Occupational Diesel Exposure, Duration of Employment, and Lung Cancer: An Application of the Parametric G-Formula

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.