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.

中文翻译：

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在护士健康研究队列中，吸烟与系统性红斑狼疮的总体风险和抗双链 DNA 抗体亚型的风险

目的 系统性红斑狼疮 (SLE) 是一种异质性自身免疫性疾病，根据临床表现和自身抗体进行亚型分类。关于吸烟和 SLE 风险的证据一直相互矛盾。我们在两项前瞻性队列研究中调查了吸烟和 SLE 风险的总体情况和抗双链 DNA (dsDNA) 的存在情况。方法护士健康研究（NHS）于1976年招募了121 701名美国女护士；护士健康研究 II (NHSII) 于 1989 年招募了 116 430 人。生活方式、环境和医疗数据是通过每两年一次的问卷调查收集的。病历审查证实了事件 SLE。Cox 回归模型估计 SLE 的 HR，整体和 dsDNA 亚型，与诊断前 2 年周期中随时间变化的吸烟状况和累积吸烟包年相关联，控制潜在的混杂因素。结果 在确定的 286 例 SLE 病例中（NHS 159 例（1978-2012 年）和 NHSII 127 例（1991-2013 年）），平均年龄为 49.2（10.3）岁，42% 在 SLE 诊断时为 dsDNA+。在基线时，45% 的女性曾经吸烟，其中 51% 目前吸烟。与从不吸烟者相比，当前吸烟者的 dsDNA+ SLE 风险增加 (HR 1.86 (1.14–3.04))，而既往吸烟者则没有 (HR 1.31 (0.85–2.00))。与从不吸烟者相比，吸烟超过 10 包年（与从不吸烟相比）的女性 dsDNA+ SLE 风险升高（HR 1.60（95% CI 1.04 至 2.45））。未观察到吸烟状况或包年与总体 SLE 或 dsDNA-SLE 之间存在关联。结论 观察到当前吸烟和超过 10 包年的吸烟与 dsDNA+ SLE 之间存在强烈且特定的关联。