Airborne lead and polychlorinated biphenyls (PCBs) are associated with amyotrophic lateral sclerosis (ALS) risk in the U.S

Amyotrophic lateral sclerosis (ALS) risk is linked to environmental exposures. The National Emissions Inventory (NEI) database compiles mandatory reports of levels of airborne contaminants from a variety of stationary and mobile pollution sources across the U.S. The objective of this study was to identify airborne contaminants that may be associated with ALS etiology for future study. We geospatially estimated exposure to airborne contaminants as risk factors for ALS in a nationwide large de-identified medical claims database, the SYMPHONY Integrated Dataverse®. We extracted zip3 of residence at diagnosis of ~26,000 nationally distributed ALS patients and n = 3 non-ALS controls matched per case for age and sex. We individually aggregated the median levels of each of 268 airborne contaminants recorded in the NEI database for 2008 to estimate local residential exposure. We randomly broke the dataset into two independent groups to form independent discovery and validation cohorts. Contaminants associated with increased ALS risk in both the discovery and validation studies included airborne lead (false discovery rate (FDR) = 0.00077), and polychlorinated biphenyls (PCBs), such as heptachlorobiphenyl (FDR = 3.60E−05). Small aircraft were the largest source of airborne lead, while the PCB emissions came from certain power plants burning biomass, and from industrial boilers. Associations with residential history of lead exposure were confirmed in two additional cohorts (10 year top quartile in New Hampshire/Vermont OR 2.46 95% CI 1.46–2.80, and in Ohio OR 1.60 95% CI 1.28–1.98). The results of our geospatial analysis support neurotoxic airborne metals and PCBs as risk factors for ALS.