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

摘要 世界贸易中心(WTC)的破坏导致数千名急救人员和 纽约市居民到WTC-颗粒物(WTC-PM)。我国消防部门的WTC-PM暴露情况 纽约(FDNY)队列与阻塞性呼吸道疾病(OAD)的发展有关， 胃食道反流病(GERD)和巴雷特食道(BE)。GERD是一个众所周知的危险因素 BE的化生改变，可随后导致腺癌。GERD也与 有职业或环境暴露相关的OAD。总体而言，接触WTC的OAD消防员有一个 患GERD的风险高三倍。至少40%的世贸中心救援和恢复人员 出现GERD症状，是9.11之前患病率的8.2倍。这就是在这些发现的背景下 我们建议研究，空气消化系统疾病在世界贸易中心暴露的纽约联邦储备银行队列：验证 生物标记物和定义裁剪疗法的风险。这将进一步定义和表型 空气消化/胃肠健康生物标志物，以及确定对肺健康的影响，以改善护理 从而履行詹姆斯·扎德罗加9/11健康和补偿法的任务：PAR-20-280。 GERD降低了与健康相关的生活质量和生产力。GERD的并发症可进一步扩大 除BE外；食道外反流可引发或加重过敏、鼻窦炎、慢性支气管炎和 哮喘。反流的管理是具有挑战性的，因为通常难以治疗，诊断可能是侵入性的和 有很大的关联成本。与WTC-PM暴露相关的哮喘患者更容易出现 持续性胃肠道反流病。此外，GERD增加了发生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系统疾病之间存在相互依赖关系，但 致病因素和具体机制尚不清楚。我们已经成功地确定了新陈代谢， WTC-气道高反应性的血管和炎性生物标志物(WTC-AHR)。我们还确认了 本中心呼吸系统疾病暴露人群中GERD/BE的生物标志物，便于鉴定 与生物相关的免疫途径。 我们提出了两个目的来探索这一假设，即血清生物标记物将区分FDNY救援和 患有空气消化系统疾病的康复人员继续发展为GERD/BE。非侵入性生物标志物将 确定可能需要改进治疗的受试者。我们正在为我们的翻译申请资金 利用纵向表型FDNY-WTC队列和识别呼吸道生物标志物的研究 疾病、Barrett‘s和漏诊的反流无创(严重烧伤)。我们将发展世贸中心 空气消化库，验证GERD和BE的生物标记物(AIM 1)，以及表型亚群 空气消化疾病识别非侵入性生物标志物的诊断/治疗效果，以告知未来 改善护理的生物学上看似合理的疗法(目标2)。

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).