title: Increased inflammation and disease activity among current cigarette smokers with rheumatoid arthritis: a cross-sectional analysis of US veterans.
abstract: Cigarette smoking is a major risk factor for RA and has been associated with increased disease severity and lower rates of disease remission. We hypothesized that inflammation and disease activity would be associated with smoking status and this would be related to levels of ACPA.
  
  
  
  RA patients from the Veterans Affairs RA registry were studied (n = 1466): 76.9% anti-CCP2 positive, 89% male, median age 63 years (interquartile range 57-72), median disease duration 8.45 years (interquartile range 2.8-18). Baseline serum samples were evaluated for levels of anti-CCP2, RF, 19 distinct ACPAs and 17 cytokines. Smoking status at baseline was recorded as current, former or never. The association of smoking status with cytokines, autoantibodies and disease activity (DAS28) was evaluated.
  
  
  
  Among anti-CCP-positive RA patients, RA-associated cytokines (false-discovery rates q < 0.1%) and DAS28 (P < 0.01) were higher in current smokers compared with former or never smokers. DAS28 and cytokine levels were similar between former and never smokers. In contrast, ACPA concentrations were higher among both current and former smokers compared with never smokers, and levels of ACPA were not associated with DAS28 or cytokine levels.
  
  
  
  Among anti-CCP2-positive RA patients, current smoking status is associated with elevations in pro-inflammatory cytokines and increased RA disease activity. Similar levels of inflammation and disease activity among former and never smokers suggests that the detrimental effects of smoking could be ameliorated through tobacco cessation. The effect of tobacco cessation on RA disease activity should be evaluated prospectively.
authors.affiliation: VA Palo Alto Health Care System sokolove@stanford.edu.|Division of Immunology and Rheumatology, Stanford University School of Medicine, Palo Alto, CA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Sokolove
authors.affiliation: VA Palo Alto Health Care System.|Division of Immunology and Rheumatology, Stanford University School of Medicine, Palo Alto, CA.
authors.forename: Catriona A
authors.initials: CA
authors.lastname: Wagner
authors.affiliation: VA Palo Alto Health Care System.|Division of Immunology and Rheumatology, Stanford University School of Medicine, Palo Alto, CA.
authors.forename: Lauren J
authors.initials: LJ
authors.lastname: Lahey
authors.affiliation: VA Nebraska Western-Iowa Health Care System.|Nebraska Arthritis Outcomes Research Center, University of Nebraska Medical Center, Omaha, NE.
authors.forename: Harlan
authors.initials: H
authors.lastname: Sayles
authors.affiliation: VA Nebraska Western-Iowa Health Care System.|Nebraska Arthritis Outcomes Research Center, University of Nebraska Medical Center, Omaha, NE.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Duryee
authors.affiliation: Dallas VA Medical Center.|Division of Rheumatic Diseases, University of Texas Southwestern University Medical Center, Dallas, TX.
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Reimold
authors.affiliation: DC VA Medical Center.|Division of Rheumatology, Georgetown University.|Division of Rheumatology, Howard University, Washington, DC.
authors.forename: Gail
authors.initials: G
authors.lastname: Kerr
authors.affiliation: VA Palo Alto Health Care System.|Division of Immunology and Rheumatology, Stanford University School of Medicine, Palo Alto, CA.
authors.forename: William H
authors.initials: WH
authors.lastname: Robinson
authors.affiliation: George E. Wahlen VA Medical Center.|Division of Rheumatology, University of Utah Health Care, Salt Lake City, UT, USA.
authors.forename: Grant W
authors.initials: GW
authors.lastname: Cannon
authors.affiliation: VA Nebraska Western-Iowa Health Care System.|Nebraska Arthritis Outcomes Research Center, University of Nebraska Medical Center, Omaha, NE.
authors.forename: Geoffrey M
authors.initials: GM
authors.lastname: Thiele
authors.affiliation: VA Nebraska Western-Iowa Health Care System.|Nebraska Arthritis Outcomes Research Center, University of Nebraska Medical Center, Omaha, NE.
authors.forename: Ted R
authors.initials: TR
authors.lastname: Mikuls
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000209:etiology* / Q000276:immunology; D001324:Autoantigens / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012907:Smoking / Q000009:adverse effects* / Q000276:immunology; D014481:United States; D014728:Veterans
chemical_list: D001324:Autoantigens; D015415:Biomarkers; D016207:Cytokines
keywords: disease activity; inflammation; rheumatoid arthritis; smoking