Willis Alette, Jerrett Michael, Burnett Richard T, Krewski Daniel
Department of Geography and Environmental Studies, Carleton University, Ottawa, Ontario, Canada.
J Toxicol Environ Health A. 2003;66(16-19):1605-24. doi: 10.1080/15287390306432.
The American Cancer Society (ACS) Study and its reanalysis are built upon in order to examine the impact of scale on the observed relationship between sulfates and mortality. The limitations of the original ACS Study (Pope et al., 1995) and the reanalysis of this study (Krewski et al., 2000) are discussed; while the latter dealt with some issues in using ecological data, it did not address scale. Next, the article outlines the county-scale study, the methods used to aggregate data, and the two-stage analysis used to derive relative risk (RR). Finally, the results of working at the county scale are compared with those obtained by the reanalysis team using larger metropolitan areas. Less than half of the cohort used in the metropolitan study were used at the county scale because of the limited availability of sulfate monitors and because five-digit ZIP codes more accurately assigned individuals to geographical areas. Therefore, the county data should be considered as new and not as a reorganization of the original data set. The reanalysis and the county studies should be considered as two separate studies that took different scales as their basic organizing principle. The RR of all-cause mortality from sulfate exposure at the county scale was 1.50 (1.30, 1.73) compared with 1.25 (1.13, 1.37) at the metropolitan scale; for cardiopulmonary mortality, the RR was 1.75 (1.48, 2.08) at the county scale compared with 1.29 (1.15, 1.46) at the metropolitan scale. Because lung cancer mortality was low in some counties, the two-stage random effects model became unstable. At the county scale, the RR from sulfates was more robust to the inclusion of ecologic covariates. Other place-specific ecologic covariates were either insignificant or barely significant (with a lower 95% confidence limit near 0.99 or 1.00) when included in the two-stage regression model for all-cause mortality with sulfates. Moreover, no ecologic covariate changed the RR of all-cause mortality from sulfates by 25% or more. Both population change and unemployment rate affected the RR for cardiopulmonary mortality from sulfate exposure by 25% or more in the county-scale analysis. However, when these two variables were entered into a multiple covariate analysis, the RR from sulfates decreased but remained strongly significant. Sulfur dioxide was not an important covariate at the county scale. Thus, at the county scale, long-term exposure to sulfates appears to be more strongly associated with increased risk of all-cause and cardiopulmonary mortality than previously indicated by the ACS study and its reanalysis.
美国癌症协会（ACS）研究及其重新分析为基础，以检验规模对所观察到的硫酸盐与死亡率之间关系的影响。讨论了原始ACS研究（Pope等人，1995年）及其重新分析（Krewski等人，2000年）的局限性；虽然后者处理了使用生态数据时的一些问题，但未涉及规模问题。接下来，文章概述了县级研究、用于汇总数据的方法以及用于得出相对风险（RR）的两阶段分析。最后，将县级研究结果与重新分析团队使用更大都市地区所获得的结果进行了比较。由于硫酸盐监测器的可用性有限，且五位数字邮政编码能更准确地将个体分配到地理区域，因此在县级研究中使用的队列不到都市研究中所使用队列的一半。因此，县级数据应被视为新数据，而非原始数据集的重新组织。重新分析和县级研究应被视为两项以不同规模为基本组织原则的独立研究。县级层面因接触硫酸盐导致的全因死亡率的RR为1.50（1.30，1.73），而都市层面为1.25（1.13，1.37）；对于心肺死亡率，县级层面的RR为1.75（1.48，2.08），都市层面为1.29（1.15，1.46）。由于某些县的肺癌死亡率较低，两阶段随机效应模型变得不稳定。在县级层面，硫酸盐导致的RR对纳入生态协变量更为稳健。当将其他特定地点的生态协变量纳入硫酸盐全因死亡率的两阶段回归模型时，它们要么不显著，要么勉强显著（95%置信区间下限接近0.99或1.00）。此外，没有生态协变量能使硫酸盐导致的全因死亡率的RR变化25%或更多。在县级层面分析中，人口变化和失业率都使因接触硫酸盐导致的心肺死亡率的RR变化25%或更多。然而，当将这两个变量纳入多协变量分析时，硫酸盐导致的RR下降但仍具有高度显著性。在县级层面，二氧化硫不是一个重要的协变量。因此，在县级层面，长期接触硫酸盐似乎比ACS研究及其重新分析先前表明的更强烈地与全因和心肺死亡率风险增加相关。
