Point of Care Breath Test for Biomarkers of COPD

描述（由申请人提供）：临床问题：慢性阻塞性肺疾病（COPD）在美国影响约1600万人，预计到2020年将从全球第六位增加到第三位最常见的死亡原因。COPD通过限制患者的日常活动（例如，爬楼梯）而给患者带来负担，并且由于用于治疗恶化的住院治疗正在增加而给社会带来经济负担。然而，COPD经常被诊断不足，更敏感和特异的疾病生物标志物可能会减轻患者和社会的负担，促进早期诊断，监测对治疗的反应，并确定将受益于定制治疗的患者亚型。 一个新的解决方案的问题：最近的研究表明，人体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COPD在内的疾病的生物标志物。目前已报道了70多项呼吸VOC肺部疾病生物标志物的研究，并初步用质谱和电子鼻鉴定了COPD的生物标志物。一种快速的新的即时呼吸测试挥发性生物标志物，呼吸链接系统，可以提供一个准确的，无痛的，完全安全的测试慢性阻塞性肺病。 该研究的目标是开发和验证一种快速准确的COPD现场呼吸测试。1期研究：在第1-12个月（生物标志物发现阶段）中，我们将在三组人类受试者中用GCxGC TOF MS分析呼吸VOC（每组n=50）：COPD; B.没有肺部疾病的对照（如阴性胸部CT所示），和c.对照组有其他肺部疾病（活检证实的肺癌）。我们将确定统计学上显著的COPD呼吸VOC生物标志物，开发疾病的多变量预测算法，并确定其灵敏度和特异性。 第2阶段研究：在12-24个月（现场系统优化），我们将：1.从商业供应商或顾问化学家处获得第1阶段鉴定的纯生物标志物VOC，顾问化学家将采用已知的合成路线合成这些生物标志物VOC。 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呼吸测试的临床研究），我们将在一组新的人类受试者的临床研究中评价所选的POC平台，该研究采用与I期研究相同的研究设计。 研究的预期影响：快速，准确和具有成本效益的现场呼吸测试可能有助于COPD的早期诊断，监测对治疗的反应，并确定将受益于定制治疗的患者亚型。 商业应用潜力：为了在美国销售COPD现场呼吸测试，我们将向食品药品监督管理局（FDA）申请上市前批准，并在欧盟申请CE标志。

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.