Occupational silica exposure and mortality from lung cancer and nonmalignant respiratory disease: G-estimation of structural nested accelerated failure time models

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Background:Occupational exposure to crystalline silica is known to increase risks of both lung cancer and noninfectious nonmalignant respiratory diseases (NMRD). However, associations between silica exposure and survival times have not been described.Methods:In a longitudinal cohort of diatomaceous earth workers exposed to crystalline silica (primarily cristobalite) and followed from 1942 to 2011, we applied g-estimation of structural nested accelerated failure time models to adjust for time-varying confounding that could result in healthy worker survivor bias. A continuous measure of exposure was used in analyses estimating the hypothetical effect of banning exposure to silica on survival time. Since a ban is infeasible, sensitivity analyses examined the hypothetical effects of enforcing various Occupational Exposure Limits.Results:The estimated median number of years of life lost per worker (for all natural causes) due to silica exposure was 0.48 (95% confidence interval = 0.02, 1.01). For NMRD deaths, the corresponding estimate was 3.22 (0.82, 7.75) and for lung cancer deaths, 2.21 (0.97, 3.56). Cause-specific estimates were sensitive to the use of weights to adjust for competing events. Lung cancer mortality, which tended to occur at younger ages, was an important competing event for NMRD mortality. Sensitivity analyses supported the main results, but with larger estimates, and suggested that a strict limit would be nearly as effective as a complete ban on silica exposure.Conclusions:Workplace exposure to crystalline silica in this industry appears to shorten survival times significantly, particularly for those who die of lung cancer or NMRD. More stringent exposure limits are probably warranted.

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