Long-Term Lung Health After Exposure to Chlorine Gas

接触氯气后的长期肺部健康

• 批准号: 8663912
• 负责人: Erik Robert Svendsen
• 金额: $ 45.98万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8663912
• 关键词: Accidents; Acute; Acute Lung Injury; Age; Allergic; Body Weight; Bronchodilator Agents; Byssinosis; Chemicals; Chlorine; Chronic; Cohort Studies; Collaborations; Communities; Community Health; Data; Defect; Diffuse; Disasters; Dose; Double-Blind Method; Dust; Enrollment; Environment; Event; Exhalation; Exposure to; Fibrosis; Gases; Goals; Gossypium; Health; Industry; Inflammation; Inflammatory; Irritants; Link; Longitudinal Studies; Lung; Lung Inflammation; Lung diseases; Measures; Medical Surveillance; Modeling; Monitor; Natural experiment; Nitric Oxide; Obesity; Occupational; Occupational Exposure; Oxidative Stress; Participant; Persons; Population; Post-Traumatic Stress Disorders; Public Health; Pulmonary Function Test/Forced Expiratory Volume 1; Pulmonary function tests; Questionnaires; Race; Recording of previous events; Research; Research Design; Research Personnel; Respiratory physiology; Sampling; Science; Series; Services; Smell Perception; Smoking; South Carolina; Spirometry; Stress; Testing; Time; Training; Transportation; Work; airway inflammation; atopy; chlorination; chlorine gas; cigarette smoking; cohort; design; experience; follow-up; functional decline; innovation; prospective; public health relevance; public health research; respiratory; response; screening; sex; weapons of mass destruction

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.

描述（由申请人提供）：氯气是一种潜在的大规模杀伤性武器，也是最常用的化学品之一[1-5]。加氯事故很常见，每年有数千人集体暴露在其中[1,2,5-16]。释放氯气的大型事故可能会导致公共卫生灾难 [6, 17]。对肺部的急性健康影响已有充分记录[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型系统性长期纵向队列研究。新科学为潜在的长期健康影响提供了证据[24]，并呼吁对刺激性气体暴露者进行至少 5 年的长期纵向研究[27]。 2005 年 1 月 6 日，南卡罗来纳州格兰尼特维尔棉纺厂镇发生火车脱轨事故，随后发生 54,422 公斤氯气泄漏 [28-33]。数百人立即患病，数千人可能受到感染，其中包括工厂工人。从 1980 年到 2006 年，工厂工人的肺部健康状况受到了棉尘中毒的监测。我们有一个由 8,234 名工厂工人组成的队列，他们拥有至少 3 年的事件前肺活量测定数据。事故后返回工作岗位的工厂工人在 2005 年和 2006 年均出现肺功能丧失 (FEV1)，这是事故发生前几年观察到的比率的两倍。我们将使用嵌套在前瞻性纵向队列研究中的双盲中断时间序列设计，评估经过 3 年新肺功能测试的工厂工人样本的事件前/事件后肺功能下降的差异，并与自然实验中事件前 3 年的数据进行对比。假设是： (H1) 肺功能随着氯气暴露的增加而下降 (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、既往肺病和肥胖改变了氯气暴露与肺功能下降的关联 (H4) 肺功能下降加剧与纤维化（限制性肺缺陷）和气道炎症（阻塞性肺缺陷）增加有关。假设每年流失率为 5%，我们将招募 670 名工厂工人来研究 600 名工厂工人，其中包括来自 3 个经过验证的羽流模型暴露估计组（室外氯气峰值持续 30 分钟浓度为 0.5 ppm、2.8 ppm 和 28 ppm 氯气）的各 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 年测量肺功能、气道炎症、气道纤维化指标、特应性、创伤后应激障碍 (PTSD) 和气道反应性。这项研究意义重大，因为这是美国人口接触过氯气事件的最大规模的研究。我们的调查人员实力雄厚、能力强，在公共卫生筛查、验证羽流模型方面取得了成功，并拥有处理其他灾害的经验。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可获得的混杂数据，这项研究具有产生强大科学影响力的独特机会。