Centre for Primary Care and Public Health, Blizard Institute, Queen Mary University of London, London, UK.
School of Public Health, Imperial College London, London, UK.
Int J Epidemiol. 2019 Jun 1;48(3):912-925. doi: 10.1093/ije/dyy230.
The aim of this paper is to investigate the causality of the inverse association between cigarette smoking and Parkinson's disease (PD). The main suggested alternatives include a delaying effect of smoking, reverse causality or an unmeasured confounding related to a low-risk-taking personality trait.
A total of 715 incident PD cases were ascertained in a cohort of 220 494 individuals from NeuroEPIC4PD, a prospective European population-based cohort study including 13 centres in eight countries. Smoking habits were recorded at recruitment. We analysed smoking status, duration, and intensity and exposure to passive smoking in relation to PD onset.
Former smokers had a 20% decreased risk and current smokers a halved risk of developing PD compared with never smokers. Strong dose-response relationships with smoking intensity and duration were found. Hazard ratios (HRs) for smoking <20 years were 0.84 [95% confidence interval (CI) 0.67-1.07], 20-29 years 0.73 (95% CI 0.56-0.96) and >30 years 0.54 (95% CI 0.43-0.36) compared with never smokers. The proportional hazard assumption was verified, showing no change of risk over time, arguing against a delaying effect. Reverse causality was disproved by the consistency of dose-response relationships among former and current smokers. The inverse association between passive smoking and PD, HR 0.70 (95% CI 0.49-0.99) ruled out the effect of unmeasured confounding.
These results are highly suggestive of a true causal link between smoking and PD, although it is not clear which is the chemical compound in cigarette smoking responsible for the biological effect.
本文旨在探讨吸烟与帕金森病（PD）之间负相关的因果关系。主要的替代解释包括吸烟的延迟效应、反向因果关系或与低风险行为特征相关的未测量混杂因素。
在一项包括 8 个国家 13 个中心的前瞻性欧洲人群队列研究——NeuroEPIC4PD 中，共确定了 715 例新发 PD 病例，该队列包含 220494 名个体。在招募时记录了吸烟习惯。我们分析了吸烟状况、持续时间和强度以及被动吸烟暴露与 PD 发病的关系。
与从不吸烟者相比，既往吸烟者 PD 的发病风险降低 20%，当前吸烟者的发病风险降低一半。吸烟强度和持续时间与 PD 发病风险呈强剂量反应关系。与从不吸烟者相比，吸烟<20 年的 HR 为 0.84（95%CI 0.67-1.07），20-29 年为 0.73（95%CI 0.56-0.96），>30 年为 0.54（95%CI 0.43-0.36）。比例风险假设得到验证，表明风险随时间没有变化，排除了延迟效应。既往和当前吸烟者之间剂量反应关系的一致性证明了反向因果关系的不成立。被动吸烟与 PD 之间的反比关系（HR 0.70，95%CI 0.49-0.99）排除了未测量混杂因素的影响。
这些结果高度提示吸烟与 PD 之间存在真正的因果关系，尽管尚不清楚香烟烟雾中的哪种化学物质导致了这种生物学效应。
