Association of Environmental Toxins With Amyotrophic Lateral Sclerosis
Association of Environmental Toxins With Amyotrophic Lateral Sclerosis
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DOI：
10.1001/jamaneurol.2016.0594
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发表时间：
2016-07-01
期刊：
影响因子：
29
通讯作者：
Feldman, Eva L.
中科院分区：
文献类型：
--
作者：
Su, Feng-Chiao;Goutman, Stephen A.;Feldman, Eva L.
目的评估职业暴露和环境毒素与密歇根州肌萎缩侧索硬化症(ALS)发病几率的关系。设计、设置和参与者2011年至2014年在ALS三级转诊中心进行的病例对照研究。病例被诊断为确诊的、可能的、可能有实验室支持的患者，或者根据修订的El Ecorial标准可能患有ALS；如果他们被诊断为ALS或其他神经退行性疾病，或者如果他们有一级或二级血亲的ALS家族史，则排除在外。参与者完成了一项评估职业和住宅暴露的调查。用气相色谱-质谱法测定了122种持久性环境污染物的血药浓度，包括有机氯农药(OCPs)、多氯联苯(PCbs)和溴化阻燃剂(BFR)。用Logistic回归模型分别对不同暴露时间窗内的自报职业暴露和环境毒物血药浓度进行多因素回归分析。使用非参数Kendall t相关系数评估调查数据与污染物测量之间的一致性。MAIN结果和测量职业性和居民性环境毒素暴露，以及122种持久性环境污染物的血液浓度，包括有机氯农药、多氯联苯和BFRR。结果参与调查的156例患者(平均年龄60.5[11.1]岁；61.5%男性)和128例对照组(平均60.4[9.4]岁；男性57.8%)；其中101例患者和110名对照组有完整的人口统计学和污染物数据。调查数据显示，在累积暴露窗口中报告的农药暴露与ALS显著相关(优势比[OR]=5.09；95%CI，1.85-13.99；P=0.002)。在两个时间窗口中，军龄与肌萎缩侧索硬化症的发生有关(整个职业史中有暴露者：OR=2.31；95%CI，1.02~5.25；P=.046；10~30年前暴露者：OR=2.18；95%CI，1.01~4.73；P=.049)。血液中测得的持久性环境污染物的多变量模型显示，2种有机氯农药(五氯苯：OR=2.21；95%CI，1.06-4.60；P=0.04；顺式氯丹：OR=5.74；95%CI，1.80-18.20；P=0.005)、2种多氯联苯(PCB175：OR=1.81；95%CI，1.20-2.72；P=0.005；以及PCB202：OR=2.11；95%CI，1.36-3.27；1 BFR(多溴二苯醚47：OR=2.69；95%CI，1.49-4.85；P=.001)。调查数据与血液中持久性环境污染物的测量值之间有较好的一致性；显著的Kendall t相关系数从-0.18(杀菌剂和“使用杀虫剂处理家居或庭院”)到0.24(反式壬草胺和“车库存放草坪护理产品”)。结论和相关性在本研究中，血液中的持久性环境污染物与肌萎缩侧索硬化症显著相关，可能是可改变的肌萎缩侧索硬化症的危险因素。
IMPORTANCE Persistent environmental pollutants may represent a modifiable risk factor involved in the gene-time-environment hypothesis in amyotrophic lateral sclerosis (ALS).OBJECTIVE To evaluate the association of occupational exposures and environmental toxins on the odds of developing ALS in Michigan.DESIGN, SETTING, AND PARTICIPANTS Case-control study conducted between 2011 and 2014 at a tertiary referral center for ALS. Cases were patients diagnosed as having definitive, probable, probable with laboratory support, or possible ALS by revised El Escorial criteria; controls were excluded if they were diagnosed as having ALS or another neurodegenerative condition or if they had a family history of ALS in a first-or second-degree blood relative. Participants completed a survey assessing occupational and residential exposures. Blood concentrations of 122 persistent environmental pollutants, including organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and brominated flame retardants (BFRs), were measured using gas chromatography-mass spectrometry. Multivariable models with self-reported occupational exposures in various exposure time windows and environmental toxin blood concentrations were separately fit by logistic regression models. Concordance between the survey data and pollutant measurements was assessed using the nonparametric Kendall t correlation coefficient.MAIN OUTCOMES AND MEASURES Occupational and residential exposures to environmental toxins, and blood concentrations of 122 persistent environmental pollutants, including OCPs, PCBs, and BFRs.RESULTS Participants included 156 cases (mean [SD] age, 60.5 [11.1] years; 61.5% male) and 128 controls (mean [SD] age, 60.4 [9.4] years; 57.8% male); among them, 101 cases and 110 controls had complete demographic and pollutant data. Survey data revealed that reported pesticide exposure in the cumulative exposure windows was significantly associated with ALS (odds ratio [OR] = 5.09; 95% CI, 1.85-13.99; P =.002). Military service was also associated with ALS in 2 time windows (exposure ever happened in entire occupational history: OR = 2.31; 95% CI, 1.02-5.25; P =.046; exposure ever happened 10-30 years ago: OR = 2.18; 95% CI, 1.01-4.73; P =.049). A multivariable model of measured persistent environmental pollutants in the blood, representing cumulative occupational and residential exposure, showed increased odds of ALS for 2 OCPs (pentachlorobenzene: OR = 2.21; 95% CI, 1.06-4.60; P =.04; and cis-chlordane: OR = 5.74; 95% CI, 1.80-18.20; P =.005), 2 PCBs (PCB 175: OR = 1.81; 95% CI, 1.20-2.72; P =.005; and PCB 202: OR = 2.11; 95% CI, 1.36-3.27; P =.001), and 1 BFR (polybrominated diphenyl ether 47: OR = 2.69; 95% CI, 1.49-4.85; P =.001). There was modest concordance between survey data and the measurements of persistent environmental pollutants in blood; significant Kendall t correlation coefficients ranged from -0.18 (Dacthal and " use pesticides to treat home or yard") to 0.24 (trans-nonachlor and " store lawn care products in garage").CONCLUSIONS AND RELEVANCE In this study, persistent environmental pollutants measured in blood were significantly associated with ALS and may represent modifiable ALS disease risk factors.