Biodesign Center for Environmental Health Engineering, Biodesign Institute, Building B, Arizona State University, 1001 S McAllister Ave, Tempe, AZ 85281-8101, USA; School for Engineering of Matter, Transport and Energy, Arizona State University, Tempe, AZ, USA.
Biodesign Center for Environmental Health Engineering, Biodesign Institute, Building B, Arizona State University, 1001 S McAllister Ave, Tempe, AZ 85281-8101, USA; School of Sustainable Engineering and the Built Environment, Arizona State University, Tempe, AZ, USA.
Sci Total Environ. 2022 Apr 15;817:152504. doi: 10.1016/j.scitotenv.2021.152504. Epub 2021 Dec 28.
The etiology of sporadic amyotrophic lateral sclerosis (ALS) is still unclear. We evaluate environmental factors suspected to be associated with ALS for their potential linkage to disease causality and to model geographic distributions of susceptible populations and expected cases worldwide. A PRISMA systematic literature review was performed 2021. Bradford Hill criteria were used to identify and rank environmental factors and a secondary review of ALS diagnoses in population studies and ALS case or cohort studies was conducted. Prevalence rate projection informed estimates of impacted regions and populations. Among 1710 papers identified, 258 met the inclusion criteria, of which 173 responded to at least one of nine Bradford Hill criteria among 83 literature-identified ALS environmental factors. Environmental determinants of ALS in order of decreasing significance were β-N-methylamino-L-alanine (BMAA), formaldehyde, selenium, and heavy metals including manganese, mercury, zinc, and copper. Murine animal models were the most common methodology for exploring environmental factors. Another line of investigation of 62 population exposure studies implicated the same group of environmental agents (mean odds ratios): BMAA (2.32), formaldehyde (1.54), heavy metals (2.99), manganese (3.85), mercury (2.74), and zinc (2.78). An age-adjusted incidence model estimated current total ALS cases globally at ~85,000 people compared to only ~1600 cases projected from the reported ALS incidence in the literature. Modeling with the prevalence microscope equation forecasted an increase in U.S. ALS cases from 16,707 confirmed in 2015 to ~22,650 projected for 2040. Two orthogonal methods employed implicate BMAA, formaldehyde, manganese, mercury, and zinc as environmental factors with strong ALS associations. ALS cases likely are significantly underreported globally, and high vulnerability exists in regions with large aging populations. Recent studies on other diseases with environmental determinants suggest the need to consider additional potential triggers and mechanisms, including exposures to microbial agents and epigenetic modifications.
散发性肌萎缩侧索硬化症（ALS）的病因仍不清楚。我们评估了疑似与 ALS 相关的环境因素，以确定其与疾病因果关系的潜在联系，并建立全球易感人群和预期病例的地理分布模型。2021 年进行了 PRISMA 系统文献回顾。使用布拉德福德·希尔标准来识别和排名环境因素，并对人群研究中的 ALS 诊断和 ALS 病例或队列研究进行了二次审查。患病率预测告知了受影响地区和人群的估计。在确定的 1710 篇论文中，有 258 篇符合纳入标准，其中 173 篇对 83 篇文献中确定的 ALS 环境因素中的 9 个布拉德福德·希尔标准中的至少一个做出了回应。ALS 按重要性降低的顺序排列的环境决定因素为β-N-甲基氨基-L-丙氨酸（BMAA）、甲醛、硒和重金属，包括锰、汞、锌和铜。探索环境因素的最常见方法是用鼠类动物模型。另一项对 62 项人群暴露研究的调查表明，同样一组环境因素（平均比值比）有问题：BMAA（2.32）、甲醛（1.54）、重金属（2.99）、锰（3.85）、汞（2.74）和锌（2.78）。年龄调整发病率模型估计目前全球 ALS 病例数约为 85000 人，而文献中报告的 ALS 发病率仅预测有 1600 例。用患病率显微镜方程建模预测，美国 ALS 病例数将从 2015 年的 16707 例确诊病例增加到 2040 年的 22650 例预计病例。两种正交方法表明，BMAA、甲醛、锰、汞和锌是与 ALS 密切相关的环境因素。全球范围内 ALS 病例的报告可能明显不足，且在老龄化人口较多的地区存在高脆弱性。最近对其他具有环境决定因素的疾病的研究表明，需要考虑其他潜在的触发因素和机制，包括接触微生物剂和表观遗传修饰。
