Background: Air pollution may increase ALS incidence, and climate change has intensified wildfire frequency and severity, yet the impact of wildfire smoke on ALS progression remains unknown. We estimated the association between wildfire-specific fine particulate matter (PM2.5) exposure and survival to ALS respiratory failure or death.
Methods: Using the MDA MOVR database (2013-2023), we analyzed 2296 participants with ALS diagnosis after 2010. Linking ZIP code to models of daily wildfire PM2.5 during the 5 years prior to ALS symptom onset, we assigned exposure in two ways: 1) days with wildfire smoke PM2.5 > 1 μg/m3, and 2) total cumulative daily smoke exposure (μg/m3). Using the Cox proportional hazards regression, we estimated time from symptom onset to respiratory failure (ALSFRS-R dyspnea score ≤1) or death, adjusting for age, phenotype (limb vs bulbar onset), and diagnosis year.
Results: Among 2,296 MOVR participants followed for a mean of 2.55 years, 214 (9.3%) had documented respiratory failure or death. Participants with increased wildfire smoke exposure had approximately double the hazards of respiratory failure or death compared to those in the lowest exposure quartiles. Compared to the lowest quartile of smoke days, hazard ratios for upper quartiles were: Q2 2.05 (95% CI: 1.34-3.16), Q3 3.27 (95% CI: 2.15-4.96), and Q4 2.21 (95% CI: 1.41-3.44). Similar patterns emerged when examining cumulative daily smoke exposure, with hazard ratios ranging from 1.71 to 2.33 across exposure quartiles (all p<0.01).
Conclusions: Wildfire smoke exposure prior to ALS onset is associated with approximately double the adjusted hazards of respiratory failure and death among MOVR ALS participants, with an apparent threshold effect above the lowest exposure quartile. Further research is urgently needed to better characterize the impact of distinct air pollution sources on respiratory outcomes and survival in ALS and to develop evidence-based environmental guidelines for the ALS community.