Neophytou Andreas M, Picciotto Sally, Costello Sadie, Eisen Ellen A
From the Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA.
Epidemiology. 2016 Jan;27(1):21-8. doi: 10.1097/EDE.0000000000000389.
If less healthy workers terminate employment earlier, thus accumulating less exposure, yet remain at greater risk of the health outcome, estimated health effects of cumulative exposure will be biased downward. If exposure also affects termination of employment, then the bias cannot be addressed using conventional methods. We examined these conditions as a prelude to a reanalysis of lung cancer mortality in the Diesel Exhaust in Miners Study.
We applied an accelerated failure time model to assess the effect of exposures to respirable elemental carbon (a surrogate for diesel) on time to termination of employment among nonmetal miners who ever worked underground (n = 8,307). We then applied the parametric g-formula to assess how possible interventions setting respirable elemental carbon exposure limits would have changed lifetime risk of lung cancer, adjusting for time-varying employment status.
Median time to termination was 36% shorter (95% confidence interval = 33%, 39%), per interquartile range width increase in respirable elemental carbon exposure. Lung cancer risk decreased with more stringent interventions, with a risk ratio of 0.8 (95% confidence interval = 0.5, 1.1) comparing a limit of ≤25 µg/m respirable elemental carbon to no intervention. The fraction of cases attributable to diesel exposure was 27% in this population.
The g-formula controlled for time-varying confounding by employment status, the signature of healthy worker survivor bias, which was also affected by diesel exposure. It also offers an alternative approach to risk assessment for estimating excess cumulative risk, and the impact of interventions based entirely on an observed population.
如果健康状况较差的工人更早终止就业，从而累积的暴露量更少，但仍面临更高的健康结局风险，那么累积暴露的估计健康影响将被低估。如果暴露也影响就业终止，那么使用传统方法无法解决这种偏差。作为重新分析矿工柴油废气研究中肺癌死亡率的前奏，我们研究了这些情况。
我们应用加速失效时间模型来评估可吸入元素碳（柴油的替代物）暴露对曾在地下工作的非金属矿工（n = 8307）就业终止时间的影响。然后，我们应用参数化g公式来评估设定可吸入元素碳暴露限值的可能干预措施将如何改变肺癌的终生风险，并根据随时间变化的就业状况进行调整。
可吸入元素碳暴露每增加一个四分位间距宽度，终止就业的中位时间缩短36%（95%置信区间 = 33%，39%）。干预措施越严格，肺癌风险越低，将可吸入元素碳暴露限值设为≤25 µg/m与不进行干预相比，风险比为0.8（95%置信区间 = 0.5，1.1）。该人群中可归因于柴油暴露的病例比例为27%。
g公式控制了就业状况随时间变化的混杂因素，这是健康工人幸存者偏差的特征，而这种偏差也受到柴油暴露的影响。它还提供了一种风险评估的替代方法，用于估计累积超额风险以及完全基于观察人群的干预措施的影响。
