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Research paper
Multicentre, population-based, case–control study of particulates, combustion products and amyotrophic lateral sclerosis risk
  1. Anne E Visser1,
  2. Fabrizio D'Ovidio2,
  3. Susan Peters1,3,
  4. Roel CH Vermeulen3,
  5. Ettore Beghi4,
  6. Adriano Chiò2,
  7. Jan H Veldink1,
  8. Giancarlo Logroscino5,6,
  9. Orla Hardiman7,
  10. Leonard H van den Berg1
  11. for the Euro-MOTOR consortium
    1. 1 Department of Neurology, Brain Centre Rudolf Magnus, University Medical Centre Utrecht, Utrecht, The Netherlands
    2. 2 Rita Levi Montalcini Department of Neuroscience, University of Torino, Torino, Italy
    3. 3 Division of Environmental Epidemiology, Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, The Netherlands
    4. 4 Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
    5. 5 Unit of Neurodegenerative Diseases, Department of Clinical Research in Neurology, University of Bari 'Aldo Moro', Pia Fondazione Cardinale G Panico, Lecce, Italy
    6. 6 Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari 'Aldo Moro', Bari, Italy
    7. 7 Academic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College, Dublin, Ireland
    1. Correspondence to Leonard H van den Berg, Department of Neurology, Brain Centre Rudolf Magnus, University Medical Centre Utrecht, Utrecht 3584CX, The Netherlands; L.H.vandenBerg{at}umcutrecht.nl

    Abstract

    Objective 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.

    Methods 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.

    Results 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 C9orf72 mutation were excluded.

    Conclusion 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.

    • Davide Bertuzzo
    • Enrica Bersano

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    Footnotes

    • AEV and FD contributed equally.

    • Collaborators Rosanna Tortelli, MD, PhD (Unit of Neurodegenerative Diseases, Department of Clinical Research in Neurology, University of Bari Aldo Moro, at Pia Fondazione 'Card G Panico', Tricase, Lecce, Italy; Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari Aldo Moro, Bari, Italy); Chiara Zecca, MSc (Department of Clinical Research in Neurology, University of Bari, 'Pia Fondazione Cardinale G Panico', Lecce, Italy); Elisabetta Pupillo (Department of Neurosciences, IRCSS, Mario Negri Institute of Pharmacological Research, Milan); Giancarlo Comi, MD; Nilo Riva, MD (IRCCS San Raffaele Hospital, Milano, Italy); Christian Lunetta, MD; Francesca Gerardi, DrBT (NEMO Clinical Centre, Serena Onlus Foundation, Niguarda Ca’ Granda Hospital, Milano, Italy); Massimiliano Filosto, MD; Maria Sofia Cotelli, MD; Fabrizio Rinaldi, MD (Civil Hospital of Brescia, Brescia, Italy); Luca Chiveri, MD (Ospedale Valduce, Como, Italy); Maria Cristina Guaita, MD; Patrizia Perrone, MD (AO Civil Hospital, Legnano, Italy); Ceroni Mauro, MD; Luca Diamanti, MD (IRCCS National Neurorological Institute 'C Mondino', Pavia); Carlo Ferrarese, MD; Lucio Tremolizzo, MD (University of Milano-Bicocca, 'San Gerardo' Hospital, Monza); Maria Luisa Delodovici, MD; Giorgio Bono, MD ('Ospedale di Circolo, Fondazione Macchi', Varese); Mark Heverin, MSc; Alice Vajda, PhD (Academic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland); Anneke J van der Kooi, MD, PhD (Department of Neurology, Amsterdam Medical Centre, University of Amsterdam, Amsterdam, The Netherlands); Joost Raaphorst, MD, PhD (Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands); Andrea Calvo, MD, PhD; Cristina Moglia, MD, PhD; Federico Casale, PhD; Giuseppe Fuda, MSc; Antonio Canosa, MD, PhD; Umberto Manera, MD; Alessandro Bombaci, MD; Maurizio Grassano, MD; Rosario Vasta, MD; Paolina Salamone, MSc, PhD; Giuseppe Marrali, MSc, PhD; Barabara Lazzolino, PsyD ('Rita Levi Montalcini' Department of Neuroscience, University of Torino, Torino, Italy); Letizia Mazzini, MD (ALS Centre, Department of Neurology, 'Maggiore della Carità', University Hospital Novara, Italy).

    • Contributors AEV, FD, RCHV, EB, AC, JHV, GL, OH and LHvdB contributed to the study concept and design and participated in data collection and processing. AEV and FD performed the statistical analyses. AEV, FD, SMP, RCHV, EB, AC, JHV, GL, OH and LHvdB contributed to the analysis and interpretation of data. AEV wrote the manuscript. FD, SMP, RCHV, EB, AC, JHV, GL, OH and LHvdB revised the manuscript for important intellectual content. SMP, RCHV, EB, AC, JHV, GL, OH and LHvdB provided study supervision. EB, AC, JHV, GL, OH and LHvdB obtained funding.

    • Funding This work was supported by the European Community’s Health Seventh Framework Programme (FP7/2007-2013) (grant agreement number 259867); the Netherlands ALS Foundation; and the Netherlands Organization for Health Research and Development (Vici Scheme, JPND (STRENGTH)).

    • 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.

    • Patient consent for publication Not required.

    • Ethics approval Ethical approval was obtained from all five institutional review boards.

    • Provenance and peer review Not commissioned; externally peer reviewed.

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