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).

总结 世界贸易中心（WTC）的破坏导致数千名第一反应人员暴露， 纽约市的居民对WTC-颗粒物（WTC-PM）。我们消防部门的WTC-PM暴露 纽约（FDNY）队列的患者与阻塞性气道疾病（OAD）的发生相关， 胃食管反流病（GERD）和巴雷特食管（BE）。GERD是一个众所周知的风险因素， BE的化生性变化，随后可导致腺癌。GERD也与 与职业或环境暴露相关的OAD。总的来说，WTC暴露的OAD消防员 发生胃食管反流病的风险高三倍。至少40%的世贸中心救援和恢复工作人员 出现GERD症状，是9/11前患病率的8.2倍。正是在这些发现的背景下， 我们建议研究，世界贸易中心暴露FDNY队列中的呼吸消化道疾病：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 因此，履行詹姆斯·扎德罗加9/11健康与赔偿法案：PAR-20-280的任务。 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延长 超过BE;食管外反流可诱发或加重过敏，鼻窦炎，慢性支气管炎， 哮喘反流的管理具有挑战性，因为通常难以治疗，诊断可能是侵入性的， 具有显著的相关成本。与WTC-PM暴露相关的哮喘患者更经常 持续性GERD。此外，GERD增加了发展WTC-AHR的几率，与暴露无关 强度。尽管许多研究表明呼吸道疾病和消化道疾病之间存在相互依赖性， 致病因素和具体机制尚不清楚。我们已经成功地鉴定出代谢， WTC-气道高反应性（WTC-AHR）的血管和炎症生物标志物。我们还确定 我们的WTC暴露人群中的GERD/BE生物标志物，有助于识别 生物学上相关的免疫途径。 我们提出了两个AIM来探讨血清生物标志物将区分FDNY急救和 患有呼吸消化系统疾病并继续发展为GERD/BE的康复工作者。非侵入性生物标志物将 确定可能需要改进治疗的受试者。我们正在申请资金， 利用纵向表型FDNY-WTC队列并确定气道生物标志物的研究 疾病，巴雷特和诊断不足反流非侵入性（BAD-BURN）。我们将开发世贸中心 呼吸消化库，验证GERD和BE（AIM 1）的生物标志物，以及 呼吸消化系统疾病，以确定诊断/治疗疗效的非侵入性生物标志物，为未来提供信息 生物学上合理的治疗，以改善护理（AIM 2）。