Objective To determine whether persistent organic pollutants (POP) affect amyotrophic lateral sclerosis (ALS) survival.
Methods ALS participants seen at the University of Michigan (Ann Arbor, MI, USA) provided plasma samples for measurement of POPs. ALS disease and clinical features were collected prospectively from the medical records. Survival models used a composite summary measure of exposure due to multiple POPs (environmental risk score or ERS).
Results 167 participants (40.7% female, n=68) with ALS were recruited, of which 119 died during the study period. Median diagnostic age was 60.9 years (IQR 52.7–68.2), median time from symptom onset to diagnosis was 1.01 years (IQR 0.67–1.67), bulbar onset 28.7%, cervical onset 33.5% and lumbar onset 37.7%. Participants in the highest quartile of ERS (representing highest composite exposure), adjusting for age at diagnosis, sex and other covariates had a 2.07 times greater hazards rate of mortality (p=0.018, 95% CI 1.13 to 3.80) compared with those in the lowest quartile. Pollutants with the largest contribution to the ERS were polybrominated diphenyl ethers 154 (HR 1.53, 95% CI 0.90 to 2.61), polychlorinated biphenyls (PCB) 118 (HR 1.50, 95% CI 0.95 to 2.39), PCB 138 (HR 1.69, 95% CI 0.99 to 2.90), PCB 151 (HR 1.46, 95% CI 1.01 to 2.10), PCB 175 (HR 1.53, 95% CI 0.98 to 2.40) and p,p′-DDE (HR 1.39, 95% CI 1.07 to 1.81).
Conclusions Higher concentrations of POPs in plasma are associated with reduced ALS survival, independent of age, gender, segment of onset and other covariates. This study helps characterise and quantify the combined effects of POPs on ALS and supports the concept that environmental exposures play a role in disease pathogenesis.
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BM, SB and ELF are joint senior authors.
SAG and JB are joint first authors.
SAG and JB contributed equally.
Contributors SAG, JB, AP, SB, ELF: Drafting/revising the manuscript for content, study concept and design, analysis and interpretation of data. BM: Analysis and interpretation of data, drafting/revising the manuscript for content, study concept and design.
Funding NIEHS K23ES027221; National ALS Registry/CDC/ATSDR CDCP-DHHS-US (CDC/ATSDR 200-2013-56856); Program for Neurology Research and Discovery, University of Michigan; Robert and Katherine Jacobs Environmental Health Initiative.
Disclaimer Study sponsors had no role in the design, collection, analysis, interpretation of the data, writing the report or decision to submit the manuscript for publication.
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval The study received Institutional Review Board approval.
Provenance and peer review Not commissioned; externally peer reviewed.
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