Objectives Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease, subtyped according to clinical manifestations and autoantibodies. Evidence concerning cigarette smoking and SLE risk has been conflicting. We investigated smoking and SLE risk, overall and by anti-double stranded DNA (dsDNA) presence, in two prospective cohort studies.
Methods The Nurses’ Health Study (NHS) enrolled 121 701 US female nurses in 1976; Nurses’ Health Study II (NHSII) enrolled 116 430 in 1989. Lifestyle, environmental and medical data were collected through biennial questionnaires. Incident SLE was confirmed by medical record review. Cox regression models estimated HRs of SLE, overall and by dsDNA subtype, in association with time-varying smoking status and cumulative smoking pack-years through the 2-year cycle prior to diagnosis, controlling for potential confounders.
Results Among 286 SLE cases identified (159 in NHS (1978–2012) and 127 in NHSII (1991–2013)), mean age was 49.2 (10.3) years and 42% were dsDNA+ at SLE diagnosis. At baseline, 45% of women had ever smoked, 51% of whom currently smoked. Compared with never smokers, current smokers had increased dsDNA+ SLE risk (HR 1.86 (1.14–3.04)), whereas past smokers did not (HR 1.31 (0.85–2.00)). Women who smoked >10 pack-years (vs never) had an elevated dsDNA+ SLE risk (HR 1.60(95% CI 1.04 to 2.45)) compared with never smokers. No associations were observed between smoking status or pack-years and overall SLE or dsDNA− SLE.
Conclusion Strong and specific associations of current smoking and >10 pack-years of smoking with dsDNA+ SLE were observed. This novel finding suggests smoking is involved in dsDNA+ SLE pathogenesis.
- systemic lupus erythematosus
- health services research
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Handling editor Tore K Kvien
Contributors MB and KHC designed the study, analysed the data and wrote the first draft. SM and BL contributed to the data analysis. MB, SKT, SM, DK, JAS, EWK and KHC were involved in data collection. All authors were involved in drafting the article and revising it critically for important intellectual content, and all authors approved the final version to be published. MB and KHC had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Funding Research reported in this publication was supported by the National Institutes of Health (NIH) grants AR049880, AR047782, AR066109, AR066953, AR070514, AR069688, CA186107, CA176726, CA49449 and CA67262. MB and JAS are both supported by the Rheumatology Research Foundation Scientist Development Awards. SKT is supported by the Lupus Foundation of America Career Development Award. The funders had no role in study design, data collection, analysis, decision to publish or preparation of the manuscript. The content is solely the responsibility of the authors and does not necessarily represent the views of the National Institutes of Health.
Competing interests None declared.
Ethics approval Partners HealthCare Institutional Review Board.
Provenance and peer review Not commissioned; externally peer reviewed.
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