Screening for Alcohol-Related Liver Disease Using Breath Signatures by DMS

使用 DMS 呼吸特征筛查酒精相关肝病

• 批准号: 8780346
• 负责人: Royce W Johnson
• 金额: $ 22.5万
• 依托单位: APPLIED NANOTECH, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-25 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8780346
• 关键词: Acetone; Acute; Address; Adult; Affect; Alcohol abuse; Alcohol consumption; Alcohol-Related Disorders; Alcoholic Fatty Liver; Alcoholic Hepatitis; Alcoholic Liver Cirrhosis; Alcoholic Liver Diseases; Alcoholic beverage heavy drinker; Alcohols; Algorithms; Anemia; Biological Markers; Breath Tests; Businesses; Cardiovascular Diseases; Caring; Chemicals; Clinic; Clinical; Clinical Trials; Comorbidity; Complex Mixtures; Dementia; Detection; Diabetes Mellitus; Diagnosis; Disease; Early Diagnosis; Early Intervention; Economics; Electronics; Excision; Fetor hepaticus; Foundations; Gas Chromatography; Gases; Gastritis; Gout; Health; Human; Infection; Injury; Intervention; Laboratories; Lead; Liver; Liver Cirrhosis; Liver diseases; Location; Maps; Measures; Medical; Metabolism; Methods; Modeling; Monitor; Nanotechnology; National Institute on Alcohol Abuse and Alcoholism; Nose; Odors; Organ; Outcome; Pancreatitis; Patients; Pattern; Pentanones; Performance; Pharmacologic Substance; Phase; Positioning Attribute; Procedures; Process; Research; Research Personnel; Risk; Running; Sampling; Selection for Treatments; Sensitivity and Specificity; Services; Small Business Innovation Research Grant; Social Problems; Specificity; Spectrometry; Staging; Stomach; Sulfides; Sulfur; Syndrome; System; Technology; Testing; Time; Tissues; Translations; Urine; Validation; Work; alcohol monitoring; alcohol screening; automobile accident; base; bench to bedside; cancer risk; chronic alcohol ingestion; clinical care; commercialization; cost; dimethyl sulfide; drinking behavior; effective therapy; fight against; gas analyzer; high risk drinking; improved; instrument; interest; ion mobility; ionization; irritation; liver biopsy; liver injury; methylethyl ketone; new technology; non-alcoholic fatty liver; novel; novel strategies; preclinical study; pressure; problem drinker; research study; response; scale up; screening; sensor; small molecule libraries; success; tool; volatile organic compound

DESCRIPTION (provided by applicant): Alcohol abuse is rampant in the U.S., estimates run as high as 1 in 20 adults, and cost tens of billions of dollars in treatment and economic loss. One especially intransigent problem has been alcohol-induced organ disease such as alcoholic hepatitis and cirrhosis. These diseases can currently be diagnosed, but this requires invasive procedures such as liver biopsy, which are typically not applied until the disease process is in a late stage. Late detection of organ disease leads to substantially worse outcomes. Organs affected by alcohol, such as the liver, are highly metabolically active, and the compounds produced by the organs are often volatile and therefore appear in the breath. Breath odor profiles are altered by disease processes, for example the clinical odor syndrome called fetor hepaticus in liver disease, and are composed of many compounds which are altered by many metabolic processes, not just the disease process. To determine the exact disease process responsible for changes in breath odor, many compounds must be measured simultaneously. Odor analysis instruments are capable of profiling complex mixtures of volatile organic compounds (VOCs) at parts-per-billion concentrations. Odor of breath and urine have long been recognized as clinically valuable but have proven to be impractical due to the complexity of chemical analyzers and difficulties in interpreting the complex mixtures of compounds. This project will investigate the feasibility of early detection of alcohol induced organ damage using a new, compact and simplified gas analyzer technology based on gas chromatography and differential ion mobility spectrometry. This technology operates at ambient pressures, does not require a carrier gas supply, and can be configured with a non-radioactive ionizer unlike typical laboratory analyzers. This instrument creates profiles of the complex mixtures of compounds present in a gas sample which can be used to assess patterns of compounds. Recent work has identified several breath marker compound candidates and these will be mapped with the gas analyzer in the breath of patients with alcoholic liver disease. Patterns of the compounds detected in patient breath will be tested against the patterns found in breath of healthy subjects to build an algorithm for detecting alcoholic liver disease. The project will proceed in two stages The first will confirm that the analyzer can detect the candidate biomarkers of alcoholic liver disease and match those candidates to compounds observed in the breath of patients. The second stage will use the sets of confirmed compounds to test the ability of the technology to distinguish another set of patients from healthy controls. Breath analysis is almost completely noninvasive and shows great promise for health surveillance. This project will apply it to a pernicious clinical and social problem, alcohol induced organ damage. Success will lead to a sensitive, specific and timely clinical tool in the fight against the consequences of alcohol abuse.

描述（由申请人提供）：酒精滥用在美国很猖獗，据估计，每20个成年人中就有一个患有这种疾病，治疗费用和经济损失高达数百亿美元。一个特别顽固的问题是酒精引起的器官疾病，如酒精性肝炎和肝硬化。这些疾病目前可以诊断，但这需要侵入性程序，如肝活检，通常不应用，直到疾病过程处于晚期阶段。器官疾病的晚期检测导致实质上更差的结果。受酒精影响的器官，如肝脏，具有高度的代谢活性，由器官产生的化合物通常是挥发性的，因此会出现在呼吸中。呼吸气味特征被疾病过程改变，例如在肝病中被称为肝恶臭的临床气味综合征，并且由许多化合物组成，这些化合物被许多代谢过程改变，而不仅仅是疾病过程。为了确定导致呼吸气味变化的确切疾病过程，必须同时测量许多化合物。气味分析仪器能够分析十亿分之一浓度的挥发性有机化合物（VOC）的复杂混合物。呼吸和尿液的气味长期以来被认为是临床上有价值的，但由于化学分析仪的复杂性和解释化合物的复杂混合物的困难，已被证明是不切实际的。该项目将研究使用基于气相色谱和差分离子迁移谱的新型、紧凑和简化的气体分析仪技术早期检测酒精引起的器官损伤的可行性。该技术在环境压力下操作，不需要载气供应，并且可以与典型的实验室分析仪不同地配置有非放射性电离器。该仪器创建气体样品中存在的化合物的复杂混合物的轮廓，其可用于评估化合物的模式。最近的工作已经确定了几种呼吸标记化合物的候选者，这些将与酒精性肝病患者呼吸中的气体分析仪进行映射。将对照健康受试者呼吸中发现的模式测试患者呼吸中检测到的化合物的模式，以建立用于检测酒精性肝病的算法。该项目将分两个阶段进行，第一阶段将确认分析仪可以检测酒精性肝病的候选生物标志物，并将这些候选物与患者呼吸中观察到的化合物相匹配。第二阶段将使用已确认的化合物来测试该技术区分另一组患者和健康对照的能力。呼吸分析几乎是完全无创的，并显示出健康监测的巨大前景。这个项目将应用于一个有害的临床和社会问题，酒精引起的器官损伤。成功将导致一个敏感，具体和及时的临床工具，在打击酗酒的后果。