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Cigarette smoking has a dose-dependent impact on progression of structural damage in the spine in patients with axial spondyloarthritis: results from the GErman SPondyloarthritis Inception Cohort (GESPIC)
  1. Denis Poddubnyy1,
  2. Hildrun Haibel1,
  3. Joachim Listing2,
  4. Elisabeth Märker-Hermann3,
  5. Henning Zeidler4,
  6. Jürgen Braun5,
  7. Joachim Sieper1,
  8. Martin Rudwaleit6
  1. 1Rheumatology, Campus Benjamin Franklin, Charité Universitätsmedizin Berlin, Germany
  2. 2 Department of Epidemiology, German Rheumatism Research Centre, Berlin, Germany
  3. 3 Dr. Horst Schmidt Kliniken, Wiesbaden, Germany
  4. 4 Medizinische Hochschule, Hannover, Germany
  5. 5 Rheumazentrum Ruhrgebiet, Herne, Germany
  6. 6 Endokrinologikum Berlin, Berlin, Germany
  1. Correspondence to Dr Denis Poddubnyy, Department of Rheumatology, Med. Department I, Campus Benjamin Franklin, Charité Universitätsmedizin Berlin, Hindenburgdamm 30, Berlin 12203, Germany; denis.poddubnyy{at}charite.de

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Recently, we demonstrated that smoking status itself is an independent predictor of radiographic spinal progression over 2 years in patients with axial SpA (axSpA).1 Here we report in more detail the relationship between tobacco smoking and development of structural damage in the spine in patients with axSpA with a focus on a dose-dependent association and a relationship between smoking and activity of systemic inflammation.

In total, 210 patients with axSpA (115 with ankylosing spondylitis (AS) and 95 with non-radiographic axSpA (nr-axSpA)) from the GErman SPondyloarthritis Inception Cohort (GESPIC)1 ,2 were included. Detailed description of the patients and radiographs scoring has been reported elsewhere.1 In the current analysis, we used an extended syndesmophytes count, which included lateral views of the cervical and lumbar spine, and also antero-posterior views of the lumbar spine. Significant radiographic spinal progression was defined as (1) worsening of the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) by ≥2 units after 2 years and (2) development of a new syndesmophyte or progression of existing syndesmophytes (formation of a bridging syndesmophyte from two single syndesmophytes) after 2 years. Smoking status and smoking intensity (non-smoker, 10 cigarettes a day and less, 11–20 cigarettes, and more than 20 cigarettes a day) were assessed every 6 months during 2 years of follow-up.

In total, 71 out of 210 patients (33.8%) with axSpA were recorded as smokers at least at one time-point over 2 years. For all smokers, an average smoking intensity over 2 years was calculated. The baseline characteristics of included patients are presented in table 1.

Table 1

Baseline demographic and clinical characteristics of patients with axial spondyloarthritis

A one-way analysis of variance revealed a significant (p=0.002) intergroup difference in the absolute mSASSS worsening over 2 years between the analysed subgroups. Importantly, this difference was mostly attributable to the group of heavy smokers (>10 cigarettes a day) with an mSASSS worsening by 2.20±4.62 units over 2 years as compared with moderate smokers (≤10 cigarettes a day): mSASSS worsening 0.48±1.48, p=0.006 versus heavy smokers, and to the non-smoking group: mSASSS worsening 0.52±1.72, p=0.001 versus heavy smokers. A separate analysis of axSpA subsets (AS and nr-axSpA) showed that differences in mSASSS worsening were clearer (and statistically significant) in the AS group (3.12±5.54 in heavy smokers, 0.57±1.70 in moderate smokers, and 0.58±1.78 in non-smokers, p=0.002 for the intergroup differences), whereas in nr-axSpA no clear difference was observed (0.77±2.21 in heavy smokers, 0.31±1.02 in moderate smokers, and 0.46±1.66 in non-smokers, p=0.77).

When frequencies of significant radiographic spinal progression (mSASSS worsening by at least 2 points—figure 1A and new syndesmophytes formation and/or growth of existing syndesmophytes—figure 1B) were analysed, the dose-dependent relationship between smoking and development of structural damage in the spine became even clearer with highest progression rates in heavy smokers. Heavy smokers had an odds ratio (OR) for mSASSS progression by ≥2 points of 3.57 (95% CI 1.33 to 9.60), p=0.012 versus non-smokers. This remained also significant in the multivariate logistic regression analysis after adjustment for baseline syndesmophytes, C-reactive protein (CRP) level, gender, presence of definite radiographic sacroiliitis, use of non-steroidal anti-inflammatory drugs and tumour necrosis factor blockers: OR=3.48 (95% CI 1.06 to 11.42), p=0.039. After inclusion of age in the multivariate model, the OR decreased to 3.10 (95% CI 0.84 to 11.44), p=0.089. Similarly, for syndesmophyte formation, heavy smoking had an OR=3.53 (95%CI 1.25 to 9.98), p=0.018 versus non-smoking, after adjustment for all factors mentioned above the OR was 4.17 (95% CI 0.79 to 22.02), p=0.093. Notably, these differences were especially evident in the AS subgroup.

Figure 1

Relation of smoking intensity to radiographic spinal progression defined as mSASSS worsening by ≥2 units over two years (A) or new syndesmophyte formation/existing syndesmophytes progression over 2 years (B) in patients with AS (n=115), non-radiographic axial spondyloarthritis (n=95), and in the whole group axial spondyloarthritis group (n=210). * p<0.05 versus non-smokers (Fischer's exact test). AS, ankylosing spondylitis; mSASSS, modified Stoke Ankylosing Spondylitis Spine Score; nr-axSpA, non-radiographic axial SpA.

Importantly, we also found the same dose-dependent relationship between smoking and the level of time-averaged CRP over two years (CRP levels were determined at baseline and every 6 months thereafter during 2 years of follow-up): 6.3±6.6 mg/l in non-smokers, 8.6±10.3 mg/l in moderate smokers, and 12.4±12.9 mg/l in heavy smokers (p=0.002 vs non-smokers).

Thus, in addition to our previous report1 we could show that the effect of smoking on radiographic spinal progression in axSpA is dependent on smoking intensity and seems to be mediated by increased systemic inflammation in smokers.

Acknowledgments

We thank Prof M Leirisalo-Repo, Finland, Prof D van der Heijde, The Netherlands, and Prof M Dougados, France, for scientific advice on the design of the cohort. We are grateful to Beate Buss and Petra Tietz for monitoring the cohort, Johanna Callhoff, Anja Weiss and Martina Niewerth for the data management support, Janis Vahldiek and Georg Heine for the x-ray images handling and for the development of the image scoring interface, and to all patients who voluntarily participated in this cohort. Further, we would like to thank the following rheumatologists for inclusion of their patients: J Brandt, H Brandt, G-R Burmester, H Deister, E Edelmann, J Emmerich, M Enderlein, A Gauliard, E Gromnica-Ihle, F Heldmann, S Hermann, U von Hinüber, Ü Hübner, K Karberg, H Nüßlein, R Pelle-Lohfink, D Pick, G Reichmuth, E Riehers, M Rihl, R Schmidt, S Schnarr, U Schneider, I-H Song, I Spiller, U Syrbe, V Walz, S Wassenberg, H M Wisseler, S Zinke.

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Footnotes

  • Funding As part of the German competence network in rheumatology (Kompetenznetz Rheuma), GESPIC has been financially supported by the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung—BMBF). As funding by BMBF was reduced according to schedule in 2005 and stopped in 2007, complementary financial support has been obtained also from Abbott, Amgen, Centocor, Schering–Plough, and Wyeth. Since 2010 additional support has being obtained also from ANCYLOSS (grant number FKZ 01EC1002D) and ArthroMark (grant number FKZ 01EC1009A) projects funded by BMBF.

  • Competing interests None.

  • Ethics approval Ethics Committee of the Charité Universitätsmedizin Berlin.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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