title: Influence of cigarette smoking on ALS outcome: a population-based study.
abstract: 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.
authors.affiliation: 'Rita Levi Montalcini' Department of Neuroscience, ALS Center, University of Turin, Turin, Italy Azienda Ospedaliero Universitaria Città della Salute e della Scienza, Turin, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Calvo
authors.affiliation: 'Rita Levi Montalcini' Department of Neuroscience, ALS Center, University of Turin, Turin, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Canosa
authors.affiliation: 'Rita Levi Montalcini' Department of Neuroscience, ALS Center, University of Turin, Turin, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Bertuzzo
authors.affiliation: 'Rita Levi Montalcini' Department of Neuroscience, ALS Center, University of Turin, Turin, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Cugnasco
authors.affiliation: 'Rita Levi Montalcini' Department of Neuroscience, ALS Center, University of Turin, Turin, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Solero
authors.affiliation: Department of Biological and Clinical Science, University of Turin, Azienda Ospedaliero Universitaria San Luigi Gonzaga, Orbassano, Italy.
authors.forename: Marinella
authors.initials: M
authors.lastname: Clerico
authors.affiliation: Department of Biological and Clinical Science, University of Turin, Azienda Ospedaliero Universitaria San Luigi Gonzaga, Orbassano, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: De Mercanti
authors.affiliation: Department of Neurology, ALS Center, Azienda Ospedaliero Universitaria Maggiore della Carità, Novara, Italy Eastern Piedmont University, Novara, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Bersano
authors.affiliation: 'Rita Levi Montalcini' Department of Neuroscience, ALS Center, University of Turin, Turin, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Cammarosano
authors.affiliation: 'Rita Levi Montalcini' Department of Neuroscience, ALS Center, University of Turin, Turin, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Ilardi
authors.affiliation: 'Rita Levi Montalcini' Department of Neuroscience, ALS Center, University of Turin, Turin, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Manera
authors.affiliation: 'Rita Levi Montalcini' Department of Neuroscience, ALS Center, University of Turin, Turin, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Moglia
authors.affiliation: Salvatore Maugeri Foundation, IRCSS, Scientific Institute of Milano, Milano, Italy.
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Marinou
authors.affiliation: Department of Neurology, Azienda Ospedaliera Regionale di Aosta, Azienda USL Valle d'Aosta, Aosta, Italy.
authors.forename: Edo
authors.initials: E
authors.lastname: Bottacchi
authors.affiliation: Salvatore Maugeri Foundation, IRCSS, Scientific Institute of Veruno (NO), Veruno, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Pisano
authors.affiliation: Salvatore Maugeri Foundation, IRCSS, Scientific Institute of Milano, Milano, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Mora
authors.affiliation: Department of Neurology, ALS Center, Azienda Ospedaliero Universitaria Maggiore della Carità, Novara, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Mazzini
authors.affiliation: 'Rita Levi Montalcini' Department of Neuroscience, ALS Center, University of Turin, Turin, Italy Azienda Ospedaliero Universitaria Città della Salute e della Scienza, Turin, Italy Neuroscience Institute of Torino (NIT), Turin, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Chiò
mesh_terms: D000203:Activities of Daily Living / Q000145:classification; D017668:Age of Onset; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis / Q000401:mortality*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D016016:Proportional Hazards Models; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000401:mortality; D012907:Smoking / Q000009:adverse effects* / Q000401:mortality*; D016019:Survival Analysis