Commentary: Mapping the Human Exposome: Without It, How Can We Find Environmental Risk Factors for ALS?
Commentary: Mapping the Human Exposome: Without It, How Can We Find Environmental Risk Factors for ALS?
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评论：绘制人体暴露组图：没有它，我们如何找到 ALS 的环境风险因素？
DOI：
10.1097/ede.0000000000000381
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Al-Chalabi A
中科院分区：
文献类型：
--
作者：
Al-Chalabi A
Al-Chalabi 和 Pearce 流行病学• 第 26 卷，第 6 期，2015822 年 11 月|万维网。流行病。 com© 2015 Wolters Kluwer Health, Inc. 保留所有权利。运动会导致细胞死亡。一项针对意大利职业足球运动员的研究显然支持运动会增加风险这一观点，其中根据使用年龄调整后的发病率估计受影响的预期人数，据报道，患 ALS 的风险增加了 6 倍。 10 然而，基于终生风险的分析表明，运动可能不会增加风险。 3 如果运动是 aLS 的一个危险因素，则意味着通过军事训练或部署进行的体力活动可能是神经变性的一个原因，但使某人倾向于运动能力的遗传或发育因素也可能是潜在的危险因素，并且对于这种关联还有其他可能的解释，包括头部创伤的可能作用。 11, 12 部署会增加暴露于爆炸弹药、被毁建筑物、车辆和景观中的毒素的机会。铅中毒可引起运动神经病，而杀虫剂等其他毒素也被认为发挥了作用。身体创伤已被视为一个危险因素，但在兵役工作中并没有表明 aLS 在身体受伤的人中更常见。此外，由于很难找到合适的比较组，因此对兵役的研究是出了名的困难。特别是，在特定冲突中部署或未部署的军人之间以及军事人员与普通民众之间可能存在重大“基线”差异。这里报道的研究表明，二战期间服兵役是肌萎缩侧索硬化症的一个危险因素。正如作者指出的那样，在其他战争中服兵役也可能是一个风险因素，但如果影响很小，则需要对大量数据进行研究，而且任何增加的风险可能要到老年，即兵役结束几十年后才会显现出来。对于第二次世界大战来说是这样，但对于最近的其他冲突则不然。因此，服兵役一般来说可能是一个风险因素。例如，在一些研究中，在第二次海湾战争中的部署被认为是 ALS 的一个强烈风险因素。 13 服兵役与 ALS 风险相关这一发现凸显了这种晚发、患病率相对较低的疾病的流行病学研究中的许多问题。该关联可以表明锻炼是一个风险因素，或者是高运动技能的倾向，或者睾酮激素的高发育水平，或者与服兵役有关的因素，或者暴露于因部署而产生的因素。换句话说，虽然这一发现很有趣，但如果没有进一步的信息，就很难将其置于上下文中。我们需要其他环境风险因素或强大的基因与环境相互作用来指导对这种关联的解释。与军事研究相比，对一般劳动力的研究有许多优点，特别是因为比较不同工人群体时的混杂程度非常低。 14 接触电击是 ALS 的一个有吸引力的候选危险因素，因为在非常简单的层面上，神经是通过电流工作的，可以想象，过多的电流可能会损坏神经。问题是，虽然众所周知，强烈的电击会损害神经系统，但它们对所有方式都会造成损害，而且造成的任何运动障碍都是固定的，而不是渐进的。 15 相比之下，aLS 主要局限于运动神经元，并且是进行性的，而不是静态的残疾。作者表明，在……中，肌萎缩性脊髓侧索硬化症（ALS）风险的增加是不精确测量的。
Al-Chalabi and Pearce Epidemiology• Volume 26, Number 6, November 2015822| www. epidem. com© 2015 Wolters Kluwer Health, Inc. All rights reserved. exercise results in cell death. evidence apparently supporting the idea that exercise increases risk comes from a study of Italian professional footballers in which a 6-fold increase in risk of aLS was reported, based on estimating the expected number affected using age-adjusted incidence. 10 However, analysis based on lifetime risk suggests that there may be no increase in risk associated with exercise. 3 If sport is a risk factor for aLS, the implication is that physical activity, through military training or deployment, might be a cause of neurodegeneration, but it is also possible that genetic or developmental factors predisposing someone to athletic ability might be the underlying risk factor, and there are other possible explanations for such associations including a possible role of head trauma. 11, 12 Deployment increases exposure to toxins from exploded munitions, destroyed buildings, vehicles, and landscape. Lead poisoning can cause a motor neuropathy, and other toxins such as pesticides have been proposed to play a role. Physical trauma has been explored as a risk factor, but there is no suggestion in the work on military service that aLS was more frequent in those with physical injuries. Furthermore, studies of military service are notoriously difficult because of the difficulties of finding an appropriate comparison group; in particular, there may be major “baseline” differences between members of the military who are deployed or who are not deployed in a particular conflict, as well as differences between military personnel and the general population. the study reported here suggests that military service in World War II is a risk factor for aLS. as the authors point out, military service in other wars may also be a risk factor, but if the effect is small, large numbers need to be studied, and any increased risk may not manifest itself until older ages, ie, several decades after military service has ended. this is true for WWII but not for other more recent conflicts. It may therefore be that military service in general is a risk factor. For example, deployment in the second Gulf War has been considered a strong risk factor for aLS in some studies. 13 the finding that military service is associated with aLS risk highlights many of the problems in epidemiologic research in a late onset, relatively low-prevalence disease. the association could indicate that exercise is a risk factor, or predisposition to high athletic skill, or high developmental levels of testosterone, or something related to military service, or exposure to a factor resulting from deployment. In other words, while the finding is intriguing, it cannot easily be put in context without further information. We need other environmental risk factors or a robust gene–environment interaction that can guide interpretation of the association. In contrast to studies of the military, studies of the general workforce have many advantages, particularly because of the very low levels of confounding when different groups of workers are compared. 14 exposure to electric shock is an appealing candidate risk factor for aLS because on a very simplistic level, nerves work by electricity, and too much electricity could conceivably be likely to damage them. the problem is that while large electric shocks are known to damage the nervous system, they do so to all modalities, and any motor impairment caused is fixed rather than progressive. 15 In contrast, aLS is confined largely to motor neurons, and is progressive, not a static disability. the authors show an imprecisely measured increase in risk of aLS in …
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