Uncontrolled Lower Respiratory Symptoms in the WTC Survivor Program

描述（由申请人提供）：暴露于世界贸易中心（WTC）灾难的灰尘和烟雾导致对响应者和社区成员人群的上呼吸道和下呼吸道症状（LRS）的不良健康影响。贝尔维尤医院世贸中心环境健康中心（WTC EHC）是一个治疗方案，于2005年开始，针对社区成员，现在称为“幸存者”，包括当地居民，当地工人和清洁工人与世贸中心的灰尘和烟雾暴露。下呼吸道症状（咳嗽、喘鸣、呼吸困难、胸闷）在该项目的患者中普遍存在。尽管进行了治疗，但在世贸中心塔楼被摧毁11年后，世贸中心EHC中的许多患者报告了不完全的临床反应，并伴有持续的下呼吸道症状。下呼吸道症状（LRS）持续不受控制的患者继续接受长期高剂量ICS治疗，通常额外使用LABA，使其面临长期ICS治疗的不良健康影响风险。尽管进行了治疗干预，但症状持续存在，需要重新评估并寻找持续症状的原因。我们的总体假设是，与那些症状得到控制的患者相比，尽管进行了积极的药物治疗，但LRS不受控制的WTC EHC患者的气道生理异常、气道炎症和共病率增加。确定这些机制不受控制的LRS是必要的，以指导治疗的重要潜力，以减少继发性不良健康后果。我们将使用一项前瞻性研究来检验这一假设，其目的如下：具体目的1：检验以下假设，即尽管对下呼吸道症状进行了积极治疗，但仍有一组患者的下呼吸道症状（ULRS）不受控制，与下呼吸道症状（CLRS）控制的患者不同。具体目标二：检验以下假设：与CLRS特定目标3相比，肺生理学的离散测量值与WTC EHC伴URLS患者相关：检验以下假设：与CLRS相比，炎症标志物（FeNO、外周嗜酸性粒细胞、C-反应蛋白、血清骨膜蛋白）水平较高与WTC EHC伴ULRS患者相关。具体目标4：检验与CLRS患者相比，WTC EHC伴ULRS患者的合并症发生率增加相关的假设。这些患者的生理学发现、炎症反应和共病状况的表征有可能指导治疗，降低该人群的药物风险，并将为其他环境诱导下呼吸道疾病或哮喘人群的未来研究提供线索。

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.