Treatment response of WTC related airway injury

WTC相关气道损伤的治疗反应

• 批准号: 9982719
• 负责人: Michael D. Weiden
• 金额: $ 79.5万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9982719
• 关键词: Treatment; response; WTC; related; airway

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. ! !

项目摘要 世界贸易中心（WTC）灾难现场的救援/恢复工作导致Fire的肺功能下降 纽约市消防局（FDNY）消防员。超过15年的暴露后随访，1/8的WTC- 暴露的消防员经历了加速的FEV 1下降，FEV 1损失>64 ml/年。FEV 1加速下降 与慢性阻塞性肺疾病（COPD）和哮喘有关。尽管负担沉重， 呼吸系统疾病，吸入性皮质类固醇（ICS）联合 长效β受体激动剂（LABA）治疗唯一定义特征为FEV 1加速的患者 下降只有35%的FEV 1加速下降的WTC暴露FDNY消防员接受了 ICS/LABA。如果FEV 1快速下降人群中FEV 1快速下降的速率没有降低， 随着FEV 1的加速下降，可能会发展为COPD，这是美国第四大死亡原因。 确定ICS/LABA治疗是否能有效减缓这些患者的FEV 1下降， 这不仅对WTC暴露队列，而且对其他工作场所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相关， 生活质量这一观察结果与适应症选择偏倚一致，即病情较重的个体是 被治疗的人。为了减轻这种偏倚的影响，我们使用接受治疗的患者作为自己的对照， 检查ICS/LABA治疗开始前后的FEV 1轨迹。开始ICS/LABA治疗后，FEV 1 轨迹改善9.9±1.1 ml/年（平均值±SEM）。该基金将探索ICS/LABA的异质性 反应目前的多中心合作旨在估计有多少未经治疗的加速 下降组具有预测显著ICS/LABA益处的预处理表型。该提案测试 ICS/LABA治疗改善FEV 1加速下降患者的FEV 1轨迹的总体假设， 并且特定的患者特征，包括血嗜酸性粒细胞升高，将与 对ICS/LABA治疗有良好反应。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开始前后的FEV 1轨迹，并测试是否存在炎症反应。 生物标志物（特别是血液嗜酸性粒细胞）、肺生理学和人口统计学因素是 对治疗反应。具体目标2将根据适应症偏倚调整选择，以识别未治疗的个体 最有可能对治疗作出反应，使用来自接受治疗和未接受治疗的WTC暴露者的完整队列的数据， 救援和恢复人员。这些数据将有助于开发预测ICS/LABA的模型 未治疗个体的治疗反应。当模拟ICS/LABA对FEV 1轨迹的影响时， 未接受治疗的工人FEV 1加速下降，我们将确定那些受益的可能性高的人 从ICS/LABA药物，NIOSH WTC健康计划的中心目标“研究护理” 平移模型 ! !

项目成果

Factors Predicting Treatment of World Trade Center-Related Lung Injury: A Longitudinal Cohort Study.

• DOI: 10.3390/ijerph17239056
• 发表时间: 2020-12-04
• 期刊: International journal of environmental research and public health
• 作者: Putman B;Lahousse L;Goldfarb DG;Zeig-Owens R;Schwartz T;Singh A;Vaeth B;Hall CB;Lancet EA;Webber MP;Cohen HW;Prezant DJ;Weiden MD
• 通讯作者: Weiden MD

Lung function decline before and after treatment of World Trade Center associated obstructive airways disease with inhaled corticosteroids and long-acting beta agonists.

• DOI: 10.1002/ajim.23272
• 发表时间: 2021-10
• 期刊: AMERICAN JOURNAL OF INDUSTRIAL MEDICINE
• 影响因子: 3.5
• 作者: Goldfarb, David G.;Putman, Barbara;Lahousse, Lies;Zeig-Owens, Rachel;Vaeth, Brandon M.;Schwartz, Theresa;Hall, Charles B.;Prezant, David J.;Weiden, Michael D.
• 通讯作者: Weiden, Michael D.

Low serum IgA and airway injury in World Trade Center-exposed firefighters: a 17-year longitudinal study.

暴露于世贸中心的消防员的低血清 IgA 和气道损伤：一项为期 17 年的纵向研究。

• DOI: 10.1136/thoraxjnl-2019-213715
• 发表时间: 2019
• 期刊: Thorax
• 影响因子: 10
• 作者: Putman,Barbara;Lahousse,Lies;Zeig-Owens,Rachel;Singh,Ankura;Hall,CharlesB;Liu,Yang;Schwartz,Theresa;Goldfarb,David;Webber,MayrisP;Prezant,DavidJ;Weiden,MichaelD
• 通讯作者: Weiden,MichaelD