• Susan Peters, Anne E Visser, Fabrizio D'Ovidio, Jelle Vlaanderen, Lützen Portengen, Ettore Beghi, Adriano Chio, Giancarlo Logroscino, Orla Hardiman, Elisabetta Pupillo, Jan H Veldink, Roel Vermeulen, Leonard H van den Berg, and Euro-MOTOR consortium.
• Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands s.peters@uu.nl.
• J. Neurol. Neurosurg. Psychiatr. 2020 Jan 1; 91 (1): 33-39.

BackgroundWe investigated the association between cigarette smoking and risk of amyotrophic lateral sclerosis (ALS) in a pooled analysis of population-based case-control studies and explored the independent effects of intensity, duration and time-since-quitting.MethodsALS cases and controls, matched by age, sex and region, were recruited in the Netherlands, Italy and Ireland (*Euro-MOTOR project). Demographics and detailed lifetime smoking histories were collected through questionnaires. Effects of smoking status, intensity (cigarettes/day), duration (years), pack-years and time-since-quitting (years) on ALS risk were estimated using logistic regression models, adjusting for age, sex, alcohol, education and centre. We further investigated effect modification of the linear effects of pack-years by intensity, duration and time-since-quitting using excess OR (eOR) models.ResultsAnalyses were performed on 1410 cases and 2616 controls. Pack-years were positively associated with ALS risk; OR=1.26 (95% CI: 1.03 to 1.54) for the highest quartile compared with never smokers. This association appeared to be predominantly driven by smoking duration (ptrend=0.001) rather than intensity (ptrend=0.86), although the trend for duration disappeared after adjustment for time-since-quitting. Time-since-quitting was inversely related to ALS (ptrend<0.0001). The eOR decreased with time-since-quitting smoking, until about 10 years prior to disease onset. High intensity smoking with shorter duration appeared more deleterious than lower intensity for a longer duration.ConclusionsOur findings provide further support for the association between smoking and ALS. Pack-years alone may be insufficient to capture effects of different smoking patterns. Time-since-quitting appeared to be an important factor, suggesting that smoking may be an early disease trigger.© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

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