate and optimize candidate onsite platforms (including GC SAW) to identify the instrument with optimal sensitivity and selectivity for the pure VOC biomarkers of COPD. In months 25-36 (clinical study of POC breath test) we will evaluate the selected POC platform in a clinical study of a new set of human subjects employing the same study design as the Phase 1 research. Expected impact of the research: A rapid, accurate, and cost-effective onsite breath test could potentially facilitate earlier diagnosis of COPD, monitor response to treatment, and identify subtypes of patients who will benefit from tailored treatments. Potential for commercial application: In order to market the onsite breath test for COPD in the USA we will apply to the Food & Drug Administration (FDA) for pre-marketing approval, and a CE Mark in the EU.

描述（由申请人提供）：临床问题：慢性阻塞性肺病 (COPD) 影响美国约 1600 万人，预计到 2020 年，该疾病将从全球第六大常见死因增至第三大常见死因。由于限制患者的日常活动（例如爬楼梯），给患者带来了负担，并且由于病情加重而住院治疗的人数不断增加，也给社会带来了经济负担。然而，慢性阻塞性肺病经常被诊断不足，该疾病更敏感和更特异的生物标志物可能会减轻其对患者和社会的负担，促进早期诊断，监测对治疗的反应，并确定将从定制治疗中受益的患者亚型。解决问题的新方法：最近的研究表明，人类呼吸中含有许多低浓度的挥发性有机化合物，其中一些是包括慢性阻塞性肺病在内的疾病的生物标志物。已有 70 多项关于肺部疾病的呼吸 VOC 生物标志物的研究报道，并已通过质谱 (MS) 和电子鼻初步鉴定了 COPD 的生物标志物。 BreathLink 系统是一种针对挥发性生物标志物的新型快速护理点呼吸测试，可以为慢性阻塞性肺病提供准确、无痛且完全安全的测试。该研究的目标是开发和验证一种快速、准确的慢性阻塞性肺病现场呼气测试方法。第 1 阶段研究：在第 1-12 个月（生物标志物发现阶段），我们将使用 GCxGC TOF MS 对三组人类受试者（每组 n=50）分析呼吸 VOC：慢性阻塞性肺病； b.没有肺部疾病的对照（如胸部 CT 阴性所示），以及 c.患有另一种肺部疾病（活检证实的肺癌）。我们将识别具有统计学意义的 COPD 呼吸 VOC 生物标志物，开发该疾病的多变量预测算法，并确定其敏感性和特异性。第 2 阶段研究：在第 12-24 个月（现场系统优化）中，我们将： 1. 从商业供应商或化学顾问处获取第 1 阶段确定的纯生物标志物 VOC，化学家将采用已知的合成路线合成那些物质。 2. 评估和优化候选现场平台（包括GC SAW），以确定对COPD纯VOC生物标志物具有最佳灵敏度和选择性的仪器。在第 25-36 个月（POC 呼气测试的临床研究）中，我们将在一组新的人类受试者的临床研究中评估所选的 POC 平台，该临床研究采用与第一阶段研究相同的研究设计。研究的预期影响：快速、准确且具有成本效益的现场呼气测试可能有助于慢性阻塞性肺病的早期诊断，监测对治疗的反应，并确定将从定制治疗中受益的患者亚型。商业应用潜力：为了在美国销售 COPD 现场呼气测试，我们将向美国食品和药物管理局 (FDA) 申请上市前批准，并在欧盟申请 CE 标志。