Treatment response of WTC related airway injury

项目摘要 世贸中心(WTC)灾难现场救援/恢复工作导致火灾中肺功能下降 纽约市消防局(FDNY)消防员。超过15年的暴露后随访，每8个WTC中就有一个- 暴露的消防员经历了FEV1加速下降，FEV1损失&毫升/年。FEV1加速下降 与慢性阻塞性肺疾病(COPD)和哮喘有关。尽管有很大的负担 呼吸系统疾病吸入皮质类固醇(ICS)联合应用尚无循证适应症 长效β-激动剂(LABA)治疗唯一特征是FEV1加速的患者 拒绝。只有35%的暴露于WTC的FDNY消防员FEV1加速下降，并接受了 ICS/LABA。如果在加速的FEV1下降人群中FEV1的快速丢失率不降低，患者 随着FEV1加速下降，COPD可能会成为美国第四大死因。 确定ICS/LABA治疗在钝化这些患者FEV1下降方面是否有效将具有重要意义 不仅对暴露于WTC的队列有影响，而且对其他工作场所的呼吸道疾病监测也有影响。 在初步分析中，我们发现ICS/LABA的使用与肺功能恶化和减少有关 生活质量。这一观察结果与通过指示偏倚进行选择是一致的，即病情较重的个体 那些接受治疗的人。为了减轻这种偏见的影响，我们将接受治疗的患者作为自己的对照， 检测ICS/LABA治疗前后FEV1的运动轨迹。ICS/LABA启动后，FEV1 眼球轨迹平均改善9.9±1.1毫升/年(平均±扫描电子显微镜)。这笔赠款将探索ICS/LABA的异质性 回应。目前的多中心合作旨在估计有多少未接受治疗的加速患者 下降组的治疗前表型预测有显著的ICS/LABA受益。这份提案测试了 ICS/LABA治疗改善加速FEV1下降患者FEV1轨迹的总体假设， 而特定的患者特征，包括血液中嗜酸性粒细胞的升高，将与 对ICS/LABA治疗反应良好。特定目标1将使用ICS/LABA治疗的患者作为自己的患者 对照组，评估ICS/LABA启动前后的FEV1轨迹，并测试是否存在炎症 生物标志物(特别是血嗜酸性粒细胞)、肺生理学和人口因素是预测 对治疗的反应。特定目标2将根据适应症偏向调整选择，以识别未治疗的个体 最有可能对治疗有反应，使用来自接受治疗和未接受治疗的WTC暴露的全部队列的数据 救援和恢复工作人员。这些数据将使开发预测ICS/LABA的模型成为可能 未经治疗的个体的治疗反应。在模拟ICS/LABA对FEV1弹道的影响时 FEV1加速下降的未经治疗的工人，我们将确定那些受益概率较高的人 来自ICS/LABA药物--NIOSH WTC健康计划“研究到护理”的中心目标 翻译模型。 好了！ 好了！

Project Summary Rescue/recovery work at the World Trade Center (WTC) disaster site caused a decline in lung function in Fire Department of the City of New York (FDNY) firefighters. Over 15 years of post-exposure follow-up, 1 in 8 WTC- exposed firefighters experienced accelerated FEV1 decline, a FEV1 loss >64 ml/year. Accelerated FEV1 decline is associated with chronic obstructive pulmonary disease (COPD) and asthma. Despite the high burden of respiratory diseases there are no evidence-based indications for inhaled corticosteroid (ICS) combined with long-acting beta-agonist (LABA) treatment in patients whose only defining characteristic is accelerated FEV1 decline. Only 35% of WTC-exposed FDNY firefighters with accelerated FEV1 decline have been treated with ICS/LABA. If the rapid rate of FEV1 loss in the accelerated FEV1 decline population is not reduced, patients with accelerated FEV1 decline will likely develop COPD, the fourth leading cause of death in the United States. Determining if ICS/LABA treatment is effective in blunting FEV1 decline in these patients would have important implications not only for WTC-exposed cohorts, but also for other workplace respiratory disease surveillance. In preliminary analyses, we found that ICS/ LABA use is associated with worse lung function and reduced quality of life. This observation is consistent with selection by indication bias, whereby sicker individuals are the ones who are treated. To mitigate the effects of this bias, we used treated patients as their own controls, examining FEV1 trajectory prior to and after initiation of ICS/LABA therapy. After ICS/LABA initiation, FEV1 trajectory improved by 9.9±1.1 ml/year (mean±SEM). This grant will explore heterogeneity in ICS/LABA response. The current multi-center collaboration aims to estimate how many in the untreated accelerated decline group have a pretreatment phenotype predictive of significant ICS/LABA benefit. This proposal tests the overall hypothesis that ICS/LABA treatment improves FEV1 trajectory in accelerated FEV1 decline patients, and that specific patient characteristics, including elevated blood eosinophils, will be associated with a favorable response to ICS/LABA treatment. Specific Aim 1 will use ICS/LABA-treated patients as their own controls, assessing FEV1 trajectory before and after ICS/LABA initiation, and testing whether inflammatory biomarkers (notably, blood eosinophils), pulmonary physiology and demographic factors are predictors of response to therapy. Specific Aim 2 will adjust for selection by indication bias to identify untreated individuals most likely to respond to treatment, using data from the full cohort of treated and untreated WTC-exposed rescue and recovery workers. These data will enable the development of models that predict ICS/LABA treatment response in untreated individuals. When modeling the effect of ICS/LABA on the FEV1 trajectory of the untreated workers with accelerated FEV1 decline, we will identify those with high probability of benefiting from ICS/LABA medications, a central goal of the NIOSH WTC Health Program's “Research to Care” translational model. ! !