Associations Between Ambient Air Pollution with Biomarkers and Functional Outcomes in Pwms

Background: Seasonal changes in disease activity have been linked to variability in Vitamin D exposures. In addition to Vitamin D, ambient air pollution varies over time. Few studies have examined the role of air pollutants in relation to multiple sclerosis (MS) disease activity. 

Objectives: : To examine effects of ambient gaseous pollutant concentrations (NO₂, CO, SO₂) on blood biomarkers and functional outcome measures in persons with MS (pwMS).  

Methods: 52 pwMS who participated in an observational study of dalfampridine-ER (D-ER) had blood collected by venipuncture at baseline (before beginning D-ER), 7 weeks later, and 14 weeks later; samples were analyzed for concentrations of phosphorylated neurofilament-heavy chain (pNF), brain derived neurotrophic factor (BDNF), and C-reactive protein (CRP).  At the same time points, functional assessments were performed including timed 25-foot walk (T25FW), six-minute walk distance (6MW), six spot step test (SSST), multiple sclerosis walking scale-12 (MSWS) score, and the performance scales – mobility subscale (PS – mobility). Subjects’ addresses were geocoded and distances to nearest Environmental Protection Agency monitoring site for each pollutant were calculated. Same-day, one day lag, 3-day average, and 7-day average concentrations from the nearest site were assigned as pollution exposures for each participant for each visit date. Mixed regression models accounting for repeated measures were run for each outcome and exposure. Pollutant concentrations and outcomes were log-transformed as necessary to normalize them. All models adjusted for age, body mass index, and D-ER use. 

Results: : Same-day ambient CO concentrations were significantly associated with higher log pNf values. Log NO₂ and 3-day average NO₂ were significantly associated with lower log CRP. Lag1, 3-day average, and 7-day average CO were associated (p<0.10) with shorter 6MW distance. Lag1 SO₂ was significantly associated (p=0.001), and 3-day and 7-day average SO₂ associated (p<0.10) with lower dom SSST. Same-day, lag1, 3-day average, and 7-day average log CO concentrations were significantly associated with higher MSWS-12 scores (p<0.02) and with higher PS – mobility scores (p<0.02). No pollutants were associated with log BDNF, T25FW or nondom SSST.

Conclusions: Ambient pollution exposures, particularly CO, may play a role in MS disease activity. Same day exposures were associated with biomarkers; lagged exposures associated with functional outcomes.