Objective To assess the prognostic influence of premorbid smoking habits and vascular risk profile on amyotrophic lateral sclerosis (ALS) phenotype and outcome in a population-based cohort of Italian patients.
Methods A total of 650 patients with ALS from the Piemonte/Valle d'Aosta Register for ALS, incident in the 2007–2011 period, were recruited. Information about premorbid cigarette smoking habits and chronic obstructive pulmonary disease (COPD) were collected at the time of diagnosis.
Results Current smokers had a significantly shorter median survival (1.9 years, IQR 1.2–3.4) compared with former (2.3 years, IQR 1.5–4.2) and never smokers (2.7 years, IQR 1.8–4.6) (p=0.001). Also COPD adversely influenced patients’ prognosis. Both smoking habits and CODP were retained in Cox multivariable model.
Conclusions This study has demonstrated in a large population-based cohort of patients with ALS that cigarette smoking is an independent negative prognostic factor for survival, with a dose–response gradient. Its effect is not related to the presence of COPD or to respiratory status at time of diagnosis. The understanding of the mechanisms, either genetic or epigenetic, through which exogenous factors influence disease phenotype is of major importance towards a more focused approach to cure ALS.
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GM, LM and ACh contributed equally to this study.
Contributors ACal, GM, LM and ACh contributed to the study concept and design. ACan, DB, PC, LS, MC, SDM, EBe, SC, AI, UM, CM, KM, EBo and FP were involved in the acquisition of data. ACal, MC, CM, EBo, FP, GM, LM and ACh conducted the analysis and interpretation of data. ACal, GM and ACh were responsible for the drafting of the manuscript. ACal, ACan, DB, PC, LS, MC, SDM, EBe, SC, AI, UM, CM, KM, EBo, FP, GM, LM and ACh performed the critical revision of the manuscript for important intellectual content. ACh obtained funding. DB, EBe, UM and KM provided administrative, technical and material support. ACal, GM, LM and ACh were involved in the study supervision. ACh had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors have approved the submitted version of the manuscript. Members of the Piemonte and Valle d'Aosta Register for ALS (PARALS) are listed in an online supplementary appendix.
Funding This work was in part supported by the Italian Ministry of Health (Ministero della Salute, Ricerca Sanitaria Finalizzata, 2010, grant number RF-2010-2309849), the European Community's Health Seventh Framework Programme (FP7/2007–2013 under grant agreement number 259867), the Joint Programme—Neurodegenerative Disease Research (Sophia Project, supported by the Italian Ministry of Health, and Strength Project, supported by the Italian Ministry of University and Research), Fondazione Mario e Anna Magnetto, Associazione Piemontese per l'Assistenza alla SLA (APASLA), and Fondazione Vialli e Mauro per la Sclerosi Laterale Amiotrofica onlus.
Disclaimer The funding sources had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Competing interests ACal has received research support from the Italian Ministry of Health (Ricerca Finalizzata). CM has received research support from the Italian Ministry of Health (Ricerca Finalizzata). GM has received research support by the Italian Ministry of Health and Agenzia per la Ricerca sulla SLA (ARISLA). ACh serves on the editorial advisory board of amyotrophic lateral sclerosis and has received research support from the Italian Ministry of Health (Ricerca Finalizzata), Regione Piemonte (Ricerca Finalizzata), University of Turin, Fondazione Vialli e Mauro onlus and the European Commission (Health Seventh Framework Programme); he serves on the scientific advisory boards for Biogen Idec, Cytokinetics, Italfarmaco, Neuraltus and Mitsubishi.
Patient consent Obtained.
Ethics approval Ethical Committee ‘Città della Salute e della Scienza’, Torino.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Additional unpublished data from the study can be obtained from the corresponding author.