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: 10459194
• 负责人: Anna Nolan
• 金额: $ 49.12万
• 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/10459194
• 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) 的毁坏导致数千名急救人员暴露在危险之中 纽约市居民在我们消防部门接触到的 WTC-PM 颗粒物 (WTC-PM)。 纽约 (FDNY) 队列与阻塞性气道疾病 (OAD) 的发展相关， 胃食管反流病（GERD）和巴雷特食管（BE）是众所周知的危险因素。 BE 的化生改变也可能导致胃食管反流病 (GERD)。 与职业或环境暴露相关的 OAD 总体而言，接触过 WTC 的消防员患有 OAD。 至少 40% 的世贸中心救援和恢复工作人员患有胃食管反流病 (GERD) 的风险高出三倍。 出现 GERD 症状，是 9/11 之前患病率的 8.2 倍。 我们建议研究，世界贸易中心暴露的 FDNY 队列中的呼吸消化疾病：验证 生物标志物和定义风险以定制治疗这将进一步定义和表型。 呼吸消化/胃肠道健康生物标志物，以及确定对肺部健康的影响以改善护理 履行 James Zadroga 9/11 健康与补偿法案：PAR-20-280 的任务。 胃食管反流病会降低与健康相关的生活质量和生产力。胃食管反流病的并发症可能会进一步延长。 除了 BE 之外；食管外反流还会引发或加重过敏、鼻窦炎、慢性支气管炎和 哮喘的治疗具有挑战性，因为治疗通常难以治愈，而且诊断可能是侵入性的。 与 WTC-PM 暴露相关的哮喘患者更常发生显着的相关费用。 此外，无论是否暴露，GERD 都会增加发生 WTC-AHR 的几率。 尽管许多研究表明气道疾病和消化系统疾病之间存在相互依赖性。 我们已经成功地确定了代谢、 我们还发现了 WTC 气道高反应性的血管和炎症生物标志物 (WTC-AHR)。 在世贸中心暴露的患有呼吸道疾病的人群中进行 GERD/BE 生物标志物，有助于识别 生物学相关的免疫途径。 我们提出两个目标来探索血清生物标志物将区分 FDNY 救援和 患有呼吸消化疾病的康复工作者将继续开发 GERD/BE。 确定可能需要改进治疗的受试者。我们正在请求为我们的转化提供资金。 研究利用纵向表型 FDNY-WTC 队列并识别气道生物标志物 我们将开发 WTC。 呼吸消化存储库，验证 GERD 和 BE (AIM 1) 的生物标志物以及表型亚组 呼吸消化疾病，以确定诊断/治疗效果的无创生物标志物，为未来提供信息 改善护理的生物学上合理的疗法（AIM 2）。