Elevated levels of plasma neurofilament light chain (pNfL) is associated with increased disease activity, physical disability and reduced treatment response in persons with multiple sclerosis (MS). However, the association between environmental exposures such as cigarette smoking and pNfL levels is not clear.
To investigate the association between cigarette smoking, as one of the most prominent environmental factor associated with MS disease activity, and pNfL-levels in MS.
This is a retrospective population-based cohort study. Blood samples from incident MS cases were collected at time of diagnosis (from 2001). Concentrations of pNfL were determined using antibodies from UmanDiagnostics and the high-sensitive Single Molecule Array (SimoaTM) NF-light® Advantage kit. We assessed the impact of self-reported cigarette smoking habits at time of sampling on age-stratified pNfL levels above 80th, 95th, and 99th of non-MS controls' percentiles (>C80, >C95, and >C99).
pNfL levels were measured in 2881 MS cases with smoking history of which 320 (11.1%) were current regular smokers and 828 (28.7%) were past regular smokers (median years since quitting 6; IQR 1 to 14). Current smoking was associated with significantly increased odds ratios (OR) of having pNfL-levels >C80, >C95 and >C99 with OR ranging from 1.27 (95% CI: 0.96-1.68) to 1.70 (95% CI: 1.24-2.33) comparing current smokers to never smokers and 1.44 (95% CI: 1.06-1.94) to 1.6 (95% CI: 1.12-2.27) comparing current smokers to past smokers. The OR of having pNfL-levels >C80, >C95 and >C99 in past smokers who quitted 6 to 10 years ago, compared to current smokers, ranged from 0.6 (95% CI: 0.39-0.92) to 0.55 (95% CI: 0.30-0.95), and from 0.62 (95% CI: 0.43-0.89) to 0.53 (95% CI: 0.31-0.87) in those with >10 years since quitting smoking. Although decreased, the ORs were not significant among those quitting smoking 1 to 5 years before sampling (P>0.05).
Current regular smoking is associated with significantly increased risk of displaying high pNfL levels in MS patients, which argue for a negative effect on disease activity. In contrast, there was a beneficial effect of quitting smoking that increased with time since stopping. Our findings support the rational for life style counselling in MS.