title: Smoking as a risk factor for the radiological severity of rheumatoid arthritis: a study on six cohorts.
abstract: BACKGROUND
  Smoking is a risk factor for the development of anti -citrullinated protein antibodies (ACPA) positive rheumatoid arthritis (RA). Whether smoking predisposes to severe joint damage progression is not known, since deleterious, protective and neutral observations have been made.
  
  
  OBJECTIVE
  To determine the effect of smoking on joint damage progression.
  
  
  METHODS
  Smoking status was assessed in 3158 RA patients included in six cohorts (Leiden Early Arthritis Clinic (Leiden-EAC), BARFOT, Lund, Iceland, NDB and Wichita). In total 9412 radiographs were assessed. Multivariate normal regression and linear regression analyses were performed. Data were summarised in a random effects inverse variance meta-analysis.
  
  
  RESULTS
  When comparing radiological progression for RA patients that were never, past and current smokers, smoking was significantly associated with more severe joint damage in Leiden-EAC (p=0.042) and BARFOT (p=0.015) RA patients. No significant associations were found in the other cohorts, though a meta-analysis on the six cohorts showed significantly more severe joint damage progression in smokers (p=0.01). Since smoking predisposes to ACPA, analyses were repeated with ACPA as additional adjustment factor. Then the association was lost (meta-analysis p=0.29).
  
  
  CONCLUSIONS
  This multi-cohort study indicated that the effect of smoking on joint damage is mediated via ACPA and that smoking is not an independent risk factor for radiological progression in RA.
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: D P C
authors.initials: DP
authors.lastname: de Rooy
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: J A B
authors.initials: JA
authors.lastname: van Nies
authors.affiliation: Section of Rheumatology, Department of Clinical Sciences, Lund University, Lund, Sweden Department of Rheumatology, Skåne University Hospital, Lund, Sweden.
authors.forename: M C
authors.initials: MC
authors.lastname: Kapetanovic
authors.affiliation: Department of Rheumatology and Center for Rheumatology Research, Landspítali-The National University Hospital of Iceland, Reykjavik, Iceland.
authors.forename: H
authors.initials: H
authors.lastname: Kristjansdottir
authors.affiliation: R and D Centre, Spenshult Hospital, Oskarström, Sweden Section of Rheumatology, Department of Clinical Sciences, Lund University, Sweden for the BARFOT study group, Lund, Sweden.
authors.forename: M L E
authors.initials: ML
authors.lastname: Andersson
authors.affiliation: Section of Rheumatology, Department of Clinical Sciences, Lund University, Sweden for the BARFOT study group, Lund, Sweden Section of Rheumatology, Department of Medicine, Helsingborg's lasarett, Helsingborg, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Forslind
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: D M F M
authors.initials: DM
authors.lastname: van der Heijde
authors.affiliation: Feinstein Institute for Medical Research and North Shore-Long Island Jewish Health System, Manhasset, New York, USA.
authors.forename: P K
authors.initials: PK
authors.lastname: Gregersen
authors.affiliation: Section of Rheumatology, Department of Clinical Sciences, Lund University, Lund, Sweden Department of Rheumatology, Skåne University Hospital, Lund, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Lindqvist
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: T W J
authors.initials: TW
authors.lastname: Huizinga
authors.affiliation: Department of Rheumatology and Center for Rheumatology Research, Landspítali-The National University Hospital of Iceland, Reykjavik, Iceland.
authors.forename: G
authors.initials: G
authors.lastname: Gröndal
authors.affiliation: Section of Rheumatology, Department of Clinical Sciences, Lund University, Sweden for the BARFOT study group, Lund, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Svensson
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: A H M
authors.initials: AH
authors.lastname: van der Helm-van Mil
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D033023:Foot Joints / Q000000981:diagnostic imaging*; D050823:Hand Joints / Q000000981:diagnostic imaging*; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010456:Peptides, Cyclic / Q000276:immunology; D011859:Radiography; D012720:Severity of Illness Index; D012907:Smoking / Q000453:epidemiology* / Q000276:immunology
chemical_list: D001323:Autoantibodies; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide
keywords: Ant-CCP; Outcomes research; Rheumatoid Arthritis; Smoking