Multi-air pollutant exposure and amyotrophic lateral sclerosis (ALS) diagnosis in Denmark

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BACKGROUND AND AIM: Amyotrophic lateral sclerosis (ALS) is a devastating and fatal neurodegenerative disease, with approximately half of patients dying within three years of symptom onset. Its aetiology remains elusive and known inherited mutated genes only account for 5–10% of the cases. There is some limited evidence to suggest ALS onset is associated with exposure to air pollution, and specifically to traffic-related pollution. However, previous smaller studies have only examined the association with relevant pollutants in separate models. METHODS: In the present study, we used prospectively collected data from the Danish National Registers system from 2,188 ALS cases diagnosed between 1989 – 2013 and matched on age, sex, and vital status to 6,766 controls. We used predictions from a validated spatio-temporal model to assign 5-year average exposures prior to diagnosis to nitrogen oxides (NOx), carbon monoxide (CO), elemental carbon (EC), fine particles (PM2.5), and ozone at residential addresses of study participants. We used a Bayesian hierarchical conditional logistic model to assess whether exposure to traffic- and non-traffic-related pollution is associated with ALS diagnosis, adjusting for potential confounders. RESULTS:We found that for an inter-quartile range (IQR) increase in 5-year average concentrations, the joint effect of included traffic-related pollutants (NOx, CO, EC) was associated with an increase in odds of ALS diagnosis (8.4%; 95% credible interval [CrI]:-1.4, 18.9%). Increases in non-traffic related pollution resulted in an increase in odds for ozone (IQR=7.9 µg/m3) (6.6%; 95%CrI: -8.5%, 21.9%), and a decrease for PM2.5 (IQR=4.0 µg/m3) (-13.1%; 95%CrI: -35.8%, 10.7%). Overall, there was a 95% posterior probability of a positive association between the joint effect of included traffic-related pollutants and ALS diagnosis. CONCLUSIONS:Our results indicate a potential positive association between ALS diagnosis and traffic-related pollution. Further work is needed to understand the role of air pollution on ALS pathogenesis and timing of onset. KEYWORDS: Air Pollution, ALS, Traffic-Related Pollution, Denmark, Motor Neuron Disease, NOx