COMMENTARY

Ecological Fallout: ALS Linked to Toxins and Pollutants

Laurie L. Barclay, MD

Disclosures

August 18, 2016

Association of Environmental Toxins With Amyotrophic Lateral Sclerosis

Su FC, Goutman SA, Chernyak S, et al
JAMA Neurol. 2016;73:803-811.

Study Summary

Exposure to environmental pollutants may be a modifiable risk factor for amyotrophic lateral sclerosis (ALS). As a result, investigators behind this case/control study examined the association of occupational exposures and environmental toxins on the odds of developing ALS in Michigan.

The study took place between 2011 and 2014 at a tertiary ALS referral center. Using the revised El Escorial criteria, investigators identified cases with definitive, probable, probable with laboratory support, or possible ALS. Exclusion criteria for controls were diagnosis with any neurodegenerative condition and family history of ALS in a first- or second-degree blood relative.

Participants completed a survey regarding occupational and residential exposures. They also provided blood samples that were measured for 122 persistent environmental pollutants, including organochlorine pesticides, polychlorinated biphenyls (PCBs), and brominated flame retardants, using gas chromatography/mass spectrometry. Four separate time windows were considered for past occupational exposures: exposure in one or more period during the participant's entire job history, and exposures in the past 10 years, 10-30 years, and > 30 years ago.

There were 156 cases (mean age, 60.5 years; 61.5% male) and 128 controls (mean age, 60.4 years; 57.8% male), of whom 101 and 110, respectively, had complete demographic and pollutant data.

Pesticide exposure in the cumulative exposure windows was significantly associated with fivefold risk for ALS (odds ratio [OR], 5.09; 95% confidence interval [CI], 1.85-13.99; P=.002). Military service was associated with doubling of ALS risk in two time windows; exposure anytime in entire the occupational history (OR, 2.31; 95% CI, 1.02-5.25; P=.046) and exposure 10-30 years ago (OR, 2.18; 95% CI, 1.01-4.73; P=.049). Suspected risk factors regarding military service may include environmental exposures, multiple vaccinations, physical activity, and traumatic injury. Surprisingly, there was a statistically significant protective effect for lead across the entire occupational history.

On the basis of cumulative occupational and residential exposure in a multivariable model of measured persistent environmental pollutants in blood, odds of ALS were increased for two organochlorine pesticides (pentachlorobenzene [OR, 2.21; 95% CI, 1.06-4.60; P=.04] and cis-chlordane [OR, 5.74; 95% CI, 1.80-18.20; P=.005]), two PCBs (PCB 175 [OR, 1.81; 95% CI, 1.20-2.72; P=.005] and PCB 202 [OR = 2.11; 95% CI, 1.36-3.27; P=.001]), and one brominated flame retardant (polybrominated diphenyl ether 47 [OR,2.69; 95% CI, 1.49-4.85; P=.001]).

Viewpoint

Possible limitations of this study include reliance on self-report for history of residential and workplace exposures, with modest concordance between survey data and the measurements of persistent environmental pollutants in blood. Nevertheless, the findings suggest that persistent environmental pollutants measured in blood are significantly associated with ALS and may represent modifiable risk factors for ALS.

Genetic data indicate that about 40% of ALS cases are environmentally determined. The gene/time/environment hypothesis suggests that toxic exposures combined with genetic susceptibility may trigger motor neuron degeneration and ALS; however, most previous studies used surveys and were therefore limited by recall bias and exposure misclassification. In contrast, this study also used measurements of pollutants in blood, as well as exposure windows, to identify periods of susceptibility for developing ALS to help clarify exposure/time interaction effects.

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