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

Our plain-English summary of Multicentre, population-based, case-control study of particulates, combustion products and amyotrophic lateral sclerosis risk, by A.E. Visser, F. D'Ovidio, S. Peters, et al (Journal of Neurology, Neurosurgery, and Psychiatry, 2019).

The study

• Authors: A.E. Visser, F. D'Ovidio, S. Peters, R.C. Vermeulen, E. Beghi, A. Chiò, J.H. Veldink, G. Logroscino, O. Hardiman, L.H. van den Berg, Euro-MOTOR consortium
• Journal: Journal of Neurology, Neurosurgery, and Psychiatry
• Published: 2019;90(8):854-860
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.

In plain English

This population-based case-control study compared 1557 people with amyotrophic lateral sclerosis (ALS) and 2922 controls matched on age, gender and residence, recruited in 2011 to 2014 in the Netherlands, Ireland and three Italian regions. Participants reported their full job histories. A job-exposure matrix was used to estimate lifetime workplace exposure to seven agents: silica, asbestos, organic dust, animal contact, endotoxin, polycyclic aromatic hydrocarbons and diesel motor exhaust. After exclusions, 1252 patients and 2590 controls were analysed. All seven exposures were positively associated with ALS. For asbestos the associations were not statistically significant: odds ratio 1.22 (95% CI 0.95 to 1.56) for low and 1.16 (0.90 to 1.51) for high cumulative exposure, compared with never exposed. For silica, odds ratios were 1.67 (1.23 to 2.25) for low and 1.73 (1.28 to 2.33) for high exposure. Only silica stayed significant when each of the other exposures was added to the model. Asbestos-exposed patients were younger at survey (mean 63.5 versus 64.9 years). The authors concluded that ALS risk was associated with silica, independent of the other exposures. They noted that recall bias could not be ruled out.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: multicentre, population-based case-control study
• Who was studied: 1557 people with ALS and 2922 controls matched on age, gender and geography, from the Netherlands, Ireland, and the Italian regions of Apulia, Lombardy, and Piedmont and Valle d'Aosta, recruited 2011 to 2014. After exclusions, 1252 patients and 2590 controls had usable occupational information.
• Exposure: Lifetime occupational exposure, estimated from job histories with the DOM-JEM job-exposure matrix, to seven agents: respirable crystalline silica, asbestos (fiber type not specified), organic dust, animal contact, endotoxin, polycyclic aromatic hydrocarbons (PAH) and diesel motor exhaust (DME). Cumulative exposure was grouped as never, low or high, split at the median of exposed controls.
• Main results:
  • Asbestos, low cumulative exposure versus never exposed: OR 1.22 (95% CI 0.95 to 1.56), p=0.12. Not statistically significant.
  • Asbestos, high cumulative exposure versus never exposed: OR 1.16 (95% CI 0.90 to 1.51), p=0.25. Not statistically significant. The p value for trend for asbestos was 0.68.
  • Associations were statistically significant for high-level exposure to silica, organic dust, endotoxin and PAH.
  • Silica versus never exposed: low exposure OR 1.67 (95% CI 1.23 to 2.25); high exposure OR 1.73 (95% CI 1.28 to 2.33).
  • When exposures were treated as continuous, significant linear associations were found for silica, organic dust and DME.
  • When each other exposure was added to the model in turn, only silica remained significantly associated with ALS risk.
  • After excluding 199 patients with a C9orf72 repeat expansion, the silica results were similar: low exposure OR 1.73 (95% CI 1.27 to 2.34); high exposure OR 1.69 (95% CI 1.24 to 2.28).
  • Patients exposed to asbestos were younger at survey (mean 63.5 years) than non-exposed patients (mean 64.9 years). For patients, age at survey was highly correlated with age at onset. This was not found for the other six exposures.
• The authors' conclusion: The authors concluded that they found an association between ALS risk and silica exposure, independent of the other occupational exposures studied.
• Limitations the authors state:
  • Recall bias cannot be completely ruled out, because patients may recall job details more thoroughly than controls.
  • The job-exposure matrix gives everyone in the same job the same exposure, although people do not all perform the same tasks in the same way.
  • Military jobs had to be excluded because their exposures could easily be misclassified.

Topics

Medical terms in this study, explained in our Lexicon: Case-Control Study, Habit, Occupational History, Occupational Exposure, Confounding.

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