New Serodiagnostics for Isocyanate Exposure, A Major Cause of Occupational Asthma

针对异氰酸酯暴露（职业性哮喘的主要原因）的新血清诊断方法

• 批准号: 7482584
• 负责人: ADAM WISNEWSKI
• 金额: $ 20.27万
• 依托单位: L2 DIAGNOSTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7482584
• 关键词: Accounting; Adhesives; Adult asthma; Aerosols; Air; Albumins; Antigens; Applications Grants; Archives; Asthma; Binding; Biological Assay; Biological Markers; Businesses; Charge; Chemicals; Clinical; Competitive Binding; Complex; Diagnosis; Diagnostic; Disease; Economics; Effectiveness; Enzyme-Linked Immunosorbent Assay; Facility Construction Funding Category; Funding; Health; Health Benefit; Health Insurance; Health Personnel; Hot Spot; Human; Hypersensitivity; IgE; Immunoglobulin G; Immunologic Markers; Immunologics; Individual; Industrial Health; Industry; Isocyanates; Laboratories; Lead; Light; Liquid substance; Maps; Marketing; Measures; Mechanical Ventilators; Medical; Medical Surveillance; Military Personnel; Monitor; Occupational Asthma; Occupational Exposure; Occupational Health; Patients; Performance; Phase; Physicians; Polyurethanes; Prevention; Proteins; Provider; Public Health; Publishing; Research; Respiratory physiology; Risk; Risk Factors; Sampling; Scientist; Screening procedure; Serologic tests; Serum; Shapes; State Government; Study of serum; Symptoms; System; Techniques; Technology; Test Result; Work; Workers' Compensation; Workplace; base; consumer demand; disorder prevention; experience; human subject; novel; practical application; response; success; synthetic peptide; vapor

DESCRIPTION (provided by applicant): Occupational exposures are estimated to account for 9-15% of adult asthma cases. Among the most common causes of occupational asthma are isocyanates, reactive chemicals necessary to make polyurethane products (construction, automotive, military, medical, foam, coatings, adhesives). Millions of people are currently employed in industries that utilize isocyanates, and the work-force at risk for exposure continues to grow along with consumer demand for polyurethane. Recognition and diagnosis of isocyanate asthma can be challenging for both patients and physicians. Symptoms can be insidious and difficult to associate with the workplace, especially delayed responses, which are often mistakenly attributed to environmental triggers. In workers that develop immunologic hypersensitivity to isocyanate, long-lasting decrements in lung function may occur, and persist years after exposure ceases. Exposure is the only known risk factor for isocyanate asthma, and is the major target for disease prevention. Contemporary industrial hygiene technologies (respirators, "spray booths") reduce, but cannot eliminate workplace exposure. New cases of isocyanate asthma continue to occur in an estimated 5 - 10 % of those occupationally exposed, and represent a substantial public health problem. Despite the well-known allergenicity of isocyanates, occupational exposure assessment and disease screening is limited. Diagnostic assays that reliably differentiate sensitivity to isocyanate vs other asthma triggers are greatly needed for clinical practice as well as workplace screening. Biomarkers of isocyanate exposure are also needed to help guide and monitor industrial hygiene efforts. We hypothesize that isocyanate serology assays can be developed as a strategy for disease surveillance and industrial hygiene (exposure) monitoring to help protect individuals who are occupationally exposed to isocyanate. The serodiagnostics that would be developed in this project are new in two major ways. (1) They would be based upon novel "isocyanate antigens", produced using a mixed phase (vapor/aerosol/liquid) exposure system developed by our laboratory, which mimics the air/liquid interface of the bronchial fluid that lines human airways. (2) They would utilize biomarkers of allergy (IgE) to detect hypersensitive individuals, AND make use of immunologic markers of isocyanate exposure (IgG), to help target and monitor industrial hygiene efforts. The final product of this project would be a sensitive and specific ELISA kit, incorporating these unique qualities, which would have widespread value for clinicians, research scientists, industrial management and health care providers. Published findings from our laboratory predict the ELISA kit will be far superior to the only 1 other similar product currently available commercially (by a single supplier that dominates the market), and will dispel false conclusions that may have been drawn from previous studies using isocyanate antigens of questionable biologic relevance. PUBLIC HEALTH RELEVANCE: This grant application focuses on developing a better understanding the allergenicity of isocyanates, a major cause of occupational asthma world-wide. The expected product of the study will be a serodiagnostic assay, based upon novel isocyanate-protein complexes, that can be used to protect workers health by (1) identifying hypersensitive workers, (2) identifying exposure hot spots in the workplace (3) monitoring internal exposure and (4) monitoring the effectiveness of industrial hygiene efforts.

描述（由申请人提供）：职业暴露估计占成人哮喘病例的9-15%。职业性哮喘最常见的原因是异氰酸酯，这是制造聚氨酯产品（建筑，汽车，军事，医疗，泡沫，涂料，粘合剂）所必需的反应性化学品。目前有数百万人受雇于使用异氰酸酯的行业，并且随着消费者对聚氨酯的需求，暴露风险的劳动力继续沿着增长。异氰酸酯哮喘的识别和诊断对患者和医生都具有挑战性。症状可能是潜伏的，很难与工作场所联系起来，特别是延迟反应，这往往被错误地归因于环境触发。在对异氰酸酯产生免疫超敏反应的工人中，可能会发生肺功能的长期下降，并在接触停止后持续数年。暴露是异氰酸酯哮喘的唯一已知危险因素，也是疾病预防的主要目标。现代工业卫生技术（消毒器、“喷雾室”）减少但不能消除工作场所的接触。异氰酸酯哮喘的新病例继续发生在估计5 - 10%的职业接触者中，并代表了一个重大的公共卫生问题。尽管异氰酸酯的致敏性众所周知，但职业暴露评估和疾病筛查是有限的。临床实践以及工作场所筛查都非常需要可靠区分对异氰酸酯敏感性与其他哮喘触发因素的诊断测定。还需要异氰酸酯暴露的生物标志物来帮助指导和监测工业卫生工作。我们假设，异氰酸酯血清学检测可以开发为一种战略，疾病监测和工业卫生（暴露）监测，以帮助保护个人谁是职业暴露于异氰酸酯。本项目将开发的血清诊断学在两个主要方面是新的。(1)它们将基于新的“异氰酸酯抗原”，使用我们实验室开发的混合相（蒸气/气溶胶/液体）暴露系统产生，该系统模拟了衬在人类气道中的支气管流体的空气/液体界面。(2)他们将利用过敏生物标志物（IgE）来检测过敏个体，并利用异氰酸酯暴露的免疫标志物（IgG）来帮助瞄准和监测工业卫生工作。该项目的最终产品将是一个敏感和特异的ELISA试剂盒，结合这些独特的品质，这将对临床医生，研究科学家，工业管理和卫生保健提供者具有广泛的价值。我们实验室发表的研究结果预测，ELISA试剂盒将远远上级目前市售的唯一一种其他类似产品（由主导市场的单一供应商提供），并将消除可能从先前使用生物相关性可疑的异氰酸酯抗原的研究中得出的错误结论。公共卫生关系：这项拨款申请的重点是更好地了解异氰酸酯的过敏性，这是全球职业性哮喘的主要原因。这项研究的预期成果将是一种基于新型异氰酸酯-蛋白质复合物的血清诊断测定法，可用于保护工人的健康，方法是：（1）识别过敏工人;（2）识别工作场所的暴露热点;（3）监测内部暴露;（4）监测工业卫生工作的有效性。