Untangling the relationship between smoking and systemic sclerosis: an analysis of the EUSTAR cohort

RMD Open, vol. 10, pp. e004101

Abstract

OBJECTIVES: To untangle the association between smoking and systemic sclerosis (SSc). METHODS: In the European Scleroderma Trials and Research cohort, the autoantibody status was compared between ever-smokers and never-smokers. Time until disease progression was assessed using Kaplan-Meier curves. Cox models were built to investigate the influence of smoking over 15 years of follow-up. All analyses were performed for the total cohort and stratified for sex and for positivity of anti-centromere (ACA) and anti-topoisomerase antibodies (ATA). RESULTS: Overall, 12 314 patients were included in the study. Of these, 10 393 were women (84%), 4637 were ACA-positive (38%), 3919 were ATA-positive (32%) and 4271 (35%) were ever-smokers. In men, but not in women, smoking was associated with mortality (HR 1.63, 95% CI 1.23 to 2.16, p=0.001). Ever-smoking women were at higher risk for skin progression (HR 1.10, 95% CI 1.00 to 1.22, p=0.046) and for 'any organ progression' (HR 1.07, 95% CI 1.00 to 1.13, p=0.036). In women, 34% of never-smokers were ATA-positive compared with 21% of ever-smokers (p<0.001). In the group of ever-smokers, higher exposure rates, reflected by the number of pack-years (OR 0.98, 95% CI 0.97 to 0.99, p<0.001) and by smoking duration (OR 0.96, 95% CI 0.95 to 0.97, p<0.001), were associated with lower frequency of ATA. In ACA-positive patients, the risk of mortality (HR 1.29, 95% CI 1.02 to 1.63, p=0.033), cardiac involvement (HR 1.25, 95% CI 1.03 to 1.43, p=0.001), skin progression (HR 1.21, 95% CI 1.03 to 1.42, p=0.018) and 'any organ progression' (HR 1.14, 95% CI 1.05 to 1.24, p=0.002) was increased among smokers. In ATA-positive smoking patients, mortality (HR 1.40, 95% CI 1.10 to 1.78, p=0.006), skin progression (HR 1.19, 95% CI 1.03 to 1.37, p=0.020) digital ulcers (HR 1.17, 95% CI 1.02 to 1.34, p=0.029) and 'any organ progression' (HR 1.11, 95% CI 1.00 to 1.22, p=0.048) occurred more frequently. CONCLUSIONS: Our stratified analysis demonstrates that smoking is associated with an increased risk for mortality in male SSc patients but not in women. Strikingly, smoking is associated with lower prevalence of ATA positivity, in particular in women. In both ATA-positive and ACA-positive patients, smoking is a risk factor for mortality, skin progression and 'any organ progression'.

Authors 19

1. Jacopo Ciaffi corresponding

   Istituto Ortopedico Rizzoli · University of Bologna

   Affiliation as printed

   Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum University of Bologna, Bologna, Italy

   Medicine and Rheumatology Unit, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy

2. Sophie I E Liem Aachen Department of Rheumatology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Rheumatology, Leiden University Medical Centre (LUMC), Leiden, The Netherlands

3. Suzanne C. Cannegieter Aachen Department of Clinical Epidemiology Department of Internal Medicine Division of Thrombosis and Haemostasis

   Leiden University Medical Center

   Affiliation as printed

   Department of Clinical Epidemiology, Leiden University Medical Center (LUMC), Leiden, The Netherlands

   Department of Internal Medicine, Division of Thrombosis and Haemostasis, Leiden University Medical Center (LUMC), Leiden, The Netherlands

4. Saad Ahmed Aachen Department of Rheumatology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Rheumatology, Leiden University Medical Centre (LUMC), Leiden, The Netherlands

5. Eva M. Hoekstra Aachen Department of Rheumatology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Rheumatology, Leiden University Medical Centre (LUMC), Leiden, The Netherlands

6. Piotr Wiland

   Wroclaw Medical University

   Affiliation as printed

   Department of Rheumatology and Internal Medicine, Wroclaw Medical University, Wroclaw, Poland

7. Tatsuya Atsumi

   Hokkaido University

   Affiliation as printed

   Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan

8. Gabriella Szűcs

   University of Debrecen

   Affiliation as printed

   Department of Rheumatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

9. Alexandra Balbir‐Gurman

   Technion – Israel Institute of Technology · Rambam Health Care Campus

   Affiliation as printed

   Rheumatology Department, Rambam Health Care Campus, Rappaport Faculty of Medicine, Technion, Haifa, Israel

10. László Czirják

    University of Pecs

    Affiliation as printed

    Department of Rheumatology and Immunology, Medical School, University of Pécs, Pécs, Hungary

11. Elisabetta Zanatta

    University of Padua · Azienda Ospedale - Università Padova

    Affiliation as printed

    Department of Medicine-DIMED, Unit of Rheumatology, Padova University Hospital, Padova, Italy

12. Ina Kötter

    Asklepios Klinik Altona

    Affiliation as printed

    Medical Department 4, Rheumatology, Immunology, Nephrology, Asklepios Klinik Altona, Hamburg, Germany

13. Jörg Henes

    University of Tübingen

    Affiliation as printed

    Internal Medicine II - Oncology, haematology, clinical immunology and rheumatology, University Hospital and Faculty of Medicine, University of Tübingen, Tubingen, Germany

14. Marco Matucci‐Cerinic

    Vita-Salute San Raffaele University · IRCCS Ospedale San Raffaele · Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele

    Affiliation as printed

    Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy

15. Paolo Airò

    Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

    Affiliation as printed

    Rheumatology and Clinical Immunology Service, Spedali Civili di Brescia, Brescia, Italy

16. Francesco Ursini

    Istituto Ortopedico Rizzoli · University of Bologna

    Affiliation as printed

    Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum University of Bologna, Bologna, Italy

    Medicine and Rheumatology Unit, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy

17. Tom W. J. Huizinga Aachen Department of Rheumatology, Leiden University Medical Center

    Leiden University Medical Center

    Affiliation as printed

    Department of Rheumatology, Leiden University Medical Centre (LUMC), Leiden, The Netherlands

18. Jeska Kirsten De Vries-Bouwstra Aachen Department of Rheumatology, Leiden University Medical Center

    Leiden University Medical Center

    Affiliation as printed

    Department of Rheumatology, Leiden University Medical Centre (LUMC), Leiden, The Netherlands

19. EUSTAR collaborators
    Affiliation as printed

    EUropean Scleroderma Trials And Research group, None, UK