Long-Term Lung Health After Exposure to Chlorine Gas

描述（由申请人提供）：氯气是一种潜在的大规模杀伤性武器，是最常用的化学品之一[1-5]。氯化事故很常见，每年使成千上万的人集体暴露[1,2,5 -16]。释放氯气的大型事故可能导致公共卫生灾难[6,17]。对肺部的急性健康影响有充分的文献记载[1,7,9,18 -22]，但尚未对暴露于单一高浓度氯气事件的人群进行大规模系统的长期纵向队列研究。新的科学已经提供了潜在的长期健康影响的证据，并呼吁对接触刺激性气体的人进行至少5年的长期纵向研究。2005年1月6日，南卡罗来纳州格兰尼特维尔镇的一列火车脱轨，随后发生54,422公斤氯气泄漏[28-33]。数百人立即生病，数千人可能受到感染，其中包括工厂工人。从1980年到2006年，对工人的肺部健康状况进行了监测。我们有一组8234名工厂工人，他们至少有3年的事件前肺活量测定数据。2005年和2006年，在事故发生后重返工作岗位的工人肺功能丧失（FEV1）是事故发生前几年的两倍。我们将采用前瞻性纵向队列研究中嵌套的双盲中断时间序列设计，对经过3年新肺功能测试的工厂工人样本与事件发生前3年的自然实验数据进行对比，评估事件发生前后肺功能下降的差异。假设是:（H1）肺功能下降随着氯气暴露的增加而增加（H2）气道反应性随着氯气暴露的增加而增加（H3）年龄、性别、种族、吸烟、创伤后应激障碍（PTSD）、特应性、肺刺激物暴露的职业史、既往肺部疾病、和肥胖改变了暴露于氯气与肺功能下降的关系（H4）肺功能下降的加剧与纤维化（限制性肺缺陷）和气道炎症（阻塞性肺缺陷）的增加有关。假设年损失率为5%，我们将招募670名工厂工人进行600项研究，其中包括来自3个经过验证的烟雾模型暴露估计组（室外持续30分钟的峰值浓度为0.5 ppm， 2.8 ppm和28 ppm氯气）的150名工厂工人和150名未暴露的工厂工人。我们将在事件发生后6-10年内测量肺功能、气道炎症、气道纤维化指标、特应性、PTSD和气道反应性。这项研究意义重大，因为它是有史以来暴露于氯气事件的最大的美国普通人口。我们的调查人员强大而有能力，已经成功地进行了公共卫生筛查，验证了羽流模型，并具有其他灾难的经验。由于创新和稳健的研究设计，个人暴露组双盲，每个参与者作为自己的对照，以及暴露前的混杂数据，本研究具有强大的科学影响力的独特机会。

DESCRIPTION (provided by applicant): Chlorine gas is a potential weapon of mass destruction and is one of the most commonly used chemicals [1-5]. Chlorination accidents are common, exposing thousands of people collectively each year [1, 2, 5-16]. A large accident releasing chlorine gas could result in a public health disaster [6, 17]. The acute health effects on the lungs are well documented [1, 7, 9, 18-22], but there has been no large systematic long-term longitudinal cohort study of a population exposed to a single high-concentration chlorine gas event. New science has provided evidence for potential long-term health effects [24], and called for long-term longitudinal study of irritant gas exposed persons for at least 5 years [27]. On January 6, 2005 a train derailment and subsequent 54,422 kg chlorine gas spill occurred in the cotton mill town of Graniteville, South Carolina [28-33]. Several hundred people became immediately sick and thousands were potentially exposed, including millworkers. Millworkers had their lung health monitored for byssinosis from 1980 to 2006. We have a cohort of 8,234 millworkers with at least 3 years of pre-event spirometry data. Millworkers who returned to work after the accident had lung function loss (FEV1) in both 2005 and 2006 that was twice the rate observed in the years immediately before the accident. We will assess differential pre/post-event lung function decline in a sample of millworkers with 3 years of new lung function tests contrasted with data from 3 years pre-event in a natural experiment, using a double-blinded interrupted time-series design nested within a prospective longitudinal cohort study. Hypothesis are: (H1) Lung function decline increases with increasing chlorine gas exposure (H2) Airway responsiveness increases with increasing chlorine gas exposure (H3) Age, sex, race, smoking, post traumatic stress disorder (PTSD), atopy, occupational history of lung-irritant exposures, pre-existing lung disease, and obesity modify the association of exposure to chlorine gas with lung function decline (H4) Increased lung function decline is associated with increased fibrosis (restrictive lung defects) and airway inflammation (obstructive lung defects). Assuming a 5 percent annual attrition, we will enroll 670 millworkers to study 600, including 150 millworkers from each of the 3 validated plume model exposure estimate groups (peak sustained 30-minute concentrations of 0.5 ppm, 2.8 ppm, and 28 ppm chlorine gas outdoors) and 150 unexposed millworkers. We will measure lung function, airway inflammation, indicators of airway fibrosis, atopy, PTSD, and airway responsiveness at 6-10 years post- event. This study is significant because it is the largest general US population ever exposed to a chlorine gas event. Our investigators are strong and capable, having succeeded with public health screening, validated plume modeling, and experience with other disasters. This study has the unique opportunity for strong scientific influence due to the innovative and robust study design, having personal exposure group double blinded, each participant serving as their own control, and confounder data available from before the exposure. PUBLIC HEALTH RELEVANCE: Chlorine gas is a potential weapon of mass destruction and is one of the most commonly used chemicals in industry [1-5]. In a natural experiment, using a double-blinded interrupted time-series design nested within a prospective longitudinal cohort study, we will assess differential pre/post-event lung function decline with 3 years of new post-event lung function test data contrasted with data from 3 years pre-event in a sample of 600 millworkers from our cohort of 8,234 with at least 3 years of pre-event data who were potentially exposed to chlorine gas from the January 6, 2005 chlorine gas accident in Graniteville, South Carolina. This study of the largest general US population ever exposed to a chlorine gas event has the unique opportunity for significant scientific influence due to the innovative and robust study design, having personal exposure group double blinded, each participant serving as their own control, and confounder data available from before the exposure.