Te-Wei Wang1, Joanne Wuu2, Anne Cooley2, Tian-Shin Yeh3,4, Michael Benatar2, Marc Weisskopf1,3. 1. Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 2. Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA. 3. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA, and. 4. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Abstract
Objective: Lead exposure has been hypothesized to increase the risk of ALS, but only two studies have examined the association with ALS survival, and with inconsistent results. The use of occupational history to assess lead exposure can avoid reverse causation that may occur in epidemiologic analyses that use biomarkers of lead exposure collected after ALS onset. Methods: We evaluated the relationship of occupational lead exposure to ALS survival among 135 cases from an international ALS cohort that included deep phenotyping, careful follow-up, and questionnaires to quantify participants' occupation history. ALS patients were recruited in 2015-2019. We determined occupational lead exposure using a job-exposure matrix. We estimated hazard ratios (HR) and 95% confidence intervals (CI) for survival using Cox proportional hazard analysis with adjustment for covariates. Results: A total of 135 ALS patients completed the environmental questionnaires, among whom 38 reached a survival endpoint (death or permanent assisted ventilation). The median survival was 48.3 months (25th-75th percentile, 30.9-74.1). Older patients and those with initial symptom other than limb onset had shorter survival time. There were 36 ALS cases with occupational lead exposure. After adjusting for age, sex, site of onset, smoking, and military service, lead exposure was associated with an HR of 3.26 (95%CI 1.28-8.28). Results with adjustment for subsets of these covariates were similar.Conclusions: These results suggest that lead exposure prior to onset of ALS is associated with shorter survival following onset of ALS, and this association is independent of other prognostic factors.
Objective: Lead exposure has been hypothesized to increase the risk of ALS, but only two studies have examined the association with ALS survival, and with inconsistent results. The use of occupational history to assess lead exposure can avoid reverse causation that may occur in epidemiologic analyses that use biomarkers of lead exposure collected after ALS onset. Methods: We evaluated the relationship of occupational lead exposure to ALS survival among 135 cases from an international ALS cohort that included deep phenotyping, careful follow-up, and questionnaires to quantify participants' occupation history. ALS patients were recruited in 2015-2019. We determined occupational lead exposure using a job-exposure matrix. We estimated hazard ratios (HR) and 95% confidence intervals (CI) for survival using Cox proportional hazard analysis with adjustment for covariates. Results: A total of 135 ALS patients completed the environmental questionnaires, among whom 38 reached a survival endpoint (death or permanent assisted ventilation). The median survival was 48.3 months (25th-75th percentile, 30.9-74.1). Older patients and those with initial symptom other than limb onset had shorter survival time. There were 36 ALS cases with occupational lead exposure. After adjusting for age, sex, site of onset, smoking, and military service, lead exposure was associated with an HR of 3.26 (95%CI 1.28-8.28). Results with adjustment for subsets of these covariates were similar.Conclusions: These results suggest that lead exposure prior to onset of ALS is associated with shorter survival following onset of ALS, and this association is independent of other prognostic factors.
Authors: A Al-Chalabi; F Fang; M F Hanby; P N Leigh; C E Shaw; W Ye; F Rijsdijk Journal: J Neurol Neurosurg Psychiatry Date: 2010-09-22 Impact factor: 13.654
Authors: Michael Benatar; Joanne Wuu; Peter M Andersen; Nazem Atassi; William David; Merit Cudkowicz; David Schoenfeld Journal: Neurology Date: 2018-01-24 Impact factor: 9.910