Skip to main content

Smoking quantity determines disease activity and function in Chinese patients with ankylosing spondylitis


The objective of this study was to systemically and comprehensively evaluate the associations between smoking and disease outcomes in patients with ankylosing spondylitis (AS). Information on smoking, clinical features, and sociodemographic characteristics was collected by a questionnaire administered directly to the patient. Group differences were analyzed by t test or chi-square test. Logistic regression analysis was conducted with the Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), C-reactive protein, and erythrocyte sedimentation rate as the dependent variables and different stratification of smoking duration, smoking intensity, and cumulative smoking as independent variables. In order to compare our results with previous studies, meta-analysis was performed to calculate standardized mean difference (SMD) for relationship between outcomes and smoking status. A total of 1178 AS patients were analyzed. Compared with non-smokers, the risk of having active disease (BASDAI ≥ 4) was higher in patients who smoked at least 15 years, or 15 cigarettes per day, or 15 pack-years (OR = 1.70 [1.06, 2.73], 1.75 [1.08, 2.82], and 1.97 [1.06, 3.67], respectively); and smokers had increasing risk of BASDAI ≥ 4 with increasing years of smoking, or cigarettes per day, or pack-years (p-trend = 0.010, 0.008 and 0.006, respectively). The risk of having active disease was higher in patients who smoked at least 15 cigarettes per day or 15 pack-years (OR = 1.74 [1.06, 2.84] and 2.89 [1.56, 5.35], respectively), with increasing number of cigarettes per day and pack-years. Smokers had an increased risk of BASFI ≥ 4 (p-trend = 0.040 and 0.007, respectively). By meta-analysis, current, former and ever smokers had significantly higher BASDAI (SMD = 0.34 [0.18, 0.48], 0.10 [0.01, 0.19], and 0.27 [0.20, 0.34], respectively) and BASFI (SMD = 0.35 [0.16, 0.55], 0.30 [0.22, 0.39], and 0.35 [0.21, 0.50], respectively) compared to non-smokers. Smoking is a risk factor for greater disease activity and worse functioning in AS patients.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3


  1. 1.

    Corona-Sanchez EG, Munoz-Valle JF, Gonzalez-Lopez L, Sanchez-Hernandez JD, Vazquez-Del Mercado M, Ontiveros-Mercado H, Huerta M, Trujillo X, Rocha-Munoz AD, Celis A et al (2012) −383 A/C tumor necrosis factor receptor 1 polymorphism and ankylosing spondylitis in Mexicans: a preliminary study. Rheumatol Int 32(8):2565–2568.

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Jimenez-Balderas FJ, Mintz G (1993) Ankylosing spondylitis: clinical course in women and men. J Rheumatol 20(12):2069–2072

    CAS  PubMed  Google Scholar 

  3. 3.

    Dean LE, Jones GT, MacDonald AG, Downham C, Sturrock RD, Macfarlane GJ (2014) Global prevalence of ankylosing spondylitis. Rheumatology (Oxford, England) 53(4):650–657.

    Article  Google Scholar 

  4. 4.

    Zeng QY, Chen R, Xiao ZY, Huang SB, Liu Y, Xu JC, Chen SL, Darmawan J, Couchman KG, Wigley RD et al (2004) Low prevalence of knee and back pain in southeast China; the Shantou COPCORD study. J Rheumatol 31(12):2439–2443

    PubMed  Google Scholar 

  5. 5.

    Dai SM, Han XH, Zhao DB, Shi YQ, Liu Y, Meng JM (2003) Prevalence of rheumatic symptoms, rheumatoid arthritis, ankylosing spondylitis, and gout in Shanghai, China: a COPCORD study. J Rheumatol 30(10):2245–2251

    PubMed  Google Scholar 

  6. 6.

    Wigley RD, Zhang NZ, Zeng QY, Shi CS, Hu DW, Couchman K, Duff IF, Bennett PH (1994) Rheumatic diseases in China: ILAR-China study comparing the prevalence of rheumatic symptoms in northern and southern rural populations. J Rheumatol 21(8):1484–1490

    CAS  PubMed  Google Scholar 

  7. 7.

    Liao ZT, Pan YF, Huang JL, Huang F, Chi WJ, Zhang KX, Lin ZM, Wu YQ, He WZ, Wu J et al (2009) An epidemiological survey of low back pain and axial spondyloarthritis in a Chinese Han population. Scand J Rheumatol 38(6):455–459.

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Ye Z, Zhuang J, Wang X, Li J, Zhang L (2006) Epidemiological survey on prevalence of ankylosing spondylitis in 5992 Shenzhen inhabitants. Chin J Clin Rheumatol 10:159–161

    CAS  Google Scholar 

  9. 9.

    Joo YB, Bang SY, Kim TH, Shim SC, Lee S, Joo KB, Kim JH, Min HJ, Rahman P, Inman RD (2014) Bone morphogenetic protein 6 polymorphisms are associated with radiographic progression in ankylosing spondylitis. PLoS One 9(8):e104966.

    Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Cortes A, Maksymowych WP, Wordsworth BP, Inman RD, Danoy P, Rahman P, Stone MA, Corr M, Gensler LS, Gladman D, Morgan A, Marzo-Ortega H, Ward MM, SPARCC (Spondyloarthritis Research Consortium of Canada)., TASC (Australo-Anglo-American Spondyloarthritis Consortium), Learch TJ, Reveille JD, Brown MA, Weisman MH (2015) Association study of genes related to bone formation and resorption and the extent of radiographic change in ankylosing spondylitis. Ann Rheum Dis 74(7):1387–1393.

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Ramiro S, Landewe R, van Tubergen A, Boonen A, Stolwijk C, Dougados M, van den Bosch F, van der Heijde D (2015) Lifestyle factors may modify the effect of disease activity on radiographic progression in patients with ankylosing spondylitis: a longitudinal analysis. RMD Open 1(1):e000153.

    Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Lu B, Rho YH, Cui J, Iannaccone CK, Frits ML, Karlson EW, Shadick NA (2014) Associations of smoking and alcohol consumption with disease activity and functional status in rheumatoid arthritis. J Rheumatol 41(1):24–30.

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Chung HY, Machado P, van der Heijde D, D'Agostino MA, Dougados M (2012) Smokers in early axial spondyloarthritis have earlier disease onset, more disease activity, inflammation and damage, and poorer function and health-related quality of life: results from the DESIR cohort. Ann Rheum Dis 71(6):809–816.

    Article  PubMed  Google Scholar 

  14. 14.

    Papadopoulos NG, Alamanos Y, Voulgari PV, Epagelis EK, Tsifetaki N, Drosos AA (2005) Does cigarette smoking influence disease expression, activity and severity in early rheumatoid arthritis patients? Clin Exp Rheumatol 23(6):861–866

    CAS  PubMed  Google Scholar 

  15. 15.

    Wolfe F (2000) The effect of smoking on clinical, laboratory, and radiographic status in rheumatoid arthritis. J Rheumatol 27(3):630–637

    CAS  PubMed  Google Scholar 

  16. 16.

    Zhang S, Li Y, Xu X, Feng X, Yang D, Lin G (2015) Effect of cigarette smoking and alcohol consumption on disease activity and physical functioning in ankylosing spondylitis: a cross-sectional study. Int J Clin Exp Med 8(8):13919–13927

    PubMed  PubMed Central  Google Scholar 

  17. 17.

    Chen CH, Chen HA, Lu CL, Liao HT, Liu CH, Tsai CY, Chou CT (2013) Association of cigarette smoking with Chinese ankylosing spondylitis patients in Taiwan: a poor disease outcome in systemic inflammation, functional ability, and physical mobility. Clin Rheumatol 32(5):659–663.

    Article  PubMed  Google Scholar 

  18. 18.

    Kaan U, Ferda O (2005) Evaluation of clinical activity and functional impairment in smokers with ankylosing spondylitis. Rheumatol Int 25(5):357–360.

    Article  PubMed  Google Scholar 

  19. 19.

    Gaber W, Hassen AS, Abouleyoun II, Nawito ZO (2015) Impact of smoking on disease outcome in ankylosing spondylitis patients. Egypt Rheumatol 37(4):185–189.

    Article  Google Scholar 

  20. 20.

    Reed MD, Dharmage S, Boers A, Martin BJ, Buchanan RR, Schachna L (2008) Ankylosing spondylitis: an Australian experience. Intern Med J 38(5):321–327.

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Mattey DL, Dawson SR, Healey EL, Packham JC (2011) Relationship between smoking and patient-reported measures of disease outcome in ankylosing spondylitis. J Rheumatol 38(12):2608–2615.

    Article  PubMed  Google Scholar 

  22. 22.

    Videm V, Cortes A, Thomas R, Brown MA (2014) Current smoking is associated with incident ankylosing spondylitis—the HUNT population-based Norwegian health study. J Rheumatol 41(10):2041–2048.

    Article  PubMed  Google Scholar 

  23. 23.

    van der Linden S, Valkenburg HA, Cats A (1984) Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 27(4):361–368.

    Article  PubMed  Google Scholar 

  24. 24.

    Wilson D, Wakefield M, Owen N, Roberts L (1992) Characteristics of heavy smokers. Prev Med 21(3):311–319.

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A (1994) A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. J Rheumatol 21(12):2286–2291

    CAS  PubMed  Google Scholar 

  26. 26.

    Calin A, Garrett S, Whitelock H, Kennedy LG, O'Hea J, Mallorie P, Jenkinson T (1994) A new approach to defining functional ability in ankylosing spondylitis: the development of the Bath Ankylosing Spondylitis Functional Index. J Rheumatol 21(12):2281–2285

    CAS  PubMed  Google Scholar 

  27. 27.

    Adomaviciute D, Pileckyte M, Baranauskaite A, Morvan J, Dadoniene J, Guillemin F (2008) Prevalence survey of rheumatoid arthritis and spondyloarthropathy in Lithuania. Scand J Rheumatol 37(2):113–119.

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558.

    Article  PubMed  Google Scholar 

  29. 29.

    Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22(4):719–748

    CAS  PubMed  Google Scholar 

  30. 30.

    DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188.

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50(4):1088–1101.

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Sterne JA, Egger M (2001) Funnel plots for detecting bias in meta-analysis: guidelines on choice of axis. J Clin Epidemiol 54(10):1046–1055.

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    Wiebe N, Vandermeer B, Platt RW, Klassen TP, Moher D, Barrowman NJ (2006) A systematic review identifies a lack of standardization in methods for handling missing variance data. J Clin Epidemiol 59(4):342–353.

    Article  PubMed  Google Scholar 

  34. 34.

    Kydd AS, Chen JS, Makovey J, Chand V, Henderson L, Buchbinder R, Lassere M, March LM (2015) Smoking did not modify the effects of anti-TNF treatment on health-related quality of life among Australian ankylosing spondylitis patients. Rheumatology (Oxford, England) 54(2):310–317.

    CAS  Article  Google Scholar 

  35. 35.

    Sakellariou GT, Anastasilakis AD, Kenanidis E, Potoupnis M, Tsiridis E, Savvidis M, Kartalis N, Sayegh FE (2015) The effect of smoking on clinical and radiographic variables, and acute phase reactants in patients with ankylosing spondylitis. Rheumatol Int 35(12):2109–2114.

    Article  PubMed  Google Scholar 

  36. 36.

    Glintborg B, Hojgaard P, Lund Hetland M, Steen Krogh N, Kollerup G, Jensen J, Chrysidis S, Jensen Hansen IM, Holland-Fischer M, Hojland Hansen T et al (2016) Impact of tobacco smoking on response to tumour necrosis factor-alpha inhibitor treatment in patients with ankylosing spondylitis: results from the Danish nationwide DANBIO registry. Rheumatology (Oxford, England) 55(4):659–668.

    CAS  Article  Google Scholar 

  37. 37.

    Jones GT, Ratz T, Dean LE, Macfarlane GJ, Atzeni F (2016) In axial spondyloarthritis, never smokers, ex-smokers and current smokers show a gradient of increasing disease severity—results from the Scotland Registry for Ankylosing Spondylitis (SIRAS). Arthritis Care Res

  38. 38.

    Ward MM, Weisman MH, Davis JC Jr, Reveille JD (2005) Risk factors for functional limitations in patients with long-standing ankylosing spondylitis. Arthritis Rheum 53(5):710–717.

    Article  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Spadaro A, Lubrano E, Marchesoni A, D'Angelo S, Ramonda R, Addimanda O, Perrotta FM, Olivieri I, Punzi L, Salvarani C (2013) Remission in ankylosing spondylitis treated with anti-TNF-alpha drugs: a national multicentre study. Rheumatology (Oxford, England) 52(10):1914–1919

    CAS  Article  Google Scholar 

  40. 40.

    van der Heijde D, Breban M, Halter D, DiVittorio G, Bratt J, Cantini F, Kary S, Pangan AL, Kupper H, Rathmann SS, Sieper J, Mease PJ (2015) Maintenance of improvement in spinal mobility, physical function and quality of life in patients with ankylosing spondylitis after 5 years in a clinical trial of adalimumab. Rheumatology (Oxford, England) 54(7):1210–1219.

    Article  Google Scholar 

  41. 41.

    van der Heijde D, Schiff MH, Sieper J, Kivitz AJ, Wong RL, Kupper H, Dijkmans BA, Mease PJ, Davis JC Jr (2009) Adalimumab effectiveness for the treatment of ankylosing spondylitis is maintained for up to 2 years: long-term results from the ATLAS trial. Ann Rheum Dis 68(6):922–929.

    Article  PubMed  Google Scholar 

  42. 42.

    Huang F, Gu J, Zhu P, Bao C, Xu J, Xu H, Wu H, Wang G, Shi Q, Andhivarothai N, Anderson J, Pangan AL (2014) Efficacy and safety of adalimumab in Chinese adults with active ankylosing spondylitis: results of a randomised, controlled trial. Ann Rheum Dis 73(3):587–594.

    CAS  Article  PubMed  Google Scholar 

  43. 43.

    Baraliakos X, Haibel H, Fritz C, Listing J, Heldmann F, Braun J, Sieper J (2013) Long-term outcome of patients with active ankylosing spondylitis with etanercept-sustained efficacy and safety after seven years. Arthritis Res Ther 15(3):R67.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  44. 44.

    Saougou I, Markatseli TE, Voulgari PV, Drosos AA (2010) Maintained clinical response of infliximab treatment in ankylosing spondylitis: a 6-year long-term study. Joint, bone, spine: Rev Rhum 77(4):325–329

    CAS  Article  Google Scholar 

Download references


Computational support was provided by the High-End Computing Center located at Fudan University.


The study was supported by research grants from the National Basic Research Program (2014CB541801), National Natural Science Foundation of China (31521003), Ministry of Sciences and Technology (2011BAI09B00), US NIH NIAID U01 (1U01AI090909), International S&T Cooperation Program of China (2013DFA30870), and 111 Project (B13016).

Author information



Corresponding authors

Correspondence to Hejian Zou or Jiucun Wang.

Ethics declarations

This study was approved by the Ethics Committees of the School of Life Sciences of Fudan University, and informed consent was obtained from each participant.



Electronic supplementary material


(DOCX 193 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Zhang, H., Wan, W., Liu, J. et al. Smoking quantity determines disease activity and function in Chinese patients with ankylosing spondylitis. Clin Rheumatol 37, 1605–1616 (2018).

Download citation


  • Ankylosing spondylitis
  • Cumulative smoking exposure
  • Outcomes
  • Smoking duration
  • Smoking intensity