Point of Care Breath Test for Biomarkers of COPD

描述(申请人提供)：临床问题：慢性阻塞性肺疾病(COPD)在美国估计有1600万人受到影响，预计到2020年将从全球第六大最常见的死亡原因增加到第三大最常见的死亡原因。慢性阻塞性肺病通过限制患者的日常活动(如上楼)给患者带来负担，并给社会带来经济负担，因为因病情恶化而住院治疗的人数正在增加。然而，COPD往往被低估，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，监测治疗反应，并确定将从量身定制的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COPD在内的疾病的生物标志物。目前已有70多项研究报道了肺部疾病的呼气VOC生物标记物，并用质谱仪和电子鼻初步鉴定了COPD的生物标记物。一种针对挥发性生物标志物的快速新的护理点呼气测试--BreathLink系统--可能为COPD提供一种准确、无痛和完全安全的测试。 这项研究的目标是开发和验证一种快速、准确的COPD现场呼气测试。第1阶段研究：在第1-12个月(生物标志物发现阶段)，我们将用GCxGC TOF MS分析三组人类受试者(每组50人)的呼气VOCs：a.COPD；b.没有肺部疾病的对照组(如胸部CT阴性所示)，以及c.有其他肺部疾病的对照组(经活检证实的肺癌)。我们将确定有统计学意义的COPD呼吸VOC生物标志物，开发多变量预测算法，并确定它们的敏感性和特异性。第二阶段研究：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那里获得第一阶段确定的纯生物标志物VOCs，后者将合成那些采用已知合成路线的VOCs。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)，我们将在一组新的人类受试者的临床研究中评估选定的POC平台，该研究设计与第一阶段研究相同。 研究的预期影响：快速、准确和经济高效的现场呼气测试可能有助于COPD的早期诊断、监测治疗反应，并确定将从量身定制的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，我们将向食品和药物管理局(FDA)申请上市前批准，并在欧盟获得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.