Uncontrolled Lower Respiratory Symptoms in the WTC Survivor Program

描述(由申请人提供)：暴露在世界贸易中心(WTC)灾难的粉尘和烟雾中会对健康造成不良影响，在反应人员和社区成员中出现上呼吸道和下呼吸道症状(LRS)。贝尔维尤医院WTC环境健康中心(WTC EHC)是一项始于2005年的治疗计划，目标是社区成员，现在被称为“幸存者”，包括当地居民、当地工人和接触WTC灰尘和油烟的清洁工人。下呼吸道症状(咳嗽、喘息、呼吸困难、胸闷)在本方案的患者中普遍存在。尽管进行了治疗，但在世贸中心塔楼被摧毁11年后，WTC EHC中的许多患者报告临床反应不完全，并持续出现下呼吸道症状。持续不受控制的下呼吸道症状(LRS)的患者仍在接受长期大剂量ICS治疗，通常同时使用额外的LABA，使他们面临长期ICS治疗的不良健康影响的风险。尽管采取了治疗措施，但症状的持续存在需要重新评估和寻找持续症状的原因。我们的总体假设是，与那些有控制症状的患者相比，WTC EHC患者尽管接受了积极的药物治疗，但仍有不受控制的LRS，其气道生理异常、呼吸道炎症和合并症的发生率较高。确定失控的LRS的这些机制对于指导治疗具有重要的潜力，以减少二次不良健康后果是必要的。我们将通过一项具有以下目的的前瞻性研究来检验这一假设：具体目标1：检验这一假设，即尽管对下呼吸道症状进行了积极的治疗，但仍有一组患者具有不同于那些有控制下呼吸道症状(CLR)的不受控制的下呼吸道症状(ULR)。特定目的2：验证肺生理指标的离散指标与WTC EHC中有URL的患者相比与CLRS患者相关的假设。特定目的3：测试较高水平的炎症标记物(FeNO、外周血嗜酸粒细胞、C反应蛋白、血清Periostin)与WTC EHC患者ULRS相比与CLRS相关的假设。具体目的4：验证WTC EHC患者与CLRS患者相比，合并疾病发生率增加与ULRS患者相关的假说。这些患者的生理表现、炎症反应和合并症的特征有可能指导治疗，降低这一人群的用药风险，并将为未来对其他患有环境诱导性下呼吸道疾病或哮喘的人群的研究提供线索。

DESCRIPTION (provided by applicant): Exposure to the dust and fumes of the World Trade Center (WTC) disaster resulted in adverse health effects with upper and lower respiratory symptoms (LRS) in populations of responders and community members. The Bellevue Hospital WTC Environmental Health Center (WTC EHC) is a treatment program started in 2005 to target community members, now called "Survivors," including local residents, local workers and clean-up workers with WTC dust and fume exposures. Lower respiratory symptoms (cough, wheeze, dyspnea, chest tightness) are prevalent in patients in this program. Despite treatment, eleven years after the destruction of the WTC towers, many patients in the WTC EHC report incomplete clinical response with continued lower respiratory symptoms. Patients with continued uncontrolled lower respiratory symptoms (LRS) remain on treatment with long-term high dose ICS often with additional LABA use, rendering them at risk for adverse health effects of long term ICS treatment. The persistence of symptoms, despite therapeutic interventions, necessitates a reevaluation and a search for causes of persistent symptoms. Our overall hypothesis is that WTC EHC patients with uncontrolled LRS despite aggressive medical therapy have increased rates of abnormal airway physiology, airway inflammation and co-morbid conditions when compared to those with controlled symptoms. Identifying these mechanisms for uncontrolled LRS is imperative to guide therapy with the important potential to reduce secondary adverse health outcomes. We will test this hypothesis using a prospective study with the following aims: Specific Aim 1: To test the hypothesis that despite aggressive treatment for lower respiratory tract symptoms there is a continued group of patients with uncontrolled lower respiratory symptoms (ULRS) that differ from those with controlled lower respiratory symptoms (CLRS). Specific Aim 2: To test the hypothesis that discrete measures of lung physiology are associated with patients in the WTC EHC with URLS compared to CLRS Specific Aim 3: To test the hypothesis that higher levels of inflammatory markers (FeNO, peripheral eosinophils, C-reactive protein, serum periostin) are associated with WTC EHC patients with ULRS compared to CLRS. Specific Aim 4: To test the hypothesis that increased rates of comorbid conditions are associated with WTC EHC patients with ULRS compared to those with CLRS. Characterization of the physiologic findings, inflammatory response and co-morbid conditions in these patients has the potential to guide treatment with reduced medication risk for this population and will provide clues for future investigations in other populations with environmental induced lower respiratory disease or asthma.