OBJECTIVE Inflamed airways are hypothesized to contribute to rheumatoid arthritis (RA) pathogenesis due to RA-related autoantibody production, and smoking is the strongest environmental RA risk factor. However, the role of chronic airway diseases in RA development is unclear. We undertook this study to investigate whether asthma and chronic obstructive pulmonary disease (COPD) were each associated with RA. METHODS We performed a prospective cohort study of 205,153 women in the Nurses' Health Study (NHS, 1988-2014) and NHSII (1991-2015). Exposures were self-reported physician-diagnosed asthma or COPD confirmed by validated supplemental questionnaires. The primary outcome was incident RA confirmed by medical record review by 2 rheumatologists. Covariates (including smoking pack-years/status) were assessed via biennial questionnaires. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for RA were estimated using Cox regression. RESULTS We identified 15,148 women with confirmed asthma, 3,573 women with confirmed COPD, and 1,060 incident RA cases during 4,384,471 person-years (median 24.0 years/participant) of follow-up in the NHS and NHSII. Asthma was associated with increased RA risk (HR 1.53 [95% CI 1.24-1.88]) compared to no asthma/COPD after adjustment for covariates, including smoking pack-years/status. Asthma remained associated with increased RA risk when analyzing only never-smokers (HR 1.53 [95% CI 1.14-2.05]). COPD was also associated with increased RA risk (HR 1.89 [95% CI 1.31-2.75]). The association of COPD with RA was most pronounced in the subgroup of ever-smokers age >55 years (HR 2.20 [95% CI 1.38-3.51]). CONCLUSION Asthma and COPD were each associated with increased risk of incident RA, independent of smoking status/intensity and other potential confounders. These results provide support for the hypothesis that chronic airway inflammation may be crucial in RA pathogenesis.

中文翻译：

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女性哮喘、慢性阻塞性肺疾病以及随后发生类风湿性关节炎的风险：一项前瞻性队列研究。


目的 由于 RA 相关自身抗体的产生，推测气道炎症会导致类风湿性关节炎 (RA) 发病，而吸烟是 RA 最强的环境危险因素。然而，慢性气道疾病在 RA 发展中的作用尚不清楚。我们进行这项研究是为了调查哮喘和慢性阻塞性肺疾病 (COPD) 是否都与 RA 相关。方法 我们对护士健康研究（NHS，1988-2014 年）和 NHSII（1991-2015 年）中的 205,153 名女性进行了前瞻性队列研究。暴露是自我报告的医生诊断的哮喘或慢性阻塞性肺病，并通过经过验证的补充调查问卷证实。主要结局是 2 名风湿病专家通过病历审查确认的 RA 事件。通过每两年一次的调查问卷评估协变量（包括吸烟年数/状态）。使用 Cox 回归估计 RA 的多变量风险比 (HR) 和 95% 置信区间 (CI)。结果 在 NHS 和 NHSII 的 4,384,471 人年（中位 24.0 年/参与者）随访期间，我们确定了 15,148 名确诊为哮喘的女性、3,573 名确诊为 COPD 的女性以及 1,060 例 RA 病例。调整协变量（包括吸烟年数/状态）后，与无哮喘/慢性阻塞性肺病相比，哮喘与 RA 风险增加相关（HR 1.53 [95% CI 1.24-1.88]）。仅分析从不吸烟者时，哮喘仍然与 RA 风险增加相关（HR 1.53 [95% CI 1.14-2.05]）。 COPD 还与 RA 风险增加相关（HR 1.89 [95% CI 1.31-2.75]）。 COPD 与 RA 的关联在年龄> 55 岁的曾经吸烟者亚组中最为明显（HR 2.20 [95% CI 1.38-3.51]）。 结论 哮喘和 COPD 均与 RA 发生风险增加相关，与吸烟状况/吸烟强度和其他潜在混杂因素无关。这些结果支持了慢性气道炎症可能在 RA 发病机制中至关重要的假设。