Multicentre, population-based, case-control study of particulates, combustion products and amyotrophic lateral sclerosis risk.

To investigate whether exposure to particulates and combustion products may explain the association between certain occupations and amyotrophic lateral sclerosis (ALS) risk in a large, multicentre, population-based, case-control study, based on full job histories, using job-exposure matrices, with detailed information on possible confounders. Population-based patients with ALS and controls were recruited from five registries in the Netherlands, Ireland and Italy. Demographics and data regarding educational level, smoking, alcohol habits and lifetime occupational history were obtained using a validated questionnaire. Using job-exposure matrices, we assessed occupational exposure to silica, asbestos, organic dust, contact with animals or fresh animal products, endotoxins, polycyclic aromatic hydrocarbons and diesel motor exhaust. Multivariate logistic regression models adjusting for confounding factors were used to determine the association between these exposures and ALS risk. We included 1557 patients and 2922 controls. Associations were positive for all seven occupational exposures (ORs ranging from 1.13 to 1.73 for high vs never exposed), and significant on the continuous scale for silica, organic dust and diesel motor exhaust (p values for trend ≤0.03). Additional analyses, adding an exposure (one at a time) to the model in the single exposure analysis, revealed a stable OR for silica. We found similar results when patients with a In a large, multicentre study, using harmonised methodology to objectively quantify occupational exposure to particulates and combustion products, we found an association between ALS risk and exposure to silica, independent of the other occupational exposures studied.

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Competing interests: EB reports grants from UCB-Pharma, Shire, EISAI; personal fees from Viropharma; grants from the Italian Ministry of Health, the European Union and Fondazione Borgonovo; grants from Associazione IDIC 15, outside the submitted work. AC reports personal fees from Biogen Idec and Cytokinetics; grants from Italfarmaco; personal fees from Mitsubishi, outside the submitted work. OH reports grants from Framework 7 EUROMOTOR project, Health Research Board Ireland and Science Foundation Ireland, during the conduct of the study; personal fees from ALS FTD Journal, outside the submitted work. JHV reports other from Vertex Pharmaceuticals, outside the submitted work. LHvdB reports grants from Netherlands ALS Foundation and the Netherlands Organization for Health Research and Development, during the conduct of the study; grants from Baxalta, Prinses Beatrix Spierfonds, European Community’s Health Seventh Framework Programme, outside the submitted work; and LHvdB serves on scientific advisory boards for the Prinses Beatrix Spierfonds, Thierry Latran Foundation, Biogen and Cytokinetics. Serves on the editorial board of Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration and The Journal of Neurology, Neurosurgery, and Psychiatry. AEV, FD, SMP, RCHV and GL report no disclosures.