Bench-to-Bedside: Identification of Predictive Biomarkers of Asthma Exacerbation

摘要： 哮喘是一个主要的公共卫生问题，与显着的发病率和死亡率。哮喘失代偿的高风险患者包括那些患有难治性重度哮喘的患者，以及由于治疗不充分而疾病控制不佳的患者。我们相信，开发一种非侵入性的方法来检测与哮喘加重相关的哮喘特异性生物标志物，将促进临床管理。此外，由于哮喘相关的发病率的不成比例的负担影响少数群体和妇女，临床上有用的生物标志物的鉴定可以解决健康差距。因此，这个从实验室到床边的建议的目标是使用一种新的设备来收集哮喘患者的呼出气冷凝物，这些患者是频繁加重的高危人群， 通过质谱（MALDI-TOF）测定气道炎症的特异性生物标志物。 这将是NHLBI校内研究部门的研究人员与约翰霍普金斯大学的校外研究人员之间的合作研究，他们正在开发用于诊断呼吸道感染的应用物理实验室检测平台。从临床到临床的奖励计划促进了这一合作提案的概念，该提案解决了一个重要的临床问题，并将在NIH临床研究中心产生一个新的临床方案。Levine博士将担任主要临床研究者，Jackman博士将担任主要基础科学家。Rothman博士是项目6.3（通用诊断平台， 生物恐怖事件）的NlAlD计划项目赠款（Al 57168 -04：中间- 大西洋地区生物防御和新兴传染病卓越中心 疾病研究）。

Abstract: Asthma is a major public health problem that is associated with significant morbidity and mortality. Patients at high-risk for asthma decompensations include those with severe asthma that is refractory to therapy, as well as patients with poorly controlled disease due to inadequate treatment. We believe that the development of a non-invasive method for the detection of asthma-specific biomarkers that correlate with exacerbations will advance clinical management. Furthermore, since a disproportionate burden of asthma-related morbidity affects minority populations and women, the identification of clinically useful biomarkers may address a health disparity. Thus, the goal of this bench-to-bedside proposal is to use a novel device to collect exhaled breath condensates from asthmatic patients who are at high-risk for frequent exacerbations and identify disease specific biomarkers of airway inflammation by mass spectroscopy (MALDI-TOF). This will be a collaborative study between investigators in the Division of Intramural Research, NHLBl and extramural Investigators at the Johns Hopkins University, who are developing an Applied Physics Lab detection platform for the diagnosis of respiratory infections. The bench-to-bedside award program facilitated the conception of this collaborative proposal that addresses an important clinical problem and will result in a new clinical protocol at the NIH Clinical Research Center. Dr. Levine will be the Principal Clinical Investigator and Dr. Jackman will be the Principal Basic Scientist. Dr. Rothman is the Principal lnvestigator for Project 6.3 (Universal Diagnostic Platforms for Bioterrorist Events) on a NlAlD Program Project Grant (Al57168-04: The Middle- Atlantic Regional Center of Excellence for Biodefense and Emerging infectious Diseases Research).