Amyotrophic Lateral Sclerosis Survival and Occupational Lead Exposure in the Danish National Patient Registry
Ian Tang1, Aisha Dickerson2, Johnni Hansen3, Marc Weisskopf1
1Harvard TH Chan School of Public Health, 2Johns Hopkins Bloomberg School of Public Health, 3Danish Cancer Society Research Center
Objective:

We investigated the relationship between occupational lead (Pb) exposure and ALS survival using the Danish registry.

Background:
Risk factors associated with amyotrophic lateral sclerosis (ALS) survival are not well understood. Lead is a known neurotoxicant, but only few studies have examined its effect on ALS survival.
Design/Methods:

We identified 2,161 ALS cases diagnosed between 1982-2013 with full employment history, and at least two ALS diagnoses, one of them being in an inpatient setting. Cases were followed until March 1, 2017, or until censored. We examined Pb exposure as ever/never exposed to a Pb-job, and to a Pb-job by probability, based on a Danish job-exposure matrix. Pb exposure was also evaluated in 5 and 10-year lags. We evaluated survival using Cox proportional hazard models, adjusted for age, socioeconomic status, marital status, and diagnosis year, and stratified by sex and age of diagnosis.

Results:

Median survival and age at diagnosis of ALS cases was 16.8 months and 63.5 years, respectively. Survival was worse for women ever exposed to Pb with a high probability (no lag hazard ratio (HR): 1.17, 95%CI: 0.92, 1.48) compared to non-exposed women, and this was similar with either a 5 or 10 year lag period. Hazards ratios (HR) were slightly negative for high probability Pb-exposed men diagnosed at age 60-69 (lag 5 HR: 0.66, 95%CI: 0.45, 0.98), but reversed for men diagnosed at age 70 and later (lag 5 HR: 2.03, 95%CI: 1.13, 3.64).

Conclusions:

Occupational lead exposure contributed to shorter survival among women with occupational Pb exposure, and differences in survival by age of diagnosis among men. Our study adds to three others, one of which observed higher HRs among women. The lagged analysis results could suggest some healthy-worker effect or that earlier lead exposures before ALS onset are more relevant for survival. Supported by T32ES007069, P30ES000002, and R01ES019188.

10.1212/WNL.0000000000206397