High plasma concentrations of organic pollutants negatively impact survival in amyotrophic lateral sclerosis
High plasma concentrations of organic pollutants negatively impact survival in amyotrophic lateral sclerosis
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DOI：
10.1136/jnnp-2018-319785
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发表时间：
2019-08-01
影响因子：
11
通讯作者：
Feldman, Eva L.
中科院分区：
文献类型：
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作者：
Goutman, Stephen A.;Boss, Jonathan;Feldman, Eva L.
目的探讨持久性有机污染物（POP）是否会影响肌萎缩侧索硬化症（ALS）患者的生存。方法在密歇根大学（Ann Arbor， MI， USA）看到的ALS参与者提供血浆样本用于测量持久性有机污染物。前瞻性地从病历中收集ALS的疾病和临床特征。生存模型使用多种持久性有机污染物暴露的综合综合测量（环境风险评分或ERS）。结果167名ALS患者（40.7%为女性，n=68）被纳入研究，其中119人在研究期间死亡。中位诊断年龄为60.9岁（IQR 52.7 ~ 68.2），从症状出现到诊断的中位时间为1.01年（IQR 0.67 ~ 1.67），球部发病28.7%，颈椎发病33.5%，腰椎发病37.7%。经诊断时年龄、性别和其他协变量调整后，ERS最高四分位数（代表最高复合暴露）的参与者的死亡率危险率是最低四分位数的2.07倍（p=0.018, 95% CI 1.13至3.80）。对ERS贡献最大的污染物是多溴联苯醚154 (HR 1.53, 95% CI 0.90至2.61)，多氯联苯（PCB） 118 (HR 1.50, 95% CI 0.95至2.39),PCB 138 (HR 1.69, 95% CI 0.99至2.90),PCB 151 (HR 1.46, 95% CI 1.01至2.10),PCB 175 （HR 1.53, 95% CI 0.98至2.40）和p，p '-DDE （HR 1.39, 95% CI 1.07至1.81）。结论血浆中持久性有机污染物浓度升高与ALS患者生存期降低相关，且与年龄、性别、发病期等相关变量无关。这项研究有助于描述和量化持久性有机污染物对ALS的综合影响，并支持环境暴露在疾病发病机制中发挥作用的概念。
Objective To determine whether persistent organic pollutants (POP) affect amyotrophic lateral sclerosis (ALS) survival. Methods ALS participants seen at the University of Michigan (Ann Arbor, MI, USA) provided plasma samples for measurement of POPs. ALS disease and clinical features were collected prospectively from the medical records. Survival models used a composite summary measure of exposure due to multiple POPs (environmental risk score or ERS). Results 167 participants (40.7% female, n=68) with ALS were recruited, of which 119 died during the study period. Median diagnostic age was 60.9 years (IQR 52.7-68.2), median time from symptom onset to diagnosis was 1.01 years (IQR 0.67-1.67), bulbar onset 28.7%, cervical onset 33.5% and lumbar onset 37.7%. Participants in the highest quartile of ERS (representing highest composite exposure), adjusting for age at diagnosis, sex and other covariates had a 2.07 times greater hazards rate of mortality (p=0.018, 95% CI 1.13 to 3.80) compared with those in the lowest quartile. Pollutants with the largest contribution to the ERS were polybrominated diphenyl ethers 154 (HR 1.53, 95% CI 0.90 to 2.61), polychlorinated biphenyls (PCB) 118 (HR 1.50, 95% CI 0.95 to 2.39), PCB 138 (HR 1.69, 95% CI 0.99 to 2.90), PCB 151 (HR 1.46, 95% CI 1.01 to 2.10), PCB 175 (HR 1.53, 95% CI 0.98 to 2.40) and p,p '-DDE (HR 1.39, 95% CI 1.07 to 1.81). Conclusions Higher concentrations of POPs in plasma are associated with reduced ALS survival, independent of age, gender, segment of onset and other covariates. This study helps characterise and quantify the combined effects of POPs on ALS and supports the concept that environmental exposures play a role in disease pathogenesis.