Wilcosky T C
Center for Epidemiologic and Medical Studies, Research Triangle Institute, NC 27709-2194.
Environ Health Perspect. 1993 Dec;101 Suppl 4(Suppl 4):193-7. doi: 10.1289/ehp.93101s4193.
Biological markers of intermediate health outcomes sometimes provide a superior alternative to traditional measures of pollutant-related disease. Some opportunities and methodologic issues associated with using markers are discussed in the context of exposures to four complex mixtures: environmental tobacco smoke and nitrogen dioxide, acid aerosols and oxidant outdoor pollution, environmental tobacco smoke and radon, and volatile organic compounds. For markers of intermediate health outcomes, the most important property is the positive predictive value for clinical outcomes of interest. Unless the marker has a known relationship with disease, a marker response conveys no information about disease risk. Most markers are nonspecific in that various exposures cause the same marker response. Although nonspecificity can be an asset in studies of complex mixtures, it leads to problems with confounding and dilution of exposure-response associations in the presence of other exposures. The timing of a marker's measurement in relation to the occurrence of exposure influences the ability to detect a response; measurements made too early or too late may underestimate the response's magnitude. Noninvasive markers, such as those measured in urine, blood, or nasal lavage fluid, are generally more useful for field studies than are invasive markers. However, invasive markers, such as those measured in bronchoalveolar lavage fluid or lung specimens from autopsies, provide the most direct evidence of pulmonary damage from exposure to air pollutants. Unfortunately, the lack of basic information about marker properties (e.g., sensitivity, variability, statistical link with disease) currently precludes the effective use of most markers in studies of complex mixtures.
中间健康结局的生物标志物有时可为与污染物相关疾病的传统测量方法提供更好的替代方案。本文结合四种复杂混合物的暴露情况，讨论了与使用生物标志物相关的一些机遇和方法学问题，这四种混合物分别是：环境烟草烟雾和二氧化氮、酸性气溶胶和氧化性室外污染、环境烟草烟雾和氡，以及挥发性有机化合物。对于中间健康结局的生物标志物而言，最重要的特性是对感兴趣的临床结局的阳性预测值。除非该生物标志物与疾病存在已知关联，否则生物标志物反应并不能传达有关疾病风险的信息。大多数生物标志物具有非特异性，即各种暴露会导致相同的生物标志物反应。尽管非特异性在复杂混合物研究中可能是一项优势，但在存在其他暴露的情况下，它会导致混杂和暴露-反应关联稀释的问题。生物标志物测量时间与暴露发生时间的关系会影响检测反应的能力；测量过早或过晚可能会低估反应的程度。非侵入性生物标志物，如在尿液、血液或鼻腔灌洗液中测量的生物标志物，通常比侵入性生物标志物在现场研究中更有用。然而，侵入性生物标志物，如在支气管肺泡灌洗液或尸检肺标本中测量的生物标志物，能提供暴露于空气污染物导致肺部损伤的最直接证据。不幸的是，目前缺乏关于生物标志物特性的基本信息（例如，敏感性、变异性、与疾病的统计关联），这使得大多数生物标志物无法在复杂混合物研究中得到有效应用。
