Air pollution and disease progression in a University of Michigan amyotrophic lateral sclerosis cohort

Amyotrophic lateral sclerosis (ALS) is a rare, fatal, neurodegenerative disease without effective treatments. Therefore, identifying modifiable risk factors to slow disease progression is important. We aimed to identify whether air pollution may be a modifiable risk factor associated with ALS progression. We recruited patients with ALS from the University of Michigan Pranger ALS Clinic from 2009 to 2022. Patient functional status was assessed at clinic evaluations approximately every three months using the ALS Functional Rating Scale Revised (ALSFRS-R); the change in total ALSFRS-R score over time was used to assess disease progression. The repeated ALSFRS-R overall scores were linked to spatiotemporal prediction model estimates of 3-month and 5-year average residential exposures to fine particulate matter mass (PM_2.5) and components (sulfate, nitrate, black carbon), ozone, nitrogen dioxide, and sea salt (negative control expected to be nontoxic) before baseline and each clinical assessment. We used longitudinal linear mixed-effects models to assess associations between air pollution and the rate of disease progression, using the overall ALSFRS-R score, controlling for potential confounders. Among 469 participants with 3147 valid overall ALSFRS-R scores (44.8 % female; 62 ± 11 years at symptom onset; 3.6 ± 2.9 years follow-up) who resided in areas with PM_2.5 levels near and below US regulatory standards, average rates of decline were 11.6 ± 24.0 ALSFRS-R points/year. In multi-pollutant models adjusted for potential confounders, one interquartile range (IQR) higher 5-year average black carbon (0.2 μg/m³) and nitrate (0.4 μg/m³) concentrations were associated with 2.4 (95 % CI: -3.4, -1.4) and 1.2 (95 % CI: -1.9, -0.5) ALSFRS-R points/year faster rates of decline, respectively. One IQR higher 3-month average ozone concentrations (1.4 ppb) were also associated with a faster rate of decline (-0.3 [95 % CI: -0.5, -0.1] ALSFRS-R points/year). Sea salt was not associated with ALS progression. These observed differences between high and low exposure participants reflected 3-21 % of the observed average annual ALSFRS-R decline.