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Research paper
Influence of cigarette smoking on ALS outcome: a population-based study
  1. Andrea Calvo1,2,
  2. Antonio Canosa1,
  3. Davide Bertuzzo1,
  4. Paolo Cugnasco1,
  5. Luca Solero1,
  6. Marinella Clerico3,
  7. Stefania De Mercanti3,
  8. Enrica Bersano4,5,
  9. Stefania Cammarosano1,
  10. Antonio Ilardi1,
  11. Umberto Manera1,
  12. Cristina Moglia1,
  13. Kalliopi Marinou6,
  14. Edo Bottacchi7,
  15. Fabrizio Pisano8,
  16. Gabriele Mora6,
  17. Letizia Mazzini4,
  18. Adriano Chiò1,2,9
  1. 1‘Rita Levi Montalcini’ Department of Neuroscience, ALS Center, University of Turin, Turin, Italy
  2. 2Azienda Ospedaliero Universitaria Città della Salute e della Scienza, Turin, Italy
  3. 3Department of Biological and Clinical Science, University of Turin, Azienda Ospedaliero Universitaria San Luigi Gonzaga, Orbassano, Italy
  4. 4Department of Neurology, ALS Center, Azienda Ospedaliero Universitaria Maggiore della Carità, Novara, Italy
  5. 5Eastern Piedmont University, Novara, Italy
  6. 6Salvatore Maugeri Foundation, IRCSS, Scientific Institute of Milano, Milano, Italy
  7. 7Department of Neurology, Azienda Ospedaliera Regionale di Aosta, Azienda USL Valle d'Aosta, Aosta, Italy
  8. 8Salvatore Maugeri Foundation, IRCSS, Scientific Institute of Veruno (NO), Veruno, Italy
  9. 9Neuroscience Institute of Torino (NIT), Turin, Italy
  1. Correspondence to Professor Adriano Chiò, ‘Rita Levi Montalcini’ Department of Neuroscience, University of Torino, via Cherasco 15, Torino 1026, Italy; achio{at}


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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