Association of smoking with amyotrophic lateral sclerosis: A systematic review, meta-analysis, and dose-response analysis

INTRODUCTION Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder primarily affecting the voluntary motor nervous system. Several observational studies have provided conflicting results regarding the association between smoking and ALS. Therefore, our objective was to investigate this association through a systematic review, meta-analysis, and dose-response analysis. METHODS On 16 January 2023, we initially extracted records from medical databases, which included Medline, Embase, Web of Science, Scopus, and ScienceDirect. We included case-control and cohort studies as eligible studies. Subgroup analyses were performed based on sex, study design, and current smoking. Restricted cubic-spline analysis was utilized to assess the dose-response relationship between smoking (pack-years) and ALS. RESULTS Twenty-eight case-control and four cohort studies met the inclusion criteria. The unadjusted OR for the overall association between smoking and ALS was 1.14 (95% CI: 1.06–1.22, I²=44%, p<0.001), and the adjusted OR (AOR) was 1.12 (95% CI: 1.03–1.21, I²=49%, p=0.009). Subgroup analysis revealed a more pronounced association among current smokers, with an AOR of 1.28 (95% CI: 1.10–1.49, I²=66%, p<0.001) and AOR of 1.28 (95% CI: 1.10–1.48, I²=58%, p=0.001). In the dose-response analysis, the non-linear model revealed an inverted U-shaped curve. CONCLUSIONS Our study provides evidence of a positive relationship between smoking and the risk of ALS. To mitigate the risk of developing ALS, discontinuing smoking, which is a modifiable risk factor, may be crucial.