Aerodigestive Disease in the World Trade Center Exposed FDNY Cohort: Validation of Biomarkers and Defining Risk to Tailor Therapy

世界贸易中心暴露的 FDNY 队列中的呼吸消化疾病：生物标志物的验证和定义定制治疗的风险

• 批准号: 10313876
• 负责人: Anna Nolan
• 金额: $ 48.67万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10313876
• 关键词: Aerodigestive; Disease; World; Trade; Center

SUMMARY The destruction of the World Trade Center (WTC) led to the exposure of thousands of first responders and inhabitants of New York City to WTC-particulate matter (WTC-PM). WTC-PM exposure in our Fire Department of New York (FDNY) cohort is associated with the development of obstructive airways disease (OAD), gastroesophageal reflux disease (GERD) and Barrett’s Esophagus (BE). GERD is a well-known risk factor of the metaplastic changes of BE, which can subsequently lead to adenocarcinoma. GERD is also associated with occupational or environmental exposure related OAD. Overall, WTC-exposed firefighters with OAD had a three times higher risk of developing GERD. At least 40% of WTC rescue and recovery workers have developed GERD symptoms, which is 8.2 times its pre-9/11 prevalence. It is in the context of these findings that we propose to study, Aerodigestive Disease in the World Trade Center Exposed FDNY Cohort: Validation of Biomarkers and Defining Risk to Tailor Therapy. This will further define and phenotype aerodigestive/gastrointestinal health biomarkers, as well as determine impact on lung health to improve care thereby fulfilling the mandate of the James Zadroga 9/11 Health & Compensation Act: PAR-20-280. GERD diminishes health-related quality of life and productivity. Complications of GERD can further extend beyond BE; extra-esophageal reflux can incite or exacerbate allergies, sinusitis, chronic bronchitis, and asthma. Management of reflux is challenging, as often refractory to therapy, diagnosis can be invasive and have significant associated costs. Patients with WTC-PM exposure associated asthma more often had persistent GERD. Furthermore, GERD increases the odds of developing WTC-AHR, independent of exposure intensity. Although many studies have suggested interdependence between airway and digestive diseases, the causative factors and specific mechanisms remain unclear. We have successfully identified metabolic, vascular and inflammatory biomarkers of WTC-airway hyperreactivity (WTC-AHR). We have also identified biomarkers of GERD/BE in our WTC exposed population with respiratory disease, facilitating the identification of biologically relevant immune pathways. We propose two AIMs to explore the HYPOTHESIS that serum biomarkers will differentiate FDNY rescue and recovery workers with aerodigestive morbidity who proceed to develop GERD/BE. Noninvasive biomarkers will identify subjects that may require improved treatment. We are requesting funding of our translational research to leverage the longitudinally phenotyped FDNY-WTC cohort and identify Biomarkers of Airway Disease, Barrett’s and Underdiagnosed Reflux Noninvasively (BAD-BURN). We will develop the WTC aerodigestive repository, validate biomarkers of GERD and BE (AIM 1), and phenotype subgroups with aerodigestive disease to identify noninvasive biomarkers of diagnosis/treatment efficacy to inform future biologically plausible therapies to improve care (AIM 2).

概括 世界贸易中心（WTC）的破坏导致成千上万的第一响应者和 纽约市的居民WTC合时物质（WTC-PM）。我们消防部门的WTC-PM暴露 纽约（FDNY）队列与阻塞气道疾病（OAD）的发展有关 胃食管反射疾病（GERD）和Barrett的食道（BE）。 GERD是众所周知的风险因素 BE的化生变化，随后会导致腺癌。 GERD也有关联 与占领或环境暴露有关的OAD。总体而言，与OAD接触WTC的消防员有一个 开发GERD的风险高三倍。至少40％的WTC救援和恢复工人有 开发的GERD症状，是9/11前患病率的8.2倍。在这些发现的背景下 我们建议研究世界贸易中心裸露的FDNY队列中的机化疾病：验证 生物标志物和定义裁缝疗法的风险。这将进一步定义和表型 机修工/胃肠道健康生物标志物，并确定对肺部健康的影响以改善护理 从而履行了詹姆斯·扎德罗加（James Zadroga）9/11卫生与薪酬法案的任务：PAR-20-280。 GERD降低了与健康相关的生活质量和生产力。 GERD的并发症可以进一步扩展 超越;食道外回流会促使或加剧过敏，鼻窦炎，慢性支气管炎和 哮喘。 Refertionx的管理是具有挑战性的，因为对治疗的难治常常，诊断可能是侵入性的，并且 有大量相关成本。 WTC-PM暴露与哮喘相关的患者经常发生 持续的gerd。此外，GERD增加了开发WTC-AHR的几率，独立于暴露 强度。尽管许多研究表明气道和消化疾病之间的相互依赖性，但 因果因素和特定机制尚不清楚。我们已经成功识别了代谢， WTC-Airway高反应性（WTC-AHR）的血管和炎症生物标志物。我们还确定了 GERD/BE的生物标志物在我们的WTC暴露于患有呼吸道疾病的人群中，支持鉴定 生物学相关的免疫途径。 我们提出了两个旨在探讨血清生物标志物将区分FDNY救援和 恢复患有机动性发病率的工人，他们开始发展GERD/BE。无创生物标志物会 确定可能需要改善治疗的受试者。我们要求资助我们的翻译 研究纵向表型FDNY-WTC队列的研究并确定气道的生物标志物 疾病，巴雷特和诊断不足的反流（燃烧）。我们将开发WTC 机水存储库，验证GERD和BE（AIM 1）的生物标志物，以及具有表型亚组 鉴定诊断/治疗效率的非侵入性生物标志物的机动性疾病，以告知未来 生物学上合理的疗法以改善护理（AIM 2）。